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          PRELIMINARY DATA SUMMARY
                   FOR THE
        PHARMACEUTICAL MANUFACTURING
            POINT  SOURCE  CATEGORY
  Office of Water Regulations and Standards
               Office of Water
United States Environmental Protection Agency
               Washington,  D.C.

                 August 1989

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                             PREFACE


     This is one of a series of Preliminary Data Summaries
prepared by the Office of Water Regulations and Standards of the
U.S. Environmental Protection Agency.  The Summaries contain
engineering, economic and environmental data that pertain to
whether the industrial facilities in various industries discharge
pollutants in their wastewaters and whether the EPA should pursue
regulations to control such discharges.  The summaries were
prepared in order to allow EPA to respond to the mandate of
section 304(m) of the Clean Water Act, which requires the Agency
to develop plans to regulate industrial categories that
contribute to pollution of the Nation's surface waters.

     The Summaries vary in terms of the amount and nature of the
data presented.  This variation reflects several factors,
including the overall size of the category (number of
dischargers), the amount of sampling and analytical work
performed by EPA in developing the Summary, the amount of
relevant secondary data that exists for the various categories,
whether the industry had been the subject of previous studies  (by
EPA or other parties), and whether or not the Agency was already
committed to a regulation for the industry.  With respect to the
last factor, the pattern is for categories that are already the
subject of  regulatory activity  (e.g., Pesticides, Pulp and Paper)
to have relatively short Summaries.  This is because the
Summaries are intended primarily to assist EPA management in
designating industry categories for rulemaking.  Summaries for
categories  already subject to rulemaking were developed for
comparison  purposes and contain only the minimal amount of data
needed to provide some perspective on the relative magnitude of
the pollution problems created across the categories.

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                        ACKNOWLEDGEMENTS


Preparation of this Preliminary Data Summary was directed by Dr.
Frank H. Hund, Project Officer, of the Industrial Technology
Division.  Preparation of the economic analysis sections was
directed by Mr. Rob Esworthy, Mr. Mitchell Dubensky, and Ms.
Debra Nicoll of the Analysis and Evaluation Division.  Mr. Rod
Frederick of the Assessment and Watershed Protection Division was
responsible for preparation of the environmental assessment
analysis.  Support was provided under EPA Contract Nos. 68-03-
3412, 68-03-6302, 68-03-3366 and 68-03-3339.

Additional copies of this document may be obtained by writing to
-,he following address:

          Industrial Technology Division  (WH-552)
          U.S. Environmental Protection Agency
          401 M Street, S.W.
          Washington, D.C. 20460

          Telephone  (202)  382-7131

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                        TABLE OF CONTENTS

Section    	  Title	Page No.


        SUMMARY	i

  I.    INTRODUCTION  	   1

        A.   PURPOSE	2

        B.   AUTHORITY	2

        C.   REGULATORY STATUS 	 5

        TECHNICAL SUPPORT STUDY

 II.    DESCRIPTION OF THE INDUSTRY	13

        A.   SUMMARY OF METHODOLOGY AND INFORMATION
             SOURCES	13

        B.   INDUSTRY PROFILE	14

        C.   MANUFACTURING PROCESSES 	 15

        D.   INDUSTRY SUBCATEGORIZATION	28

        E.   METHOD OF DISCHARGE	32

 III.    WASTE CHARACTERIZATION	34

        A.   SUMMARY OF METHODOLOGY AND DATA SOURCES  .  . 34

         B.   EXISTING DATA SOURCES	35

         C.   NEW DATA SOURCES	59

         D.   POLLUTANT MASS LOADINGS AND SOLID WASTE
             GENERATION	105

  IV.     CONTROL AND TREATMENT TECHNOLOGY	113

         A.  INTRODUCTION	113

         B.  IN-PLANT SOURCE CONTROL 	  113

         C.  IN-PLANT TREATMENT	114

         D.  END-OF-PIPE TREATMENT  	  139

         E.  ULTIMATE DISPOSAL  	  155

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                    TABLE OF CONTENTS (continued)

 Section	Title	Page No.

             ECONOMIC IMPACT ANALYSIS                     158

   V.     INTRODUCTION TO ECONOMIC IMPACT STUDY	159

  VI.     ECONOMIC CHARACTERISTICS AND OUTLOOK	161

         A.   INDUSTRY CHARACTERISTICS	161

         B.   OUTLOOK	163

 VII.     PRODUCT GROUPS - DESCRIPTION AND OUTLOOK .  . .  .170

         A.   PREPARATIONS AFFECTING NEOPLASMS, ENDOCRINE
            SYSTEM  AND  METABOLIC DISEASES	170

         B.   PREPARATIONS AFFECTING CENTRAL NERVOUS AND
            SENSE ORGANS	173

         C.   PREPARATIONS AFFECTING THE CARDIOVASCULAR
            SYSTEM	173

         D.   PREPARATIONS AFFECTING THE RESPIRATORY
            SYSTEM	174

         E.   PREPARATIONS AFFECTING THE DIGESTIVE AND
            GENITO-URINARY  SYSTEMS	174

         F.   PREPARATIONS AFFECTING THE SKIN	175

         G.   VITAMINS,  NUTRIENTS AND HEMATINIC
            PREPARATIONS	175

         H.   PREPARATIONS AFFECTING PARASITIC AND
            INFECTIOUS  DISEASES	176

         I.   PREPARATIONS FOR VETERINARY USE	176

         J.   BLOOD AND BLOOD DERIVATIVES FOR HUMAN USE .  176

         K.   PREPARATIONS FOR ACTIVE AND PASSIVE
            IMMUNIZATION AND THERAPEUTIC COUNTERPARTS.  .176

VIII.    FINANCIAL ANALYSIS  OF PHARMACEUTICAL FIRMS  .  .  .178

         A.   RATIO ANALYSIS	178

         B.   PROFITABILITY	178

         C.   LIQUIDITY	179

         D.   SOLVENCY	182

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                       TABLE  OF CONTENTS  (continued)




Section	Title	Page No.




        E.   LEVERAGE	182




        F.   SUMMARY	183




 IX.    PHARMACEUTICAL PLANT PROFILE  	  184




        A.   GEOGRAPHICAL DISTRIBUTION OF THE INDUSTRY .  .184




        B.   PLANT SIZES	187




  X.    TREATMENT TECHNOLOGY AND  COSTING 	  189




 XI.    ESTIMATED ECONOMIC IMPACTS  	  198




        A.   COMPLIANCE COST  TO SALES  RATIO	200




        B.   CHANGE IN PROFITS	207




        C.   CONCLUSIONS	214




        ENVIRONMENTAL IMPACT ANALYSIS                    215




 XII.   ENVIRONMENTAL IMPACT ANALYSIS	216




        A.   METHODOLOGY	216




        B.   DATA SOURCES	218




        C.   SUMMARY  OF ENVIRONMENTAL  IMPACTS	219




XIII.   REFERENCES	229




XIV.    GLOSSARY OF ACRONYMS	231

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                          LIST OF TABLES

Table No.	Title 	Page No,

         ESTIMATED ANNUAL MASS LOADINGS  -  PHARMACEUTICAL
         MANUFACTURING  INDUSTRY 	  V
 1-1    CURRENT  STATUS  OF  EFFLUENT  LIMITATIONS GUIDELINES AND
        STANDARDS  FOR THE  PHARMACEUTICAL MANUFACTURING
        CATEGORY 	  H

II-l    PHARMACEUTICAL  INDUSTRY - GEOGRAPHICAL
        DISTRIBUTION  	  16

II-2    PRODUCTION OPERATION BREAKDOWN 	 19

II-3    SUBCATEGORY BREAKDOWN	30

II-4    SUMMARY  OF METHOD  OF DISCHARGE AT PHARMACEUTICAL
        PLANTS	33

III-l   SUMMARY  OF LONG-TERM DATA	37

III-2   SUPPLEMENTAL BIOLOGICAL TREATMENT DATA SUMMARY .  . 39

III-3   EFFLUENT FILTER PERFORMANCE INFORMATION	40

III-4   LIST OF  PRIORITY POLLUTANTS	41

III-5   SUMMARY  OF PRIORITY POLLUTANT USE:  PEDCo REPORTS. 43

III-6   COMPILATION OF  DATA SUBMITTED BY THE PMA FROM 26
        MANUFACTURERS OF ETHICAL DRUGS:  1975 OAQPS STUDY. 44

III-7   SUMMARY  OF VOC  EMISSION DATA:  1975 OAQPS STUDY.  . 45

III-8   DATA SUBMITTED  BY  PMA FROM 22 PHARMACEUTICAL
        MANUFACTURERS:  1985 OAQPS STUDY	47

111-9   SUMMARY  OF PRIORITY POLLUTANT DATA FROM THE 1983
        TTVO QUESTIONNAIRE	48

111-10  SUMMARY  OF PRIORITY POLLUTANT OCCURRENCE SCREENING
        PLANT DATA	53

III-11  SUMMARY  OF PRIORITY POLLUTANT CONCENTRATIONS
        SCREENING/VERIFICATION DATA BASE	56

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                    LIST OF TABLES  (continued)

Table No.	Title	Page No.

111-12   SUMMARY OF  ANALYTICAL  DATA:   PLANT  12342  	  60

111-13   SUMMARY OF  ANALYTICAL  DATA SUBMITTED BY THE LOCAL
        POTW FOR PLANT 12342	61

111-14   ITD AND/OR  DSS  LISTED  VOLATILE  ORGANIC COMPOUNDS
        REVIEWED FOR MENTION IN PHARMACEUTICAL
        PRODUCT PATENTS	64
111-15  ITD AND/OR  DSS  LISTED VOLATILE  ORGANIC COMPOUNDS
        IDENTIFIED  IN PATENTS AS  POTENTIALLY  USED IN
        PHARMACEUTICAL PRODUCT MANUFACTURE	66

111-16  NUMBER OF PHARMACEUTICAL  PRODUCTS THAT MAY USE THE
        FOLLOWING PRIORITY  POLLUTANTS IN THEIR
        MANUFACTURE	68

111-17  SUMMARY OF  REPORTED ANALYTICAL  RESULTS FOR PLANT
        12135	74

111-18  ITD/RCRA SAMPLING PROGRAM:   SUMMARY OF REPORTED
        ANALYTICAL RESULTS:  PLANT 12204	.  .  .78

111-19  ITD/RCRA SAMPLING PROGRAM:   SUMMARY OF REPORTED
        ANALYTICAL RESULTS:  PLANT 12236	83

111-20  ITD/RCRA SAMPLING PROGRAM:   SUMMARY OF REPORTED
        ANALYTICAL RESULTS:  PLANT 12447	88

111-21  ITD/RCRA SAMPLING PROGRAM:   SUMMARY OF REPORTED
        ANALYTICAL RESULTS:  PLANT 99999	92

111-22  SUMMARY OF  ANALYTICAL RESULTS FOR SPECIFIC ORGANIC
        COMPOUNDS AT PLANT  88888  	 98

111-23  SUMMARY OF  DETECTED ANALYTICAL  RESULTS - ITD LISTED
        COMPOUNDS	99

111-24  ESTIMATED ANNUAL RAW WASTE LOADINGS - PHARMACEUTICAL
        MANUFACTURING INDUSTRY  	 107

111-25  SUMMARY OF  ANALYTICAL RESULTS FOR SLUDGE SAMPLES:
        ITD/RCRA SAMPLING PROGRAM	Ill

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                    LIST OF TABLES (continued)

Table No.	Title     	Page No.

IV-1     INDUSTRIAL  STEAM-STRIPPERS  	  120

IV-2     METHYLENE CHLORIDE REMOVAL  IN PACKED COLUMN STEAM
         STRIPPER AT PLANT  12003	126

IV-3     TOLUENE  REMOVAL IN STEAM DISTILLATION FLASH TANK
        AT PLANT 12003	132

IV-4     SUMMARY  OF  EOF TREATMENT PROCESSES
         (DATA BASE:  308)	141

IV-5     HENRY'S  LAW CONSTANTS FOR SELECTED VOLATILE
        ORGANIC  COMPOUNDS	143

IV-6     AVERAGE  WASTEWATER POLLUTANT LEVELS:  ITD/RCRA
        SAMPLING PROGRAM:   PLANT  12236	149

IV-7     AVERAGE  WASTEWATER POLLUTANT LEVELS:  ITD/RCRA
        SAMPLING PROGRAM:   PLANT  99999	151

IV-8     AVERAGE  WASTEWATER POLLUTANT LEVELS:  ITD/RCRA
        SAMPLING PROGRAM:   PLANT  12204.	154

IV-9     SUMMARY  OF  WASTEWATER DISCHARGES 	  156

VI-1     PHARMACEUTICAL INDUSTRY CHARACTERISTICS	162

VI-2     VALUE OF SHIPMENTS - PHARMACEUTICAL INDUSTRY .  .  165

VI-3     TRADE  DATA  - PHARMACEUTICAL INDUSTRY 	  167

VI-4     AFTER  TAX RATES OF PROFIT	169

VII-1    PHARMACEUTICAL FINAL PRODUCTS -  VALUE SHIPMENTS
         BY ALL PRODUCERS	171

VIII-1   FINANCIAL RATIOS OF 43 PUBLICLY OWNED
         PHARMACEUTICAL FIRMS 	  180

IX-1     PHARMACEUTICAL PLANT PROFILE BY  PLANT,  SALES BY
         PLANT, SALES,  EMPLOYMENT 	  185

IX-2     PLANT  SIZES:  SALES AND EMPLOYMENT  	 188

X-l      CALCULATION OF ANNUALIZED COSTS FOR PLANTS WITH
         PROCESS  WASTEWATER  FLOW	192

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                    LIST OF TABLES (continued)

Table No.	Title	Page No.

XI-1     NUMBER OF PLANTS BY DISCHARGE STATUS AND
        SUBCATEGORIES  	 199

XI-2     PLANTS BY DISCHARGE STATUS,  SUBCATEGORY AND ANNUALIZED
         COMPLIANCE COSTS AS PERCENTAGE OF SALES. .  .  .  201

XI-3    EFFECT OF REGULATION ON PROFITS	208

XII-1   SUMMARY OF VOLATILE ORGANICS AND  RECEIVING  STREAMS WITH
         PROJECTED HUMAN HEALTH AND AQUATIC LIFE IMPACTS AT LOW
         FLOW UNDER CURRENT CONDITIONS,  DIRECT DISCHARGERS
         (SUBCATEGORY A,  B,  AND C)	222

XII-2    SUMMARY OF VOLATILE ORGANICS PROJECTED TO EXCEED
         CRITERIA  AT LOW FLOW UNDER CURRENT CONDITIONS,  DIRECT
         DISCHARGERS (SUBCATEGORY  A,  B,  AND C)	223

XII-3    SUMMARY OF MONITORED RECEIVING STREAM IMPACTS -
         DIRECT AND INDIRECT DISCHARGERS (SUBCATEGORY A, B,
        AND C)	224

XII-4   SUMMARY OF MONITORED POLLUTANT IMPACTS  - DIRECT
        DISCHARGERS  (SUBCATEGORY A,  B, AND C)	Z25

XII-5   SUMMARY OF VOLATILE ORGANICS AND  RECEIVING  STREAMS WITH
         PROJECTED HUMAN HEALTH AND AQUATIC LIFE IMPACTS AT LOW
         FLOW UNDER CURRENT CONDITIONS,  INDIRECT DISCHARGERS
         (SUBCATEGORY A,  B,  AND C)	226

XII-6    SUMMARY OF VOLATILE ORGANICS PROJECTED TO EXCEED
        CRITERIA AT LOW FLOW UNDER CURRENT CONDITIONS,  INDIRECT
         DISCHARGERS  (SUBCATEGORY  A,B,AND  C)	  227

XII-7    SUMMARY OF MONITORED POLLUTANT IMPACTS - INDIRECT
        DISCHARGERS  (SUBCATEGORY A,B, AND C)	229

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                         LIST OF FIGURES

Figure No.	Title	Page No.

II-l    PHARMACEUTICAL INDUSTRY - GEOGRAPHICAL
        DISTRIBUTION 	 20

III-l   PRODUCT PATENT COVERAGE	63

III-2   VOLATILE ORGANIC COMPOUNDS  POTENTIALLY USED IN
        SUBCATEGORY  A,  B,  AND C PRODUCT MANUFACTURE . . .67

III-3   PLANT NO.  12135:  WASTEWATER  PRETREATMENT  SYSTEM.73

III-4   PLANT NO.  12204:  WASTEWATER  PRETREATMENT  SYSTEM.77

III-5   PLANT NO.  12236:  WASTEWATER  TREATMENT SYSTEM .  .82

III-6   PLANT NO.  99999:  WASTEWATER  PRETREATMENT  SYSTEM.91

IV-1    TYPICAL EQUIPMENT FOR STEAM STRIPPING SOLVENTS FROM
        WASTEWATER	117

IV-2    PACKED COLUMN STEAM STRIPPER  AT PLANT 12003 .  .  .131

IV-3    STEAM DISTILLATION  FLASH TANK AT PLANT 12003.  .  .135

IV-4    ACTIVATED  CARBON ADSORPTION UNIT	138

IV-5    EXAMPLES OF  AUGMENTED BIOLOGICAL SYSTEMS	147

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                             SUMMARY

The Industrial Technology Division  (ITD) of the U.S. Environmental
Protection Agency  (EPA)  conducted  a study of  the pharmaceutical
manufacturing industry as a result  of  findings from the Domestic
Sewage Study (DSS)  and from concern  for the potential discharge of
toxic and hazardous pollutants  from this  industry.   The purposes
of the study were to

    o   provide  technical,  economic, and environmental  bases to
        determine   whether    additional    effluent   limitation
        guidelines and standards to control the discharge of toxic
        and   hazardous   pollutants   are  necessary   for   the
        pharmaceutical manufacturing industry; and

    o   serve  as a source  of  information to  be used  by permit
        writers  and  publicly  owned treatment works  (POTWs)  in
        controlling   hazardous   wastes  until   final  rules  are
        published.

The  study  consisted  of  the  following  three interrelated  but
independent undertakings

    o   a technical support study;

    o   an  economic impact analysis; and

    o   an  environmental  impact analysis.

The technical support  study consisted of two parts:  the collection
and  analysis of  wastewater and waste solids samples  from  the
pharmaceutical  manufacturing  industry,   and   the  collection  of
sufficient information about the industry  to develop a preliminary
updated industry technical profile.   The economic impact study
consisted of  a review and update of the  economic profile of the
industry  and an  analysis of  the  projected  economic  impact of
additional   wastewater   regulation  on  the   industry.     The
environmental  impact  study was  an  evaluation of  the  impacts of
wastewater  discharges  from  direct  discharging   pharmaceutical
manufacturing  facilities  on  their receiving  streams  and  from
indirect discharging  facilities  on  publicly owned treatment works
(POTWs) and their receiving streams.

Technical Support Study

For the technical study,  EPA directed its  efforts  toward reviewing
available information, as well as gathering new information through
a  sampling  and analysis program, on the  wastewater discharge of
conventional,  priority,   and   nonconventional  pollutants  from
pharmaceutical manufacturing  facilities.   The sampling program,
conducted at  four  pharmaceutical plants,  helped characterize the
industry's wastewater with respect to approximately  250 additional

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compounds not included in previous sampling efforts,  the sampling
and in   include in previous sampling efforts. The  250  compounds
plus those included in previous sampling efforts constitute the ITD
List of Analytes.  This was the first ITD study to involve
the sampling and analysis of sludges generated at wastewater
treatment  facilities  in  this  industry.As part of the  study,  EPA
estimated  the   total  mass   of   conventional,   priority,   and
nonconventional pollutants present in the wastewater generated by
the pharmaceutical manufacturing industry.  The  following  table
summarizes EPA's  bestestimate  of  the  mass  discharge  of  these
pollutants, by direct and indirect discharging plants.

The  results  confirm  the  DSS  findings  that the  pharmaceutical
manufacturing   industry  discharges   significant  quantities   of
potentially   hazardous  compounds    (especially  priority   and
nonconventional  volatile   organic   compounds   [VOCs])   in  raw
wastewater.  Based on information obtained  in the  screening  and
verification sampling program, EPA estimates  that 4.7  million
pounds per year of priority pollutant VOCs  are  discharged in  the
industry's raw  wastewater.  Based on information obtained in  the
recent sampling  program  EPA estimates that  16 million  pounds  per
year  of  nonconventional  pollutant  VOCs  are discharged in  the
industry's raw wastewater.   Not shown on the table are 41 million
additional pounds  of  VOCs  not on the ITD List of Analytes  which
are estimated to be discharged annually in the industry wastewater.
The industry's  use,  disposition,  and the treatability  of  these
additional compounds were  not  characterized  in  this report  since
they  were  not  analyzed  for in the past or in  recent  sampling
programs.

Additional studies are warranted to accomplish the following:

    o   verify   EPA's  present  assessment  of the  discharge  of
        priority pollutant VOCs;

    o   better   characterize   the   industry's   discharge   of
        nonconventional  VOCs  detected   in   the  recent  sampling
        program (wastewater sampling data are presently available
        for  only six  of  the 464 plants in the industry);

    o   expand   the  list  of  VOCs  to  be  characterized  in  the
        wastewater discharges  to include those  commonly  used by
        the  industry  (e.g., alcohols) which  have  never been listed
        for  analysis  in  industry studies; and

    o   obtain  additional information on VOC control and treatment
        technologies  (e.g., steam-stripping).

Economic Impact Analysis

The economic study consisted  of a preliminary  economic  impact
analysis of possible regulations affecting pharmaceutical
                                ii

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manufacturing facilities,  particularly regulations  limiting  the
release of volatile  organic chemicals (VOCs).   A profile  of  the
industry, covering characteristics and trends for product groups,
individual plants and companies, and the industry as a whole was
included.  In addition, this report presents an assessment of the
ability of this industry to incur wastewater treatment costs.

The analysis described in this report was based on data currently
available from secondary sources,  data provided by earlier surveys
of this  industry,  and data provided  in the  technical section of
this document.   The analysis was limited by the  small amount of
plant-specific data  available  and the age of some  of this data.
However, the main conclusions are well supported.

Three sections of  this report  present an economic profile of the
pharmaceutical industry.  Section VI describes the characteristics
of the industry, including  foreign  trade, and its future outlook.
Section VII provides a detailed description of the various product
groups  and  their  growth  prospects.   Section  IX  presents  the
characteristics of pharmaceutical plants, including their location,
sales and employment  levels.

Sections  VIII,  X,  and XI present  the economic  impact analysis.
Section   VIII   describes  the   financial  characteristics   of
pharmaceutical companies based on a financial ratio  analysis of 43
firms.    Section  X  describes  the  procedures  used  to estimate
compliance  costs for  each  individual plant  with wastewater  dis-
charge.   Section XI  presents  the economic impacts on  individual
plants.

The  economic analysis concludes that  the pharmaceutical industry
continues  to be financially  healthy  and  that  most plants would
experience little or no impact  from regulating VOCs.   However,  some
plants  may  experience  substantial  impacts from  this  level of
compliance  costs.   For  example,  approximately  20 percent of the
plants would experience a decline in profits of 10 percent or move.

Environmental  Impact Analysis

The  environmental  impact study is  presented in Section XII.  The
study evaluated the  impacts of direct discharging  pharmaceutical
manufacturing plants on  their receiving streams and the impacts  of
 indirect discharging plants on the publicly  owned treatment works
 (POTWs)  to  which the plants discharge and on the  POTWs1  receiving
streams.  Two different  approaches  were used in the analyses.  The
 first  approach  involved  projecting instream  pollutant   con-
centrations of volatile  organic compound (VOCs)  from industry-wide
 average  pollutant  concentrations.    The  projected  pollutant
 concentrations were then compared to EPA water quality criteria  or
 toxic effect levels.
                                iii

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The  second  approach  employed  actual  VOC  monitoring  data from
streams receiving direct wastewater discharges from pharmaceutical
plants  and  monitoring  data  from  streams  receiving  indirect
discharges (via POTWs) .   Monitoring data were compared to EPA water
quality criteria or toxic effect levels.

Water quality impacts were projected  for 22 direct and 28 indirect
discharging plants in subcategories A, B, and C.   Fifteen VOCs were
evaluated  for  direct dischargers, eight of which  (all known or
suspected  carcinogens)   were  projected  to  exceed   human  health
criteria in  86 percent  of  the  stream segments.   None of the VOCs
evaluated were projected to exceed aquatic life criteria or toxic
effect levels.

The effects of 28 indirect  discharging plants were also evaluated.
Twenty-one volatile pollutants were  evaluated and  six  (all known
or suspected carcinogens)  were projected to exceed human health
criteria for carcinogens in 60 percent  of  the  streams receiving
discharges  from  the  POTWs to which the plants discharge.   No
volatile pollutants were projected to exceed aquatic  life criteria
or toxic effect levels.   No inhibition of POTW treatment processes
were  projected  for  the 12 VOCs  which  have inhibition  values.
Sludge contamination could not be evaluated.

The impacts by VOCs,  as  monitored  on  five streams receiving direct
discharges from pharmaceutical  plants and on six streams receiving
discharges from  facilities discharging  to POTWs were evaluated.
Nine of the  15 pollutants evaluated were detected in four streams
receiving direct discharges. Two  of  the  pollutants exceeded human
health  criteria   in  three  of the  streams.    Eight  of  the  21
pollutants  evaluated were detected  in  four  streams  receiving
indirect discharges.  Three of the pollutants exceeded human health
criteria in three of the streams.  All of the pollutants are known
or suspected carcinogens.  None of the volatile pollutants exceeded
aquatic life criteria or aquatic life toxic effect  levels.

Volatile  pollutant  data   for  pharmaceutical   facilities  with
monitoring  requirements or limitations were  also  summarized.
Eleven of the evaluated  pollutants were  monitored or limited for
36 percent of  the direct  discharging  facilities.    Eight  of the
evaluated pollutants were monitored  or  limited  for  19 percent of
the POTWs receiving discharges from indirect facilities.
                               IV

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                                                                ESTIMATED ANNUAL MASS  LOADINGS
                                                              PHARMACEUTICAL MANUFACTURING  INDUSTRY
                                                                                                      Mass  Loadings  For  Indirect Discharges  (I.OOP  Ib/yr)
Pollutants
Conventional Pollutants
o BODS
o TSS
Priority Pollutants
o Volatile Organics
o Semivolatile Organics
o Pesticides
o Metals
o Cyanide
Nonconventional Pollutants
o COD
o Volatile Organics
o Semivolatile Organics
o Pesticides/Herbicides
Industry Characteristics
o Number of Facilities
o Wastewater Flow (mgd)
Subcategories
Raw
Wastewater

83,000
45,000

2,000
120
--
60
22

192,000
5,100
59
63

30*
21.38
A, B, S, C*
Final
Effluent

5,900
4,600

77
2
—
22
7

44,000
**
**
**



Subcategory
Raw
Wastewater

4,100
1,200

240
17
—
1.2
0.3

7,500
1,000
10
11

21
3.54
D
Final
Effluent

300
290

6
0.2
—
0.7
0.2

800
**
**
**



Subcategories
Raw
Wastewater

169,000
64,500

2,400
390
0.02
51
4.3

411,000
7,700
87
92

130
31.1
A, B, & C
Discharge
to POTW

169,000
64,500

2,000
330
0.02
45
4.1

411,000
**
**
**



Subcategory
Raw
Wastewater

5,600
3,000

18
16
—
2
0.3

24,000
2,200
25
26

155
8.8
D
Discharge
to POTW

5,600
3,000

18
16
--
2
0.3

24,000
**





*  Excluding Plant 12256
— Negligible
** Insufficient data available

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                         I.   INTRODUCTION

This  document  comprises  three   interrelated  but  independent
studies relating to wastewater discharges from the pharmaceutical
manufacturing industry.  The studies  include a technical support
study, an  economic  impact analysis, and an  environmental impact
analysis.  The  technical  support  section   summarizes  current
information   available   on   the   wastewater   discharge   of
conventional,  priority,  and  nonconventional  pollutants  from
pharmaceutical manufacturing facilities.  As the result of recent
sampling and other data-gathering efforts,  it contains an updated
technical  industry profile and  wastewater  characterization.   The
recent   sampling  program  helped  characterize  the  industry's
wastewater with respect to approximately 250 additional compounds
not  included in previous  sampling efforts.   The  document  also
provides  a  technical  basis   for  determining  whether additional
national regulations should  be  developed for the industry.  Also
included is  information that can be used by permit writers and by
waste treatment system operators  in controlling hazardous wastes
and hazardous constituents until final rules are published.

The pharmaceutical manufacturing point source category is defined
and  described in  Section II,  along  with the subcategorization
scheme   used  in  previous   rulemaking  efforts.     Section  III
characterizes pharmaceutical manufacturing wastewater in terms of
the  presence  of  conventional,  priority,  and  nonconventional
pollutants.   Pollutant  control  and  treatment  technologies are
discussed  in Section IV.

The  economic impact analysis consists of  a  review  of economic
data   provided  by   earlier   surveys  of   the  pharmaceutical
manufacturing  industry   and  by   some  current  data  gathering
efforts.   The  data were used  to develop  an  updated economic
profile  of the industry.    These  data and data  provided in the
technical  support  section were the basis  of  an  analysis of the
impact  that wastewater  regulations  of  VOCs  would have  on the
industry.

The   analysis  concludes  that  the pharmaceutical   industry  is
financially  healthy  and that most plants would experience little
or no impact from regulation of VOCs.  However, the analysis does
project  that  approximately  20  percent  of  the  plants  in the
industry would  experience a decline  in profits of 10 percent or
more.

Three sections of  this report present an economic profile of the
pharmaceutical  industry.    Section  VI describes the  economic
characteristics of the industry,  including foreign  trade,  and its
future  outlook.   Section VII provides a  detailed description of
the  various  product groups  and their growth prospects.   Section
IX   presents  the   characteristics  of  pharmaceutical   plants,
including  their location, sales and employment levels.

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Sections  VIII,  X,  and  XI present  an economic  impact  analysis.
Section   VIII  describes   the   financial  characteristics   of
pharmaceutical companies based on an analysis of financial ratios
for  43  firms.    Section  X  describes  the procedures  used  to
estimate  compliance  costs   for  each   individual   plant  with
wastewater discharge.   Section XI presents  the  economic impacts
on individual plants.

The environmental impact study  evaluated the impacts  of direct
discharging   pharmaceutical    manufacturing  plants   on   their
receiving streams and the  impacts of indirect discharging plants
on the publicly owned treatment works (POTWs) to which the plants
discharge and on  the POTWs1  receiving streams.   A description of
the study and the results are presented in Section XII.

The impacts  of  a number of  VOCs on  receiving streams  from both
direct and indirect dischargers were evaluated.   Several known or
suspected carcinogens were found to exceed  or were  projected to
exceed human  health criteria  in  one or more streams.   However,
none  of   the  pollutants  evaluated  were  found  or projected  to
exceed aquatic life criteria or aquatic life toxic effect levels.
No evaluated pollutants were  projected  to inhibit POTW treatment
processes.

A.  PURPOSE

The  purposes of  this  decision  document  are to (1)  establish
technical,  economic,  and environmental  bases  for  determining
whether additional  national  regulations should  be developed for
the  pharmaceutical  manufacturing   industry;  and  (2)   provide
information  to  guide  permit  writers and  POTWs  in  controlling
hazardous wastes and hazardous constituents until final rules are
published.

B.  AUTHORITY

1.  Clean Water Act (CWA)

The U.S.  Environmental  Protection  Agency  (EPA)  is  required  by
Sections  301, 304,  306, and  307  of the  Federal  Water  Pollution
Control Act Amendments of  1972  and  1977  (the Clean Water Act,  or
CWA)  to  establish  technology-based  effluent  limitations  and
standards to  reduce the discharge of pollutants  to  the nation's
waters.    To achieve   these   goals,  the  Industrial  Technology
Division  (ITD)  is responsible  for:   (1)  developing,  proposing,
and  promulgating  effluent  limitations  guidelines,  new  source
performance   standards,   pretreatment   standards,    and   Best
Management   Practices    (BMPs)   for   industrial  point   source
discharges; (2)  assuring the adequacy and validity of scientific,
economic, and  technical data  and findings  used to  support the
effluent  limitations  and  standards;  (3)  gathering,  developing,
and analyzing data and background information basic to the annual
review and  periodic revision  of  limitations and  standards;  and
(4) developing technical information required for the judicial
review of effluent limitations guidelines and standards.

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This study was  conducted under the authority  of  Sections 301 (d)
and 304 (m) of the CWA, which require periodic review and revision
of limitations promulgated pursuant to Sections 301, 304, and 306
of the CWA.

    Section 301
    Any effluent limitation  required  by  paragraph (2)  of subsec-
    tion  (b)  of this  section shall  be  reviewed at  least  every
    five  years  and,   if  appropriate,  revised  pursuant to  the
    procedure established under such paragraph.

    Section 304 (m)

    Schedule for Review of Guidelines -

    (1) Publication.   Within  12 months  after  the  date of  the
        enactment   of   the  Water  Quality  Act of   1987,   and
        biennially  thereafter,  the  Administrator shall publish
        in the  Federal Register a plan which shall:

        (A) establish  a   schedule  for  the  annual  review  and
            revision   of   promulgated  effluent  guidelines,   in
            accordance with  subsection  (b) of  this section;

        (B) identify  categories of sources discharging  toxic or
            nonconventional   pollutants  for   which   guidelines
            under  subsection (b) (2)  of this section  and Section
            306 have not previously been published; and

        (C) establish  a  schedule  for  promulgation of  effluent
            guidelines for categories identified in subparagraph
             (b) ,  under  which  promulgation  of  such  guidelines
            shall be no  later than  four years  after such date of
            enactment  for  categories  identified in  the  first
            published  plan or three  years after the  publication
            of   the plan  for  categories  identified   in  later
            published  plans.

    (2) Public  Review.    The  Administrator   shall  provide  for
        public  review and  comment on  the plan prior  to  final
        publication.

As part of its review of effluent limitations,  EPA announced in a
Federal Register Notice (50 FR 36638,  September 9, 1985)  that new
information had  been  received concerning methylene chloride  and
other  toxic volatile  organic substances,  including new data on
air  emissions  of  methylene  chloride.    The  new  information
indicated that methylene chloride causes cancer in  animals,  such
that   the  effects  of   methylene   chloride    discharges   from
pharmaceutical manufacturing plants may be more harmful than
previously believed.  EPA became concerned about air emissions of
methylene  chloride and  other  toxic volatile  pollutants  from
biological treatment systems of pharmaceutical  manufacturing

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plants and POTWs receiving pharmaceutical wastewater.   The
presence of high concentrations of  toxic and/or hazardous (i.e.,
those identified as  hazardous constituents in  the  RCRA program)
volatile  organic  compounds  (VOCs)  within  sewer  systems  may
endanger  workers  or  create  conditions  leading  to  explosions
and/or fires.  Accordingly, EPA decided  to  review and update its
data  on  the   discharge  of  toxic  and   hazardous   VOCs  from
pharmaceutical manufacturing facilities.

2.  Resource Conservation and Recovery Act  (RCRA)

In  addition to responsibilities  under  the  CWA,  EPA is  also
charged  by  the  1976  RCRA with  oversight of  "cradle-to-grave11
management of hazardous solid wastes.  Section 3018(b) of RCRA is
specifically related to this study.

    Section 3018fb);  Revision of Regulations

    Within  18  months  after submitting  the report specified  in
    subsection   (a),  the  Administrator  shall  revise  existing
    regulations  and  promulgate   such   additional  regulations
    pursuant  to this  subtitle (or any other  authority  of the
    Administrator,  including Section  307  of  the  Federal Water
    Pollution  Control  Act)  as   are necessary to  assure  that
    substances  identified  or listed  under  Section   3001 which
    pass  through a  sewer  system to  a  publicly  owned treatment
    works are  adequately controlled to protect human health and
    the environment.

Section  3018 (a)  of RCRA,  as  amended by  the 1984  Hazardous and
Solid Waste Amendments  (HSWA), directs EPA  to submit  a report to
Congress  concerning  wastes discharged  through sewer  systems  to
POTWs that  are exempt  from RCRA regulation  as a result  of the
Domestic Sewage Exclusion  (DSE) of RCRA.   The DSE, established by
Congress in Section 1004(27) of RCRA, provides that solid  or dis-
solved material  in domestic sewage  is not solid waste as  defined
in  RCRA,  and  such materials  cannot be  considered  a hazardous
waste for RCRA  purposes.   The DSE applies to domestic sewage and
industrial wastes discharged to POTW sewers that contain domestic
sewage,   even   if  the  industrial   wastes  would  otherwise  be
considered hazardous.

The report  (the Domestic  Sewage  Study,  or DSS) was  prepared by
EPA's Office  of Water  and submitted to Congress on  February 7,
1986.   The  DSS examines  the nature  and  sources of hazardous
wastes discharged  to POTWs, measures the  effectiveness of EPA's
programs in dealing  with such discharges,  and recommends ways to
improve  the programs   to  achieve  better  control  of  hazardous
wastes entering POTWs.

Implicit  in the DSE  is  the  assumption  that  the  pretreatment
program mandated by the CWA can ensure adequate control of
industrial  discharges  to  sewers.   This program,  detailed under
Section  307 (b)  of the  CWA and implemented in 40 CFR Part 403,
requires EPA to establish pretreatment standards for pollutants

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discharged to POTWs by industrial facilities for those pollutants
which interfere with, pass through, or are otherwise incompatible
with the operation of POTWs.

In  follow-up to  the DSS,  Section 3018 (b)  of  RCRA  directs  the
Administrator to  revise existing regulations and  promulgate any
pretreatment  standards  controlling  the discharge  of individual
hazardous constituents  necessary  to  ensure that hazardous wastes
discharged  to POTWs are  adequately  controlled to  protect human
health  and  the  environment.    These  regulations  are  to  be
promulgated  pursuant to  RCRA,  Section  307 of  the CWA,  or any
appropriate  authority possessed by EPA.   The regulations must be
promulgated  within  18  months  after  submission  of  the  DSS  to
Congress  (i.e., by August 1987).

The  study  concludes that  the  DSE   should be  retained  at  the
present time, and recommends ways to  improve various EPA programs
under  the  CWA to   obtain  better  control  of  hazardous  wastes
entering  POTWs.   In  addition, the DSS  recommends study efforts to
fill  information  gaps,  and indicates  that other statutes  (e.g.,
RCRA and  the Clean  Air  Act)  should be considered with the CWA to
control either  hazardous waste dischargers,  receiving POTWs, or
both,  if  the  recommended  research   indicates  the  presence  of
problems  not adequately addressed by  the CWA.

A  main  recommendation of the study  is that EPA review and amend
categorical  pretreatment standards to achieve  better control of
the  constituents  of hazardous  wastes.  The  DSS recommends that
EPA  modify  existing standards  to   improve  control  of  organic
priority  and non-priority pollutants, and  promulgate  categorical
standards for industrial categories  not  included  in the  Natural
Resources Defense Council  Consent  Decree  (NRDC v.  Train, 8 ERC
2120, D.C.C., 1976).

Because the DSS findings identified  pharmaceutical  manufacturing
facilities  as  a  significant source   of organic  pollutants, and
found  that discharges  from these facilities are largely  unregu-
lated  for these pollutants, EPA decided to review  and update its
data  on the discharge of  hazardous nonconventional  pollutants, as
well  as priority  pollutants,  from the industry.

While  direct dischargers  are not affected by the DSE, EPA has
intentionally  included  direct  dischargers  in  its review  of
hazardous  waste  discharges  from  pharmaceutical   manufacturing
facilities.   EPA  is interested  in evaluating existing regulations
established under the CWA for the control  of both  toxic priority
pollutants   and  hazardous  noncoventional  pollutants  at  direct
discharging facilities.

C.  REGULATORY  STATUS

Regulatory  control  of  the discharge of  priority and  hazardous
nonconventional  pollutants  from  pharmaceutical   manufacturing
facilities involves both RCRA and the CWA.  The following

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paragraphs present an overview of the  status  of EPA's efforts to
control hazardous waste discharges to POTWs with respect to RCRA,
and  to control the  discharge of conventional,  nonconventional,
and  priority  pollutants to  POTWs and  the nation's  waters  with
respect to the CWA.

1.  Status of RCRA Regulations

On August  22,  1986,  EPA published an Advance  Notice  of Proposed
Rulemaking (ANPR), which was EPA's first step toward promulgating
the  regulations  required  by  Section  3018(b)  of RCRA   (51  FR
30166).   The  ANPR contained  no  formal proposals  for regulatory
amendments.    Instead,   EPA   suggested  a  range  of  preliminary
approaches to  improve the  control of hazardous wastes discharges
to  POTWs  and  solicited comments.   EPA has  not  yet determined
whether  to regulate the  discharge of priority  and  hazardous
nonconventional pollutants under the CWA or to copromulgate with
RCRA.

2.  Status of  the  CWA's Effluent  Limitations  Guidelines and
    Standards for the Pharmaceutical Manufacturing Point Source
    Category

EPA  promulgated  several  effluent  limitations  guidelines  and
standards  for  the  pharmaceutical  manufacturing  point  source
category  under the  authority  of  the  CWA  (40  CFR Part  439,
Subparts  A-E).    These regulations were  established  for  the
following five subcategories of the industry

    o   Subpart A  -  Fermentation Products Subcategory

    o   Subpart B  -  Extraction Products Subcategory

    o   Subpart C  -  Chemical Synthesis Products  Subcategory

    o   Subpart D  -  Mixing/Compounding  and  Formulation
                     Subcategory
    o   Subpart E  -  Research Subcategory

The  timing  and  status of   regulations  are  discussed  in  the
following paragraphs.  A discussion of  regulations that have been
finalized  is  followed  by  a  similar  discussion  on  proposed
regulations.   Table 1-1 a summarizes the timing and status of all
CWA regulations.

a.   Final Regulations.   The  following paragraphs  summarize the
limitations,  new  source performance standards,  and pretreatment
standards  that  have   been   finalized   for  the  pharmaceutical
manufacturing point source category.

Best Practical  Control  Technology (BPT) Limitations.        BPT
limitations  are  generally based  on  the   average of  the  best
existing performance by plants  of various sizes,  ages,  and unit
processes  within   the   industry  or  Subcategory for  control  of
familiar (i.e., classical)  pollutants.   EPA promulgated interim

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final BPT regulations  for  the pharmaceutical manufacturing point
source category on November 17, 1976 (41 FR 50678).

The  1976  BPT  regulations  set  monthly  limitations  for  five-day
biochemical oxygen demand  (BOD5) and chemical oxygen demand (COD)
based  on percent removals   for  all  subcategories.    No  daily
maximum  effluent  limitations  were established   for  these  two
parameters.    The  pH  was  set  within  the  range   of  6.0  to  9.0
standard units  for all  subcategories.   The  regulation  also set
maximum 30-day  average total  suspended  solids  (TSS)  limitations
for  Subcategories B,  D,  and  E only.    No TSS limitations were
established for Subcategories A and C.   Subpart A  (applicable to
the  fermentation  operations  subcategory)  was amended on February
4, 1977, to  improve the language  referring to  separable mycelia
and  solvent  recovery  (42  FR  6814) .  In  addition, the amendment
allowed  the  inclusion  of spent  beers  (i.e.,  broths)   in  the
calculation of  raw waste loads for  Subpart A in  those instances
where  the  spent  beer  is  actually  treated in   the  wastewater
treatment system.

On   October   27,   1983,  EPA  promulgated   BPT  limitations  to
(1)  control the discharge of TSS  from  pharmaceutical  plants in
Subcategories  A and C;  (2)   modify existing BPT  BOD5,  COD, and
TSS  effluent  limitations  in  Subcategories  B,  D,  and  E;  and
(3)  control the discharge of cyanide  in Subcategories  A,  B, C,
and  D.

It  is  important  to  note  that EPA excluded  the research-only
subcategory    (Subcategory E)    from  development  of    further
regulations  beyond  the  1983  BPT  limitations.    Pharmaceutical
research does  not fall within  Standard Industrial  Classification
(SIC) Codes 2831,  2833,  and 2834 (designated for  study by  EPA in
the  Settlement Agreement)  and  does not involve  production and
wastewater  generation  in  appreciable  quantities  on  a  regular
basis to warrant  development  of further  national regulations.

Best Conventional  Pollutant Control Technology  fBCT) Limitations.
The  1977 Amendments  to the CWA added Section 301(b)(2)(E), which
established   BCT  to  control   the  discharge   of  conventional
pollutants   from  existing   industrial   point   sources.     BCT
limitations,   like   Best   Available   Technology  Economically
Achievable   (BAT)  limitations,   represent  the   best  existing
performance in  the industrial subcategory or category.

On   December   16,  1986,   EPA  promulgated   BCT  limitations  for
existing  pharmaceutical  manufacturing  facilities.    Existing
plants  that  use  Subcategory  A,  B,   C,  and  D  operations to
manufacture   pharmaceutical   products   are   covered   by   this
regulation.   Facilities  that  engage  in pharmaceutical research
 (Subcategory  E)  only are not  covered by  this regulation.   BCT
limitations  were  set  equal  to  BPT limitations  promulgated on
October 27, 1983  (48 FR 49808).

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BAT Limitations.  In general,  BAT  limitations  represent the best
existing performance  in the industrial category  or subcategory.

The  CWA  established  BAT  as  the  principal   national  means  of
controlling  the direct  discharge of  toxic and  nonconventional
pollutants to U.S. waters.   Final BAT limitations controlling the
discharge  of  the  toxic  pollutant  cyanide from  pharmaceutical
plants  in Subcategories  A,  B,  C,  and  D were  promulgated  on
October 27, 1983.

New Source Performance Standards (NSPS).    NSPS are based  on the
best  available demonstrated technology because new plants have
the opportunity to install the best and most efficient production
processes and  wastewater treatment technologies.   On October 27,
1983,  EPA  promulgated  NSPS  limitations  for pH and cyanide for
Subcategories A, B,  C, and D (48 FR 49810).

Pretreatment Standards for Existing and New Sources (PSES and PSN
S) .   PSES  and PSNS  are designed  to prevent the discharge  of
pollutants that pass  through,  interfere  with, or  otherwise are
incompatible with the operation  of POTWs.   On October  27, 1983,
EPA  promulgated PSES  and  PSNS for  only  one  priority  pollutant
(cyanide) for Subcategories A, B,  C, and D  (48  FR 49808) .

b.  Proposed Regulations.  The following paragraphs summarize the
limitations, new  source performance standards,  and pretreatment
standards  proposed  for the  pharmaceutical manufacturing point
source category.

BAT Limitations.    On   November 26,  1982,   EPA   proposed  BAT
limitations   designed   to   control  the   discharge   of   the
nonconventional pollutant COD from pharmaceutical facilities.

Industry  commented  that  the  technical  basis  supporting  the
proposed  COD  limitations  was inadequate  and   that  EPA had not
indicated which chemical pollutants  it was attempting  to control
through  the  COD limitations.   EPA  decided to postpone a final
decision on  appropriate  BAT  limitations  for COD until  additional
information  was obtained regarding  identity   of pollutants that
contribute to COD and applicable COD-removal technologies.

To respond to these additional information needs, EPA initiated a
work/study program designed to

    o    determine   the   constituents    of    the   high   COD
         concentrations   in   biologically   treated  effluents  of
         pharmaceutical  manufacturing plants; and

    o    evaluate  the   ability  of  activated  carbon  adsorption
         (ACA)  technologies to  reduce the effluent COD levels.

An important part of the second objective involved demonstrating,
through pilot  plant studies,  the  capability of ACA technology to
reduce pharmaceutical  plant effluent COD levels.  On April 27,

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1984,  ITD  requested  assistance   from   the  Water  Engineering
Research  Laboratory  in  Cincinnati,  Ohio,  in  conducting  the
necessary pilot plant evaluations.

Two  technologies  were   evaluated   at   a  Subcategory A  and  C
pharmaceutical manufacturing plant which used advanced biological
treatment  and   reported  high  COD  levels   in   its  discharge
monitoring report

    o   Powdered  Activated   Carbon  (PAC)   addition  to   the
        activated-sludge aeration basin  for the treatment of raw
        wastewater

    o   Granular  Activated   Carbon  (GAC)  treatment   of   the
        secondary effluent

This  study   was  conducted   at  a   pharmaceutical  plant  from
September 1 to  December  7,  1984.   However,  operational problems
occurred with the PAC pilot plant,  causing the need for a follow-
up study.   The  follow-up  study  was initiated  in  March 1987 and
completed in  July  1987.   The  final  report  on  the  study was made
available.

In the  preamble to the  final  regulations for  the pharmaceutical
manufacturing  point  source  category (48  FR 49808),  EPA  stated
that it had decided not  to issue categorical regulations limiting
methylene chloride,  chloroform,  benzene,  and  toluene discharges
from  pharmaceutical  facilities.    However,  EPA  received  new
information  concerning  possible harmful  effects  of discharges
containing methylene chloride, and  is reconsidering the question
of whether to regulate methylene chloride and other VOC priority
pollutants as well.  As  part of EPA's investigation,  a notice was
published  in  the Federal  Register   on September  9,  1985  (50 FR
36638)  to  (1)   summarize previously  available  data;   (2)  make
available new information;  (3) present cost estimates associated
with  the  ability  of   steam-stripping   technology  to  reduce
discharges  of water-borne VOC priority  pollutants;  (4)  request
comments  on  the available  information;   and  (5)  seek additional
information concerning steam-stripping technology.

NSPS.     On   October  27,  1983,   EPA   proposed   NSPS  for  the
conventional  pollutants,  BODS  and TSS, for  Subcategories A, B, C,
and  D  (48  FR  49832) .    EPA  has  not promulgated NSPS  for the
nonconventional  pollutant COD.  Additional information regarding
the  identity  of  the  pollutants   that   contribute  to COD  and
applicable  COD-removal   technologies  is   required  before  EPA can
evaluate   COD   control   options.     EPA   is   continuing   its
investigation of appropriate  COD-removal technologies and their
costs  (refer  to the  previous discussion on BAT COD limitations).


As  in the case  of  BAT,   EPA  decided not to  issue NSPS limiting
methylene  chloride  discharges from  the  pharmaceutical industry.
However,  if  EPA reaches new conclusions  on possible  harmful
effects of discharges containing methylene  chloride and other

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toxic  VOCs,  reconsideration  of   the   decision  not  to  issue
regulations may be warranted.

PSES and PSNS.  In the preamble  to  the  final regulations for the
pharmaceutical manufacturing point source category (48 FR 49808),
EPA  stated  that it  was  not establishing  pretreatment standards
controlling  the  discharge  of  toxic   pollutants,   other  than
cyanide, from pharmaceutical plants.   However,  EPA  received new
information  concerning possible  harmful  effects of  discharges
containing methylene chloride and other  toxic pollutants,  and is
reconsidering   the   question  of   whether  to   regulate   toxic
pollutants discharged to POTWs.
                               10

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                                                       TABLE  1-1
                                   CURRENT  STATUS  OF EFFLUENT LIMITATIONS  GUIDELINES
                                         AND STANDARDS FOR THE PHARMACEUTICAL
                                                MANUFACTURING CATEGORY
                                                                                                Subcategory E
ou
Notices
BPT Limitations
BODS
TSS
pH
COD
Total Cyanide
BCT Limitations
BODS
TSS
pH
BAT Limitations
COD
Total Cyanide
TTVO 9/9/85
NSPS
BODS
TSS
pH
COD
Total Cyanide
TTVO 9/9/85
PSES & PSNS
Total Cyanide
TTVO 9/9/85
LUldLegUL J.c» n w u
Proposed Final
Regulation Regulation
11/17/76
10/27/83
11/17/76
11/17/76
10/27/83

12/16/86
12/16/86
12/16/86

11/26/82
10/27/83
_- --

10/27/83
10/27/83
10/27/83
11/26/82
10/27/83
__ — —

10/27/83
"
Proposed Final
Notices Regulation Regulation Notices
11/17/76
10/27/83(a)
11/17/76
10/27/83(a)
11/17/76
11/17/76
10/27/83(a)
10/27/83

12/16/86
12/16/86
12/16/86

11/26/82
10/27/83
9/9/85

10/27/83
10/27/83
10/27/83
11/26/82
10/27/83
9/9/85

10/27/83
9/9/85
Proposed Final
Regulation Regulation
11/17/76
10/27/83(a)
11/17/76
10/27/83(a)
11/17/76
11/17/76
10/27/83(a)
..


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— — — —
_ -. — —
__




(a)  Existing BPT,  BODS,  TSS,  and COD
    48 FR 49808, October 27,  1983.
       4.89.90T
       0048.0.0

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TECHNICAL SUPPORT STUDY
           12

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            II.  DESCRIPTION OF THE INDUSTRY

This  section  presents  information  assembled  to  describe  the
pharmaceutical manufacturing industry.   The data are derived from
industry responses  to EPA  questionnaires,  industry  comments  on
proposed rulemakings,  plant  contacts,  literature  searches,  and
other   sources.     The   industry   profile  was   updated  using
information gathered in recent data collection efforts to Provide
the best current  description  of  the  industry.   The manufacturing
processes,  the current subcategorization scheme, and the modes of
wastewater discharge are discussed.

A.  SUMMARY OF METHODOLOGY AND INFORMATION SOURCES

in  this   study,   EPA  directed   its  efforts  toward  reviewing
available  information, as well as gathering new information.  The
data-gathering  efforts  and  subsequent  information  assessments
conducted  for  this  study can be  divided into the following three
tasks:     gathering   information  to  be  used  in  the   industry
description  (discussed  in this  section),  obtaining analytical
data  used  to characterize  pharmaceutical  manufacturing wastes
 (discussed in  Section  III),  and information  used  to   evaluate
industry waste treatment systems  (discussed  in  Section IV).

1.  Review and Assessment of  Existing Information

Previous regulatory  efforts  conducted by  EPA provided substantial
information regarding  the  industry  profile,  the manufacturing
processes,  and  water  use  in  the  pharmaceutical manufacturing
 industry.   The  development  documents,  as  well as the technical
records supporting each of the rulemaking efforts,  were initially
reviewed  to  assess  data gaps  and requirements.    This  review
 identified the   308  Portfolio  Survey  as  the  major  source  of
 information pertaining to this study.

 The 308 Portfolio Survey is an  invaluable source  of information
 for    developing    profiles    and    characterizing    industry
 subcategories.   It was the first major  data source on the use and
 generation of priority pollutants by this industry.

 The  308   Portfolio  Survey  was  conducted  in  two phases.    The
 original 308 Survey  distributed questionnaires to  members of the
 Pharmaceutical Manufacturers  Association  (PMA),  in  the  fall  of
 1977.  The  second phase involved sending  a  second questionnaire
 to the remainder of the industry in the spring of 1979.

 2.   New Data

 The major source of  new data was  a  product patent search.  Based
 on the  initial  review of available information,  it  was  apparent
 that  VOCs  (being used as  process solvents)  were the  likely
 priority and nonconventional pollutants of concern. In an attempt
 to better  characterize  VOC  usage  in the pharmaceutical  industry,
 EPA reviewed all patents identified for the approximately 1,300
 Subcategory A, B, and C products in its data base.  This patent
                                 13

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 review provided  information regarding which VOCs were most likely
 to  be used  in the  manufacture  of pharmaceutical  products,  and
 which plants were most likely to be using them.

 3.  Industrial Profile and Subcategorization

 Detailed  information collected in previous data-gathering efforts
 was the  basis for  the  industry profile.   Information collected
 during the  present study was compared  to  earlier information to
 update  and  revise  (as  necessary)  the  industry  profile  and
 subcategorization scheme.

 B.  INDUSTRY PROFILE

 The   pharmaceutical  manufacturing   industry  encompasses   the
 manufacture, extraction,  processing,  purification,  and packaging
 of  chemical  materials to be  used  as  medication for  humans  and
 animals.(1)    The  broad  range  of  industry  products  includes
 natural substances  extracted  from plants  or  animals,  chemically
 modified   natural   substances,   synthetically   made   organic
 chemicals,  metal-organics,   and  wholly   inorganic  materials.
 Packaging is equally varied.   Some products are  sold  in bulk to
 other companies within the industry;  some  are  sold  to the public
 as  creams,  tablets,  capsules,  solutions,  suspensions,  and other
 forms.

 EPA  identified  464  facilities  involved  in  the  manufacture,
 extraction,    processing,    purification,    or   packaging    of
 Pharmaceuticals.   The  estimate  is  based primarily on the  end
 result  of  two questionnaire  mailings  conducted  by  EPA  under
 authority of Section 308 of the CWA.

 The original   308  Questionnaire  was  developed by  EPA  with  the
 cooperation of the PMA Environmental Task Force during the spring
 and summer of  1977.  Questionnaires were sent  only  to PMA member
 firms and to nonmember plants included in previous EPA guidelines
work.    PMA member  firms  are  the principal  manufacturers  of
prescription Pharmaceuticals, medical  services,  and diagnostics,
and also  produce a  significant portion of over-the-counter drugs
 on the market.   PMA members account  for approximately  90  to 95
percent of  U.S.  sales  of prescription products,  and  about  50
percent   of   the    free   world's   total   output   of   ethical
Pharmaceuticals.   A total  of  244 pharmaceutical  manufacturing
plants was identified from responses to the questionnaire.

A second  308 Questionnaire was developed during the fall of 1978
 in  an  attempt to  define the  entire  pharmaceutical population,
obtain a  more  complete  profile of the  industry,  and confirm  the
assumption that  PMA  member  firms included in the initial  survey
do indeed represent  the  industry.   This questionnaire identified
220 additional plants as pharmaceutical manufacturers.

However,   since  the mailing  of  the  two  questionnaires,  four
pharmaceutical plants (i.e.,  Plants 11111,  33333,  44444,  and


                               14

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55555) not  in  EPA's data base  supplied data.   EPA  also learned
that three facilities  (i.e.,  Plants  20153,  12006,  and 12112)  are
no longer manufacturing Pharmaceuticals and that Plants 12084 and
20366 are really  the same plant.  Consequently, there are still
464 plants in EPA's data base.

Table II-l shows  the geographic distribution of the industry and
the number of manufacturing plants by state and EPA region.  Also
shown  are the  average  number  of  employees per  plant  and  the
average plant startup year. Most of the pharmaceutical plants are
located in  the eastern half  of the  U.S.  (see  Figure  II-I) .   Of
the  464  manufacturing  plants  in the  comprehensive  data base,
almost 80  percent are  in the  East.   New Jersey  (with  about 16
percent)   and  Region II  (with approximately 36 percent)  are the
largest  pharmaceutical   manufacturing   state   and  EPA   region,
respectively.   The  data  show  that Regions  II, III,  V,  and VII
(the  Northeast and  Midwest)  generally have  older  plants  than
Regions IV, VI, VIII,  and IX (the South and West).  Puerto Rico,
with  close  to  10 percent  of the industry,  has  become  a major
pharmaceutical manufacturing  center.

C.  MANUFACTURING PROCESSES

Pharmaceuticals are  manufactured by batch,  continuous, and semi-
continuous manufacturing  operations.  Batch-type production is by
far  the  most common manufacturing technique,   as  can  be seen by
the  production  operation breakdown in Table II-2.   The processes
used  in the manufacture of Pharmaceuticals are (1)  fermentation,
(2)  biological and  natural  extraction,  (3)  chemical synthesis,
and   (4)  mixing/compounding/formulating.    The   four types  of
manufacturing  operations  are  discussed  in this  section.

1.   Fermentation

Fermentation  is the usual  method for producing most  antibiotics
and  steroids.    The fermentation process   involves  three basic
steps:   inoculum and seed preparation, fermentation,  and product
recovery. Production of a fermentation  pharmaceutical  begins with
spores  from the  plant master  stock.   The  spores are  activated
with water,  nutrients,  and warmth;   they  are then propagated
through  the use  of  agar plates, test tubes, and  flasks until
enough mass is produced  for  transfer to  the seed  tank.   In  less
critical  fermentations,  a  single seed  tank  may serve  several
fermenters.   In  this  type of  operation, the  seed tank  is never
emptied  completely,  so the remaining seed serves  as  the  inoculum
for  the  next  batch.  The  seed tank is emptied,  sterilized,  and
reinoculated only when contamination occurs.
                                 15

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                          TABLE II-l

                    PHARMACEUTICAL INDUSTRY
                    GEOGRAPHIC DISTRIBUTION
Location
EASTERN U.S. (REGIONS I-V)
Connecticut
Maine
Massachusetts
New Hampshire
Rhode Island
Vermont
REGION I TOTALS
New Jersey
New York
Puerto Rico
Virgin Islands
REGION II TOTALS
Delaware
Maryland
Pennsylvania
Virginia
West Virginia
District of Columbia
REGION III TOTALS
Alabama
Georgia
Florida
Mississippi
North Carolina
South Carolina
Tennessee
Kentucky
Number of
Plants
367
8
0
7
0
1
1
17
75
43
46
2
166
2
6
27
7
2
0
44
3
6
8
2
12
3
10
5
Percent of
Total Plants
79.1
1.7
0.0
1.5
0.0
0.2
0.2
3.6
16.1
9.2
9.9
0.4
35.7
0.4
1.3
5.8
1.5
0.4
- 0.0
9.5
0.6
1.3
1.7
0.4
2.6
0.6
2.2
1.1
Average
Number
Employees
Per Plant
268
195
-
77
-
(2)
(2)
161
346
211
216
13
239
121
65
370
138
151
-
267
15
189
95
759
456
87
301
12
Average
Plant
Startup
Year(l)
1952
1963
.
1961
_
(2)
(2)
1960
1950
1943
1970
-
1956
1965
1938
1949
1950
-
-
1950
1958
1956
1967
1949
1971
1968
1940
-
REGION IV TOTALS
49
10.5
250
1962
                            16

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                   TABLE II-l (continued)

                   PHARMACEUTICAL INDUSTRY
                   GEOGRAPHIC DISTRIBUTION
Number of
Location Plants
Illinois
Indiana
Ohio
Michigan
Wisconsin
Minnesota
REGION V TOTALS
WESTERN U.S. (Regions VI-X)
TOTAL
Arkansas
Louisiana
Oklahoma
Texas
New Mexico
REGION VI TOTALS
Iowa
Kansas
Missouri
Nebraska
REGION VII TOTALS
Colorado
Utah
Wyoming
Montana
North Dakota
South Dakota
REGION VIII TOTALS
Arizona
California
Nevada
Hawaii
38
17
14
14
4
4
91
97

2
2
0
13
0
17
3
4
18
4
29
5
1
0
0
0
0
6
1
37
1
0
Percent of
Total Plants
8.2
3.7
3.0
3.0
0.9
0.9
19.6
20.6

0.4
0.4
0.0
2.8
0.0
3.7
0.6
0.9
3.9
0.9
6.2
1.1
0.2
0.0
0.0
0.0
0.0
1.3
0.2
8.2
0.2
0.0
Average
Number
Employees
Per Plant
305
664
203
423
54
41
351
152

1558
9
—
127
—
129
77
123
108
201
117
96
(2)
—
•
—
•
162
(2)
139
(2)
-
Average
Plant
Startup
Year(l)
1951
1944
1929
1933
1957
*
1943
1962

1970
•
~
1967
—
1968
1963
1954
1943
1962
1951
1967
(2)
•*
™
—
**
1968
(2)
1967
(2)
~
REGION IX TOTALS
39
8.6
137
1967
                             17

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                            TABLE II-1 (continued)

                            PHARMACEUTICAL INDUSTRY
                           GEOGRAPHICAL DISTRIBUTION
Location
Number of
 Plants
Percent of
Total Plants
 Average    Average
 Number      Plant
Employees  Start-up
Per Plant   Year(l)
Alaska
Idaho
Oregon
Washington
        REGION X TOTALS
    0
    0
    2
    4
    0.0
    0.0
    0.4
    0.9

    1.3
    25
    33

    30
                                           1955
(1)  Since data concerning plant startup year were not solicited from the
     Supplemental 308 plants, the figures were calculated using only the
     original 308 plants responses.

(2)  Employment and startup year figures are not presented to avoid
     disclosing individual plant data.
                                    18

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                                                                   TABLE  II-2

                                                         PRODUCTION  OPERATION  BREAKDOWN
vo
Manufacturing Processes
Type of Operation 	
Batch
Continuous

Total Number of Operations
Percent of Total Operations
Percent of Subcategory Operations
which are Batch

Fermentation
32
3
n
46
7
70

Biological
Extraction
76
0
9
85
12
89


Mixing/ 1
Chemical Compounding/ '
Synthesis Formulating Total i
129 359
14 16
19 17
162 392
24 57
80 92

596
33
56
685
100
87

Percent
of Total
Operation
87
5
8
100



            NOTE:  These data apply to 462 manufacturing plants.  For two plants, no information was available on
                   subcategories and types of production operations.

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        FIGURE  1-1
 PHARMACEUTICAL INDUSTRY
GEOGRAPHICAL DISTRIBUTION
                                  DISTRICT
                                   or O
                                  COLUMBIA
                            PUIIITO RICO-
                            VIIIOIN ISLAND*-£

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Fermentation is conventionally a  large-scale batch  process.   The
cycle begins  with a  water wash  and  steam sterilization  of  the
fermenter vessel.   Sterilized nutrient raw materials in water are
then charged to the fermenter.  Microorganisms are transferred to
the fermenter from the seed tank and fermentation begins.  During
fermentation, air  is sparged into  the batch and temperature is
carefully controlled.   After a  period of  from 12  hours  to  one
week, the  fermenter batch whole  broth is  ready  for  filtration.
Filtration removes mycelia (i.e., remains of the microorganisms),
leaving  the  filtered  aqueous   broth  containing   product  and
residual nutrients ready to enter the product recovery phase.

There  are  three  common methods  of product  recovery:   solvent
extraction, direct precipitation, and ion exchange or adsorption.
Solvent  extraction is  a   recovery  process in  which  an organic
solvent  is  used to  remove the  pharmaceutical  product  from  the
aqueous  broth  and  form   a  more  concentrated   solution.    With
subsequent  extractions,   the product  is  separated  from  any
contaminants.   Further removal  of  the product  from  the solvent
can  be  done  by  either precipitation,  solvent  evaporation,  or
further  extraction  processes.    Normally,  solvents  used  for
product  recovery  are  recovered  and   reused.    However,  small
portions left  in  the aqueous phase during  the  solvent "cut" can
appear in the plant's wastewater stream.   The priority pollutant
solvents most often used in fermentation operations are methylene
chloride,  benzene,  chloroform,   1,1-dichloroethylene,   and  1,2-
trans-dichloroethylene.(1)     Based   on   fermentation  product
patents, typical  nonconventional  solvents used  in fermentation
operations are  acetone, ethyl acetate,  and methanol (see Section
III) .

Direct precipitation  using heavy metal precipitating agents is  a
common  method of  product  recovery.   The  method  involves first
precipitating the product  as  a metal salt from  the aqueous broth,
then filtering the broth,  and finally extracting the product from
the  solid residues.   Copper  and  zinc are the priority pollutants
known to be used in the precipitation process.(1)

Ion  exchange  or adsorption involves removal  of the product from
the  broth,  using  solid materials  such  as ion  exchange resin,
adsorptive resin,  or activated  carbon.  The product is  recovered
from the solid phase using  a solvent;  it is  then recovered by
evaporation of the solvent.

Occasionally, a fermentation  batch becomes  infested with a phage;
that is, a virus that attacks microorganisms.   Phage infection is
rare  in a well-operated  plant,   but  when  it occurs,  very large
wastewater discharges may  be  necessary  in a short period of time.
Typically,  the  batch  is  discharged  early,   and  its nutrient
pollutant concentration is higher than  that of  spent broth.

Steam  is  the  major  sterilizing  medium  for most   equipment.
However, to  the extent that  chemical  disinfectants may be used,
they can contribute  to waste  loads.  An example of  a commonly


                                21

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used chemical disinfectant is phenol, a priority pollutant.
Another  fermentation  wastewater  source  is  the  air  pollution
control equipment sometimes installed to clean fermentation waste
off-gas.   The  air  and  gas  vented  from  the fermenters  usually
contain  odoriferous substances  and large  quantities of  carbon
dioxide.   Treatment  is  often  necessary  to deodorize  the  gas
before release  to  the  atmosphere.   Some plants  use incineration
methods;  others  use   liquid   scrubbers.     The  blowdown  from
scrubbers may  contain  absorbed chemicals,   light  soluble  organic
compounds,  and heavier  insoluble  organic  oils   and   waxes.
Wastewater from this  source  generally does not  contain  priority
pollutants in appreciable concentrations.

The pollution  contribution of  spent beer  results from the food
materials  contained  in  the  beer,  such  as  sugars,  starches,
protein, nitrogen,  phosphate,  and other nutrients.   Fermentation
wastes are very amenable to  biological treatment.   Although the
spent  beers,   even in  a  highly  concentrated  form,   can  be
satisfactorily  handled by biological  treatment  systems,  system
upsets can  be  avoided  if the wastes  are  first diluted  to some
degree with other wastewater.  Dilution normally results from the
equalization  of  fermentation  wastes  with  other  wastestreams.
This prevents  biota from receiving  too high  feed concentrations
at one time.

Data  from the  308  Survey generally  show  that wastewater from
fermentation plants is characterized  by high BOD, COD,  and TSS
concentrations; large flows;  and  a  pH  range of  about 4.0  to 8.0.

2.  Biological  and Natural Extraction

Many  materials used  as  Pharmaceuticals  are derived from such
natural sources as the roots  and leaves of plants, animal glands,
and parasitic  fungi.    These  products  have numerous  and  diverse
pharmaceutical  applications,   ranging from  tranquilizers  and
allergy-relief  medications  to   insulin  and  morphine.     Also
included in this group is blood fractionation, which involves the
production of plasma and its  derivatives.

Despite their  diversity,  all  extractive  Pharmaceuticals  have a
common  characteristic:    They  are too  complex  to  synthesize
commercially.   They are either very large molecules, and/or their
synthesis  results   in  the production  of  several  stereosiomers,
only one  of  which  has  pharmacological value.  Extraction is an
expensive  manufacturing  process.    It requires  collecting  and
processing large volumes of specialized plant or animal matter to
produce small quantities of products.

The extraction  process  consists of a  series  of  operating steps.
In almost  every step,  the volume  of  material  being  handled is
reduced significantly.   In some processes,  reductions may be in
orders of  magnitude,  and complex  final purification operations
may  be   conducted   on  quantities  of  materials   only   a  few
thousandths of  the volume handled in earlier steps.  Neither


                                22

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continuous processing methods nor  conventional  batch methods are
suitable  for   extraction  processing.     Therefore,   a  unique
assembly-line, small-scale batch processing method was developed.
Material is transported  in  portable  containers  through the plant
in 75- to 100-gallon batches.  A continuous line of containers is
sent  past  a  series of  operating stations.    At each station,
operators perform  specific  tasks  on  each batch in turn.   As the
volume  of  material being  handled decreases, individual batches
are   continually   combined  to  maintain   reasonable  operating
volumes, and  the  line  moves more slowly.    When the  volume is
reduced  to  a  very small  quantity,  the  containers  also  become
smaller, with laboratory-size equipment used in many cases.
An  extraction plant may produce  one  product  for  a  few  weeks;
then, by changing  the logistical  movement  of pots and redefining
tasks to be conducted  at each station, the  plant can convert to
the manufacture of a different product.

Residual  wastes from  an  extraction plant  essentially will be
equal to the weight of raw material,  since the active ingredients
extracted are generally present at very low levels.  Solid wastes
are the greatest source  of the  pollutant load;  however, solvents
used  in  the   processing steps  can  cause  both  air  and  water
pollution.

The nature of  the  pharmaceutical  industry  products dictates that
any  manufacturing  facility  maintain a  standard of cleanliness
higher  than   that required  for most  industrial  operations.
Because most  of these plants are  cleaned  frequently, detergents
and disinfectants  are normally found in the wastewater.

As  in  the  fermentation process,  a  small  number   of priority
pollutants was identified as being used in  the manufacturing of
extractive Pharmaceuticals.(2)  The  cations  of  lead and zinc are
known to be used as precipitating agents.   Phenol was  identified
as  an  equipment-sterilizing  chemical,  as  well as  an  active
ingredient.  Otherwise, priority pollutants were  found to be used
only  as processing solvents, including  benzene,  chloroform, and
1,2-dichloroethane.     Based  on   Subcategory B,  product  patent
information,  nonconventional  pollutants  that  may   be used as
solvents  are  acetone,  1,4-dioxane,  ethyl  acetate,  and methanol
(see  Section III).

Solvents are used  in two ways in extraction operations.  Firstly,
they  are used  to remove fats and  oils that would contaminate the
products.   These  "defatting"  extractions  use  an organic liquid
that  dissolves the fat but  not the  product material.   Secondly,
solvents are  used to extract  the product itself.   For example,
when  plant alkaloids are treated with a base, they become soluble
in  such selected  organic  solvents  as benzene,  chloroform, and
1,2-dichloroethane.

Ammonia  is used   in  many  extraction  operations because  it is
necessary to  control  the pH of water  solutions from both animal
and  plant  sources to  achieve separation  of valuable  components
from  waste materials.  Ammonium salts are used  as buffering
                                23

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chemicals,  and  aqueous  or anhydrous  ammonia  is  used  as  an
alkalinizing reagent.   The  high degree  of  water solubility  of
ammonium  salts prevents  unwanted precipitation  of  salt;  also,
ammonia does not react chemically with  animal or plant  tissue.
Such  basic materials  as  hydroxides and carbonates  of  alkali
metals do not have these advantages.

The  principal  sources  of  wastewater  from  biological/natural
extraction operations  are processes  that generate (1)  spent raw
materials  (e.g., waste plasma  fractions,  spent eggs,  spent media
broth, plant residues);  (2)  floor and equipment wash  water; (3)
chemical wastes  (e.g.,  spent solvents);  and (4) spills.

In general, the bulk of spent raw materials is collected and sent
to  an incinerator  or  landfill.    Likewise,   the  nonrecoverable
portions  of  the  spent solvents  are  incinerated or  landfilled.
However,  in both cases,  portions of the  residual materials find
their  way  into  a  plant's wastewater.    Floor  and  equipment
washings and spills also contribute to ordinary waste loads.

Pollutant  information  for the  biological/natural   extraction
operations in the pharmaceutical data base was limited due to the
relatively small number  of  plants  engaged in  these  operations.
However,  available  data  did allow for general  conclusions to be
drawn.     Generally,  wastewater  from   extraction   plants  is
characterized  by  low  BOD,  COD,  and  TSS concentrations;  small
flows; and pH values of approximately 6.0 to 8.0.

3.  Chemical Synthesis

Most  compounds currently  used  as drugs are  prepared  by chemical
synthesis  (generally  by   a batch  process).    The  basic  major
equipment  item is  the  conventional  batch  reaction vessel,  one of
the most standardized equipment designs in industry.

Generally, the vessel is equipped  with  a motor-driven agitator
and an internal  baffle.   It is made of  either stainless steel or
glass-lined carbon-steel, and  it contains a  carbon-steel outer
shell  suitable for  either cooling water  or steam.    Vessels of
this  type are made  in  many  different  sizes, with  capacities
ranging from 0.02 to 11.0  m2 or more.

The basic  vessels  may  be  fitted with many different attachments.
Baffles usually  contain sensors to measure the temperature of the
reactor contents.  An entire reactor may be mounted on load cells
to  accurately  weight  the  reactor  contents.   Dip  tubes  are
available  to introduce reagents into the vessels below the liquid
surface.   One  of the top  nozzles may be fitted with a floodlight
and another with a glass  cover to enable an operator to observe
the  reactor contents.    Agitators  may be powered by two-speed
motors  or  by  variable-speed  motor  drives.    Typically,  batch
reactors  are  installed with only the top heads extending  above
the  plant operating  floor  to  provide  the  operator  with easy
access for loading and cleaning.  With other suitable accessories,
the vessels can  be used in several ways.  Solutions can be mixed,
                                24

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boiled, and chilled in them.  By addition of reflux condensation,
complete reflux operations  (i.e.,  recycling of condensed vapors)
are possible.   By  application of a  vacuum, the  vessels  become
evaporators.   Solvent extraction operations can be  conducted in
them and, by  operating the agitator at a  slow speed,  they serve
as crystallizers.

Synthetic pharmaceutical manufacture  consists of  using  one or
more of these  vessels to perform,  in  a step-by-step fashion, the
various operations  necessary to make  the product.   Following a
definite  recipe,  the operator  (or,  increasingly,  a  programmed
computer) adds reagents;  increases or  decreases the flow rate of
cooling  water, chilled  water,  or  steam;  and starts  and stops
pumps  to transfer  the  reactor  contents  into another  similar
vessel.   At   appropriate  steps in  the  process,  solutions  are
pumped  either through  filters or centrifuges,  or  into solvent
recovery headers or waste sewers.

The vessels with an  assembly  of auxiliary equipment are usually
arranged  into independent process units;  a large pharmaceutical
plant may contain many such units.  Each unit may be suitable for
the   complete   or    partial   manufacture   of  many   different
pharmaceutical compounds.   Only with  the highest volume products
is the  equipment  "dedicated"  or modified to be suitable for  only
one process.

Each   pharmaceutical   product  is  usually  manufactured   in  a
"campaign," in which  one or more process units are used for a few
weeks  or months  to  manufacture enough  compound  to satisfy the
projected sales demand.  Campaigns are usually tightly scheduled,
with  detailed  coordination  extending  from  procurement  of raw
materials  to  packaging  and   labeling  of  the product.    For a
variable  period  of  time,  therefore,  a  process unit actively
manufactures  a specific compound.   At the end of this campaign,
another is  scheduled  to  follow.  The same  equipment  and operating
personnel are then used to make a completely different product,
using  different  raw materials, executing a different recipe, and
creating different  wastes.

The  synthetic Pharmaceuticals industry uses  a wide  variety of
priority  pollutants  as  reaction  and  purification solvents.(3)
Water  was  reported to be used more often than would be expected
in  an  industry whose products are organic chemicals.   However,
benzene and toluene  were the  most widely used organic  solvents,
because they  are  stable  compounds  that do  not  easily take  part in
chemical  reactions.   Similar, six-member  ring compounds  (e.g.,
xylene,  cyclohexane,  pyridine) also were  reported as being  used
either in  the  manufacture  of  synthesized  Pharmaceuticals or
resulting from unwanted  side  reactions.

A recent review of product patents for  synthetic  Pharmaceuticals
shows  two  additional priority pollutants  used  as solvents in
chemical  synthesis  operations, chloroform and methylene chloride,
and the nonconventional  pollutants acetone, 1,4-dioxane,


                                25

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ethylacetate, and  methanol.   Section III contains  more detailed
information on results of this review.

Solvents serve  several  functions in a chemical  synthesis.   They
dissolve  gaseous,   solid,   or viscous  reactants  to  bring  all
reactants into close molecular proximity.   They serve to transmit
heat to or from the reacting molecules.   By physically separating
molecules from each other,  solvents slow down some reactions that
would otherwise take place too rapidly, and that would result in
excessive temperature increases and unwanted side reactions.

There are other less obvious uses of solvents.  One is the use of
a solvent in  the  control of reaction temperature.   It is common
practice  in  a  batch-type  synthesis  to select  a  solvent  whose
boiling point is the same as the desired reaction temperature and
which is compatible with the reaction.   Heat  is then applied to
the  reaction mass at  a rate  sufficient  to keep the  mixture
boiling continuously.  Vapors that  rise from the reaction vessel
are condensed, and the liquefied solvent is allowed to drain back
into  the  reaction   vessel.    Such  refluxing  prevents   both
overheating  and overcooling of the  reactor  contents,  and  can
automatically compensate for variations in the rate of release or
absorption of chemical energy.

Essentially  all   production plants  operate  solvent  recovery
facilities that  purify contaminated  solvents  for reuse.   These
facilities usually contain  distillation  columns,  and may also
include extraction facilities where still  another solvent is used
to  separate  impurities.     Many  wastes   from  the  synthetic
pharmaceutical  industry  will  be discharged  from  these  solvent
recovery facilities.   Aqueous wastes that  may result from  these
operations   include   residues   saturated   with  the  recovered
solvents. Another  cause  of  solvent  loss  is storage practice.
Bulk  storage  is usually in  an unpressurized  tank that  is only
partially filled.  The level of  the liquid  in the tank rises and
falls as liquid is added to  or removed  from the  tank.  The vapor
in  the  tank  above  the surface  of  the   liquid,  therefore,  is
exhausted when the liquid  level  is rising.  As  the level falls,
fresh  air  (or  nitrogen  from  a  padding  system) is  introduced.
Even if  no liquid  is  added  or removed,  the tank "breathes" as a
result of temperature and barometric pressure changes.  Each time
a tank  "exhales,"  the released  vapor is  saturated  with  solvent
vapor.   Rather  large  quantities  of solvent  can be  lost to  the
atmosphere through this mechanism.

Chemical synthesis operations also produce large  quantities of
pollutants,   normally  measured as   BOD  and  COD.   Wastewater is
generally produced with  each chemical modification  that requires
the filling and emptying of  the  batch reactors.   This wastewater
can  contain  the  unreacted  raw  materials,  as  well  as  some
solvents. The effluent from  chemical  synthesis operations is the
most complex to treat because of the many  types of operations and
chemical  reactions  (e.g.,   nitration,  amination,  halogenation,
sulf©nation,  alkylation)  which generate a  large number of


                               26

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different compounds.

These substances  vary considerably with respect  to  toxicity and
biodegradability.    The  production  steps  may  generate  acids,
bases,  cyanides,  metals,  and many  other pollutants.   In  some
instances,  process  solutions and  vessel  wash  water  may  also
contain  residual  solvents.    Occasionally,   this wastewater  is
incompatible with biological  treatment systems.  Although it is
possible  to acclimate  the bacteria  to the  various substances,
there may be  instances  where  certain chemical  wastes are too
concentrated or too toxic to make this feasible.  Thus,  it may be
necessary  to equalize  and/or chemically  pretreat  some  process
wastewater prior  to conventional treatment.

Primary sources  of wastewater from chemical synthesis operations
are  (1)  process  wastes such as  spent solvents,  filtrates, and
concentrates;  (2)  floor and equipment wash water;  (3)  pump seal
water;  (4) wet scrubber spent water;  and  (5)  spills.  Wastewater
from  chemical  synthesis  plants  can  be characterized  as  having
high BOD, COD, and TSS  concentrations; large  flows; and extremely
variable pH, ranging  from 1.0 to 11.0.

4.  Mixing/Compoundinq/Formulating

Although pharmaceutically active ingredients  are produced  in bulk
form, they must  be  prepared  in dosage  form for  consumer use.
Pharmaceutical   compounds  can   be   formulated   into   tablets,
capsules, liquids, or ointments.

Tablets  are formed  in a tablet press machine by  blending the
active  ingredient, filler, and binder.  The filler  (e.g.,  starch,
sugar)  is required to  dilute the  active  medicinal ingredient to
the  proper  concentration, and  a  binder  (e.g.,  corn syrup or
starch)  is  necessary to  bind the tablet particles  together.   A
lubricant  (e.g.,  magnesium  stearate)  may be  added for  proper
tablet  machine  operation.  The dust  generated  during the mixing
and   tableting   operation  is  collected   and  usually  recycled
directly  to  the  same  batch.     Broken  tablets generally are
collected and  recycled to the granulation  operation in a subse-
quent lot.   Some  tablets are coated  by  tumbling with  a  coating
material  and drying.   After  the  tablets  have been  coated and
dried,  they are  bottled and packaged.  Tablet-coating operations
can  be  a significant  source of  air  emissions  of  solvents if
solvent-based  coatings  are used, and can contribute solvents to
the  plant wastewater if  certain types of  air  pollution  control
equipment  are in use.   If  wet scrubbers  are used  to   capture
solvent vapors   from  tablet-coating  operations,   the  scrubbing
water  containing  the  solvents  is  likely to  be  sewered.   If
activated   carbon  is  used  to   capture  solvent  vapors,  the
condensate  from  the  steam  used   to regenerate  the  carbon is
sometimes sewered.

Capsules  are produced  by first  forming  a hard  gelatine shell.
The  shells  are  produced  by  machines  that  dip  rows  of  rounded
metal dowels into a molten gelatine  solution, and then strip the


                                27

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capsules  from the  dowels  after the  capsules  have cooled  and
solidified.  Imperfect capsules are remelted and reused, if
possible,  or sold  for  glue  manufacture.   Most  pharmaceutical
companies purchase empty capsules from a few specialty producers.
The active ingredient and filler are mixed before being poured by
machine  into the empty  gelatine  capsules.   The  filled capsules
are bottled  and  packaged.   As in the  case  of  tablet production,
some dust is generated.  Although this is recycled, small amounts
of waste  dust must  be disposed.   Some glass and packaging waste
from broken bottles and cartons also results from this operation.

Liquid preparations are formulated for injection or oral use.   In
both cases,  the liquid  is  first weighed  and  then  dissolved in
water.     Injectable solutions  are  bulk-sterilized  by heat  or
filtration and then poured  into  sterilized  bottles.   Oral liquid
preparations can be bottled  directly without  the sterilization
steps.    Wastewater  is generated by  general clean-up operations,
spills,  and breakage.   Bad  batches  can  create  a  solid  waste
disposal problem.

The    primary    objective    of    mixing/compounding/formulating
operations is to convert the  manufactured products into a final,
dosage form.  The necessary production steps have typically small
wastewater flows because very few of the unit operations generate
wastewater.  The primary uses of  water in the  actual formulating
process  are for cooling water  in  the  chilling  units  and  for
equipment and floor washing.

Wastewater sources from mixing/compounding/formulating operations
are  (1)  floor  and equipment  wash water,  (2) wet  scrubbers,  (3)
spills, and  (4)   laboratory wastes.  The use of water to clean out
mixing  tanks  can  flush   materials  of   unusual  quantity  and
concentration into  the  plant sewer system.   The  washouts  from
recipe kettles may  be  used  to prepare the  master  batches of  the
pharmaceutical compounds and may contain inorganic salts, sugars,
and syrup.  Other sources of contaminated wastewater are dust and
fumes  from  scrubbers,  either in building ventilation systems or
on specific  equipment.   In general, this  wastewater is readily
treatable by biological treatment systems.

An analysis  of   the pollutant information  in  the pharmaceutical
data     base     shows     that   wastewater   from
mixing/compounding/formulating plants  normally  has low BOD,  COD,
and TSS concentrations;  relatively  small  flows;  and pH values of
6.0 to 8.0.

D.  INDUSTRY SUBCATEGORIZATION

The   pharmaceutical    industry    subcategories   selected   and
established for  data analysis are as follows:
    Subcategory  A - Fermentation
    Subcategory  B - Biological Extraction
    Subcategory  C - Chemical  Synthesis
    Subcategory  D - Mixing/Compounding/Formulating


                               28

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These are  identical  to four of the  subcategories  established in
the  original  BPT  rulemaking  (41   FR  50676).    An  additional
subcategory  (Subcategory E  -  Research)  was identified earlier in
the 1976 Development Document.  However,  since research does not
fall within  SIC  Codes 2831,  2833,  or 2834  (designated   to be
studied by EPA in  the Settlement Agreement)  and does  not have
wastewater   characteristics   warranting  the   development  of  a
national regulation, it is not included in this study.

Table   II-3   presents   a   distribution   of   the   industry  by
manufacturing   subcategory.         Subcategory    D
(Mixing/Compounding/Formulating)    is    the    most    prevalent
pharmaceutical  manufacturing  operation,  with 80 percent  of the
plants  in  the  industry  engaged  in  this   activity.   Fifty-eight
percent of these plants conduct  Subcategory  D  operations only.
The remainder also have operations in other subcategories.

1.  Subcategory Characteristics

There  are  discernible differences  among  the subcategories when
viewed  in  terms  of  effluent concentration averages or ranges and
wastewater   flow   rates.      These   differences   support  the
identification  and  use  of  these  subcategories  for regulatory
purposes.

a.   Subcategory A  - Fermentation.    Fermentation  is  the basic
processing method used in  the production  of most antibiotics and
steroids.    The  steps  used are   (1)  preparation  of  a  seed, (2)
inoculation  of  the  nutrient  batch,   (3) fermentation  of  the
nutrient raw materials,  and (4)  recovery  of the product by means
such as extraction, precipitation, or ion exchange.

Fermentation processes  are  typically  very  large  water  users.
Spent beers  are the major source  of  characteristically high BOD5_,
COD, and suspended  solids  levels  in the wastewater.  Average raw
waste  flow,  BOD!, COD,  and TSS values for  Subcategory A  plants
are    0.622  mgd,    1,668 mg/1,    3,452 mg/1,    and   1,023 mg/1,
respectively.(4)

b.  Subcatecrorv B -  Biological Extraction.  Biological or  natural
extraction is the extractive  removal of therapeutic products  from
natural  sources  such  as plant parts   (e.g.,   roots  and  leaves),
animal  parts (e.g., glands), and parasitic  fungi (e.g.,  molds).
In  contrast  to  fermentation,  biological  extraction processes are
normally  small-volume  water  users  with lower  BOD5,   COD,  and
suspended  solids  levels.   Average raw waste  flow, BOD5, COD, and
TSS  values  for  Subcategory B  plants are   0.197 mgd,   42 mg/1,
132 mg/1,  and 93  mg/1, respectively.(4)

c.   Subcategorv  C  - Chemical Synthesis.   Chemical  synthesis  is
used widely  in  the  manufacture of many drugs  currently  marketed.
Most production  is  in batch reactors, which can be used for  a
wide variety of  process steps (i.e.,  heating,  cooling,  mixing,
evaporation, condensation,  crystallization, and  extraction).


                                29

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                                  TABLE II-3

                             SUBCATEGORY BREAKDOWN
Manuf a c turing
Subcategory
Combination
Number of
 Plants
Percent of
  Total
  Plants
A
AB
ABC
ABCD
ABD
AC
ACD
AD
B
BC
BCD
BD
C
CD
D
Not Available

Total Plants
    3
    1
    2
    8
    4
    3
   10
    6
   21
   12
    8
   23
   50
   43
  268
    2

  464
  100.0
                                    30

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The reactor  vessels  generally are constructed  of  glass-lined or
stainless  steel.   Their  versatility permits multiple functions
and production of many different compounds.

Chemical  synthesis processes  are relatively  large water  users
with high  pollutant  loadings.   Also, a wide variety of chemical
pollutants can be  expected.   Average raw  waste flow,  BOD5_,  COD,
and  TSS  values   for   Subcategory C   plants  are  0.477 mgd,
2,385 mg/1, 4,243 mg/1, and 414 mg/1, respectively.(4)

d.  Subcategory D - Mixing/Compounding/Formulating.
In  formulation  (i.e., mixing,   compounding,   and   formulating),
Pharmaceuticals are  prepared in  such  useable  forms as tablets,
capsules,  liquids,  and   ointments.     Active  ingredients  are
physically mixed with  filler,  formed into dosage quantities, and
packaged for distribution.

Formulation  is normally  a low-level water user (in  many cases a
dry  operation)  with  low  pollutant  levels.    Average  raw  waste
flow,  BOD5_,  COD,  and TSS values  for  Subcategory D  plants are
0.296 mgd, 339 mg/1, 846 mg/1, and 308 mg/1,  respectively.(4)

Variations  in process routes  used by  different producers are
common  in  the pharmaceutical  industry.    Process  variations (in
chemical synthesis  plants manufacturing the same  product)  occur
because  different  starting materials and  reaction sequences are
used.   Two plants making the same product, but using different
starting materials, may use  different  reaction sequences.  It is
possible that once a common intermediate compound is derived, the
remaining  processing  steps will mirror each other.   Even if the
same  starting  material  is  used  by  different  plants,  it  is
possible,  due to  the complexity of a  synthesis,  that several
feasible  routes  to  an end product  exist.   The decision  as to
which route  will be  used  can  depend on the chemical yield (i.e.,
economics),  patent coverage,  corporate  history, or even personal
preferences.  In some  cases, synthetic routes are modified to use
less toxic and oxygen-demanding  substances or  to  generate  fewer
of these substances as by-products.

In  fermentation and  material  extraction processes,   the  major
differences  will occur in the extraction method.  In many cases,
extractions  can  be  accomplished  by  any number  of  solvents.
Choice  of  a  solvent  will  depend on environmental impact, company
history,  economics,  patents,  and  other  factors.    Due to the
number  of  variables  involved,  it  is  not surprising  that   these
processes vary widely  between plants.

2.  Subcategorization  Analysis

As  explained  in  the  preamble   to  the  regulation proposed in
November 1982  (47  FR 53584; November 26,  1982),  EPA proposed to
combine  four subcategories into a single Subcategory.  Along with
comments on  the November 1982  proposal,  EPA received new  plant
data that were added to the existing data base.  EPA statis-


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tically analyzed these data on influent and effluent
characteristics  of  all direct  dischargers to  determine if  the
proposed change  to  create a single subcategory was appropriate.
A discussion of  the data  sources  and  the  statistical comparisons
used  is presented  in detail  in Section  IV  of  the 1983  Final
Development Document.(4)   Results of the statistical analysis are
summarized in the following paragraph.

Analyses indicate that the subcategorization scheme should separate
fermentation and chemical synthesis plants (Subcategory A  and C
plants) from extraction and formulation plants (Subcategory B and
D plants),  insofar  as regulations  controlling the  discharge of
conventional pollutants and the nonconventional pollutant COD are
concerned.   Specifically,  the analyses show that the influent and
effluent   conventional   pollutant    concentrations   and   COD
concentrations, as well as discharge flows of  Subcategory A and C
plants, are similar and that  these  same characteristics are also
similar for Subcategory B  and D plants.  The analyses also indicate
that characteristics of the Subcategory A and C plant group are not
similar to the corresponding characteristics of the Subcategory B
and  D plant group.   These  differences indicate that  different
effluent discharge  levels  of  conventional and  nonconventional
pollutants would be expected when plants in these groups used the
same control technology.   However, the existing subcategory scheme
accommodates these  differences.   Because  permitting authorities
and  the  regulated  industry  are  familiar  with  the  original
subcategorization     scheme     and     the    format    in    the
Code of Federal Regulations.  EPA decided to maintain the existing
subcategorization scheme.

E.  METHOD OF DISCHARGE

Table II-4  presents  information  on methods  of wastewater discharge
at the 464  pharmaceutical  manufacturing plants in EPA's data base.
At 11  percent  of the  plants,  wastewater is treated on-site in a
treatment  system operated by plant  personnel and  is discharged
directly to  U.S. waters.   At  62 percent of  the  pharmaceutical
facilities, wastewater is discharged to a POTW.  At 27 percent of
the pharmaceutical plants, wastewater either  is  not generated or
is not discharged to navigable waters or POTWs.
                                32

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                                  TABLE II-4

                        SUMMARY OF METHODS OF DISCHARGE
                           AT PHARMACEUTICAL PLANTS
                                        Ho. of Plants
Wastevater (mgd)
Direct Dischargers
Indirect Dischargers
Zero Dischargers
Total Plants
52
285
127
464
24.9*
39.9
__^
64.8*
*  Wastewater flow estimate excludes flow from Plant 12256.  It was not
   possible to determine representative flow for Plant 12256 from the
   available data.
                                    33

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                   III.  WASTE  CHARACTERIZATION

EPA, through  several data-gathering efforts, studied wastewater
of  the  pharmaceutical  manufacturing  industry.    These  efforts
provided  the   baseline  data  necessary   for   determining  the
significant pollutants  present  in  the  wastewater of the industry
and, subsequently,  the regulatory  scope for the pharmaceutical
manufacturing point source category.

Past efforts  focused on determining the presence and  levels of
conventional  pollutants  (i.e., BOD5,   TSS,  and  pH) ,  priority
pollutants,  and nonconventional pollutants (i.e., COD).  The most
recent efforts  focused  on determining  the presence and levels of
approximately 250  additional  pollutants not  previously analyzed
for in this industry's wastes.

This  section  summarizes:     (1)  past   data  collection  efforts
conducted to  characterize  the industry's wastes  with respect to
conventional pollutants, priority pollutants, and nonconventional
pollutants;   (2)  recent data   collection  efforts  conducted  to
characterize  industry waste  with   respect  to approximately  250
additional nonconventional pollutants;  and (3) an estimate of the
annual   mass   discharge   of  conventional,    priority,    and
noncoventional pollutants by the industry.

A.  SUMMARY OF METHODOLOGY AND DATA SOURCES

In  this  study,   EPA  directed its   efforts  toward  reviewing
available  information,   as well   as  gathering  new  information
through a sampling  and  analysis program, regarding the discharge
of  priority   and  hazardous   nonconventional   pollutants   from
pharmaceutical  manufacturing  facilities.     The  data-gathering
efforts and subsequent information assessments conducted for this
study were divided into the following tasks.

1.  Review and Assessment of Existing Information

Previous regulatory efforts conducted by EPA provided substantial
information regarding wastewater and other  waste characteristics
in  the pharmaceutical  manufacturing industry.    The  development
documents, as  well as  the  technical  records supporting  each of
the rulemaking  efforts, were  initially reviewed to  assess data
gaps and requirements.   This review  identified the  following
major  sources of  information pertaining to  this  study  (discussed
in detail in Section B).

o   308 Portfolio Survey.    A  survey   distributed in  1977  and
    1979.

o   PEDCo Reports.    A  literature  review  to identify priority
    pollutants   associated  with   the  production   of  various
    pharmaceutical products.

o   OAQPS Study.    A   1975  survey  to  determine  the  use  and
    disposition of VOCs.


                                34

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o   Toxic Volatile Oraanics fTVOl Questionnaire.   An EPA  survey
    requesting   analytical   information   on   TVO   levels   in
    wastewater.

o   state and Local Data.   Limited  state  and  local  POTW  data
    were obtained.

o   RSKERL/ADA Study.    "Industry  Fate  Study"  to determine  the
    fate of  specific priority pollutants as they  pass  through a
    biological treatment system.

o   Screening and Verification Sampling  Program.        An    EPA
    Sampling Program for priority and traditional pollutants.

2.  New Data Sources.

The  following  sources  of  new  data  are  discussed in  detail  in
Section C.

o   OAOPS Data.  A supplement to the 1975 study.

o   Sampling and Analysis  Program.       A   program   to   obtain
    wastewater  and  wastewater treatment plant  sludge  samples at
    four  pharmaceutical manufacturing  facilities.   The samples
    were     analyzed    for    conventional,     priority,    and
    nonconventional  pollutants  on the  ITD List  of Analytes.

3.  Water Use. Solids Generation, and Waste Characterization

The  data  bases previously established  by  EPA and the  new data
were  reviewed  to  update water use and waste characterization for
the industry.

4.  Pollutant Mass Load Estimates

The  analytical data  base  was  updated to  include  data obtained
during previous industry studies and the current study.  The data
base  was  used  to  estimate   the  mass load  of  conventional,
priority,  and  nonconventional  pollutants  discharged  in  the
wastewater and waste solids generated  by the industry.

B.  EXISTING DATA SOURCES

Past  data   collection  efforts  conducted  by  EPA  focused  on
determining  the presence  and levels  of conventional pollutants
 (i.e.,   BOD5,   TSS,    and   pH),   priority   pollutants,   and
nonconventional  pollutants  (i.e.,  COD).   This  section briefly
discusses  these past data  collection  efforts  and summarizes the
results.

1.  Conventional  and Nonconventional Pollutants

The CWA defined  four conventional pollutants:   BOD5, TSS, pH,  and
fecal coliform.   An  additional  pollutant, oil  and  grease, was


                                35

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defined  by  EPA as  a  conventional pollutant  under  procedures
established  in Section  304  of  the CWA.   As  a  result  of  past
efforts, effluent limitations were established for control of the
conventional pollutants  BOD5, TSS,  and  pH  in discharges from the
pharmaceutical manufacturing industry.

The  nonconventional  pollutants  of COD,  total  organic  carbon
(TOC), color,  ammonia,  nitrogen, and phosphorus  were considered
for  regulation in  past  rulemaking  efforts.   Of  these,  only COD
was  chosen  as a  representative of  a  specific  and  persistent
pollution problem across the industry.

These pollutants  (i.e.,  BOD.5,  TSS,  COD, and  pH)  were identified
in all plant effluents analyzed.   Pollutant  levels  in treatment
plant  influent  and   effluent   streams were  frequently  high,
particularly at Subcategory A and C facilities  (fermentation and
chemical synthesis, respectively).

Efforts  to  characterize the wastewater of  this industry  with
respect  to  conventional  and   nonconventional  pollutants  are
summarized in the following paragraphs.

a.   308 Survey.   The pharmaceutical manufacturing  industry was
surveyed  in 1978  to obtain  wastewater data  and related plant
information.   The  first  308 Questionnaire  was sent  to PMA member
companies.   The questionnaire  is included as  Appendix  B of the
1982 Proposed  Development  Document.(5)   The  second  phase of this
survey  was  aimed  at  the  remainder  of   the   industry;   the
questionnaire  is  in  Appendix D  of  the  Proposed  Development
Document.   Substantial  differences  in both the form and content
of these questionnaires  resulted from shifts of program emphasis
between the  times  of their distribution.  Recipients are listed
in  Appendices   C  and  E of  the  Proposed  Development  Document.
Survey/  response  statistics  are reviewed in Section II  of the
Proposed  Development  Document.    Traditional  pollutant  (i.e.,
BOD!5, COD,  and TSS)  levels,  as  indicated  in  the  308  Portfolio
data, and  flow data are summarized  in Appendices I  and  J of the
Proposed Development Document, respectively.

b.   Long-term  Data.   EPA selected 22 plants  to  provide long-term
BOD5, COD,   and  TSS  data  on their end-of-pipe  (EOP)  treatment
system's influents and effluents.  The development of a long-term
data  base,    covering   at  least   a    full   year's  data   for
representative  plants,  was necessary to allow EPA  to establish
performance  averages   for representative   groups   of  industry
treatment plants in terms  of both  pollutant  levels  and effluent
variability.   A summary of long-term data is presented in Table
III-l.
                                36

-------
                                                                                      TABU III-I

                                                                               SIMUBT OF LONC-TEIM DATA
                                                                            (Averafe Valuta foe Daily Data)
OJ
•vl

12015
12022
12026
12036
12097
12098
12117
12123
12160
12161
12186
12187
12236
12248
12257
12294
12307
12317
12420
12439
12459
12462
Sub-
D
A C
C
A C
C D
D
C D
D
A C D
C D
C
C
D
A B C D
C D
D
D
B D
C D
D
A
Flow
0.101
1.448
0.161
.092
.064
.006
.101
.931
.029
.653
.037
1.065
0.816
0.110
0.755
0.118
0.002
0.740
0.164
o!o49
0.209
ftobi
232.6
2,141.6 I
3,670.0
1,570.8
1,577.3
34is
490.2
1,538.9
•
742.0
294.4
2,961.7
1.584.3
1.003.7
•
1,805.0
HAW
192.8
(5,880.0
4,869.7
14,490.0
844.3
26is
11,142.0

5,149.6
281.3
18,750.0
1,537.6
5,985.6
•
It. I
3,074.8
VAS1
	 coo"
552.7
7,334.7
3.542.3
1.884.8
95^4
2.160.4
4,332.6
•
2,009.7
473.9
3.429.6
1,102.3

298.9
5,168.2
re LOAD
462.5 123.1
9,700.6 87^9
32,358.0 1,059
984.7
76.6
449.6 1,615
59.231.0 795.
• *
13.277.0
455.2
1,009
3,332.3
6,887.7 41.4
• *
91.9 58.6
8,866.5 2,012
fs5 	
db/d)
1 102.6
113.5
.1 9.812.4
.
.2 282.2
» 10,680.0

.4 6.306.4
247.7
'
23.7
.9 3,308.7
BODS
9.7
110.2
108.1
33.0
49.3
409 9
1.9
166.9
19.8
77 0
707 3
126.2
26.0
228.4
44.7
11 4
7.9
786 8
495 4
3.8
726.8

flb/d)
7.8
1,308.3
136.4
293.6
30.6
12 8
1.7
41.8
276.4
27. 1
6 380.9
886.3
25.5
1,439.5
43.9
0.2
43.7
1,097.2

1.6
1,272.6
FINAL E
COO
44.0
1,221.8
444.5
37.6
24.5
516.7
850.2
447.5

501.9
95.9
232.3
106.4
42.3
971.2
112.8
2,499.3
FFLUENT
(lb/d)
35.4
1.644.7
3,919.7
20.4
20.3
137.5
11,727.0
150.2

3,451.8
90.9
228.9
2.1
254.8

48.3
4.247.0
	 tsT
•t/I)
10.8
84.9
283.7
78.1
18.1
392.1
16.0
115.4
31.6
119.3
60.5
62.0
60.4
715.3
59.2
32.3
9.8
966.4

16.7
2,020.4

8.7
991.0
377.8
720.7
10.5
16.2
12.8
20.3
436.7
40.2
538.1
431.0
59.1
4,403.8
60.5
0.6
59.5
1,328.7

6.7
3.391.8
          Hates:  Period (.) indicate* no data reported.

-------
c.  308 Supplemental Survey.  Selected pharmaceutical plants were
surveyed in 1984 to obtain treatment data on biological treatment
and  effluent  filtration  technologies.    The  data  consist  of
individual observations of  pollutants  (e.g.,  BOD5_,  TSS,  and COD)
at specified  points within each  plant's treatment system.   The
period covered  by  the individual plant  observations  varies from
four  to  36 months.    Summaries  of  the  supplemental  biological
treatment data  and  the effluent  filtration  data  are presented in
Tables III-2 and III-3, respectively.

2.  Priority Pollutants

The Settlement  Agreement  list of  priority pollutants and classes
of priority pollutants potentially includes  thousands of specific
compounds.    However,  for  rulemaking purposes,  EPA  selected 126
specific pollutants for consideration; these  are  listed in Table
III-4.

Because of the  diversity  of processes and materials  used by the
industry, virtually every priority pollutant compound  listed in
the modified  comprehensive Settlement Agreement was  found to be
present in the  effluent of  at least  one  plant.   However, cyanide
was  the  only  priority   pollutant   detected  frequently  and  at
sufficient levels to  warrant development of national regulations
in past rulemaking efforts.

a.    308 Portfolio  Survey.    The  308 Portfolio  Survey  was  an
invaluable  source  for developing   profiles  and  characterizing
industry wastes.   It  was the first  major source of  data on the
use and/or generation of priority pollutants by this industry.

The 308 Portfolio Survey allowed quantification of the nature and
extent of priority pollutants in the pharmaceutical manufacturing
industry.   Of  the  464  plants  in the 308 Portfolio  Survey data
base,  212   responded  to  the   questions   concerning  priority
pollutants.  Of the 115 different priority pollutants identified,
chloroform, methylene chloride,  phenol,  toluene,  and  zinc were
reported  as   the  most   frequently  used   raw  materials  for
manufacturing operations.   None  of  the  priority pollutants was
reported by  as  many  as  10 respondents as being  intermediate or
final products.   Some priority pollutants  (e.g.,  the pesticide-
related compounds endrin  and heptachlor) were reported  as being
analyzed in  the effluents of the manufacturing  plants (believed
to  be from   non-pharmaceutical  sources),  but  not  as   being  a
pharmaceutical manufacturing raw material or final product.

Although the  industry uses  and therefore might  discharge a large
number of priority pollutants,  the 308 Portfolio Survey data base
indicates that broad occurrence of specific chemical compounds is
limited.       Priority   pollutant   information   submitted   by
pharmaceutical manufacturing plants is presented in Appendix A.
                                38

-------
                                                                             TABLE III-2
                                                            SUPPLEMENTAL BIOLOGICAL TREATMENT DATA SUMMARY
                                                        Raw Waste
                                                                                                           Treated Effluent
Plant
Nuaber
12015
12022
12026
12036
12097
12132
12236
12307
12459
12462
55555
vO
Sub-
Category
D
AC
CD
AD
C
AC
C
D
C
A
C

Flow
(•gd)
NA
1.45
0.096
. 1.43
0.061
1.04
NA
NA
0.053
0.155
0.17?

BODS
(•g/t)
313
2,132
1,932
1,119
1,597
2,916
1,264
NA
NA
NA
1,618

COD
NA
(a)
3,259
NA
1,944
6,825
2,043
NA
NA
NA
2,312

TSS
(•g/t)
NA
NA
20
NA
NA
NA
NA
NA
NA
NA
360

BODS
(.g/D
20
111
33
11
68
NA
128
18
3.5
252
33

COD
NA
(a)
248
122
158
1,201
489
86
87
882
NA

TSS
(.g/t)
NA
85
42
24
17
NA
104
17
6
707
75

Tiaw Period
1/1/76 to 12/31/76
5/31/78 to 6/30/79
1/5/83 to 12/28/83
4/1/83 to 4/1/84
11/1/78 to 11/30/79
8/2/82 to 12/31/83
1/1/81 to 12/31/83
1/1/83 to 1/31/83
1/5/83 to 12/28/83
3/1/81 to 4/30/83
1/1/82 to 12/31/82

NA = Not available
(a)  Plant does not use Standard Methods  for the COD test.

-------
                                      TABLE III-3
                         EFFLUENT FILTER PERFORMANCE  INFORMATION
•DOS
                                       COO
                                                                                 TSS
Influent Effluent Reduction Influent Effluent Reduction Influent Effluent
Plant
11111
120S3

12161



12317
33333
44444
NA "
(a)
(b)
(c)
(d)
Subcstetory
C
D

AC



D
D
Not sva liable
Influent tiaw
Effluent tisw
(•I/O (
HA
24

26.1
30.4
23.6
-•
HA
2.54(c)
period
period
Hicroscreen influent not tested
Hicroscreen effluent not tested
•i/O 1
HA
10 SI

2S.7 4
29.7 2
24.1
--
S
l.S5(d)


; flocculatian,
(•i/O
HA
97

HA
HA
NA
271
33
63(c)


clarification, and
(•*/«) 1
HA
(4 13

766
S19
341
270 3
17 41
49(d)


final neutralisation sre
(•i/O <
110
25

61.6
S3
IS
--
19
17.7(c)


between the secondary
; chlorioatioa and post aeration are between the •icroscreen unit effluent and the
•I/O
71
S

11.6
31
10
--
6
I.S(d)


effluent
final pi
Reduction
I
29
6S

70
42
33
--
61
~~



Tim*
Period
3/26/14
2/16/12
11/19/74
6/1/11 -
1/1/M -
1/1/13 -
1/25/14
1/1/13 -
1/1/13 -


- 4/11/14
- 2/!l/83(a>
- 3/2S/l3(b)
12/31/11
12/31/12
12/31/13
- 11/20/14
12/31/13
11/26/13


and the •icroscreen unit Influent.
lant effluent.



-------
    I. METALS
                                              TABLE M-4
                                        LIST Or  MIOilTT POLLUTANTS

                                          V.  EXTRACTARLE
                                              A.   PESTICIDES
                                                I.  ORCANOHAtlDI
   II. MISCELLANEOUS
       ASRP.STOS *
       CTANIOf.S
ill.  OIRENZO-P-DIOXINS
      AND OIRENZOFURANS
      2.J.I.8-TCOD

 iv.  ruiciAiu
           ,1.1-TRICHLOROETNANE
           .1.1, 2-TETRACNLOROETHANC
           . 1,2-TRICHLOROETNAHE
           ,1-DICNLOROETMANE
           ,1-niCNLOROETNENI
           ,2-DICHLOROETNANE
           ,2-DICNLOROPROPANE
           . )-DICHLOROPROPYLENE
          2-CllLOROETNYL VINYL ETHti
          ACIOI.CIH
          ACIYLONITIILB
          ICNZIHE
          RROHOFORH
          UOHOOICMUMDMTNANt
          RROHOMETHANE
          CARRON TETIACHLCMIDE
          CNLORORENZENE
          CHLOROETHANE
          CIILOIOFOIH
          CMLOROHF.THANE
          01 RROHOCNI.OROMETNANE
          ETHYL lENZKNE
          METUTLEHE CHLORIDE
          TETRACHLOROETMENE
          TOLUENE
          TRANS.I.l-DICNLOROETNENE
          TRICIILOROF.THENE
          VINVL CHLORIDE
      4.4>-DOD
      4.*>-DDE
      *.*'-ODT
      AI.ORIN
      ALPHA-RUG
      RETA-IHC
      DILORDANE
      OCLTA.RHC
      Dltl.ORIH
      rnnosiM.fAN i
      ENOOSULfAN II
      ENOnSUI.rAM SUI.PATE
      ENDRIN
      ENORIN ALDEHYDI
      CAHHA-RHC
      HCPTACHI.OR
      HCPTACHLOR EPOS I DP.
      PCR-IOU
      PCR-I12I
      PCR-1212
      PCR-1242
      PCR-I24I
      PCR.I2I*
      PCR-1260
      TOXAPNENE

I.  S EH I-VOLATILE!
  I.  ACIDS
I.  SF.MI-VOLATILE*
  2. RASES

      01 -N-PROPYI.NITROSAHINE
      ri.UORENE
      ISOPHOROHI
      N-NITROSOOINETNYLAHINE
      N-NITROSODIPHENVLAHINE
      NITRORENZENI
      PYRENK
                                                                                        1.  NEUTRALS
                                                                                          • .  PHTHALATF.S
      2. *. *-TI ICNLOROPNENOL
      2.4-OICHLOROPHENOL
      2.4-OIHETNYLPMEHOL
      2.4-OINITROPHENOL
      2-CHLOROPMENOL
      2-NITROPHENOL
      4-NITROPHENOL
      DINITROCRESOL
      rENTACHLOROPHENOL
      PHENOL
  2.  RASES
      1,2-OIPHENTLNVDRAZINE
      2.4-DINITROTOLUENE
      2.6-DINITROTOLUENE
      l.l.OICIILORORENZIDINE
      t-IRONOPHENYL PHENYL ETHER
      <.-CHIORO-)-HETH»LPHINOL
      4-CIILOROPIIENTL PHENYL ETHER
      RENZIDINE
      hlf(2-CHLOROETHYL) ETHKR
      bl>(2-CIILOROISOPROPYL) ETHER
        RIS(2-ETNYI.NEIVL) PNTHALATE
        RIITYL iEN/.YL PNTHALATE
        DI-N-RUTYL PNTHALATE
        DUN-OCTYI. PNTHALATE
        01 ETHYL PHTHAI.ATE
        DIHETHYL PHTHALATE

    k.  POLYHUCLEAR AROMATIC

        2-CHLORONAPNTHALf.NE
        ACENAPHTIIFHE
        ACEHAPNTHYLENC
        ANTHRACENE
        REHZO (A) ANTHRACENE
        RENZO (A) PYRENE
        RENZO 
-------
b.   PEDCo Reports.   Concurrent with  the efforts to profile  the
pharmaceutical  manufacturing  industry  using the  308  Portfolio
Survey, PEDCo  studied  the various manufacturing  processes/steps
used in the  production of fermented, extracted, and  synthesized
Pharmaceuticals.(1,2,3)

PEDCo examined  industry  data  and identified those products that
comprise  the major  areas  of production for each  of the  three
manufacturing subcategories (A, B, and  C) .   Available literature
describing the step-by-step procedures  used  in  the  production of
each substance was  reviewed  and the priority pollutants  used by
the  industry were  identified.   These  pollutants  are listed in
Table III-5.

It was  not practical  to  identify every priority pollutant that
could be  used,  because of the limited  scope of the  PEDCo study,
the  size   and  complexity  of  the industry,  and the  myriad  of
products manufactured.

c.   OAQPS Study.    EPA's  OAQPS  published a document  in  December
1978 providing  guidance  on air pollution control techniques  for
limiting   emissions   of   VOCs    from   the   chemical   synthesis
subcategory  (C) of the pharmaceutical industry.(6)

As part of this study, the PMA  surveyed selected  pharmaceutical
plants to  determine  estimates of  the  10 largest volume VOCs that
each company purchased and the mechanism by  which they leave the
plant  (i.e., sold  as  product,  sewered, or emitted  as an  air
pollutant).

Table III-6 presents a compilation of the survey results.  Of the
26 responding  companies,  25 indicated  that  the 10 VOCs  used in
the greatest quantities accounted for 80 to  100 percent of total
plant use.  The other  company stated that the 10 VOCs used in the
greatest  quantities  accounted for only  50 percent of total plant
use.  These  26 companies accounted for 53 percent of the domestic
sales of ethical Pharmaceuticals  in 1975.

Included  in  the list of 46 compounds presented in Table III-6 are
seven  priority  pollutants.     These  compounds  are  methylene
chloride,   toluene,   chloroform,   benzene,  carbon  tetrachloride,
1,1,1-trichloroethane,  and 1,2-dichlorobenzene.

Table III-7  presents a summary  and  analysis  of  the  data outlined
in  Table   III-6.    Priority  pollutants  represent  approximately
28 percent of  total VOC usage in the industry  segment analyzed.
However,  priority  pollutants  represent  only  13 percent of  the
total mass discharge of VOCs to the plant sewers.

Table III-7  also indicates that of the total quantity of all VOCs
discharged,  only a fraction  (16.6  percent)  is discharged  via
wastewater.  The priority pollutant  VOCs are discharged with the
wastewater in an even  lower proportion  (9.6 percent).
                                42

-------
                                       TABLE III-5
                    SUMMARY OF PRIORITY POLLUTANT USE:   PELCo REPORTS
Priority Pollutants Identified As Used In:

Subcategory A1                             Subcategory B2

benzene                                    benzene
chloroform                                 carbon tetrachloride
1,1-dichloroethylene                       1,2-dichloroethane
1,2-trans-dichloroethylene                 chloroform
phenol                                     methylene chloride
copper                                     phenol
zinc                                       toluene
                                           cyanide
                                           lead
                                           mercury
                                           nickel
                                           zinc
Subcategory C3

benzene
carbon tetrachloride
chlorobenzene
chloroethane
chloroform
1,1-dichloroethylene
1,2-trans-dichloroethylene
methylene chloride
methyl chloride
methyl bromide
nitrobenzene
2-nitrophenol
4-nitrophenol
phenol
toluene
chromium
copper
cyanide
lead
zinc
 1 Reference No.  1
 2 Reference No.  2
 3 Reference No.  3
                                     A3

-------
                                                       TABU

                                       COMPILATION OF DATA SUBMITTED  BT THE  FMA FROM
                                   26  MANUFACTURERS OF ETHICAL DRUGS:  1975  OAQPS STUDT
Type of VOC
Priority Pollutants
benzene*
carbon tetrachloride
chloroform
o-di chlorobenseoe
•ethylene chloride
toluene*
trichloroethane
Subtotal
ITD-Listed Nooconventio
acetone
dimethyl formamide*
1,4-dioxane
ethyl ether
freons
methyl ethyl ketone
methyl isobutyl ketone*
pyridine
Subtotal
Annual ~
Purchase

1,010
1,850
500
60
10,000
6,010
135
19,565

Air

270
210
280
1
5.310
1.910
135
S7IT6"
Ai


350
120
23
60
455
885
T7893
mual Disoositi


150
1,510

2,060
1,590
57515
on (metric
Contract
Haul

80
175
2,180
1,800
57235

Other
Disposal**

--
17
-.
17

Product

90
—
5
55
Solvent

20,500
1,210
7,060
73,400
23,850
126,020
nal Pollutants
12,040
1,630
43
280
7,150
260
260
3
21,000
1.560
1.350
2
240
6
170
260
57515
2,580
60
12
30
3
27555
4,300
380
--
60

57755
770
120
41
30

~
96T
~
«

—
—
2,210
7, * •
.145
65
97525
40,760
5,100
110,800
*"
6J160
169,240
Non-ITD- Listed Nonconventional Pollutants
acetic acid
acetic anhydride
acetonitrile
amyl acetate
amyl alcohol*
Blendan (Amoco)
butanol*
cyclohexylamine
diethylamine
diethyl carbonate
diethyl-ortho formate
dlmethylacetamide
dimethylsulfoxide
ethanol
ethyl acetate
ethyl bromide
ethylene flycol
formaldehyde
formamide
hexane*
isobutyraldehyde
Isopropanol*
isopropyl acetate
isopropyl ether
methanol
methyl cellosolve
methyl formate
polyethylene glycol 600
skelly solvent 8
tetrahydrofuran
xylene*
Subtotal
Totals
930
1.265
35
285
1,430
530
320
3,930
SO
30
54
95
750
13,230
2,380
45
60
30
440
530
85
3,850
480
25
7,960
195
415
3
1.410
4
3.090
43,936
85,167
12
8
30
120
775
85
SO
1

7
4
1.250
710

_.
5

120
40
1,000
105
12
2,480
90

410

170
77555
19,188
770
550
6
165

30
3
20
21

210
785
1.110
45
60
20
290
40
1.130
45
12
3,550
100
310
23

510
97105
14,383
—
__
--
5
•>*
mm
mm
^^
535
915
480

_—
— _
..
too
1,150
230
1.120
—
980
4
1.910
77559
17,479
..

0
130
__

__


200
80

__
__
110
475
470
410
SO

__
140
2.155
7,351
.•

—
--



"

—



._
—
25
30
«


55
72
160
410

9
C4n
530
110
3Q^A
»yjv

•**
33

10.000



30

3.090
340
60
3

3
18,716
28,231
1,040
300
125
3cm
,510
76,900
1,040
"
300

""
47AA
, /ou
7,570

7, 170
60

25,670
t /.f
1**5
3,880
1,840

360
1,130


9.400
146,017
441,317
Notes ~ 	 	 ' 	
Source - 26 member companies of the PMA reported these data which they felt represented 85 percent of the
         VOCs used in their operations; these reporting companies accounted for approximately S3 percent
         of the 1975 domestic sales of ethical Pharmaceuticals.

**Deep»ell or landfill.

'Annual disposition does not closely approximate annual purchase.

-------
Ln
                                                    TABLE  III-7
                                  SUMMARY OF VOC EMISSION  DATA:   1975 OAQPS STUDY

                                                        ITD-Listed    Non-ITD-Listed
                                         Priority    Non-Conventional Nonconventional     Total
                                        Pollutants      Pollutants     Pollutants        Compounds

Amount purchased
(metric tons)
Amount discharged
(metric tons)
Amount recovered
within the plant
(metric tons)
Total amount used in
plant (sum of items 1
and 3; metric tons)
Percent recovered
Percent of total used
(total of 7)
19,565

19,666

126,020


145,585


86.6
13.5
(total of 8)
21,666

21,394

169,280


190,946


88.7
11.2
(total of 31)
43,936

45,644

146,017


189,953


76.9
24.0
(total of 46)
85,167

86,704

441,317


526,484


83.8
16.5
          that is discharged

          Percent of total used
          that is discharged to
          sewer

          Percent of total
          discharged that is
          discharged to sewer
1.3
9.6
 1.4
12.6
 5.2
21.5
 2.7
16.6

-------
OAQPS again worked  with the PMA  in  1986 to update purchase  and
disposition   data   for   seven   VOCs   used  in   pharmaceutical
manufacturing  processes.(7)    The  seven VOCs  included  in  the
survey are carbon tetrachloride,  chloroform, ethylene  dichloride,
ethylene  oxide,  methylene  chloride,  perchloroethylene,   and
trichloroethylene.

Results  from   the  22  firms that  responded  to the  survey  are
summarized in Table III-8.  The PMA indicated that the responding
firms represent  approximately  70 percent of  U.S.  pharmaceutical
sales for 1985.

d.   RSKERL/ADA Study.   RSKERL/ADA conducted  an applied research
study   entitled,   "Industry  Fate   Study,"  for  the   Effluent
Guidelines Division (now the ITD).(8)  The purpose of  this report
was to determine the fate of specific priority pollutants as they
pass  through   a  biological  treatment  system.     In  the  study,
priority   pollutants   associated   with   the   manufacture   of
Pharmaceuticals  at  two  industrial  facilities  were  identified.
Results of these wastewater  analyses are reported in  Appendix B.
RSKERL/ADA data are limited  since they are  from only  two plants;
however, they do supplement the other data.

e.    Total Toxic Volatile  Oraanics  (TTVOs)  Questionnaire.     To
determine  the  extent  to  which  the  wastewater  of  indirect-
discharging pharmaceutical  plants was contaminated by  TVOs,  EPA
sent 308 Questionnaires to nine indirect-discharging plants which
had  indicated  the use of TVOs.   EPA also  sent  questionnaires to
six  other plants that had commented  on the proposed pretreatment
standard  for  TTVOs  (see 47 FR  53585,  November  26,   1982).  EPA
sought  information on wastewater contamination by TVOs to develop
plant-by-plant cost estimates for steam-stripping  technology.  A
copy    of   the   questionnaire   sent   to   the   participating
pharmaceutical  plants   is   in   Section  22-6-1  of  the  record
supporting the 1983 rulemaking efforts.

Questionnaire  responses were received  from  16 plants  (one company
responded  for another  plant not  sent  a  questionnaire).    Five
plants   reported  contamination   of   part  of   their  process
wastestream by one or more TVOs at concentrations greater than 10
mg/.  A summary  of  the priority  pollutant data obtained from the
questionnaire  is presented in Table  III-9.  The median percentage
of process wastewater contaminated by TVOs  was 26 percent at the
five plants.   This  percentage  was used to develop plant-by-plant
steam-stripping  costs (see  Appendix A of  the  Final  Development
Document).

f.   State and Local  Data.   State  and  local data presented in
Appendix C  verify that  several  volatile  hazardous  constituents
are  present in wastewater discharged to  POTWs from pharmaceutical
manufacturing    facilities.       Specifically,    high   average
concentrations are  shown for acetone  (9.65 mg/1),  toluene (2.84
mg/1),  and xylene (1.0 mg/1).
                                46

-------
                                                        TABLE III-8

                                                   DATA SUBMITTED BY PMA
                                           FROM 22 PHARMACEUTICAL MANUFACTURERS
                                                     1985 OAQPS STUDY
                                                         Annual Disposition (metric tons)
Type of VOC
carbon tetra chloride
chloroform
ethylene dichloride
ethylene oxide „
methylene chloride
pferchloroethylene
trichloroethylene
Totals
Annual
Purchase
13
686
1,111
9,587
1,539
6.5
2
14,054.5 [SIC]
Air
Emissions
12
261
125
34
1,031
--
"
1,462
Sewer
._
124
41
6.7
118
--
""
289.7
Incineration
^ _
91
833
1
62
2
2
991
Contract
Haul
— —
67
79
2.5
154
--

302.5
Other
Disposal*
. «.
132
—
--
113
--

245
Product
..
1.4
—
9.5081
41
2.3

9,552.7
Source -  Data are from a letter to OAQPS from PMA.  Data represent estimates for 1985 use and disposition.
          22 PMA member firms responded, representing approximately 70% of pharmaceutical sales for 1985.

Ethylene oxide use is primarily as a reactant in pharmaceutical manufacturing processes; that is, converted
 into drug product.

2Data for methylene chloride do not include figures already submitted from 9 of the reporting firms.
 (Estimated to be  13,700 metric tons).

*0ther disposal modes:  fractional dilution; off-site recovery; deep well; conversion; and solvent recovery.

-------
Plant
                                       TABLE III-9
                           SUMMARY OF PRIORITY POLLUTANT DATA
                            FROM THE 1983 TTVO QUESTIONNAIRE

                                           Wastewater Concentration
Compound
Undiluted
Process
(MS/*)
                                                          Discharge
                                                          to POTW
          Manu-
          facturing
          process
12003
12057
12107(b)

12112(c)
12123
12168

12252



12254
chloroform
methylene chloride
toluene

carbon tetrachloride
1,2-trans-dichloroethylene
methylene chloride
toluene
benzene
carbon tetrachloride
chlorobenzene
chloroform
1,2-dichlorobenzene
1,2-dichloroethane
methylene chloride
toluene
1,2,4-trichlorobenzene
trichloroethylene

bis(2-chloroethoxy)methane
chloroform
cyanide
1,2-dichloroethane
ethylbenzene
ethyl chloride
methylene chloride
toluene

toluene

chloroform
methylene chloride
toluene

chloroform
methylene chloride
        0
        0
        0
        0
   21,000
    6,000
    7,000
    6,000
    3,000
    5,000
   32,000
   21,000
    3,000
      200

       50
      <50
      <50
      <30

    2,600
    3,400

  500,000

    4,800
    6,500
    6,200

   60,000
    5,000
                l,843(a)
               18,591(a)
                l,921(a)
640
859
819
              C
              C
              C

              C
              C
              C
              C
              D
              D
              D
              D
              D
              D
              D
              D
              D
              D

              C
              C
              C
              C
              C

              C
              C
 C
 C
 C

A,C
 C
                                     48

-------
                                 TABLE III-9 (continued)



Plant
12257







Compound
carbon tetrachloride
1 ,2-dichloroe thane
chloroform
methylene chloride
toluene
Wastevater Concentration
Undiluted Discharge
Process. to POTW
(MR/A) (MB/A)
nd
nd
12
nd
nd

Manu-
facturing
process
C
C
C
C,D
C
12275
12310(d)

12330

12339(e)

12447(f)


12477
acetone
bromoform
chlorobenzene
chloroform
di chlo rob romomethane
1,2-dichloroethane
methylene chloride
2,2,2*-oxybispropane
1-propyl alcohol
1-propyl acetate
toluene
cyanide
methylene chloride
methylene chloride
toluene

chlo robenzene
chloroform
methylene chloride
toluene
20,000,000
         0
     3,000
    72,000
   ao3,ooo
                    5-414
                    0-139
                  112-190
                    39-55
                     0-14
                    32-48
                        0
                    0-552
                     0-12
                     0-10
                 431-1090
45,000
                                                                              C
                                                                              C
                                                                              C
                                                                              C
                 A
                 C

                 C
                B,C
                 C
                 C

-------
                                 TABLE III-9 (continued)

                                           Wastewater Concentration
                                           Undiluted      Discharge       Manu-
                                           Process        to POTW         facturing
Plant       Compound	(ug/A)	(ug/A)	process

12481       methylene chloride                     0             —           D

20349(g)


      Data not available.
(a)   Flow-weighted average of 19 24-hour composite samples.
(b)   Process wastewater does not contain volatile priority pollutants.
(c)   This plant no longer produces Pharmaceuticals.  However, data shown are from a
      a period when Pharmaceuticals were manufactured at this plant.
(d)   This facility does not engage in manufacturing activities.
(e)   No wastewater at this facility is discharged to a POTW.
(f)   Methylene chloride and toluene discharged during production of certain products;
      see questionnaire.
(g)   This facility does not use or produce any TTVOs.
nd    Not detected.
                                    50

-------
g.  Screening and Verification Sampling Programs.   Information on
priority pollutants  from  the previously  mentioned reports  and
surveys was  largely  qualitative.   Moreover, the  earlier reports
did not always distinguish between pollutants used by a plant and
those  found  in  the  final effluent.    Beginning  in  1978,  EPA
initiated the Screening and Verification Sampling Program, in which
a number of  plants representing  the pharmaceutical manufacturing
industry were sampled  for priority  pollutants  and  traditional
pollutants (BOD5, COD,  and TSS) in a two-phase program.  The first
phase, called the screening phase, involved 26 plants and covered
a broad  cross section of the  industry.   This was  followed  by a
verification  phase  which  limited the sampling to  only  five
carefully selected plants.  Augmentation of the existing data base
with analytical results of the Screening and Verification Sampling
Program, along with  the  qualitative information from other data-
gathering   efforts,   provided  EPA  with   information  used  to
characterize the industry's wastewater.

The screening program was conducted to determine  the presence or
absence  of  priority  pollutants in the wastewater of  a number of
pharmaceutical  plants,  and  to   quantify  those  present.    The
information was then used to limit the  search to specific priority
pollutants  for  the  verification  program and to  identify plants
likely to provide information to accurately characterize industry
wastewater.

Major  processing  areas  and  subcategory  coverage,   range  of
wastewater  flows,  and  an  assortment  of  both  in-plant  and EOP
treatment technology/techniques  were used as  selection criteria
for the screening plants.  Multiple subcategory  plants, as well as
plants  within only  one  subcategory,  were  deliberately sought.
Similarly,  EPA  made a  special   effort to  include plants  with
wastewater  flows  less  than   100  gpd  and  more   than  2.5  mgd.
Descriptions  of  the  plants and sampling points are presented in
Appendix 0 of the Proposed  Development  Document.

Included in the screening group were nine direct  dischargers, seven
indirect dischargers, three zero dischargers, and seven plants that
used more than one mode  of  discharge.   In  the latter group, three
plants were both indirect  and zero  dischargers,  three were both
direct  and  zero  dischargers, and  one  used  all  three  modes of
discharge.  The screening plants  with subcategory  designations are
as follows:

  Plant ID No.   Subcateqorv     Plant  ID  No.      Subcateaorv

       12015       D               12210               BC
       12022       AC              12231               AD
       12026       C               12236                C
       12036       A               12248               D
       12038       ABCD            12256                ABCD
       12044       AD              12257                ABCD
       12066       BCD             12342                ACD
       12097       CD              12411               BCD
                                51

-------
 Plant ID No.
12108
12119
12132
12161
12204
ACD
AB
AC
CD
ABCD
12420
12439
12447
12462
12999
BD
CD
ABCD
A
CD
The verification program was developed to confirm the presence of
the priority pollutants identified by the screening program and to
provide  quantitative  pollutant  data  with  known precision  and
accuracy.  The  analytical  results  from these episodes serve as a
basis to  confirm the presence of the  pollutants  of  interest, as
well as to  identify effective control  and  treatment technologies
for these pollutants.

Selection of the five plants for the verification program was based
in part on general criteria presented in Section  II of the Proposed
Development  Document.  A criterion  mentioned earlier, and  which
weighed heavily in the final selection  process, was the assortment
of major priority pollutants  being  used as raw  materials for the
manufacture  of  Pharmaceuticals.   Table 111-10 lists  the  priority
pollutants that appear in the  wastestreams  at detectable levels at
each of the screening plants.   Other plant-specific characteristics
that were considered in the final selection process are summarized
in the following paragraphs on a plant-by-plant basis.

Plant 12411.  Three of the common priority pollutants used by the
industry were found in the  wastestreams of  Plant 12411:  methylene
chloride,  chloroform,  and  toluene.    The  presence  of  these
pollutants,   a process  area involving three subcategories,  use of
a solvent recovery system,  and pretreatment of wastewater followed
by aerated lagoon treatment justified this  plant for verification
sampling.

Plant 12038.    This  plant was   selected  for  sampling  in  the
verification program because   it  used  potential  BAT  technology,
including  steam-stripping,  aerobic  biological  treatment,  and
thermal oxidation.   The presence of several  priority pollutants
(including nitrosamines), the  existence of  a large historical data
base relating to nitrosamines, and the inclusion  of both pesticides
and Pharmaceuticals  in  the manufacturing operations  at the plant
were also considered in the selection process.

Plant 12236.   Limitation to  one  subcategory, reported  flows of
about 0.81 mgd, use  of  cyanide as  raw  material,  and  treatment of
wastewater by the activated sludge process qualified this plant for
the verification program.  Also of interest  was the use of in-plant
treatment processes,  including cyanide destruction and  solvent
recovery.
                               52

-------
                        TABLE 111-10
SUMMARY OF PRIORITY POLLUTANT OCCURRENCE SCREENING PLANT DATA
                   Number of Occurrences
Detected Above 500

Compound
acenaphthene
benzene
benzidine
carbon tetrachloride
chlorobenzene
1 ,2-dichloroethane
1,1, 1-trichloroethane
1 , 1-dichloroethane
1 , 1 ,2-trichlorethane
chlo roe thane
bis (2-chloroethyl)ether
2,4, 6- trichlorophenol
chloroform
2-chlorophenol
1 ,2-di chlorobenzene
1 ,4-dichlorobenzene
1 , 1-dichloroethylene
1-2-trans-
dichloroethylene
2 -4-dime thy Ipheno 1
2-4-dinitrotoluene
2-6-dinitro toluene
1 , 2-diphenylhydrazine
ethylbenzene
fluoranthene
bis (2-chloroisopropyl)
ether
methylene chloride
methyl chloride
methyl bromide
bromoform
isophorone
napthalene
nitrobenzene
2-nitrophenol
4-nitrophenol
4 , 6-dinitro-o-cresol
N-nitrosodiphenylamine
penta chl o r opheno 1
phenol
bis(2-ethylhexyl)
phthalate
Influent
(25)*
4 (16%)
15 (60%)
1 (4%)
3 (12%)
5 (20%)
5 (20%)
8 (32%)
4 (16%)
4 (16%)
2 (8%)
1 (4%)
1 (4%)
16 (64%)
1 (4%)
2 (8%)
1 (4%)
5 (20%)
1 (4%)

1 (4%)
2 (8%)
1 (4%)
1 (4%)
12 (48%)
I (4%)
3 (12%)

17 (68%)
1 (4%)
1 (4%)
1 (4%)
2 (8%)
1 (4%)
1 (4%)
3 (12%)
3 (12%)

1 (4%)
2 (8%)
U (54%)
*Q (40%)

Effluent ug/1 in
(20)* Effluent(20)*

3 (15%)

1 (5%)

4 (20%) 1
4 (20%)

1 (5%)

1 (5%)

9 (45%)



2 (10%)


1 (5%)
1 (5%)


2 (10%)

2 (100%)

15 (75%) 2


1 (5%)




1 (5%)
1 (5%)


4 (20%)
8 (40%)

                                                        Max. Effluent
                                                            Level
                                                            ug/1
                                                            120

                                                             16

                                                            500
                                                             33

                                                             14

                                                             20

                                                            110



                                                            180
                                                             15
                                                             14
                                                            160



                                                           2600


                                                             44
                                                             15
                                                             15
                                                            120
                                                             68
                       53

-------
                                TABLE 111-10  (continued)
              SUMMARY OF PRIORITY POLLUTANT OCCURRENCE SCREENING PLANT DATA
                                 Number of Occurrences
Detected Above 500

Compound
butyl benzyl phthalate
di-n-butyl phthalate
diethyl phthalate
anthracene
fluorene
phenanthrene
tetrachloroethylene
toluene
trichloroethylene
antimony (total)
arsenic (total)
beryllium (total)
cadmium (total)
chromium (total)
copper (total)
cyanide (total)
lead (total)
mercury (total)
nickel (total)
selenium (total)
silver (total)
thallium (total)
zinc (total)
Influent
(25)*
2 (8%)
3 (12%)
1 (4%)
2 (8%)
1 (4%)
1 (4%)
4 (16%)
16 (64%)
3 (12%)
10 (40%)
5 (20%)
4 (16%)
8 (32%)
23 (92%)
24 (96%)
11 (44%)
13 (52%)
16 (64%)
14 (56%)
7 (28%)
7 (28%)
5 (20%)
21 (84%)
Effluent ug/1 in
(20)* Effluent (20)*

4 (20%)
1 (5%)



2 (10%)
5 (25%) 1
2 (10%)
3 (15%)
3 (15%)
2 (10%)
5 (25%)
15 (75%)
16 (80%)
10 (50%)
9 (45%)
12 (60%)
9 (45%)
3 (15%)
3 (15%)
4 (20%)
17 (85%)
Max. Effluent
Level
ug/1

15
20



18
1350
11
90
30
2.0
40
304
63
7700
400
1.58
310
56
40
29
403
* Indicates number of plant streams
                                    54

-------
Plant 12026.  Plant 12026 is  a  single  subcategory (C)  plant with
a reported  flow of 0.101 mgd.   A treatment train  consisting of
activated sludge,  an  aerated  lagoon,  and a polishing  pond after
in-plant treatment by solvent  recovery were the reasons this plant
was selected for verification sampling.

Plant 12097.  Plant 12097 is a multiple  subcategory (CD) plant with
a reported  flow of  0.035 mgd.   The  use of cyanide in production,
in-plant solvent recovery, and an activated sludge  treatment system
were considered in selecting this plant.

A plant-by-plant summary of analytical  results  from the sampling
program  is  presented in Appendix G of the  Proposed Development
Document.(5)

Table III-ll lists the conventional, nonconventional, and priority
pollutants  that were  identified and the  frequency  at  which they
were  found  in  the  wastestream.  Although  a number of priority
pollutants  appeared   in  the  wastestream,  only   a   few  were
sufficiently  repetitive to cause concern.   Pesticides  and PCBs
detected in one plant's effluent are  not believed to  be  due to
pharmaceutical-related  activity.

Wastewater entering and leaving the  EOP wastewater treatment train
were   among  those   wastestreams  sampled   in   this  program.
Concentration levels  for many of the  priority  pollutants  in the
final effluent are relatively  low because of  (1)  in-plant treatment
and  process controls to minimize specific  wastewater pollution,
(2) dilution  of concentrated process wastewater  with  other less
concentrated  wastewater,  and   (3)  incidental  removal  of  some
specific chemical pollutants by EOP treatment.

h.  Pharmaceutical/POTW Sampling.  A six-day sampling episode was
conducted concurrently  at  Plant 12342  and  the  POTW which treats
its wastewater in May 1983.(9)  The  purpose  of the sampling was to
define  and  document the mass  of toxic pollutants discharged  from
a  major pharmaceutical facility  and  to monitor  the  fate and
treatability  of these toxic pollutants at  the  POTW treating the
wastewater.   Sampling  results were  evaluated for  the possible
"pass-through"  of  toxic pollutants  to the receiving water and the
interference of treatment processes by the toxins  which,  in either
situation,  would  support the  recommendation  for toxic pollutant
pretreatment  standards  for the  industry.  Plant  12342,  on average,
discharges  about   1  mgd  of   solvent-laden  wastewater.     This
wastestream combines with  approximately 79 mgd  of residential,
commercial, and industrial sewage before being treated at the POTW.
The  POTW is  a well-maintained and properly  operated  secondary
treatment   facility  which  uses  the  activated  sludge process.
Average BOD5_  and TSS  effluent concentrations were 12 and 24  mg/1,
respectively, during  the most recent 12-month period prior to the
sampling episode. Plant 12342 effluent concentrations of methylene
                                55

-------
                                                                                 TABLE  111-11
                                                                 SUMMARY  OF  PRIORITY  POLLUTANT  CONCENTRATIONS
                                                                       SCREENING/VERIFICATION DATA  BASE
                                                        Influent
                                                                                                                    Effluent (pg/l)
      Priority Pollutant
                                Number of
                                 Plants
                                       Number of
                                      Observations
                                                            Minimum    Maximum
                                                                                  Median
                                     Number of
                               Mean    Plants
                                                               Number  of
                                                             Observations
                                                                             Minimum
                                                                                        Maximum
                                                                                                   Median
                                                                                                             Mean
Ln
Volatile Organics

acrolein                     0
benzene                     11
hromoform                    1
carbon tetrachloride         3
chlorobenzene                4
chloroform                  14
1,2-dichloroethane           8
1,1-dichloroethylene         1
1,3-dichloropropylene        1
ethylbenzene                 9
methylene chloride          18
methyl chloride              2
1,1,1-trichloroethane        8
1,1,2-trichloroethane        2
trichlorofluoromethane*      1
1,1,2,2-tetrachloroethane    1
tetrachloroethylene          8
toluene                     14
trichloroethylene            2
vinyl chloride               1
 0
19
 2
 5
 6
22
17
 1
 1
18
31
 4
11
 2
 1
 1
 4
29
 2
 1
 15
 12
 12
 11
 26
 12
230
100
 11
 16
 59
 17
 19
970
 20
 14
 50
 11
 14
--
10,300
12
300
123,000
1,620
14,000
230
100
42,000
200,000
13,000
1,300
20
970
20
36
227,000
124
14
--
120
1.2
18
3,206
170
62
230
100
24

8,600
22
20
970
20
31
310
68
14
--
1,586
12
81
36,405
396
2,516

100
3,237
11,356
7,565
169
20
970
20
28
21,075
68
14
1
1
0
2
0
6
5
1
0
3
14
2
4
0
1
0
1
4
1
0
 1
 1
 0
 2
 0
 7
 9
 1
 0
 3
21
 4
 6
 0
 1
 0
 1
 4
 1
 0
                                                                                                                                100
                                                                                                                                120

                                                                                                                                 16
                                                                                                                                420

                                                                                                                                 18
                                                                                                                                100
                                                                                                                                 14
100
120

 61
420

 18
315
 14
100
120

 39
420

 18
185
 14
100
120

 39
14
22
180
14
12
100
10
150
500
180
22
8,100
410
33
90
62
180
17
120
310
20
79
158
180
18
863
283
21
420

 18
196
 14

-------
                                                                           TABLE  111-11  (continued)
Ol
      Priority Pollutant
                                Number of
                                 Plants
                                       Number of
                                      Observations
                                                        Influent  (pg/l)
                                                            Minimum
                                                                       Maximum
                                                                                  Median
Semivolatile Organics

acenaphthene                 2
anthracene                   1
bis(2-chloroisopropy1)
  ether                      2
bis(2-ethylhexyl) phthalate  8
butyl benzyl phthalate       3
2-chlorophenol               1
1,2-dichlorobenzene          2
1,4-dichlorobenzene          1
2,4-dichlorophenol           1
diethyl phthalate            1
2,4-dimethylphenol           1
di-n-butyl phthalate         4
4,6-dinitro-o-cresol         1
2,4-dinitrotoluene           1
fluorene                     1
isophorone                   2
2-nitrophenol                2
4-nitrophenol                2
N-nitrosodiphenylamine       1
pentachlorophenol            2
phenanthrene                 1
phenol                      20
2,4,6-trichlorophenol        1
 2
 1

 2
10
 3
 1
 2
 1
 1
 3
 1
 4
 1
 1
 1
 2
 2
 2
 1
 2
 ]
36
 1
                                                                                           Mean
                                                 Number of
                                                   Plants
35
14
300
10
12
50
12
90
ID
61
62
18
15
68
27
11
23
181
12
42
14
12
20
92
14
448
760
719
50
20
90
10
61
62
20
15
68
27
1,014
119
1,600
12
62
14
51,000
20
64
14
374
105
18
50
16
90
10
61
62
20
15
68
27
513
71
891
12
52
14

20
64
14
374
157
250
50
16
90
10
61
62
19
15
68
27
513
71
891
12
52
14
7,529
20
0
0
1
6
0
0
0
0
0
2
1
2
0
0
1
0
0
1
0
0
0
9
0
 Number of
Observations
                                                                                                                   Effluent (Me/I)
                                                                                                                             Minimum
                                                                                                                                        Maximum
         Median
     0
     0

     1
     9
     0
     0
     0
     0
     0
     2
     1
     2
     0
     0
     1
     0
     0
     1
     0
     0
     0
    12
     0
                                                                                                                               181
                                                                                                                                10
                                                                                                                                 10
                                                                                                                                 15
                                                                                                                                 10
                                                                                                                                 10


                                                                                                                                 15



                                                                                                                                 10
181
 68
 20
 15
 15
                                                                                                                                           10
 15
126
181
 30
 15
 15
 13
 10


 15



 23
                   Mean
181
 36
 15
 15
 13
                                                                                                                                                              10
                    15
                    47

-------
                                                                             TABLE III-11 (continued)
oo
Priority Pollutant
Metals
antimony
arsenic
cadmium
chromium
copper
lead
mercury
nickel
selenium
silver
thallium
zinc
Other
cyanide

Number of
Plants

8
It
4
18
21
9
16
11
4
2
2
20

8

Influent (|jg
Number of
Observations Minimum

9
4
5
30
39
13
31
19
5
2
3
37

16

12
13
10
13
14
16
0.1
15
16
24
18
29

18
/£) Effluent (ue/t)
Maximum

210
43
40
650
7,030
500
0.1
630
60
40
43
2,070

540
Median

27
31
32
39
63
39
28
32
40


140
Number of
Mean Plants

45
29
25
117
571
119
3.9
103
31
32
34
363

153

2
3
1
13
13
9
11
8
2
1
2
17

6
Number of
Observations Minimum

5
6
1
21
25
14
19
16
5
1
5
32

11

20
10
40
10
14
13
0.1
19
12
40
10
13

30
Maximum

51
20
40
304
106
400
1.3
300
56
40
129
2,009

7,700
Median

31
12
40
27
31
33
0.7
51
45
40
11
118

100


34
13
40
77
38
64
0.7
83
42
40
37
240

827
        * Deleted from the list of priority pollutants as per 46 CFR 2266.

-------
chloride ranged  from  13,400 to 166,000 mg/1 during  the sampling
episode.  The average  effluent concentration of methylene chloride
was 50,030  mg/1; the median concentration  was 30,450 mg/1.   On
average, 85  percent of the methylene  chloride mass in  the POTW
influent originates from Plant 12342.  The average POTW methylene
chloride  influent  concentration  was  414  mg/1.     The  average
secondary effluent methylene chloride concentration at the POTW was
177 mg/1; daily methylene chloride removals ranged  from nine to 72
percent. Other toxic pollutants at detectable concentrations  in the
pharmaceutical effluent wastestream  were  phenol,  isophorone,  and
toluene.  These  pollutants were reduced to much  lower secondary
effluent levels  than  methylene  chloride at  the POTW.  Analytical
results  for  the six-day  sampling  episode  at Plant   12342  are
summarized in Table 111-12.

Additional analytical  data characterizing the wastewater from Plant
12342 with  respect to VOCs were supplied by the  local  POTW.   In
their comments on  EPA's  November  26, 1982,  proposed regulations,
POTW officials provided a  summary of the sampling and  analysis done
of Plant 12342 wastewater.  The data indicate that Plant 12342 is
a significant source of acetone, methanol, methylene  chloride, and
MIBK.   A summary of the  sampling,  and analysis of data collected
by the  POTW,  is presented in Table 111-13.

C.  NEW DATA  SOURCES

EPA recently undertook additional qualitative and quantitative data
collection  programs,  to  more fully  evaluate the  extent to which
hazardous   constituents   are  being   discharged  to  POTWs  from
pharmaceutical manufacturing facilities.

Results of  the qualitative assessment of priority and hazardous
nonconventional pollutant solvent usage by the industry  (based on
a review of product patents) and the  sampling and analysis program
conducted  at  six  pharmaceutical manufacturing   facilities  are
discussed in  the following paragraphs.

1.  Product Patent  Review

Most processes used to produce Pharmaceuticals  contribute a variety
of  volatile organic  solvents  to  industry wastewater.   Previous
research  conducted by EPA characterized the industry's  use of
priority pollutant solvents and extractive agents  through a  review
of  literature and  product patents.(1,2,3)   Because EPA's list of
pollutants  of  concern  expanded  beyond  the   list  of  priority
pollutants to include those on the ITD List  of  Analytes,  a follow-
up  review  of pharmaceutical  product patents was  conducted to
determine which  ITD-listed VOCs are  likely being used as solvents
and/or  extractive  agents by the industry and,   therefore may be in
the industry  wastewater.
                                59

-------
                                      TABLE 111-12
                               SUMMARY OF ANALYTICAL DATA
                                       PLANT 12342
Pollutant
 Day 1
 (pg/A)
Day 2
(pg/A)
Day 3
(pg/A)
Day 4
(Pg/A)
Day 5
(Pg/A)
Day 6
(Pg/A)
Volatile Organics

methylene chloride
toluene
13,400    37,600   166,000
                   32,800
                      620
                    22,300
                    28,100
                     5,200
Semivolatile Organics

1,2-dichlorobenzene
1,4-dichlorobenzene
isophorone
naphthalene
phenol
Metals and Cyanide
chromium
copper
cyanide
mercury
zinc
Nonconventional Metals
aluminum
barium
boron
calcium
iron
magnesium
manganese
sodium
3.9
6.9
3,240

• •
—
50
0.4
80

— —
—
200
126,000
100
21,000
100
109,000
2.2
5.2
4,540

40
100
30
0.5
300

1,300
50
100
146,000
2,250
30,900
250
1,118,000
3.2
7.0
3,320

40
—
40
0.2
320

1,200
—
"
151,000
2,400
34,800
200
587,000
2.1
6.3
2,340

40
100
30
0.4
360

800
—
—
183,000
1,800
39,400
300
831,000
2.9
8.9
2,560

40
—
30
0.2
1,160

1,000
--
—
134,000
2,200
31,600
300
692,000
4.1
6.6
4,090

40
--
20
0.4
600

800
—
—
156,000
1,900
33,400
200
627,000
Parameters not listed were not detected above the analytical detection limit.
— = Not detected.
                                        60

-------
                                                                          TABLE 111-13
                                                                   SUMMARY OF ANALYTICAL DATA
                                                                   SUBMITTED BY THE LOCAL POTW
                                                                         FOR PLANT 12342
Sample Date
4/19/82
4/20/82
4/21/82
4/22/82
4/23/82
4/24/82
4/25/82
7/27/82
7/28/87
8/3/82
8/24/82
8/25/82
Flow
(mgd)
0.920
0.948
0.731
0.813
0.761
0.772
0.773
0.864
0.787
0.665
0.810
0.865
Methanol
(MR/t)
70,000
45,000
560,000
110,000
120,000
540,000
50,000
46,000
91,000
510,000
240,000
170,000
Acetone
(MR/*)
180,000
240,000
510,000
550,000
190,000
800,000
120,000
68,000
910,000
83,000
57,000
180,000
MIBK
(MR/*)
40,000
110,000
270,000
120,000
50,000
55,000
50,000
49,000
26,000
24,000
18,000
< 15,000
Methylene
Chloride
(MR/4)
46,000
89,000
65,000
32,000
180,000
830,000
360,000
8,100
6,200
24,000
5,200
3,400
Chloroform
(MR/*)
780
160
2,600
160
320
<100
<100
150
280
180

-------
a.   Identification of Patents.   With the  aid of the  1983  Merck
Index  (10), 729 U.S.  Patents were  identified  as  being associated
with the manufacture of the  1,311 Subcategory A, B, and C products
in EPA's data base.   Patent information was found for 59 percent
of Subcategory A products,  14 percent of Subcategory B products,
and 42 percent of Subcategory C products.  Figure III-l summarizes
information on the extent of patent coverage.

b. Identification  of Volatile Organic Solvents of Interest.  Each
product patent was reviewed to determine which,  if any, of the 89
VOCs listed in Table 111-14  may be used as a solvent or extractive
agent in the manufacture of that product.   The list of 89 VOCs is
a compilation from two sources:   (1) the ITD List of Analytes (see
Appendix D); and (2) the DSS List of Pollutants (see Appendix E).

c.  Results.   Results of the patent search indicate that 43 of the
89 VOCs  reviewed are possibly being used  in the manufacture of
Pharmaceuticals.   Eleven of the 43 VOCs identified  are priority
pollutants.  Table 111-15 shows the Subcategory  in  which the 43
compounds  are  likely to  be used.    Figure III-2 summarizes  the
number of products  in which  any of the 43 VOCs  may be used in their
manufacture.  This  information should be a good  indicator of the
solvents  most   commonly used   in  Subcategory  A,   B,   and  C
manufacturing operations.

Results  of the patent  review also  indicate  that a significant
portion of the plants manufacturing Subcategory A,  and/or B, and/or
C  products are  potentially  using one  or more of  the  listed
solvents.  Sixteen of a possible 31 direct-discharging plants (52
percent),  59  of a  possible 131 indirect-discharging  plants  (45
percent), and 11 of a possible  33  zero  dischargers  (33 percent),
are possibly using  one or more of the listed solvents.  Information
on the number of products at each plant that may use any of the 43
VOCs in their manufacture is presented in Appendix F.

d.  Discussion.   Some insight on the accuracy of the patent review
method to  identify nonconventional pollutant  VOCs being  used in
process operations,  and  which plants are most likely using them,
can be  obtained by  reviewing the  accuracy of the patent search
process to  identify plants  known to be using priority pollutant
solvents.  Table 111-16 summarizes the number of products that each
Subcategory A, and/or B, and/or C facility manufacturers that may
use  a  given  priority  pollutant  solvent,  according to  patent
information.  The number of  products is enclosed in parentheses if
available 308 Portfolio Survey information indicates they actually
do use or have used that compound as a raw, intermediate, or final
material in pharmaceutical product manufacture.

The  following  general  observations  can  be  made  based  on  a
comparison of the  predicted (based on patent review)  and actual
(based  on 308  Portfolio)  solvent  use  information  for  priority
pollutants contained in Table 111-16.
                                62

-------
                                    Subcategory "A" Products
                                              91
                       In Merck Index                        Not In
                            69                             Merck Index

                                                                22
           w/Patent Info.          w/o Patent Info.
                54                      15
                I
       I                   I
w/Solvent Info.    w/o Solvent Info.
      48                  6
                                    Subcategory "B"  Products
                                             304
                             	  T
                            I                                   I
                       In Merck  Index                        Not In
                           115                             Merck Index
                            I                                  189
                I                       I
          w/Patent Info.         w/o  Patent  Info.
                44                      71
                I
       I                   I
w/Solvent Info.    w/o Solvent Info.
      30                 14
                                   Subcategory "C" Products
                                             916
                            	         T
                            I                                    I
                      In Merck Index                         uot In
                           652                              Merck Index
                                                               264
                                        I
          w/Patent Info.         w/o Patent Info.
               383                     269
                I
      I                  I
w/Solvent Info.    w/o Solvent Info.
     322                 61
                        Figure III-l.  Product  Patent  Coverage
                                       63

-------
Compound
Name
                                 TABLE 111-14
               ITD AND/OR DSS LISTED VOLATILE ORGANIC COMPOUNDS
                            REVIEWED FOR MENTION IN
                        PHARMACEUTICAL PRODUCT PATENTS
Common Name
                                                                     Source
acetaldehyde
acetonitrile
acetophenone
acetyl chloride
acrylonitrile
aniline
benzene
bromodichloromethane
bromomethane
2-butanone (MEK)
carbon disulfide
chlorobenzene
chloroethane
2-chloroethylvinyl ether
chloroform
chloromethane
3-chloropropene
3-chloropropionitrile
cumene
cyclohexane
dibromochloromethane
1,2-dibromoethane
dibromomethane
dichlorodifluoromethane
1,1-dichloroethane
1,2-dichloroethane
1,1-dichloroethene
1,2-dichloroethylene
1,2-dichloropropane
1,3-dichloro-2-propanol
cis-1,3-dichloropropene
diethyl ether
dimethyl sulfoxide
dimethylamine
1,4-dioxane
epichlorohydrin
ethanol, 2-chloro
ethyl acetate
ethylbenzene
ethyl cyanide
ethyl methacrylate
ethylene oxide
dichlorobromoethane
methyl bromide
methyl ethyl ketone
allyl chjoride
3-chloropropanenitrile
ethylene dibromide
methylene bromide
1,1-dichloroethylene
p-dioxane

ethylene chlorohydrin


propionitrile

oxirane
(b)
(a,b)
(a,b)
(b)
(a,b)
(b)
(a,b)
(a)
(a,b)
(a,b)
(a,b)
(a,b)
(a,b)
(a)
(a,b)
(a,b)
(a)
(a)
(b)
(b)
(a)
(a)
(a,b)
(a,b)
(a,b)
(a,b)
(a,b)
(b)
(b)
(a,b)
(a)
(a,b)
(a)
(b)
(a,b)
(b)
(a)
(b)
(a,b)
(a)
(a)
(a)
                                    64

-------
Compound
                             TABLE III-14 (Continued)

                            	Common Name
                                                                      iourcc
  formaldehyde
  formic  acid
  furan
  furfural
  2-hexanone
  hydrazine
  iodome thane
  isobutyl alcohol
 methanol
 methyl mercaptan
 methyl methacrylate
 methyl methanesulfonate
 4-methyl-2-pentanone
 methylene chloride
 N-butyl alcohol
 2-nitropropane
 N-nitrosodiethylamine
 N-nitrosomethylethylamine
 propanedinitrile^
 2-propanone
 2-propen-l-ol
 2-propenal
 2-propenenitrile , 2-methyl
 2-propyn-l-ol
 pyridine
 resorcinol
 styrene
 1,1,1, 2-tetrachloroethane
 1,1,2, 2-tetrachloroethane
 tetrachloroethene
 t e t r a chl o r ome thane
 tetrahydro furan
 toluene
 total xylenes
 trans- 1 ,2-dichloroethene
 trans- 1 , 3-dichloropropene
 trans- 1 ,4-dichloro-2-butene
 tribomome thane
 1,1, 1-trichloroethane
 1,1, 2- trichloroethane
 trichloroethene
 trichlorome thane thiol
 trichloromoaofluorome thane
 1,2,3-trichloropropane
 trichlorotrifluoroethane
vinyl acetate
vinyl chloride
                                 methyl iodine

                                 methyl alcohol
                                 methanthiol

                                 methylsulfonic acid
                                 MIBK
                                 dichloromethane
                                acetone

                                acrolein
                                methacryloinitrile
                                propargyl alcohol
                                trichloroe:thylene
                                carbon tetrachloride
                                zylene



                                bromoform


                                trichloroethylent

                                trichlorofluoromethane
 (a,b)
 (a,b)
 (b)
 (b)
 (a)
 (b)
 (a)
 (a)
 (b)
 (b)
 (a)
 (a)
 (a,b)
 (a,b)
 (b)
 (b)
 (a)
 (a)
 (a)
 (a,b)
 (a)
 (a,b)
 (a)
 (a)
 (a,b)
 (a)
 (b)
 (a,b)
 (a,b)
 (a,b)
 (a,b)
 (b)
 (a,b)
 (a,b)
 (a,b)
 (a)
 (a)
 (a)
 (a.b)
 (a,b)
 (a,b)
 (a)
 (a,b)
 (a)
(b)
(a)
(a,b)
    ITD listed volatile organic  cofflpbunuT       ^~" -
    DSS listed volatile organic  compound (Tables 2-2 and/or 4-1)
                                   65

-------
                                 TABLE III-15
               ITD AND/OR DSS LISTED VOLATILE ORGANIC COMPOUNDS
                 IDENTIFIED IN PATENTS AS POTENTIALLY USED IN
                      PHARMACEUTICAL PRODUCT MANUFACTURE

                                              Subcateftorv Usage
Compound
Priority Pollutants
acrylonitrile
benzene
bromomethane
chlorobenzene
chloroform
chloromethane
ethylene diehloride
methylene chloride
tetrachloromethane
toluene
trichloroethylene

Non-Priority Pollutants
acetaldehyde
acetonitrile
acetophenone
acetyl chloride
aniline
2-butanone (MEK)
n-butyl alcohol
 carbon disulfide
 cyclohexane
 diethylamine
 dimethylamine
 n,n-dimethy1formanide
 dimethyl suIfoxide
 1,4-dioxane
 ethanol, 2-chloro
 ethyl acetate
 ethylene oxide
 ethyl ether
 formaldehyde
 formic  acid
 furfural
 hydrazine
  iodomethane
  isobutyl  alcohol
 methanol
  methyl mercaptan
  methyl methacrylate
  4-methyl-2-pentanone (MIBK)
  2-propanone (acetone)
  pyridine
  tetrahydrofuran
  total xylenes
  vinyl acetate
A

X

X
X
X

X
X
X


X
X
X
X
X
X

X


X
X
X

X
X
X
X
X
X

X

X


X
X
X
X
X

B C
X
x x
X
X
x x
X
X
x x
x x
x x
x x
X
x x
£
x x
X
X
x x
X
X
X
X
X
x x
x x
X
x x
X
x x
x x
x x

X
X
x x
x x
X
X
X
x x
x x
X
x x
X
                                       66

-------
                           NUMBER OF PRODUCTS
o
m
O
a
o

z
o
o
o

•o
o


o
0 O 0 0 O O O
HtNlENC-
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CHLOHOMETHANE-
aftOMOMETHAME-
AamOMTMLE-
TMOtOftOETHYLENE-
EIHVLElC OCHLOMIE-
METHANOL-
ACETOnc-
ETHYl ACElATE-
PYNUME-
I.4UKMAM:-
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IE TRAM VONOFUHAN •
ETMYl ETHHt-
ACETOMTMLE •
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FOHMAL06HYI* -
ACE in CMiomiE-
CYOOKXAK-
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METHVl METHACMALAlE*
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-------
                                                                           TABU 111-16

                                                          MUHBER OF PHARHACEUTICAL PRODUCTS THAT HAY USE
                                                      THE FOLLOWING PRIORITY POLLUTANTS IN THEIR MANUFACTURE
Plant/Subcatetory
                     acrylo-
                     oitril*
                                 beiuene
broeio-
•ethane
chloro-
bcozeot
                                                                         Priority Pollutant Coapoundi
                                                                                     cbloro-
           chlorofora
ethane
            etbylcpc
           dichloride
            ewtbylene
            chloride
              carbon
           tetracbloride
                                                      toluene
                        trichloro-
                         ethylene
Direct Dtacharteri
11111 C
12022 A.C
12026 C
12036 A.D
12034 A.B.C.D
12097** C,D
12132 A.C (0)*
12161 A.C.D
12187 C
12236 C
122S6 A.B.C.D
12407 C (0)
12462 A
12471 B
<£ 2024S A.C (0)
00 20246 C
20257 C
20297 C
33333 C 1
Huaber of Direct Diicbarte Uieri
Patent Data 1
306 Data 4
Indirect Diacbarteri
12003 A.C.D
12004 C.D
12005
12012
12016 .C.D
12037 ,0
12040 ,D
12042** ,B,D
12043** C
12044 A.D
12048 C.D
120S2 C.D
12057 C.D
12062 C.D
12066 B.C.D
12077 C.D
12084 B.C.D
12087 C



( )


(3)
(U*
3
(2)
(9)«
(0)


(0)*
2
(0)
(1)
1

13
10

(16)
I



(0)
1
2
1
(0)
(1)

(2)

1
(2)
(5)
4
                                                 2
                                                (0)
                                                              1
                                                             (0)
              (0)*
               1

              (0)
                                                              0*
                                                              1
                                                (1)
              (3)
                                                 (0)
                                                             (1)
              2
             (9)

              1
              6
              4
             (3)
             (I)
              1

             (I)
             (0)
                           1*
                           I

                           1
                           1
                                                                         14
                                                                          6
             (8)*
              1
             (0)*
             (0)
             (2)

              1
              1

             (0)
             (1)
                          (0)
                           1
                          (1)
                          (5)
                          (3)
                                       (0)
(1)
(0)
             (0)
(0)
 1
(1)
(0)
                                                                                                   (0)
                                                                                                   (0)
                                       (0)
                                       (0)
             (4)
 1
 3
(2)
 1

 0*
(0
(0)
                                                     0*
                                                     1
(S)*
                                                                                                                (0)*
                                                                                                                (0)
                           (0)
                           (0)
                            1

                           (0)
                           (0)
 3
 2
 3
 I*

 0*

(0)
 2

(0)*
                                                                   (0)

                                                                    I
 1
(1)
 1
(0)
 2
 3
(2)
(0)
(!)*
(0)*
(5)
(0)
                                                      (0)*
                                                       I
                                                      (0)
                                                      (0)
                                                                                             »
                                                                                            12
(5)*
 1
                                         2

                                         (0)


                                         (0)

                                         1
                                         (1)
                                         (7)
                                         (I)
(0)




(0)


 1*

-------
                                                      69
                  IUUU>UIUUUU>U>K>N>N>rON>K>N>N>K>K>K>K>K>K>N>MM— — — — — — — — —
nv«t»r>M<*M»>r>r»>»nr>r>Bg»>>>
  n n n•o oo
               nnnno  taomo   one»«on  om
               • »••     •    •           •«•     •
               oooo    n   n          on  o    n

                           o   o            o
                                                              a    Bnvonoonoe
                                                       -—   —    e>«»o«   —3
                > w — >~> o — K> — K> o   ». *• o — i* — ••   owe—   —i
                                 o   —      —  o
                *   » »     »
                                le   — o o o K> o o
                                *^^   ^^ ^^ ^^ ^p* ^^ ^^ ^^
                                     »       *  *
                                                      MO   O  —  —   K> O W ff.     O
                                                      <^f^   taC      ^   «V«I^^P'^^     **

                                                      »                »   » *
                                                                                         *^ n

                                                                                          -
                                                                                         sS
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                                                                                         U
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•^     •< n   M
                                                                                             e     > *v  n
                                                                                             c    is  g


-------
                                                                     TABU III-I6 (continued)

                                                          NlMBEt OF PHARMACEUTICAL PRODUCTS THAT HAY USE
                                                      THE FOLLOWING PRIORITY POLLUTANTS IN THEIR MANUFACTURE
                                                                         Priority Pollutant Coapounda

Plant/Subcatetory
2013* C.D
20177 C
20203 C
20205** C.O
20234 C
20254 C
20310 C
20311** C
20312 B.C.D
20331 C
20349 C
203SO C.D
20473 B
Hunter of ladirtct
Patent
308
Mo loagtr uted
308 Intonation
308 Intonation
308 laforutioD
308 loforaatioa
acrylo-

•itrll* benzene













Dlacharte Uaen
3
2

indicate* uaage
indicate* uaage
indicate* oioor
indicate* usage
( ) Pareatheie* indicate that the
* Indicate! tha
t the coanound b
a

1
1
2

2
1

»




44
27

i* le**
in 120
mag*.
i* l.J
coaipou
a* been
broew- cbloro-

•etbane . benzene chlorofon
3

(0)






(0) 1




1 S
8 6

than SO «l/yr.
gallon* per year.

gallona per week.
nd* uied la BaoufacCuriog
detected in tbe nlanta wa
4
1



1
(0)
2

1




4S
38





operation* bated
atevater.
chloro- etbylene
•ethane dicbloride
1

(0)
0




(0)
(0)

(0)»


8 1
10 13





on 308 portfolio inform

•etbylene
chloride


(0)
0


(0)
1

(0)




16
41





ition.

carbon
tetracblorid* toluene
(1)
(1)
(0) (1)
1
1 2
(0)
(2)
1

(5)
1 (2)

(0)»

17 36
14 46







trichloro-
ethylene














1
6







**   308 portfolio information  for this plant i* confidential.

-------
    o   The patent search method was very  accurate in indicating
        which priority pollutant solvents are commonly used (i.e.,
        benzene, chloroform, methylene chloride, and toluene).

    o   The  patent  search  method was  relatively  accurate  in
        determining which plants were likely to be using the more
        common priority pollutant  solvents; with the accuracy of
        the   method   increasing   as   the   number   of   products
        potentially using a given  solvent  increases.

    o   The   patent   search  method  showed  poor  accuracy  in
        identifying plants  using  the less common  solvents (e.g,
        bromomethane, ethylene dichloride,  and trichloroethylene) .

It  is  expected that  these  observations  would  be true  for  the
hazardous nonconventional pollutant solvents as well.

2.  Sampling and Analysis Programs

Since   1985,   EPA  has  conducted  sampling  episodes   at  six
pharmaceutical manufacturing facilities, providing information that
characterizes   industry   wastes   with  respect  to   hazardous
constituents  beyond those  on  the  priority pollutant list.   The
first episode was conducted at Plant 12135.  This sampling effort
was conducted concurrent with,  and in  support of,  preparation of
the DSS.   At this facility,  a single raw wastewater  sample was
collected and analyzed for conventional pollutants (excluding fecal
coliform),   priority   pollutants    (excluding   asbestos),   and
approximately 250 additional organic and inorganic parameters.  A
complete  list  of  parameters  analyzed  for  at Plant  12135  is
presented in Appendix G.

Four additional  pharmaceutical manufacturing  facilities   (Plants
12204,   12236, 12247, and 99999) were  sampled  in 1986 and 1987 to
provide data for this  document.    The four  plants  chosen were
selected  from  a  field  of  candidates producing  pharmaceutical
products by fermentation and/or chemical synthesis processes

(Subcategories A and/or C).  Based on information available to
EPA (e.g., literature, previous sampling episodes, patent review),
Subcategory  A and C facilities have the  greatest potential for
discharging  significant   quantities  of  priority  and  hazardous
nonconventional pollutant solvents. Subcategory B and D facilities
were excluded because  they  generally produce  low volume,  low
strength wastewater,  resulting in low potential for discharging
significant quantities of the pollutants of concern.  The  field of
candidates   included  96   indirect  dischargers  and  26  direct
dischargers.

Even though  the primary objective  of this  sampling was to obtain
additional information on the discharge of hazardous constituents
to POTWs,  EPA intentionally chose one direct discharger to evaluate
                                71

-------
the presence, treatability, and fate of the pollutants of concern
at direct discharging pharmaceutical manufacturing facilities.
Raw wastewater samples were collected at all four plants.  Treated
effluents and sludges were also collected whenever possible.  With
a few minor  exceptions, all  samples were  analyzed for pollutants
on the 1987 ITD List of Analytes.  The list includes conventional
pollutants (excluding  fecal  coliform)  and 285 other  organic and
inorganic parameters (see  Appendix D).  Methods used to analyze the
wastewater and  sludge sampled for the  ITD List of Analytes are
listed in Appendix H.

Between January and June 1987, limited sampling was done  at a sixth
pharmaceutical   facility    (Plant   88888).      This  plant   was
participating in a pilot program, with EPA evaluating the ability
of ACA technologies  to reduce COD  levels.   The  raw wastewater at
this facility was sampled on ten occasions and was analyzed for a
limited  number  of   constituents  that are  on  the ITD List  of
Analytes.  Results  of  all six sampling  episodes  are presented in
the following paragraphs.

a.     Plant  12135.     This  plant  is  a   large  pharmaceutical
manufacturing facility producing products by extraction, chemical
synthesis, and formulation operations (Subcategories B,  C, and D,
respectively).   It  generates  approximately  1.0  mgd of  process
wastewater that is  discharged  to a  POTW.   This  facility  also
discharges sanitary  and some additional wastewater (normally from
research operations) to a separate POTW.

Wastewater treatment at  this  facility consists  of  equalization
followed by pH adjustment.  The neutralized wastewater is sent to
the  local POTW.    A  single  24-hour  composite sample  of  the
neutralized process wastewater was collected.   A schematic of the
wastewater treatment system showing the sampling point is shown in
Figure III-3.

Analytical results of the  sample  collected are summarized in Table
111-17.  Only the analytical parameters yielding a detected value
are reported.

b.     Plant  12204.     This  plant  is  a   large  pharmaceutical
manufacturing   facility   producing  products  by  fermentation,
extraction, chemical synthesis, and mixing/compounding/formulating
operations  (Subcategories A,  B, C,  and  D,  respectively) .    It
generates  approximately   0.8 mgd of  process  wastewater  that is
pretreated prior to discharge  to the local POTW.   The principal
sources of wastewater are the fermentation and chemical synthesis
operations.  Wastewater treatment at this facility consists of pH
adjustment with  lime, followed by primary clarification, followed
by  oxygen-activated  sludge  treatment.   Waste  sludge  from the
primary and  secondary  clarifiers is  dewatered separately on belt
                                72

-------
                    SANITARY  WASTE
                    RESEARCH WASTE
                                                          t
TO
POTW
                    PRODUCTION RAW WASTE
OJ
                                                      NEUTRALIZATION
                                                           -"
                                                          Y'°
   SAMPLING POINT
       POTW
    FIGURE MI-3
    PLANT NO. 12135
    WASTEWATER PRETREATMENT SYSTEM

-------
                                      TABLE III-17

                         SUMMARY OF REPORTED ANALYTICAL RESULTS
                                       PLANT 12135
Pollutant
Category                                      Raw Waste
and Pollutant	(M8/&)

Volatile Organics

benzene*                                            17
chlorobenzene*                                      19
chloroform*                                         50
1,1-dichloroethane*                                 76
1,2-dichloroethane*                              2,497
1,1-dichloroethene*                                 22
trans-1,2-dichloroethene*                          442
ethylbenzene*                                      136
nethylene chloride*                              2,760
tetrachloroethene*                                  43
1,1,1-trichloroethane*                             393
trichlorosthene*                                    87
toluene*                                         1,565
vinyl chloride*                                     42

acetone                                          4,592
2-butanone (MEK)                                 1,566
diethylether                                       287

Semivolatile Organics

1,2-dichlorobenzene*                             2,280

Pesticides/Herbicides

BHC, Beta*                                       1.198
BHC, Delta*                                      0.012
4,4'-DDD*                                        0.914
endrin ketone                                     1.20

Dioxins/Furans

2,3,7,8-TCDD*
                                74

-------
                                TABLE 111-17 (continued)
Pollutant
Category                                      Raw Waste
and Pollutant
Metals

antimony*                                           15
arsenic*                                             8
cadmium*                                             8
chromium*                                           99
copper*                                             45
iron                                             2 , 140
lead*                                               13
lithium                                          1,140
mercury*                                           0.4
strontium                                          410
zinc*                                              303

Classical Pollutants

ammonia, as N (mg/fc)                               561
BOD5, carbonaceous (mg/£)                        1,900
chemical oxygen demand (mg/l)                    4,350
cyanide, total*                                  <0.02
fluoride mg/fc                                      0.8
nitrate + nitrite, as N  (mg/fc)                   <0.02
total organic carbon (mg/fc)                        300
total suspended solids (mg/l)                       64

Field Measurements

temperature, water (°C)                          23-29
pH                                             6.5-8.0
*  Priority Pollutants
                                     75

-------
filter presses.   The dewatered sludges are combined and mixed with
fermentation wastes and leaves,  then composted on-site.  The com-
posted sludge is sold as a soil  conditioner.   Approximately 10 to
12 dry tons of waste sludge are  generated daily.

Two consecutive, separate,  and complete 24-hour samples were taken
of the raw waste and treated effluent.   Single grab samples were
collected of tap water, thickened primary  sludge, dewatered primary
sludge,  and dewatered  secondary  sludge.    A schematic of  the
wastewater treatment system showing sample point locations is shown
in Figure III-4.  Analytical results of the samples collected are
presented in Table 111-18.  Only  the analytical parameters yielding
an analytically detectable value are reported.

c.  Plant 12236.  This plant manufactures pharmaceutical products
by chemical  synthesis  processes (Subcategory C) .   Approximately
1.8 mgd  of  wastewater  is treated  in  this wastewater treatment
system prior to being  discharged to  a  river.    The  wastewater
sources  at  this facility  are process  wastewater,  air pollution
control  scrubber wastewater, wastewater  from  cyanide  destruct
units, pretreated sanitary wastewater, and some  adsorption tower
wastewater.   Noncontact  cooling  water   is  not  treated in  the
wastewater treatment facility prior to discharge.

Wastewater   treatment   at   this  facility   consists   of   flow
equalization,  followed  by pH  adjustment  with  lime  or  caustic,
followed by primary clarification,   followed by conventional air-
activated sludge treatment.  Primary and waste-activated sludges
are thickened in a  gravity thickener,  dewatered  on a belt filter
press, and disposed of  in a RCRA-licensed landfill.  Approximately
5 dry tons of sludge are disposed of daily.

Two consecutive, separate,  and complete 24-hour wastewater samples
were taken of raw waste and treated effluent.  Single grab samples
of  tap  water,  thickened  sludge,  and  dewatered  sludge  were
collected.  A schematic of the wastewater treatment system showing
sample point locations is shown in Figure III-5.

Analytical results  of the  samples  collected  are  in Table 111-19.
Only the analytical parameters yielding an analytically detectable
value are reported.

d.     Plant 12447.     This  plant  is   a  large  pharmaceutical
manufacturing facility  (Subcategories  A, B,  C,  and D) producing
ethical drugs, particularly antibiotics, antidiabetics,  steroids,
and  a  variety  of  nutritional,  veterinary,  and  agricultural
products.  Approximately 2.0 mgd of process wastewater  is generat-
ed primarily from  fermentation  operations and the production of
fine chemicals.  Wastewater is not pretreated before discharge to
the local POTW.  Due to health and  safety concerns about obtaining
combined  raw waste  samples  in  the lower level of  the sampling
station, sampling was limited to large grab samples. The first grab
                                76

-------
LIME
ADDITION


~A

PRIMARY
PUMPING

<0v FERMENTATION t CIIEM SECTION
* W 4
\
i i
i
LABORATORY - SANITARY WASTE

                                                 SLUDGE
                                                 FROM
                                              FINAL CLARIFIER
                                                          SLUDGE
                                                           CAKE
           UNOX

         SECONDARY

         BIOLOGICAL
         TREATMENT
RETURN
SLUDGE
 WASTE
ACTIVATE
 SLUDGE
          SECONDARY
           CLARIFIER
SLIIDGI: TO
COMBINED
INFLUENT
 LEGEND

(X) SAMPLE POINTS
 I  INFLUENT
 2  EFFLUENT
 •J  PRIMARY SLUDGE
 4  OEWATERED PRIMARY SLUDGE
 &  OE WATERED SECONDARY SLUDGE
                             TO  POTW
                                                                              FIGURE 111-4
                                                                       PLANT NO.  12204
                                                  WASTEWATER PRETREATMENT SYSTEM

-------
                                                                                 TABLE 111-18
                                                                           ITD/RCRA SAMPLIMC PROGRAM
                                                                    SUHMARY OF REPORTED ANALYTICAL RESULTS
                                                                                  PLANT 12204
      Pollutant
      Category
      and Pollutant
                             Tap
                            Water
                           (MR/1)
                                                Waatewater Day 1
 Raw
Waate
Treated
Effluent
 (Ug/t)
                                                                   Waatewater Day 2
                                                          Priaary Sludge
 Raw
Waate
Treated
Effluent
 (VS.lt)
                                                                          Secondary Sludge
Thickened
 Priaiary
 (•g/kg)
Dewatered
 Primary
 (•g/kg)
 TCLP
Extract
(Mg/t)
Dewatered
Secondary
(•g/kg)
  TCLP
Extract
 (Ug/t)
•vj
oo
Volatile Organica

acrolein*
benzene*
chlorofona*
1,1-dichloroethaM*         28
trans-1,2-dichloroethene*
•ethylene chloride*
toluene*                    20
1,1,1-trichloroetnane*

acetone
diethyl ether.
iaobutyl alcohol
2-butanone (HEK)
vinyl acetate

Seaivolatile Organica

phenol

Dioxina/Furana

Not Analyzed
75
24
596
—
—
4,839
504
87
173,570
16,627
—
31
62
30
25
5,167
362
62
110,395
14,288
                                                 99
                                                              63
                                                                          77
                                                                                     51
                                                                       4,696
                                                                       4,181      7,896
                                                                       5,678      1,106
                                                                                    530
                                                    0.236
                                                    7.109
                                                      500
                                                  504.209
                                                     0.929
                                                                                                                          63
                                                   282.229   14,081
                                                     2.368       61
                                                             0.155
                                                             0.114

                                                             0.100


                                                             66.955
                                                                                                                                                102
                                                                21
                                                                25
                                                                52
                                                                37
                                                             17,028

                                                                140
                                                                980
                                                                                    124
                                                   19.655
                                                     2.079
                                                    15

-------
                                                                     TABLE 111-18 (continued)
Pollutant
Category
and Pollutant
  Tap
 Water
(M/*)
                                          Hastewater Day 1
                                       Waatevater Pay 2
                                                                                                   Priamry Sludge
 Raw
Waat*
Treated
Effluent
 Raw
Waate
(HfcV*)
Treated
Effluent
                                                                                                  Secondary Sludge
Thickened
 PriMry
Dewatered
 Primary
 TCLP
Extract
 (Hi/*)
Dewatered
Secondary
  TCLP
Extract
HetaU

berylllua*
cadaiua*
chroMiuai*
copper*
lead*
•ercury*
nickel*
aeleniuai*
•liver*
xinc*

aluainua
bariua
boron
calciua
iron
•agneaiu*
aiantaneae
aodiiu
tin
titaniiw
vanadiua

Eleaienta

iodine
ncodyaiua
phosphorus
potaaaiiw
silicon
strontiuai
sulfur
               12R
               165
               —R
                71
                  5
                 16
                160
           19,000e
            5.000e     24,000e
                                       30
--
143
„»
52
--
28,900
91
8,950
..
35,000
—
—
12s+
303R
2.250
124
— R
240,000
2,110Rt+
32.800R
376R
370.000R
--R
— R
10
181
1,740
88
"
274,000
1,020
22,000
182
238,000
--
—
--
284
2,730
130
--
309,000
3,150
39,400
574
273,000
--
—
•+
124
799
79
--
231.000
721
23,400
205
264,000
--
—
l.OOOe
--
4,000e
lOOe
7.000e
24,000e
l.OOOe
lO.OOOe
200e
434,000e
9.000e
l.OOOe
lO.OOOe
300e
207,000e
29,000e
2,000e
lO.OOOe
400e
260,000e
7,000*
1 ,000e
9,000e
200e
243,000e
__
..
2
20
..
0.9
2
0.6
31
205
7
__
881
288
377
18
435
5
7
3
1
._
5
41
..
0.3
5
1.8
73
1,900
24
._
198,000
850
1,040
40
413
10
61
8
--
..
— .
219
—
0.4
--
._
212
581
591
377
2,660,000
--
—
--
6,700
--
—
—
o.s
2
6
44
16
0.9
10
1.8
3
1,610
21
--
167,000
753
923
38
653
7
24
3
«
~
-r
—
—
—
--
..
722
270
1,090
668
369,000
521
5,860
357
1,380,000
--
—
—
                                            36e

                                          1,180

                                            29e
                                             6e
                                           667e
                                                                            0.5e
                                                                            0.4e
                                                                              12e
                                                    HA
                                                    NA
                                                    MA
                                                    MA
                                                    NA
                                                    MA
                                                    NA
                                                      26e
                                                      37e
                                                   2,000e

                                                     376*
                                                      62e
                                                   2,200e
                                                   NA
                                                   MA
                                                   NA
                                                   NA
                                                   NA
                                                   NA
                                                   NA

-------
TABLE IH-18 (continued)
Wastevater Day 1
Pollutant Tap
Category Water
and Pollutant (UK/t)
Clanical Pollutanta
aawonia, at N
BODS Day (carbonaceous)
cheaucal oxygen deaund
cyanide, total*
fluoride
nitrate-nitrite, as N
nitrogen, kjeldahl, total
oil and greaae,
total recoverable
residue, filterable
oo residue, non-filterable
0 aulfide, total
(iodonetric)
total phosphorus, •• P
total organic carbon
flash point (*C)
pH, soil
residue, total (1)
residue, total volatile (X)
sulfide, total
(Monier-Williau)
corrosivity (npy)

HA
NA
NA
HA
HA
NA
NA

NA
NA
NA

NA
NA
NA
HA
NA
HA
HA

HA
HA
Raw
Vaate
(«/»)

HR
1,300
4,100
—
0.32
0.50
NR

86c
2,700
1,400

19c
19
1,100
NA
NA
NA
NA

NA
NA
Treated
Effluent
(•8/t)

NR
350
800
--
0.32
0.061
NR

36c
1,500
300

9.5c
7
210
NA
NA
NA
NA

HA
HA
Waitewater Day 2
Raw Treated
Waste Effluent
(.8/1) (a.g/1)

HR
2,100**
3,600
—
0.24
1.9**
NR

89c
2,400**
1,600

20c
21
890
NA
NA
NA
NA

NA
NA

78
380**
800
—
0.24
0.12**
190

I4c
1,900**
220

5.4c
5.6
220
NA
NA
NA
NA

HA
HA
Priawry Sludge
Thickened
Print ry
(•8/kg)

4,600
NA
NA
—
HA
1.1
4,300

NA
NA
NA

NA
NA
NA
NA
7.6
11
46

640
NA
Dewatered
Priaary
(a>8/kg)

940
NA
NA
4.S
NA
--
14,000

NA
NA
NA

NA
NA
NA
52
12.8
38
7.4

88
<10
TCtP
Extract
(M8/O

NA
NA
NA
NA
NA
NA
NA

NA
NA
NA

NA
HA
HA
HA
NA
HA
HA

HA
NA
Secondary
Dewatered
Secondary
(•K/kg)

4,600
NA
NA
—
NA
3.4
7,000

NA
NA
NA

NA
HA
HA
37
7.5
22
53

75
<10
Sludge
TCtP
Extract
(U8/C)

HA
HA
HA
HA
HA
HA
HA

HA
HA
HA

HA
HA
HA
HA
HA
HA
HA

NA
NA

-------
                                                                           TABLE 111-18 (continued)
00
Pollutant Vastewater Day 1
Category Tap Raw Treated
and Pollutant Vater Watte Effluent
Field Measurements
Vastewater Day 2
Raw
Waste

process flow fad) NA 2.12 2.12 1.93
pH MA 5. 9-10. S 7.4-9.1 6.0-10.7
settleable solids (•«/<) NA 94 IS 100
temperature , water (*C) MA 20-26 18-26 20-30
* Indicate* the correlation coefficient for Method of Standard
+» Indicates duplicate analysis Is not within control Halts.
— Indicates pollutant- concentration below detection liaiit.
NA Indicates not analyzed.
c Average of grab sample results.
e Indicates an estimated value.
t Denotes tentative identification below the detection Unit.
DET Indicates pollutant concentration qualitatively detected.
HR No value reported due to matrix interference.,
* Priority pollutant.
** Analysis performed after expiration of analytical hold-time .
R Indicates spike recovery is not within control Haiti.
S Indicates the correlation coefficient for Method of Standard
Addition.
Refer to
addition
Treated
Effluent
1.93
7.0-8.5
75
22-26
Thickened
Priam ry
NA
NA
NA
NA
report of analysis, for
is less than 0.995.
Primary Sludge
Dewatered TCLP
Primary Extract
NA HA
NA NA
NA NA
NA MA
further information.
Secondary
Dewatered
Secondary
NA
NA
NA
NA

Sludge
TCtP
Extract
NA
NA
NA
NA


-------
00
SECONDARY CLARIFIERS
rQn^
v Y
PARSHALL X 	 -"x AERATI
EFFLUENT FLUML_ \ BA9iN

"• 1  - -1 THICKENER W-E--->| ^ |
ANT i
WT-2466) 1

       EQUALIZATION BASIN EFFLUENT
       FINAL EFFLUENT

       THICKENED SLUDGE

       DEWATEREO SLUDGE
                                  FILTRATE
                                                                                        FIGURE 111-5
                                                                                 PLANT NO. 12236
                                                                 WASTEWATER TREATMENT SYSTEM

-------
                                                              TABLE 111-19
                                                        ITD/RCRA SAMPLING PROGRAM
                                                 SUMMARY OF REPORTED ANALYTICAL RESULTS
                                                               PLANT 12236
oo
co
Wastewater-Day 1
Pollutant Tap Raw
Category Water Waste
and Pollutant 	 ((Jg/£) 	 (pg/£)
Volatile Organics
carbon tetrachloride*
1 , 1-dichloroethane*
methylene chloride* — 114
toluene* 31
acetone — 1,795
2-hexanone
methacrylonitrile
Semivolatile Organics
bis(2-chloroethyl)ether*
n-octadecane
Metals
antimony*
cadmium*
chromium* — 18
copper* 51
mercury*
nickel*
silver*
zinc* — H7
Treated
Effluent

42
—
158
19
96
1,087
—

—
"

--
~ ~
22
--
—
20
Wastewater-Day 2
Raw Treated
Waste Effluent
(pg/£) (MR/*)

__
--
10,745 21
174
--
— —

__


--
_ _ » —
26
--
41
164 50
Combined Sludge
Thickened
Sludge
(mg/kg)

—
— -
--
—
~~
"

--


53

10
2r
.5
88
Dewatered
Sludge
(mg/kg)

--
0.045
0.077
0.555
"~
0.191

3.350
o n^A
Z . UjO

6
i 7
± 1
10
26
19
135

TCLP
Extract

--
20
140
--
i f\£
106

--


15

""

85
1,310

-------
                                                      TABLE 111-19 (continued)
oo
Wastewater-Day 1
Pollutant
Category
and Pollutant
Metals (continued)
aluminum
barium
boron
calcium
cobalt
iron
magnesium
manganese
osmium
sodium
tin
titanium
vanadium
Elements
iodine
lanthanum
lutetium
phosphorus
ruthenium
silicon
strontium
sulfur
thorium
uranium
zirconium
Tap
Water
(Mg/A)

113
—
--
10,400
--
60
1,590
--
--
5,420 1
--
--
--

	
--
--
—
—
4,000e
--
5,000e
--
—
—
Raw
Waste
(pg/A)

118
--
209
51,700
--
121,000
1,680
794
--
,530,000 1
--
85
86

31,000e
—
--
40,000e
--
3,000e
lOOe
614,000e
--
—
—
Treated
Effluent
(Mg/A)

_.
--
—
63,700
--
4,130
1,440
255
200e
,410,000
--
--
--

l,000e
--
--
6,000e
--
3,000e
lOOe
559,000e
--
—
--
Wastewater-Day 2
Raw
Waste
(Mg/A)

178
218
—
51,500
--
171,000
1,810
1,380
lOOe
1,720,000 1
--
126
129

39,000e
--
--
48,000e
--
3,000e
lOOe
596,000e
--
--
--
Treated
Effluent
(Mg/A)

..
--
--
51,200
--
5,710
1,340
222
300e
,650,000
--
—
--

10,000e
--
--
17,000e
—
3,000e
—
605,000e
--
--
--
Combined Sludge
Thickened
Sludge
(mg/kg)

102
37
--
8,340
--
92,900
726
365
--
23,500
60
72
77

39e
—
--
48e
--
0.5e
--
29e
—
--
—
Dewatered
Sludge
(mg/kg)

253
44
89
12,000
18
18,800
1,170
665
--
5,760 1
16
107
120

221e
3e
6e
7,260e
87e
26e
6e
3,130e
29e
58e
3e
TCLP
Extract
(Mg/A)

500
1,370
1,050
64,700
--
119,000
3,840
1,940
NA
,430,000
--
--
—

NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA

-------
                                                     TABLE 111-19 (continued)
    Pollutant
    Category
    and Pollutant
            Vaatevater-Day 1
  Tap       Raw      Treated
 Vater     Waste     Effluent
(•g/i)     (mg/l)      (.g/A)
         Wastewater-Day 2
         Raw      Treated
        Waste     Effluent
        (.g/*)    (mg/i)
                                                                                                Combined Sludge
                   Thickened
                    Sludge
                     Oewatered
                      Sludge
                        TCIP
                       Extract
00
Ln
Classical Pollutants

ammonia, as N
BODS Day (carbonaceous)
chemical oxygen demand
cyanide, total*
nitrogen, kjeldahl, total
nitrate-nitrite, as N
oil and grease,
  total recoverable
residue, filterable
residue, non-filterable
total phosphorus, as P
total organic carbon
sulfide, total (iodometric)

corrosivity (MPY)
flash point (°C)
pH, soil (s.u.)
residue, total (%)
residue, total volatile (X)
sulfide, total
 (Monier-Williaas)
NA
HA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
170
2,300
2,200
NR
240
0.26
__
4,800
340
1.0
960
3.2c
NA
NA
NA
NA
NA
120
20
380
0.025
140
3.9
lie
4,100
59
4.9
72
— •
NA
NA
NA
NA
NA
220
1,300
2,300
NR
140
0.23
13c
5,200
530
1.5
930
80c
NA
NA
NA
NA
NA
130
24
400
0.029
140
4.0
26c
4,400
66
12
79
—
NA
NA
NA
NA
NA
9,300
NA
NA
5.0
28,000**
4.5
NA
NA
NA
NA
NA
NA
<10
40
8.0
3.9
58
5,000
NA
NA
6.9
73,000
1.1
NA
NA
NA
NA
NA
NA
<10
35
7.3
22
63
                                   NA
              NA
NA
NA
NA
7,000
6,000
NA
NA
NA
NA
NA
NA

NA
NA
NA
NA
NA
NA

NA
NA
NA
NA
NA

NA

-------
                                                      TABLE  111-19  (continued)
00
      Pollutant
Wastevater-Day 1
Wastewater-Day 2
Combined Sludge
Category Tap Raw Treated Raw
and Pollutant Water Waste Effluent Waste
Field Measurements
process flow («gd) NA 1.96 1.96 1.83
pH MA 8.0-9.0 7.2-7.4 7.9-8.6
temperature, water (°C) NA 16-18 22 13-18
settleable solids (mg/i) NA 0.2 Trace 11
— Indicates pollutant concentration below detection limit.
NA Indicates not analyzed.
c Average of grab sample results.
e Indicates an estimated value.
t Denotes tentative identification below the detection limit.
* Priority pollutant.
** Mean of four replicate analysis; refer to the Laboratory Report
NR No value reported due to matrix interference.
Treated
Effluent

1.83
7.3-7.4
18-22
Trace






of Analysis.

Thickened
Sludge

NA
NA
NA
NA








Dewatered
Sludge

NA
NA
NA
NA








TCLP
Extract

NA
NA
NA
NA








      DET Indicates pollutant concentration qualitatively detected.

-------
was taken as representative of  daytime  operations  and the second
was taken as  representative of nighttime  operations.  Analytical
results from the two grab  samples  are presented in Table 111-20.
Only the analytical parameters yielding an analytically detectable
value are reported.

In June of 1989, Plant 12477 officials commented to EPA that the
volatile organic compound analytical results from the 1986 sampling
effort   (i.e.,   results   shown  in  Table   111-20)   were   not
representative of their process waste water discharge to the local
POTW.  To address  this comment, EPA  requested  and subsequently
received volatile organic compound  analytical data describing the
discharge to the POTW from this plant during the last two years.
POTW officials collect volatile  organic  samples  of this facility's
wastewater discharge quarterly as part of their  local pretreatment
program. The samples are routinely analyzed for 20 purgeable
halocarbons and 5 purgeable hydrocarbons, and periodically for
acetone and tetrahydrofuran. In the 1986 EPA sampling effort, EPA
analyzed the plant's wastewater  for all  these compounds. A summary
of  the volatile organic  compound  data provided by the  POTW is
presented in Appendix C. The number of compounds detected,
the levels at which they were  detected,  and the  frequency at which
they were detected in the POTW samples  suggest that  the limited
1986  sampling  done by EPA did  not adequately  characterize this
plant's volatile organic compound discharge to  the  local POTW.

e.     Plant 99999.    This  plant  is   a  large   pharmaceutical
manufacturing  facility  (Subcategories A,  B,  C,  and D) , producing
antibiotics  through  fermentation  processes,  fine chemicals by
reaction and synthesis, and animal  feed  supplements  recovered  from
wastes of fermentation products. This plant generates approximately
0.8 mgd of process wastewater that  is pretreated and discharged to
the  local POTW.    Ninety  percent  of  the process  wastewater is
generated in  the fermentation and chemical  synthesis areas.   Of
this,  75 percent is generated in fermentation operations.

Wastewater  treatment  at this facility  consists of pH adjustment
with lime or H.,S04,  equalization, and a  step-feed activated sludge
system  followed  by  degassification,   and  sedimentation.    The
equalization,  aeration,  and degassing  tanks are covered and the
off-gasses are vented to the power boilers.  Waste activated sludge
is dewatered in a centrifuge and disposed of by  a contract hauler.

Two consecutive, separate, and complete 24-hour  wastewater samples
were taken of  the  raw  waste and treated effluent.   As  part of the
QA/QC  program,  duplicates  of the second 24-hour sample of treated
effluent were  collected and analyzed.   Single  grab samples  were
collected of tap water and dewatered sludge.   A schematic of the
wastewater treatment system showing sample point locations is shown
in  Figure  III-6.  Analytical results of the samples collected are
presented  in  Table  11-21.   Only  the  parameters  yielding  an
analytically detectable  value are  reported.
                                87

-------
                                 TABLE III-20
                           ITD/RCRA SAMPLING PROGRAM
                    SUMMARY OF REPORTED ANALYTICAL RESULTS
                                  PLANT 12447
                                    Grab 1                         Grab 2
Pollutant                             Raw                            Raw
Category                           Wastewater                     Wastewater
and Pollutant.	(yg/t)	(yg/t)

Volatile Organics

1,2-dichloroethane*                    239                             31
toluene*                                33                            398

2-butanone (MEK)                     1,069                          2,031
isobutyl alcohol                     1,557                            881

Semivolatile Organics

bis(2-chloroethyl)ether*                11
2-chloronaphthalene*                   183                             37
2,6-dinitrotoluene*                    191
isophorone*                             84
2-nitrophenol*                          28
N-nitrosodi-n-propylamine*              45

alpha-terpineol                         --                             15
benzoic acid                           187
b-naphthylamine                         68
hexanoic acid                           11                            146
n-docosane                              61
n-eicosane                             212
n-hexadecane                            22,
n-octacosane                            29
o-cresol                                23

Pesticides/Herbicides

None Detected

Purgeable Organic
Compounds

POC                                150,000                         10,000

Dioxins/Furans

Not Analyzed
                                     88

-------
TABLE 111-20 (continued)
Pollutant
Category
and Pollutant
Metals
antimony*
arsenic*
chromium*
copper*
nickel*
zinc*
aluminum
barium
boron
calcium
cobalt
iron
magnesium
manganese
sodium
titanium
Elements
iodine
phosphorus
potassium
silicon
sulfur
Grab 1
Raw
Wastewater
(UR/A)

11
6.4
17
100
44
330
840
140
210
100,000
55
3,500
26,000
1,100
790,000
36

DET
DET
DET
DET
DET
Grab 2
Raw
Wastewater
(U8/£)

--
--
72
56
60
220
270
110
140
110,000
26
8,100
23,000
3,200
2,800,000
15

DET
DET
DET
DET
DET
           89

-------
                           TABLE 111-20 (continued)

                                   Grab 1                         Grab 2
Pollutant                             Raw                            Raw
Category                           Wastewater                     Wastewater
and Pollutant	(mg/2)	(mg/A)

Classical Pollutants

ammonia, as N                           26                             35
BOD5 Day (carbonaceous)              4,000                          4,600
chemical oxygen demand               9,700                         10,000
fluoride                                57                             29.
nitrate-nitrite, as N                   NR                           0.08
nitrogen, Kjeldahl, total              400                            330
oil and grease,
 total recoverable                     180c                           320c
residue, filterable                  6,000                         11,000
residue, non-filterable              2,000                          2,300
sulfide, total (iodometric)             19                             24
total organic carbon                 2,400                          2,300
total phosphorus, as P                  30                             29

Field Measurements

process flow (mgd)                    1.86a                          1.86a
*     Priority pollutant.
      Indicates that pollutant concentration was below detection limit.
NR    No value reported due to matrix interference.
(a)   Average daily flow during the sampling episode.
(c)   Average of grab sample results.
DET   Indicates that pollutant concentration qualitatively detected.
                                     90

-------
FERMENTATION WASTES
    CHEMICAL WASTES
 CONTRACT
  HAULER
                 NEUTRALIZATION
                rOQ
                                    EQUALIZATION
(CENTRIFUGE*—
I
I
                                     AERATION
®  SAMPLE POINTS
 1.  AERATION INFLUENT
 2.  TREATED.EFFLUENT
 3.  BIOLOGICAL SLUDGE
                                             CLARIFIERS
. 4.

— A.-
— — . — — .
I i
1

+

_ 4

— r—
1


^B
_/
	 ^yl
' 	 <^
M!
    DISCHARGE to
        POTW
                                                                        FIGURE 111-6
                                                                   PL ANT NO  99999
                                                WASTEWATER PRETREATMENT SYSTEM

-------
vO
N)
                                                               TABLE 111-21
                                                         ITD/RCRA SAMPLING PROGRAM
                                                  SUMMARY OF REPORTED ANALYTICAL RESULTS
                                                                PLANT 99999
Pollutant Tap
Category Water
and Pollutant (pg/£)
Volatile Organics
acrylonitrile*
chloroform*
ethylbenzene*
methylene chloride*
toluene*

acetone
2-butanone (MEK)
Semivolatile Organcis
benzidine*
bis(2-ethylhexyl) phthalate*
2-chloronaphthalene* 44
4-chloro-3-methylphenol*
3,3-dichlorobenzidine*
N-nitrosodi-n-propylamine*
alpha-terpineol
benzoic acid
diphenyl ether
2-methylnaphthalene
2-(methylthio)benzothiazole
n-dodecane
n-eicosane 55
n-hexacosane
n-triacontane
p-cresol
Wastewater-Day 1 Wastewater-Day 2
Raw
Waste
(MR/A)


5,044
659
2,086
c ABO
O , HO£
133,239
742


—
38
--
--
14

	
--
--
189
--
18
Treated Raw
Effluent Waste

136
8,030

14,959


797,020

224 205
22
44 37
148
87

._

14
754
--
296 206
— 	
—
Treated
Effluent
(pg/2)


97

176


1,254

19?
J. J f-
39
__
82



484
24
187
_ _
__
Treated
Effluent**
(pg/A)




113

""
104



38

--



--
28
142
81

Sludge
Thickened
Sludge
(rog/kg)



1 1 /.<;
I . 1*40

1.406
--



58.855

—


""
582.725
"_
340.855

«• •.
TCLP
Extract






79
--



44

--


65
--
11
72



-------
                                                         TABLE 111-21 (continued)
vO
U)
Uastewater-Day 1
Pollutant
Category
and Pollutant
Pesticides/Herbicidea
BHC, alpha*
BHC, beta*
captan
chloroneb
DBCP
etridazone
trifluralin
TEPP
Purgeable Organic
Compounds
POC
Dioxins/Furans
2,3,7,8-TCDD*
Metals
arsenic*
chromium*
copper*
nickel*
selenium*
silver*
zinc*
Tap
Water
(Mg/i)

__
—
__
..
—
—
—
—


100

NA

MM
--
5
—
--
—
91
Raw
Waste
(Mg/A)

--
—
_.
—
—
—
17t
I6t


76,000

NA

IB
36
500
66
16
2.1
200
Treated
Effluent
(pg/«)

6.2
—
__
—
—
—
3.9t
—


6,800

NA

14
30
53
19
8.3
—
38
Wastewater-Day 2 Sludge
Raw
Waste
(Mg/«)

-.
--
--
—
—
—
—
4,110


160,000

NA

16
18
380
33
12
--
100
Treated
Effluent
(M*/4)

—
2.2
—
74. 4t
—
—
1.9t
780


2,700

NA

12
4
29
27
—
--
26
Treated
Effluent**

-------
                                                         TABLE  111-21  (continued)
VO
Pollutant
Category
and Pollutant
Metals (continued)
aluminum
barium
boron
calcium
cobalt
iron
magnesium
manganese
sodium
tin
titanium
vanadium
Elements
germanium
iodine
lithium
phosphorus
potassium
silicon
sulfur
tellurium
Tap
Water
(P«/1)

1AO
16
—
28,000
—
47
8,400
4
4,500
--
10
—

w*
--
—
—
—
DET
DET
—
Wastewater-Day 1
Raw
Waste
(ug/*)

3,200
81
97
200,000
—
2,700
24,000
110
900,000
—
57
9

..
DET
—
DET
DET
DET
DET
—
Treated
Effluent
(Mg/£)

1,000
33
100
98,000
—
720
18,000
39
660,000
--
100
4

..
DET
DET
DET
DET
DET
DET
-_
Raw
Waste
(M*/i)

2,200
57
77
130,000
4
2,000
14,000
83
930,000
--
59
7

DET
DET
DET
DET
DET
DET
DET
__
Wastewater-Day 2
Treated
Effluent
(Mg/*)

630
33
84
98,000
--
630
17,000
50
780,000
-_
100
—

DET
DET
DET
DET
DET
DET
DET

Treated
Effluent**
(Mg/*)

640
33
75
100,000
__
690
17,000
44
760,000
__
100



DET
DET
DET
DET
DET
DET
DET
Sludge
Thickened
Sludge
(•g/kg)

3,450

MW
16,000
*-.
1,050
1,680
22
5,490
__
_ —
—


DET

DET

~*»
DET

TCLP
Extract
(Mg/£)

558
1,420
704
69,400

829
6,510
93
1,560,000
109

—

NA
NA
NA
NA
NA
NA
NA
NA

-------
                                                         TABLE 111-21  (continued)
VO
l/i
Wastewater-Day 1
Pollutant
Category
and Pollutant
Classical Pollutants
ammonia, as N
BOD-S Day (carbonaceous)
chemical oxygen demand
cyanide , total*
fluoride
nitrate-nitrite, as N
nitrogen, kjeldabl, total
oil and grease,
total recoverable
residue, filterable
residue, non-filterable
sulfide, total (iodometric)
total organic carbon
total phosphorus, as P
corrosivity (MPY)
flash point (°C)
pH, soil
residue, total (%)
residue, total volatile (X)
sulfide, total
(Monier-Williams)
Tap
Water
(mg/i)

NA
NA
NA
NA
NA
NA
NA

NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA

NA
Raw
Waste
(mg/«)

46
3,200
7,100
0.032
0.71
1.3
300

39c
4,900
1,100
lie
1,900
8.0
NA
NA
NA
NA
NA

NA
Treated
Effluent
(»*/«)

100
380
1,500
--
0.60
0.59
160

17c
2,400
310
7.1c
410
4.5
NA
NA
NA
NA
NA

NA
Wastewater-Day 2 Sludge
Raw
Waste
(.8/4)

19
2,200
7,300
— -
0.68
5.1
230

54c
4,100
780
I6c
1,400
6.4
NA
NA
NA
NA
NA

NA
Treated
Effluent
(mg/£)

62
260
1,400
--
0.63
0.56
130

lie
3,300
190
7.6c
530
2.9
NA
NA
NA
NA
NA

NA
Treated
Effluent**
(»*/£)

55
440
1,400
--
0.63
0.58
120

16c
3,400
180
3.5c
500
2.5
NA
NA
NA
NA
NA

NA
Thickened
Sludge
Gng/kg)

6,300
NA
NA
14
NA
33
100,000

NA
NA
NA
NA
NA
NA
<10
60
6.8
6.9
86

620
TCLP.
Extract
(MB/*)

NA
NA
NA
NA
NA
NA
NA

NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA

NA

-------
                                                         TABLE 111-21 (continued)
VO
Pollutant Wastewater-Day 1
category Tap Raw Treated
and Pollutant Water Waste Effluent
Field Measurements
flow (mgd) MA 0.7a 0.7a
conductivity (umhos) HA 4410-6470 4290-4940
PH NA 5.9-9.0 7.7-8.1
settleable solids (mg/1) NA 140 16
temperature (°C) NA 15.4-31.0 35.0-39.0
* Priority pollutants.
— Indicates pollutant concentration below detection limit.
NA Indicates not analyzed.
a Average daily flow.
c Average of grab sample results.
t Denotes tentative identification below the detection limit
Wastewater-Day 2
Raw
Waste

0.7a
4900-5790
7.1-10.7
46
29.3-33.0






Treated
Effluent

0.7a
5020-5110
7.8
Trace
32.6-39.0






Treated
Effluent**

0.7a
5020-5110
7.8
Trace
32.6-39.0






Sludge
Thickened TCLP
Sludge Fv«-r*r-«-

NA
NA
NA
NA
NA







NA
NA
NA
NA
NA






DET Indicates pollutant concentration qualitatively detected.
** A duplicate of the Day 2 effluent wastewater sample was taken as part of the ongoing QA/QC program.

-------
f.  Plant 88888.  This plant produces products by fermentation
and chemical synthesis (Subcategories A and C).  Approximately
1.0 mgd of wastewater is treated in the treatment system before
discharge to the river.

Between January and July 1987, EPA conducted a  pilot study at Plant
88888 to  evaluate COD removal, as  well as aquatic  toxicity and
specific organic  compound  removal  from pharmaceutical wastewater
by  the  use  of  PAC  addition  to  biological  treatment  systems.
Samples of  the raw wastewater, pilot plant  effluent,  and pilot
plant mixed liquors,  were  analyzed for  selected  volatile and
semivolatile organic compounds.  Acetone and acrylonitrile were the
specific  VOCs,  and  alpha-picoline  and  4-nitroaniline were the
specific  SVOCs,  analyzed for  in  the January and March samples,
Results of these  analyses  are listed in Table  111-22.   The high
concentration of  acetone in  the January sample required that the
sample  be diluted prior to  analysis.   This  resulted  in  a high
quantification limit for acrylonitrile.

Based on  results  of  a computer  search of data types  from the
January and  March samples,  alpha-picoline  and dicyclohexylamine
were selected  as  the  specific SVOCs, and acetone, acrylonitrile,
ethyl acetate,  ethyl benzene,  and  total xylenes were selected as
the specific VOCs to be  analyzed  for in May and June.  Methylene
chloride was also  added to the VOC list because it was thought to
be used at the plant.

Analytical results of  the  samples collected  in  May  and June are
also listed in Table  111-22.   High  concentrations of total xylenes
were  found in  all of the raw wastewater  samples.    These high
concentrations required that the samples be  greatly diluted before
analysis  resulting  in  high  detection  limits  for  the   other
compounds.

g.  Summary of Analytical Results.   Analytical results from recent
sampling  done  at  Plants 12135,  12204, 12236,  12447,  88888, and
99999 are summarized in Table  111-23.

Priority  Pollutant VOCs.   The  list of  17  VOCs detected  in the
pharmaceutical  industry's wastewater during the ITD/RCRA sampling
program is virtually  identical to  the list of those found in the
screening  and  verification sampling  program  (see Table 111-23).
Only three  compounds  were detected  in  the  ITD/RCRA program that
were not found in the screening and verification sampling program:
acrylonitrile;  1,1-dichloroethane;  and trans-l,2-dichloroethene.
However, these three compounds were neither detected  frequently nor
at high concentrations. The remaining 14 compounds detected in the
industry  wastewater during the ITD/RCRA sampling were  found less
frequently  or  at  lower   levels  than  in  the  screening and
verification program.
                                97

-------
                                                                 TABLE III-22
                                                  SUMMARY OF ANALYTICAL RESULTS FOR SPECIFIC
                                                       ORGANIC COMPOUNDS AT PLANT 88888
vo
oo
Pollutant
Category
and Pollutant
Volatile Organics
acrylonitrile*
ethylbenzene*
methylene chloride'"
acetone
ethyl acetate
total xylenes
Semivolatile Organics
alpha-picoline
dicyclohexylamine
4-nitroaniline
Raw Wastewater (Mg/£)
1/14/87
<10,000
NA
NA
33,000
NA
NA
300,000
NA
<2,000
3/18/87
<50
NA
NA
330
NA
NA
58,000
NA
<500
5/4/87
<63,000
28,000
<63,000
<63,000
<130,000
150,000
6,400
1,000
NA
5/5/87
<25
13
<25
<25
<50
68
7
,000
,000
,000
,000
,000
,000
,300
420
NA
5/11/87
<63,000
<32,000
<63,000
<63,000
<130,000
160,000
7,100
360
NA
5/13/87
<63,000
<13,000
<63,000
<63,000
<130,000
46,000
330,000
24,000
NA
6/14/87
<63,000
25,000
<63,000
<63,000
<130,000
150,000
200,000
13,000
NA
6/16/87
<13,000
39,000
< 13, 000
34,000
<25,000
220,000
39,000
39,000
NA
6/18/87
<13,000
17,000
<13,000
87,000
<25,000
88,000
5,300
28,000
NA
6/22/87
<25,000
46,000
<25,000
180,000
<50,000
300,000
2,200
6,800
NA
        *  Priority pollutants.
        NA Indicates not  analyzed.

-------
                                                                                      TABLE 111-23
                                                                        SUHHART OF DETECTED ANALYTICAL RESULTS
                                                                                  ITD LISTED COMPOUNDS
VO
vO
Raw Vaatewater
Total
Pollutant Category/ Nunber
Pollutant of Sanplea
Volatile Onanici
•crolein* 7
acrylonitrile* 7
benzene* 7
carbon tetrachloride* 2
chlorobenzene* 7
chloroform* 7
1,1-dichloroethane* 7
1 , 1 -dicbloroetbene* 7
1 , 2-dichloroethane* 7
trana-l,2-dichloroethene*7
ethylbenzene* 7
10
•etfaylene chloride* 7
10
tetrachloroethene* 7
toluene* 7
2
1,1,1-trichloroethane* 7
trichloroethene* 7
vinyl chloride* 7
acetone 7
12
2-butanone (NEK) 7
dietbyl ether 7
2-hexanone 2
iaobutyl alcohol 7
vinyl acetate 6
Senivolatile Organica
benzldine* 7
bia(2-chlorocthyl)ether* 7
bit(2-ethylhexyl)
phthalate* 7
4-chloro-3-«etJiylphenol* 7
2-chloro-napbthalene* 7
1,2-dichlorobenzene* 7
3,3-dichlorobenzene* 7
2,6-dinitrotoluene* 7
iaopborone* 7
n-nitroaodi-n-
propylanine* 7
4.89.90T
0106.0.0
Total
Nunber Concentration Average
of Detected Range Concentration Median
Analyiei (m/1) (pa/t) (u*/*)

1
1
2
0
1
5
1
1
3
1
2
7
5
2
1
6
0
2
1
1
5
6
4
2
0
2
1

1
1

0
1
4
1
1
1
1

1



75
136
17-24
—
19
50-8,030
76
22
31-2,497
442
136-659
13,000-46,000
2,086-14,959
114-10,745
43
33-8,482
—
87-393
87
42
4,592-797,020
330-180,000
742-2,031
287-16,627
..
881-1,557
99

205
11

—
148
. 37-183
2280
87
191
64

45



75
136
21
— -
19
2,759
76
22
922
442
398
28.600
5,868
5,430
43
2,527
—
240
87
42
222,820
56,000
1,352
8,457
—
1,219
99

205
11

~
148
74
2280
87
191
84

45



75
136
21
—
19
596
76
22
239
442
398
28,000
4,696
5,430
43
1,035
—
240
87
42
133,239
33,500
1,318
8,457
--
1,219
99

205
11

—
148
38
2280
87
191
84

45


Total
NuBber
of Sanplea

5
5
5
2
5
5
5
5
5
5
5
2
5
2
5
5
2
5
5
5
5
2
5
5
2
5
5

5
5

5
5
5
5
5
5
5

5


Treated Effluent
Total
Nunber Concentration Average
of Detected Range Concentration Median
Analyaea (ug/t) (vt.lt) (|l
-------
                                                                              TABLE  111-23  (continued)
                                                                              ITD/RCRA  SAMPLING  PROGRAM
                                                                       SUMMARY OF DETECTED  ANALYTICAL RESULTS
O
O


Total
Pollutant Category/ Nuaber
Pollutant of Saaqilea
2-nitrophenol*
phenol*
alpha-picoline
alpna-terpineol
benzole acid
o-creaol
p-creaol
diphenyl ether
n-docotane
n-dodecane
n-eicoaane
n-hezacoaane
n-hezadecane
hezanoic acid
2-Mthylnaphthalene
b-naphttylaaune
n-octacoaane
n-triacontane
Peaticidea/Herbicides
BHC, alpha*
BHC, beta*
BHC, delta*
4,4'DDD
endrin ketone
TEPP
Metala
antiawny*
araenic*
cadauuar*
chroBiuB*
copper*
lead*
•ercury*
7
7
12
7
7
7
7
7
7
7
7
7
7
7
6
7
7
7

5
5
5
5
5
It

7
7
7
7
2
7
7
7

Raw Waatewater
Total
NuBber Concentration Average
of Detected Range Concentration Median
Analyaea (.Mil) (Mil) (vt/l)
1
0
10
2
1
1
1
1
1
0
2
1
1
2
0
1
1
0

0


2
4
2
7
2
7
I
1
28
2,200-330,000
14-15
187
23
18
14
61
206-212
189
22
11-146
68
29

1.198
0.012
0.914
1.2
4,110

11-15
6.4-18
5-8
12-99
18-26
45-500
0.4
28
95,500
15
187
23
18
14
61
209
189
22
79
68
29

1.198
0.012
0.914
1.2
4,110

13
12
7
39
22
201
13
0.4
28
23,000
15
187
23
18
14
61
209
189
22
79
68
29

1.198
0.012
0.914
1.2
4,110

13
12
7
18
22
160
13
0.4
Total
Nuaiber
of Saaplea
5
5
2
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5

3
3
3
3
3
3

5
5
5
5
2
5
5
5
Treated Effluent
Total
Nuaiber Concentration Average
of Detected Range Concentration Median
Analyaea (pg/i) (ut/t) fu«/ll Co— ,t.
0
1
0
0
0
0
0
0
0
2
3
0
0
0
2
0
0
1

1
2
0
0
0
2

0
3
0
3
1
5
0
0
124
24-28
142-296
484-754
81

6.2
2.2
780-1,154

7.9-14
4-30
22
29-71
—
124
26
208
619
81

6.2
2.0
967

11
21
22
44
—
124
26
187
619
81

6.2
0.45
967

12
30
22
36
—
Indirect discharger
Indirect, diacharger
Direct diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect discharger
Indirect diacharger
Indirect diacharger

Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger

Indirect diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger
Direct diacharger
Indirect diacharger
Indirect diacharger
Indirect diacharger

-------
       TABLE 111-23 (continued)
       ITD/RCRA SAMPLING PROGRAM
SUMMARY OF DETECTED ANALYTICAL RESULTS
Raw Waatewater
Pollutant Category/
Pollutant 	
nickel*

seleniuB*
silver*
line*

aluBinu*

bariuB

boron

calciua

cobalt
iron

litbiua
•agneaiu*

•anganese

oaaiiH

sodium



strontium
titaniuei

vanadiusj

Claaaicals
cyanide, total*

BOD (•(/!)

Total
Nuaiber
of Samplea
7
2
7
7
7
2
6
2
7
2
6
2
6
2
7
7
2
7
6
2
6
2
7
2
6

2

7
6
2
7
2

7
MR
7
2
Total
Nuaber Concentration Average
of Detected Range Concentration Median
Analyaea (ui/t) (l>(/<) (Ug/t)
4
1
3
1
7
2
6
2
6
1
4
1
6
2
3
7
2
2
6
2
6
2
0
1
6

2

3
4
2
2
2

1
NK
7
2
33-66
41
12-16
2.1
100-330
117-164
270-3,200
118-178
57-140
218
77-210
209
100,000-309,000
51,500-51,700
4-55
2,000-8,100
121,000-171,000
1,140
14,000-39,400
1680-1810
83-3,200
794-1,380

lOOe
273,000- 1
2,800,000
1,530,000- 1
1,720,000
410
15-59
85-126
7-9
86-129

32

1,300-4,600
1,300-2,300
51
41
13
2.1
249
141
1,915
60
107
218
131
209
181,500
51,600
28
3,386
146,000
1,140
26,533
1,745
907
1,087

100
,010,500

,625,000

410
42
106
8
108

32
—
2,757
1,600
52
41
12
2.1
303
141
2,225
60
117
218
119
209
165,000
51,600
26
2,700
146,000
1,140
25,000
1,745
475
1,087
—
100
845,000

1,625,000

410
47
106
8
108

32
-.
2,200
1,800
Total
Nuaber
of Saaplea
5
2
5
5
5
2
5
2
5
2
5
2
5
2
5
5
2
5
5
2
5
2
5
2
5

2

5
5
2
5
2

5
2
5
2
Treated Effluent
Total
Nuaber Concentration Average
of Detected Range Concentration- Median
Analyae. (u«/t) (U«/« (u«/t)
3
0
2
0
5
2
5
0
5
0
3
0
5
2
0
5
2
0
5
2
5
2
0
2
5

2

0
3
0
1
0

0
2
5
2
19-27
--
8.3-10
--
26-181
20-50
630-1,740
~
33-88
--
75-100
~
98,000-274,000
51,200-63,700
~
630-1,020
4130-5710
HA
17,000-23,400
1,340-1,440
39-205
222-255
--
200e-300e
238,000-
780,000
1,410,000- 1
1,650,000
HA
100
HD
ND-4
ND

._
25-29
260-440
20-24
23
«
9
--
86
35
962
--
58
—
86
—
160,200
57,450
--
756
4920
HA
19,480
1,390
104
239
—
250
540,400

,530,000

MA
100
ND
1
ND

„
27
362
22
23
--
9
~
6O
35
799
--
33
~
84
~
100,000
57.450
— -
720
4920
HA
18,000
1,390
50
239
—
250
660, OOO

1,530,000

MA
100
ND
O
m>

__
27
380
22
CosBcnts
Indirect diacharger
Direct discharger
Indirect diacbarger
Indirect diacbarger
Indirect diacbarger
Direct diacbarger
Indirect discharger
Direct discharger
Indirect diacbarger
Direct diacharger
Indirect discharger
Direct diacharger
Indirect discharger
Direct discharger
Indirect diacharger
Indirect diacharger
Direct discharger
Indirect diacharger
Indirect diacbarger
Direct diacbarger
Indirect diacharger
Direct diachcrger
Indirect diacharger
Direct diacbarger
Indirect diacharger

Direct diacharger

Indirect discharger
Indirect diacharger
Direct diacharger
Indirect discharger
Direct diacbarger

Indirect diacbarger
Direct diacharger
Indirect diacharger
Direct diacharger

-------
                                                                        TABLE 111-23 (continued)
                                                                        ITD/RCRA SAMPLING PROGRAM
                                                                 SUMMARY OF DETECTED ANALYTICAL RESULTS
                                                Raw Waitewater
                                                                                                       Treated Effluent


Pollutant Category/
Pollutant
COD (Bg/i)

TSS (Bg/I)


Total
Number
of Sasjples
7
2
7
2
Total
NuBber
of Detected
Analyses
7
2
7
2



Concentration Average
Range
(pg/Jt)
3,600-10,000
2,200-2,300
64-2,300
340-530
Concentration
(pg/f)
6,593
2,250
1,321
435
Median
(|lg/<)
7,100
2,250
1,400
435

Total
NuBber
of SaBplet
5
2
5
2
Total




MuBber Concentration Average
of Detected
Analyses
5
2
5
2
Range
(pg/i)
800-1,500
380-400
180-310
59-66
Concentration
(pg/t)
1,180 1
390
240
63
Median
(pg/t)
,400
390
220
63

C— — -ta
Indirect discharger
Direct discharger
Indirect discharger
Direct diacharger
    *    Priority pollutant.
    —   Not  detected.
    MR   Mo value reported due to Matrix interference.
    e    Estimated value.
O
N)

-------
The priority pollutant VOCs that continue to be detected frequently
in the  industry raw wastewater at miiigram-per-liter  levels are
those  previously  identified  as  commonly used solvents  and/or
extractive agents in pharmaceutical manufacturing operations
(e.g.,  chloroform,  1,2-dichloroethane,  methylene chloride,  and
toluene).

Nonconventional Pollutant VOCs.  Acetone  was detected  in the raw
wastewater  of  five of the  six facilities sampled  (i.e.,  Plants
12135, 12204, 12236, 88888,  and 99999).  Information obtained from
the sixth facility  (i.e., Plant 12447)  indicates that acetone is
used as a solvent in the manufacture of Pharmaceuticals; however,
it is  not known  if acetone was  being used during  the sampling
episode.   Patent  search information  indicates that  all  plants
except  Plant 12336 are  likely  to  be using acetone  as a process
solvent  in  pharmaceutical  product  manufacture.   According  to
solvent-use  information  presented  in  Table  III-6,   acetone  is
commonly used,  and is ranked fourth in terms  of tons  of organic
solvents used annually by the industry.

Methyl  ethyl ketone  (MEK,  or 2-butanone) was found  in  the raw
wastewater of three plants (i.e.,  Plants  12135,  12447, and 99999).
Available  solvent-use information confirms  that MEK  is  used as
process solvent at  Plant  12447, and  indicates that it is not used
at Plant  99999.   It  is  not  known  if MEK is  used  as a process
solvent at Plant 12135.  According to industry solvent-use infor-
mation, MEK  is commonly used, and  is ranked sixteenth in terms of
tons of organic solvents used annually by  the  industry.
Diethyl ether  (ethyl  ether) was  found in the  raw  wastewater of
Plants  12135 and 12204.  Solvent-use information is not available
for Plant 12135, but for Plant 12204, it  does not indicate the use
of diethyl ether in chemical synthesis  or  fermentation operations.
Information  presented  in Table III-6 indicates that, in terms of
annual usage, ethyl ether is the most commonly used organic solvent
in the  pharmaceutical industry.

Methyl  butyl ketone (2-hexanone)  was found in one final effluent
sample  from  Plant  12236.  Plant officials  indicate that it is not
used as a raw material and they  are not sure of the source.  Methyl
butyl ketone is  not known to be commonly used in the manufacture
of pharmaceutical products.

Isobutyl alcohol was found in both raw wastewater samples collected
at Plant 12447.  Plant officials indicate that  isobutyl alcohol is
not  used   in  chemical   synthesis   or  fermentation   operations.
Isobutyl  alcohol  is not known  to  be an organic solvent commonly
used by this industry.   However,  isobutyl alcohol is known to be
produced by  the fermentation of carbohydrates.

Vinyl acetate was  found  in  raw wastewater and  pretreated effluent
sampled at  Plant  12204  at  levels  less  than  100 ppb.   Organic
solvent-use  information  for Plant  12204 does not indicate the use
                                103

-------
of vinyl acetate in chemical synthesis or fermentation operations.
Vinyl acetate is not known to be commonly used as an organic
solvent in this industry.  The process source of this compound
should be investigated further.

Priority Pollutant SVOCs.  ITD/RCRA  sampling  results added seven
compounds to the group of priority pollutants detected in the
industry wastewater  in  EPA sampling efforts:   benzidine,  bis(2-
chloroethyl)ether,  4-chloro-3-methylphenol,  2-chloronaphthalene,
3,3'-dichlorobenzene,   2,6-dinitrotoluene,   and   n-nitrosodi-n-
propylamine.    Only  2-chloronaphthalene  was  detected  with  any
significant frequency, and only  1,2-dichlorobenzene was detected
at   a  concentration   above  500   ppb.   in  raw  wastewater.
Dichlorobenzene was  found in  the  raw wastewater of  Plant 12135
only.   Dichlorobenzene  is  a  common  solvent,  and  308  Portfolio
information indicates that Plant  12135 uses 1,2-dichlorobenzene as
a raw material.  Efforts to identify the process source of the rest
of the remaining SVOCs should be conducted.

Nonconventional Pollutant SVOCs.   Fifteen SVOCs were detected in
the  industry wastewater;  however,  only alpha-picoline  and  n-
eicosane were found with significant frequency or at high levels.
The  process source  of  these  compounds  should be investigated
further.

Priority Pollutant Pesticides and Herbicides.     In  the   recent
sampling effort,  low levels  of alpha and beta  BHC  were found in
the  biologically  pretreated  effluent  from  Plant  99999,  a plant
known to produce  some pesticides.   Low levels  of beta  and delta
BHC were found in the raw wastewater of Plant 12135; however,  the
source  is  not  known.    The  308 Portfolio  information does  not
indicate that either plant uses alpha,  beta, or delta  BHC as a raw
material.  The presence of pesticides in wastewater appears to be
from  non-pharmaceutical  manufacturing  operations;  however,  the
source of these pesticides should be definitely established.

Nonconventional Pollutant Herbicides and Pesticides.        Eight
herbicides and pesticides were  detected  in the industry wastewater
in the recent sampling effort.  Only tetraethylpyrophosphate (TEPP)
was  found with any significant frequency  and  at high levels:   at
Plant 99999.  Plant  99999  is known  to produce some  pesticides as
well as pharmaceutical products.  It  is  not known if the plant was
manufacturing pesticides  during the  sampling episode.   Efforts
should be conducted to establish the source of the pesticides and
herbicides detected.

Priority Pollutant Metals.  The  metals detected in the ITD/RCRA
sampling program were found at levels  within,  or  lower than,  the
range found  in  the screening  and verification sampling program.
Effluent concentrations of priority pollutant metals found during
the  screening  and  verification  sampling  program  were  below
treatable levels;  as a result,  development of national limitations
and standards was not warranted.
                               104

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Nonconventional Pollutant Metals. Only the more common ions (i.e.,
calcium,  iron,   magnesium,   and  sodium)  were   detected  with
significant frequency and at high levels  (see Table 111-23).  High
levels of calcium and/or sodium were expected  in raw wastewater
samples, as  either lime  (Ca(OH)2)  or sodium hydroxide  (NaOH)  is
commonly used as a neutralizing agent.

Cyanide.  Cyanide is known to be used  as a raw  material in the
manufacture  of  certain Pharmaceuticals.   During the  ITD/RCRA
sampling program, cyanide was found  in the wastewater  from the two
plants (i.e., Plants 12236 and 99999) known to be using it, or have
used  it  in the  past,  as a raw material  in  the  manufacture  of
Pharmaceuticals.   As  part  of the  National Pollutant  Discharge
Elimination  System   (NPDES)  permit requirement,   Plant  12236
routinely monitors cyanide levels in treated effluent.

D.  POLLUTANT MASS LOADINGS AND SOLID WASTE GENERATION

1.  Wastewater

An  attempt  was  made  to estimate  the  total  mass discharge  of
conventional,  priority,  and  nonconventional   pollutants  in  the
wastewater  of  the pharmaceutical  manufacturing  industry.    To
provide  a  basis  for comparison, estimates  were  developed  from
previously available data (i.e.,  308 Questionnaire, screening and
verification program, and OAQPS data bases) and from the recently
acquired sampling data  (i.e., from Plants 12135,  12204,  12236,
12447, and 99999).

Mass load estimates were developed for the raw wastewater and final
effluents  for  both  direct  and  indirect  dischargers  in  the
pharmaceutical manufacturing  industry.   Also,   the  mass  loadings
were  divided between  two  types of plants:    those conducting
Subcategory A, B,  and C operations (ABC),  and those conducting only
Subcategory  D  operations.   To avoid confusion and to provide a
basis  for  comparison  of estimates  developed  from various  data
bases, only the total raw waste load estimates by major pollutant
category are presented in  this section.   Detailed mass  load
estimates categorized by discharge and plant type are appended.

a.  308 Questionnaire  Data  Base.  Analytical results  reported by
each pharmaceutical plant in  the 308 Questionnaire responses are
the best available data  for  estimating  total  mass discharge  of
conventional  pollutants (BOD and TSS),  and the  nonconventional
pollutant (COD).

For direct  dischargers, raw  waste and final effluent mass loadings
were calculated on a plant-by-plant basis.  The long-term average
flow  and  pollutant  average concentrations provided  in  the  308
Questionnaire responses, assuming 365 operating days per year, were
used.   Subcategory average  flow, BOD5_,  TSS, and  COD  values were
used when plant-specific data were not available.
                               105

-------
For  indirect  dischargers,  mass loading  estimates  were developed
using  subcategory average BOD5,  COD,  TSS values  for  each plant
because very few of the 285 indirect dischargers provided BOD, COD,
and TSS values in the 308 Questionnaire responses.   Very few plants
have pretreatment systems in place that would reduce the raw waste
discharge levels.  Therefore, no attempt was made to estimate any
difference between the total  industry  raw waste mass loading and
the estimated discharges to POTWs.

The estimated  annual  raw waste loadings  for BOD5_,  COD, and TSS,
developed from the 308 Questionnaire data base, are summarized in
Table  111-24.   The detailed  mass load  estimates  categorized by
discharge and plant type are presented in Appendix I.

b.  Screening and Verification Data Base. Analytical results from
the  26  pharmaceutical  plants  involved  in   the  Screening  and
Verification  Sampling  Program  are the  best  available data  for
developing rough estimates  of the annual mass discharge  of priority
pollutants  in  pharmaceutical manufacturing  industry wastewater.
Annual mass  loadings were  computed for  each  priority pollutant
detected  in  the  Screening  and Verification Sampling  Program by
calculating  the  product of  the  pollutant mean  concentration,
reported in Table III-ll, and the total industry flow expected to
contain  the  pollutant:     mean  (mg/1)   x  flow   (mgd)  x  8.345
(conversion factor) x 365 (days/year).  A plant's flow was used in
the total flow estimate  if:   (1)  308  Portfolio or product patent
information indicated that the plant used or was likely  to use the
pollutant in question in the manufacture of Pharmaceuticals, or (2)
the pollutant in question was detected in wastewater according to
the 308 Portfolio,  the Screening and Verification Sampling Program,
or the TTVO Questionnaire.

Estimated annual  raw  waste priority pollutant  loadings by major
pollutant category are summarized in Table 111-24.   Detailed backup
for  the  raw  waste  estimates,  as well  as for   final effluent
estimates, is presented in Appendix J.

c.  OAQPS Data Base.   Total industry mass discharge estimates for
priority and nonconventional VOCs were also estimated from the data
obtained by OAQPS in the 1975 and 1985 VOC disposition surveys (see
Tables III-6 and III-8).

Table  III-6  presents  a  compilation of the 1975  survey results.
Twenty-six PMA member  companies reported these data,  which they
felt represented 85 percent of the VOCs used in their operations.
These reporting companies  accounted for  approximately 53 percent
of the 1975 domestic  sales of  ethical  Pharmaceuticals.   Total
industry mass discharge  estimates  were developed  by assuming the
mass of pollutants sewered according to the survey represented only
53 percent of the total.
                               106

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                                                      TABLE  II1-24

                                           ESTIMATED ANNUAL  RAW WASTE LOADINGS
                                           PHARMACEUTICAL MANUFACTURING  INDUSTRY

                                                   Estimated Annual Raw Waste Loading  (1000  lbs/yr)
308 Screening/
Questionnaire Verification QAQPS
Pollutant Group Data Base1 Data Base2 Data Base3
Conventional Pollutants
o BOD5 261,700
o TSS 113,700
Priority Pollutants
o Volatile Organics -- 4,658 7,800
o Semivolatile Organics — 543
^ o Pesticides — 0.02
o Metals — 114.2
o Cyanide — 26.9
Nonconventional Pollutants
o COD 634,500
o Volatile Organics
ITD Listed — — 11,000
Non-ITD Listed — — 40,800
o Semivolatile Organics
o Pesticides/Herbicides

Method A
510,000
250,000
1,200
37
0.035
82
0.33
1,100,000
16,000
26
112
ITD/RCRA
Method B
510,000
250,000
1,300
1,100
0.62
120
4.1
1,100,000
16,000
863
192
Data Base4
Method C
510,000
250,000
2,200
630
0.42
105
6.3
1,100,000
29,000
181
411
  Excluding xylenes
1 Back-up calculations supporting these estimates can be found in Appendix I.
2 Back-up calculations supporting these estimates can be found in Appendix J.
3 Back-up calculations supporting these estimates can be found in Appendix K.
4 Back-up calculations supporting these estimates can be found in Appendix L^

-------
Table III-8 presents results from the 1985 VOC disposition survey.
The data were obtained from 22 PMA member companies that accounted
for  approximately 70  percent of pharmaceutical  sales  in 1985.
Total industry mass discharge estimates were developed by assuming
the mass of pollutants sewered according to the survey represented
only 70 percent of the total.

Estimated  annual  raw  waste  loadings  for   the  priority  and
nonconventional pollutant  VOCs  are  also summarized in Table III-
24.  Detailed backup  for the raw waste estimates is presented in
Appendix  K.    Information was  not  available  to  categorize  the
estimates by discharge or plant type.

d.  ITD/RCRA Data Base.   Analytical results  from recent sampling
done at Plants 12135, 12204,  12236,  12447, and 99999 were used to
develop rough estimates of the annual mass discharges of ITD-listed
pollutants from pharmaceutical manufacturing facilities.  The mass
loadings  were estimated  by  three  methods.    In  each  approach,
industry average concentrations were developed for all pollutants
found at  concentrations  above their  analytical  detection limit.
The average concentrations were  then used  to  calculate the total
industry loadings, using  an  estimate of the  total industry flow:
average  pollutant concentration (mg/1)  x  flow  (mgd)  x  8.345
(conversion factor) x 365  (days/year).

The differences between  the three  approaches are  in  the methods
used to calculate  the  individual  pollutant average concentrations:

    o   For Method A,  individual pollutant average concentrations
        were developed assuming  "not detected" observations equal
        to zero.

    o   For Method B,  individual pollutant average concentrations
        were developed assuming  "not detected" observations equal
        to the analytical  detection limit.

    o   For Method C,  individual pollutant average concentrations
        were developed including only observations reported above
        the analytical detection  limit.

Method A is a "best case" calculation for the average concentration
since the not detected observations are perceived as being at the
lowest  possible   concentration.    Method  B  is  a  "worst  case"
calculation for the average  concentration  since  the not detected
observations  are  perceived  as  being  the  highest  possible
concentration.   Method  C  uses  a  "censored"  data  base  for  the
calculation of the average concentration.   Method C is worst than
a "worst case" calculation for the average concentration since it
assumes  that  the  pollutants  are  found  at  levels  above  their
analytical detention  limits  in  all  samples  at all  facilities.
Actual industry mass loadings would be expected to be between the
levels predicted by Methods A and B.
                               108

-------
Raw waste  mass loading  estimates were  developed by  plant  type
(i.e., ABC, and D)  for  both  indirect  and  direct  discharging
facilities  by estimating  the wastewater  flows  for  each  group
separately.  No estimations were  made  for  treated effluents from
direct and indirect discharging facilities because of the extremely
limited pollutant treatability and/or removal data provided by the
ITD/RCRA sampling program.   The  total annual flow  estimate for
direct-discharging Subcategory ABC pharmaceutical plants is based
on the total flow from 30 facilities (21,381,000 gpd).  The total
annual flow estimate  for direct-discharging  Subcategory D plants
is based on the total  flow from 21 facilities  (3,540,000 gpd).  The
Subcategory ABC indirect discharger total annual  flow estimate is
based on total flow from 130  plants (31,144,000  gpd).   The total
annual flow estimate  for
indirect-discharging  Subcategory  D  plants  is  based on total flow
from  155 facilities (8,826,000 gpd).   All  plants were assumed to
be operating 365 days per year.

EPA recognizes that these mass loading  estimates  are rough because
the industry average  pollutant concentrations were developed from
a limited  data base,  and the  plants sampled  were not selected at
random.

The annual raw waste mass discharge  of  conventional, priority, and
nonconventional  pollutants  for the  pharmaceutical manufacturing
industry  for  Methods A,  B,  and C  is shown  in Table  111-24.
Calculations supporting these estimates are presented  in Appendix
L.

e.  Discussion.

Conventional Pollutants.    The  best  estimates   of  conventional
pollutant  discharges  (i.e., BOD5 and TSS) are those developed from
the 308  Questionnaire data  base.   These estimates were developed
with  actual  long-term average data  for each pharmaceutical plant
 (where available); Subcategory average values were used for plants
when  data  were not available.

Priority Pollutants.  The best estimates of  priority-pollutant mass
discharge  by  the pharmaceutical  manufacturing industry are those
derived from results obtained during the Screening and Verification
Sampling  Program.    These  estimates  incorporate plant-by-plant
priority-pollutant  use  information   obtained  from  the  308
Questionnaire  with  mean priority-pollutant wastewater concentra-
tions from sampling 26 pharmaceutical  plants.

Nonconventional Pollutants.  The best estimate of the discharge of
the nonconventional pollutant COD is that  developed from the 308
Questionnaire  data base.  This estimate was developed  with actual
long-term  average data for each plant (when  available);  subcategory
average values for plants were used  when data were not available.
The best  estimates  of the discharge of nonconventional pollutant
VOCs, SVOCs,  and pesticides are those developed  by Method B from
the ITD/RCRA data base.  However,  the VOCs and pesticides estimates
generated  by Methods A and B are not significantly different as the

                               109

-------
 analytical   detection   limit   for   these  compounds   are  not
 significantly  greater than  zero.

 2.   Solid Waste Generation  and Disposal

 Wastewater  treatment facilities  at  pharmaceutical manufacturing
 plants produce both primary  and biological sludges that are usually
 dewatered prior to disposal.   The amount of wastewater treatment
 sludge  generated   at  each facility  depends  on  a  number  of
 conditions,  including  (1)  raw  waste  characteristics;   (2)  the
 existence, efficiency, and/or type of primary treatment;  (3) type
 of  biological  treatment  system  employed;  and  (4)  efficiency of
 biological solids  removal from the wastewater.

 Total industry sludge generation was estimated based on information
 from each plant's  308 Portfolio  (when available).  When data were
 not  available, rough estimates were made of solids generated from
 an activated sludge treatment system.

 It  is  estimated  that the wastewater  treatment  systems at direct
 discharging facilities generate  42 million pounds (dry basis)  of
 wastewater treatment plant  sludge annually.  This estimate does
 not  include an estimate  for Plant 12256.   Sufficient  information
 was  not available to determine  how much of  the sludge generated at
 Plant 12256, as indicated in their 308 Questionnaire, was related
 to pharmaceutical  manufacturing operations.  It is estimated that
 an additional 7 million pounds  (dry basis)  of wastewater treatment
 plant sludge is generated at indirect discharging facilities.

 a-   Sludae Characteristics.   The data collected by  EPA in the
 recent  sampling   program  are  the  only  data   available  for
 characterizing wastewater treatment plant sludge generated by the
 industry. Wastewater treatment plant sludge samples were collected
 both before and after  dewatering operations.   Analytical results
 are summarized in Table 111-25.  Sludge analyses were conducted for
 most of the ITD-listed compounds.

 Only the sludge from Plant  12236  is  known  to  be disposed of in a
 hazardous  waste  landfill.    Plant  12204   composts  primary  and
 secondary sludges  and sells it as soil  conditioner.   Plant 99999
 uses a contract hauler to dispose of waste sludge.

 Sludge samples  were also analyzed using the Toxicity Characteristic
 Leaching Procedure (TCLP).   The  sludge leachate  produced by the
 TCLP was also analyzed  for most of the pollutants  on the ITD list.
Results are shown in Table 111-25, as  well as the proposed toxicity
 characteristic regulatory levels.

None of the  sludges exhibited the  characteristic of toxicity based
on the  proposed and final levels.   However,  primary sludge at Plant
 12204  has  the  potential for  exhibiting  the characteristic  of
corrosivity with a pH greater than 12.5.
                               110

-------
                             TABLE 111-25
           SUMMARY OF ANALYTICAL RESULTS FOR SLUDGE SAMPLES
                       ITD/RCRA SAMPLING PROGRAM

Plant 12204	           	Plant 12236
Plant 99999
Prinary Sludge
Thickened
(•It/kg)
Volatile Organic!
ac role in*
1 , 1-dichloroe thane*

„_
—
Deuatered
(•g/kg)

__
--
TCLP
(pg/t)

_.
--
trans- 1,2-dichloroethene* 0.236
•ethylene chloride*
toluene*
acetone
diethyl ether
ethylbenzene
isobutyl alcohol
•ethacrylonitrile
•ethyl ethyl ketone
Se*i volatile Organics
bi» (2-chloroethyl )ether*
2-chloronaphthalene*
phenol*
benzoic acid
2-mtthy Inaphtha lene
7.109
0.500
504.209
—
—
—
--
—

__
--
19.800
	
—
0.929
--
282.229
2.368
—
—
—
—

__
—
2.079
	
—
63
—
14,081
61
—
•-
--
--

_..
--
15
_.
—
Secondary
Dewatered
(•g/kg)

	
0.155
0.114
--
0.100
66.955
--
—
—
—
—

	
--
—
„
—
Sludge
TCLP
(Mg/t)

102
21
25
52
37
17,028
—
--
140
--
980

	
--
*-
	
—
Contained Sludge
Thickened
(ng/kg)

„
--
—
—
—
—
— •
--
--
—
-•

__
—
— -
—
—
Dewatered
(•g/kg)

„
0.045
..
—
0.077
0.555
—
—
—
0.191
-•

3.350
—
—
—
—
TCLP
(pg/«)

_.
20
—
—
140
—
—
—
—
106
—

_.
—
--
—
—
Secondary
Dewatered
(ng/kg)

	
—
—
«
1.406
—
--
1.145
—
--
•~

..
58.855
•••
..
582.725
2(awthyl thio)benzathiazole
n-eicosane
n-octadecane
Metals
antimony*
berylliw*
cadaiuaf*
chroaiuB*
copper*
lead*
•ercury*
nickel*
silver*
zinc*
aliBBinoB
bariual
boron
calciuB
cobalt
5.87.23T
0068 .0.0
— .
—

„
—
..
2
20
—
0.9
2
0.6
31
205
7
—
881
--


«
—

	
1
.-
5
41
--
0.3
5
1.8
73
1,900
24
--
198,000 2
—


—
—

„
--
..
..
219
_-
0.4
«
--
212
581
591
377
,660,000
—


--
—

._
0.5
2
6
44
16
0.9
10
1.8
3
1,610
21
—
167,000
—


--
—

._
—
—
—
—
—
--
—
--
722
270
1,090
688
369,000
—


—
—

53
—
—
10
--
—
2.5
--
--
88
102
37
—
8,340
—


--
2.036

6
—
17
10
26
—
1.6
19
2
135
253
44
89
12,000
18


—
—

—
—
15
--
—
--
--
85
«
1,310
500
1,370
1,050
64,700
•~


340.855
—

..
—
—
—
185
--
~
--
--
79
3,450
—
—
16,000
•~


Sludge
TCLP
(pg/t)

—
--
—
—
79
—
—
—
—
—
-~

—
44
~~
65
—
11
72
—

—
--
—
—
—
--
—
--
--
1,200
558
1,420
704
69,400
~~


Regulatory
Levels
(M*/t)

—
—
—
8,600(p)
14,400(p)
—
—
—
--
—
7,200(p)

50(p)
...
14,400(p)
—
—
--
—
••

—
--
l.OOO(f)
5,000(f)
~
5,000(£)
200(f)
--
5.000(f)
~~
..
lOO.OOO(f)
—
--
~~



-------
K>
                                                                                 TABLE  111-25  (continued)
                                                                     SUMMARY OF ANALYTICAL  RESULTS  FOR SLUDGE SAMPLES
                                                                                 ITD/RCRA SAMPLING  PROGRAM

                                                           Plant  12204                                 Plant 12236
                                                                                                                                   Plant 99999
Priaary Sludge

iron
•atnesius
•anganese
sodiius
tia
titanium
vanadiua
Thickened
f«/kg)
288
377
18
435
5
7
3
Devatered
(•g/kg)
850
1,040
40
413
40
61
8
TCIP
(M/«)

--
«
6,700
--
--
--
Secondary Sludge
Dewatered TCLP
(•g/kg) (Mg/»)
753
923
38
653
7
24
3
521
5,860
357
1,380,000
--
«
--
Combined Sludge
Thickened
(•g/kg)
92,900
726
365
23,500
60
72
77
Dewatered TCLP
(•8/k«) (M/<)
18,800
1,170
665
5,760
16
107
120
119,000
3,840
1.940
1,430,000
--
--
..
Secondary Sludge
Dewatered TCLP
(•g/kg) (MK/O
1,050
1,680
22
5.490
—
--
..
829
6,510
93
1,560,00
109
..
—
Regulatory
Levels
(Mg/t)

..
..
...
..
..
..
             Miscellaneous Pollutants

             cyanide,  total*

             Classical Pollutants
4.5
           N/A
N/A
5.0
          6.9
                     N/A
                                                                                  14
                                                                                           M/A
asaonia. as M 4,600 940 H/A 4,600 N/A
nitrate-nitrite, as H I.I — N/A 3.4 N/A
nitrogen, kjeldahl, total 4,300 14.000 N/A 7,000 N/A
flash point (*C) N/A 52 N/A 37 N/A
pH 7.6 12.8 N/A 7.5 N/A
residue, total (I) 11 38 N/A 22 N/A
residue, total volatile(X) 46 7.4 N/A 53 N/A
sulfide, total 640 88 N/A 75 N/A
(Honier-Williasw)
corrosivity («py) N/A <10 N/A <10 N/A
N/A Indicates not analyzed.
** Mean of four replicate analyses; refer to the Laboratory Report of
Indicates pollutant concentration below detection li»it.
(f) Final rules for EP Toxicity Characteristic, see 40 CFR 261 Subpart
(p) Proposed rules for Toxicity Characteristic, see 51 FR 21648.
9,300
4.5
28,000**
40
8.0
3.9
58
7,000

<10

Analysis.

C.

5,000
1.1
73,000
35
7.3
22
63
6,000

<10





N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A

N/A





6,300
33
100,000
60
6.8
6.9
86
620

<10





N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A

H/A






..
_.
<60»C(f)
12.52SO(f)






-------
         IV.  TECHNICAL CONTROL AND TREATMENT TECHNOLOGY

A.  INTRODUCTION

As  indicated  in  Section  III,  VOCs  are  the major  unregulated
priority and hazardous nonconventional pollutants being discharged
by  the  pharmaceutical manufacturing industry.   For the  sake of
brevity,  discussions  in  this  section  are  limited  to  those
technologies currently used or available to remove or reduce VOCs
discharged in the  industry wastewater. Technologies currently used
or  available  to  remove  or reduce  other wastewater  pollutants
generated by this  industry are discussed in Section VII of the 1983
Final Development Document.(4)

Many possible  combinations of in-plant source controls, treatment
technologies,  and EOF treatment systems  are  capable  of reducing
VOC pollutant discharges.  However,  each plant must make the final
decision concerning the  specific combination of pollution control
measures best  suited  to  its particular situation.

The  treatment technologies currently  in-place  at plants  in the
pharmaceutical industry, as reported in 308  responses, are listed
in  Appendix  L of  the  Proposed  Development  Document.(5)    The
technologies  described  herein  are  those which  can  reduce the
discharge  of  volatile pollutants  into navigable waters or POTWs.
They are divided  into two broad classes:  in-plant and EOF tech-
nologies.

Since the  ultimate receiving point  of a  plant's wastewater  (e.g.,
POTW vs.  stream,  river, or lake)  can  be critical in determining
the overall treatment  effort required,  information  on ultimate
discharge  is  also presented in this  section.

B.   IN-PLANT  SOURCE CONTROL

The intent of in-plant  source control  is to reduce or eliminate
hydraulic  and/or pollutant loads generated  by specific sources
within  the overall manufacturing process.  By implementing controls
at  the source,   the  impact  on  and requirements  of subsequent
downstream treatment  systems  can  be minimized.

The overall  planning and  plant  design  criteria of  many  newer
pharmaceutical manufacturing plants  include the reduction  of water
use and subsequent minimization of contamination.  Existing  plants
have  also  made   improvements  to  provide  better  control   of
manufacturing  processes  and  other  activities,  resulting   in
environmental benefits.    Examples  of  in-plant  source  controls
effective  in  reducing volatile  organic pollutant loads  are  as
 follows:

     o   Processes have  been  reviewed and  revised  to reduce  the
         number of toxic  VOCs  used.     Less  toxic  non-priority
         pollutants have been substituted  for some  of the  more
         toxic priority pollutants  (e.g., benzene).
                                113

-------
    o    The recovery  of  waste solvents  used  in  manufacturing
         processes is a common practice among plants.  However, to
         further reduce  the amount  of  waste  solvent discharge,
         plants have  instituted measures such as:   (1)  incineration
         of solvents that  cannot be recovered  economically,  (2)
         incineration of  "bottoms11 from solvent  recovery units,  and
         (3)  design and  construction of  solvent recovery columns
         that operate beyond the point  at which  it  is  no longer
         economically feasible to recover solvent(s).

    o    Spill   prevention  is recognized in  the  industry  as a
         critical  aspect of pollution control.   In  addition to
         careful management of  materials  and methods, preventive
         steps  such  as  impoundment  basins,  dikes,  and  diversion
         structures are used in  many  cases.

C.  IN-PIANT TREATMENT

Besides  implementing source controls to  reduce  or  eliminate  the
waste loads generated within the manufacturing process, plants  may
also use in-plant  treatment directed at removing certain pollutants
before they are combined with the plants overall wastewater.   In-
plant  treatment  processes  are  appropriate  for  treatment  of
wastewater from particular  production processes or stage within  the
plant itself.  Although in-plant technologies can remove a variety
of pollutants,  they  are  principally  applied for the treatment of
toxic or priority pollutants.

This concept of in-plant treatment of a  segregated  stream is of
major importance.  First,  treatment  technologies can be directed
specifically toward a particular pollutant or a  group of pollutants
with  similar  physical  chemical  properties.     Since wastewater
treatment and  pollutant  removal costs are strongly influenced by
the volume of water to be treated,  the costs involved in treating
a segregated stream are often considerably less than they would be
in treating combined wastewater.  In-plant stream segregation  and
treatment also can remove substances  which may interfere with end-
of-pipe  treatment,  (e.g.,  biorefractive organics can be removed
prior to biological treatment.

The 308 Portfolio data base is the principal source of information
relating to  the use  of  in-plant treatment  in  the pharmaceutical
industry.  Most of this information came  from the Supplemental  308
Portfolio responses.  In addition, while not specifically requested
in the  308  Portfolio,  some in-plant  treatment  information was
obtained from the original  308  Portfolio plants.  It was gathered
in three ways:   (1)  some  plants  provided  "additional"  data or
comments relative to in-plant treatment on the  questionnaire;  (2)
a small amount of information was gathered by direct contact with
plant personnel; and  (3) the wastewater sampling programs discussed
in Section III identified the use of a few in-plant technologies.
Some information on in-plant steam-stripping was also obtained
                               114

-------
following proposal; as a result of the EPA's efforts to locate an
appropriate plant at which to  evaluate  the  performance of steam-
stripping technology, and as a result  of  responses obtained from
a post-proposal 308 Questionnaire concerning the discharge of toxic
VOCs by indirect-discharging pharmaceutical  plants.  The responses
to the 308 Questionnaire will be discussed later in this section.

1.  Solvent Recovery and Removal

Solvents are used extensively  in the pharmaceutical manufacturing
industry.  Because such materials are expensive, most manufacturers
try to recover and purify them  for reuse whenever possible.  Reuse
of recovered solvents in the pharmaceutical manufacturing process
is quite  limited,  however,  because of  FDA  constraints on purity
requirements for  solvents  (and other chemicals)  used in process.
Solvent  recovery  operations   typically use  techniques  such as
decontamination,  evaporation,  distillation,  and  extraction.  The
feasibility and extent  of recovery and purification are governed
largely  by the  quantities involved,  and  by the  complexity of
solvent mixtures to be separated.   If recovery is not economically
practicable, the used solvents may have to be disposed  of by means
of  incineration,  landfilling,  deep-well  injection,  or contract
disposal.   It  should be noted  that  hazardous wastes can only be
landfilled at  approval RCRA landfills.

Even when an effort  is  made  to recover solvents, some wastewater
contamination  can be expected.   Removal of  small quantities of
organic solvents from the segregated wastewater can be accomplished
by  techniques  such  as  steam-stripping  or  carbon  adsorption.
Further removal of solvents from combined EOF wastewater may  result
from biodegradation  or  air stripping during  biological treatment
or from surface evaporation in the treatment  system.

2.  Steam-stripping

a.  Introduction,  steam-stripping is the transfer of the volatile
constituents of wastewater to  the vapor phase, which  occurs  when
steam  is passed through  a preheated wastewater. Extremely volatile
compounds can  be steam-stripped  from  wastewater in flash  tanks,
which  essentially provide one  stage of liquid-vapor contact.  More
difficult separations are conducted in columns filled with packing
materials,  which  provide large  surface areas  for liquid-vapor
contact.    Conventional fractionating  columns,  which contain  a
series of  liquid-vapor contact  stages,  are used  for the  most
difficult separations.    Flash tanks,  packed towers,  and plate
columns  are used extensively  in the chemical process  industries;
their  designs  are discussed in chemical engineering textbooks.(11,
12, 13)  Hwang and Fahrenthold  considered the thermodynamic aspects
of steam-stripping organic priority pollutants from wastewater. (14)
The  authors predict  the effluent  concentrations  theoretically
achievable by steam-stripping and the actual number of liquid-vapor
contact  stages required.
                                115

-------
Recently,  EPA  promulgated  a  series  of  steam-stripper  based
regulations  for the Organic  Chemicals,  Plastics,  and Synthetic
Fibers  Industry (52 FR  42522).   The long-term  average effluent
limitations  for most of  the pollutants are  below 100 ppb.   These
priority volatile limitations were based on actual performance data
from 16 different steam strippers in-place in the OCPSF Industry.
Steam-stripping was also demonstrated to  be a reliable technology
for  the   removal  of   methylene   chloride  and   toluene  from
pharmaceutical  wastewater.    Section VIII  of  the  1983  Final
Development  Document  presents  suggested limits  for  these  four
pollutants based on the performance of wastewater steam-strippers
at  a  pharmaceutical   plant.    Appendix A  of  the  1983  Final
Development Document presents model costs for the installation of
steam-strippers  at  pharmaceutical   plants.     Steam  stripping
operations  at Plant 12003 are discussed  following  the  general
discussion of steam-stripping.

b.  General.   In a steam-stripper, the  components  of wastewater
are separated by partial  vaporization.  When contacted with steam,
the VOCs in  the wastewater are  driven into  the vapor phase.   The
extent of separation is governed by physical  properties of the VOCs
being stripped, the temperature and pressure at which the stripper
is operated, and the arrangement and type of equipment used.

A column used to steam-strip solvents from wastewater is shown in
Figure IV-1.  Solvent-contaminated process wastewater and condensed
overhead vapors from the stripper are allowed to accumulate  in a
gravity-phase separation tank.   When the equilibrium solubility of
the solvents in water is reached,  the difference  between specific
gravities of the water and  solvents results in the formation of two
immiscible  liquid  layers.    One  layer  contains the  immiscible
solvents; the other layer is an  aqueous solution that is saturated
with solvents.   The  solvent  layer  is  pumped to  storage.   The
composition  of  the recovered  solvent and economic  factors  will
determine whether the solvent  is reused within the plant, disposed
of, used as incinerator fuel,  or sold  to other industrial users or
a solvent reclamation facility.

The aqueous layer from  the  gravity-phase  separation tank is pumped
through  a preheater  where the temperature  is   raised by  heat
exchange with the  stripper effluent.   If the feed  contains  high
concentrations of suspended solids, a filter can be installed prior
to the  preheater  to  prevent  fouling in the  preheater and  the
column.

After preheating,  the solvent-saturated water is introduced at the
top or near the middle  of the  column,  and flows by gravity through
the stripper.  The hot  effluent, which is discharged at the bottom
of the stripper,  is used as a heating medium  in the feed preheater.
Steam is injected through a sparger and rises countercurrent to the
flow of  water.The solvent-laden  overhead vapors are condensed, and
the organic and aqueous layers are allowed to separate by gravity
                               116

-------
                                                   COOUM
                                                   •ATU
                                           eOlOEMCM
                                                                VflTTO
                                                                EMBIOM
                                                                cannot
                                                                  1 OPTIONAL
                                                                  I C8BOEHATE
                                                                   OMUH
   srmma
   WASTEMTM
                               omout
                               MFLUX
                                                                               RECOVERED
                                                                               SOLVENT
                                               MCXEO
                                               on
                                               TRAY
                                               COLUMi
                                                                               MCCTCU
                                                                               TO SUAVITY
                                                                               PHASE
                                                                               SEPARATION
                                                                               TAM
                                                                              mEAM
FIGURE  IV-1 TYFICAL EOUIFMENT FOR «TEA*i STRIFflNG SOLVENTS FROM WASTEWATER.
                                         117

-------
in the condensate drum.  The solvent can be recovered by decanting
the immiscible liquid layers, or by recycling the condensed vapors
directly to the gravity-phase separation tank.   This practice is
particularly  advantageous  in cases  where the  wastewater to  be
steam-stripped contains low  concentrations  of the solvent to be
recovered.  As the condensate mixes with the wastewater already in
the tank, the  solvent concentration  increases to the point where
a two-phase mixture is formed.  The aqueous phase, which is fed to
the column, will be  saturated with solvent.   Steam strippers can
be  operated  to  achieve  maximum  efficiency when  the  feed  is
saturated with the solvent to be recovered.

In certain situations, reflux may be required to produce overhead
vapors which,  when condensed, will separate into immiscible liquid
layers.  Initially,  the condensate is  allowed to accumulate  in a
condensate drum.   When the solvent concentration exceeds the water
solubility limit, two liquid layers form.   The solvent-rich layer
is pumped to storage.  A portion of the solvent-saturated aqueous
layer is returned to  the column (i.e., refluxed),  and the remainder
is recycled to the gravity-phase separation  tank.   The reflux is
introduced at a position above the point where the feed enters the
column.

At plants where  steam-pressure  fluctuations  can occur, automatic
feedback controllers are  commonly used to maintain  the  desired
solvent concentrations in the stripper bottoms and overhead vapors.
A detailed discussion of the use of automatic feedback controllers
for  this  purpose   is  included  in   the   4th   Edition  of  the
Chemical Engineer's Handbook.(15)

Information gathered by  EPA indicates that steam-stripping is used
to remove  organic  solvents  and other  pollutants from wastewater
discharges at  a  minimum of  six pharmaceutical   plants, and  that
steam-stripping is also used to treat similar wastewater in other
industries.    Data  on  the  removal  of toxic,   volatile  organic
pollutants  in steam-strippers  at  plants where pesticides  and
organic chemicals are manufactured are  presented  in the " Proposed
Development Document for Effluent Guidelines
Limitations and Standards for the Pesticide Manufacturing Point
Source Category"  . (16)

The  following additional comments  are cited  from  the  proposed
development document for  the organic  chemicals  and  plastics and
synthetic fibers point  source category:   organic steam-stripping
may be  used in  a  binary distillation, and  is   also  amenable to
multicomponent  streams; materials  commonly  encountered  (e.g.,
methylene   chloride,  toluene,   acetone,   diethyl   ether,   and
chloroform) have moderate to  high vapor pressure  and k-values, and
are thus easily separated from water solutions or mixtures.(17)

Actual column  efficiencies  are  critical parameters,  as they are
used to predict the number of trays required for a column, or the
                               118

-------
packing depth for a packed column.  For methylene chloride with a
saturated  inlet  concentration   and   less   than  50 ppb  outlet
concentration, eight  trays  would theoretically  give  100 percent
efficiency.

In  summary,   steam-stripping  columns  work  effectively on  most
solvents encountered in the  pharmaceutical industry.  The ultimate
degree of separation or removal can be theoretically predicted, as
can the  cut-off  concentration and associated  economics (cost of
recovery versus solvent value).

Substantial plant operating data  (Table  IV-1)  are also presented
showing  actual   tower  heights,   diameters,   feed   rates,   and
inlet/outlet  concentrations  for  both single solvent  and solvent
mixtures.

Further reduction of solvent losses to plant effluent streams can
be obtained by incineration  of solvents not economically recovered
by  stripping,  bottoms  incineration,  ACA,  ion-exchange  resin
adsorption, or liquid/liquid extractions.

Process  changes  minimizing wash-ups  and  clean-ups of  process
equipment,  continuous  versus  batch  production  scheduling,  and
improved  solvent handling  procedures  can  significantly  reduce
solvent losses.

Typical steam-stripping column design criteria follow:

                  STEAM-STRIPPING

FUNCTION:        Separation  of specific dissolved organics from
                wastewater
PARAMETERS
AFFECTED:        Concentration of organics,  temperature
EFFECTIVENESS:   Removal to  achievable outlet concentration,
                usually 50 ppb
APPLICATION      TSS:      50 mg/1
LIMITS:          Oil:     100 mg/1
DESIGN BASIS:    Design flow =120 percent of the average flow
                 Maximum number of trays = 22
                 Maximum column diameter = 6 feet
                 Tray spacing =2.5 feet
                 Organic concentration:  No higher than its
                solubility at ambient conditions
TREATABILITY     Pollutant molecular weight
FACTOR:          Overall column efficiency
                 Pollutant latent heat of vaporization
                 Achievable  effluent concentration (each
      pollutant)
                               119

-------
to
o
                                                                TABLE IV-1


                                                        INDUSTRIAL STEAM-STRIPPERS
Column Type
Packed*
Trays*


Packed*
Trays*
Packed
Trays*

Packed*





Trays*


Trays

Packed*
Height
(feet)
75.42
52


33.83
80
54
38

36.8





54.5


27.42

42
Diameter
(feet)
3
3.5


2.5
6.5
2.5
6

2





5.5-7.0


4.5-3

3.0
Flow Rates
Feed
17,500
6,960


2,375
70,000
33,750
40,000-
90,000
7,500





100,080


90

25,931
(lb/hr)
Bottons
1,200
5,789


5,750
99,750
34,300
13,900-
31,700
8,200





116,600


5,000

23,154
Inlet Concentration
2.63% Aniline
5.51% TOC
7.18% Aniline
0.79% Benzene
5% Aniline
NA
0.52% Nitrobenzene
NA

4,980 ppn TOC
0.18 ppm Methylene
chloride
1.05 ppn Methyl
chloride
0.001 ppm Phenols
778 ppm Sulfide
833 ppm Ammonia
510 ppm Phenols
0.3% Methylene
chloride
1.07% Aniline
Outlet Concentration
<0.001% Aniline
0.042% TOC
0.03% Aniline
0.02% Benzene
>0.0005% Aniline
NA
0.05% Nitrobenzene
NA

2,360 ppm TOC
0.001 ppm Methylene
chloride
0.0018 ppm Methyl
chloride
0.0065 ppm Phenols
"Nil" Sulfide
36 ppm Ammonia
284 ppm Phenols
0.03% Methylene
chloride
0.009% Aniline
                                                                                       0.019% Methanol
0.01-0.02% TOC

-------
to
                                                          TABLE  IV-1  (continued)



                                                         INDUSTRIAL  STEAM-STRIPPERS
Column Type 	
Packed
Trays and Packed*
Packed*
Packed
Packed*
Packed*
Trays (not
Packed*
Packed
Height
(feet)
NA
30.33
22
15
15
26
given)
8
10.5
Diameter
(feet)
2.5
1.66-3.25
1
1
2.0
4
3.5
0.5
0.33
Flow Rates (Ib/hr)
Feed
16,886
3,958
3,100
2,746
28,600
43,150
24,520
1,611
253
Bottoms
15,886
3,916
3,387
3,108
29,067
42,870
25,329
1,603
254
Inlet Concentration
0.697% TOC
1.88% BOD
0.75% Aniline
0.10% Hethanol
2.3% TOC
2.98% Aniline
1.35% DIPA
7.26% Salts
0.91% EDC
4.0% NaCl
0.79% EDC
1.04% HC1
9,400 ppm EDC
0.0595% TOC
0.076% BOD
0.05% NHs
0.256% Sul fides
6,828 ppm
Benzothiazole
620 ppm Aniline
198 ppm of H2S
Trace-CS2
Outlet Concentration
0.01-0.02% TOC
0.23% BOD
0.02% Aniline
0.077% TOC
0.076% Aniline
0.03% DIPA
6.64% Salts
3.54% NaCl
1.025% HC1
85 ppm EDC
15 ppm VCM
0.034% TOC
0.05% BOD
0.012% NHs
0.0037% Sulfides
<60 ppm
Benzothiazole
<60 ppm Aniline
Trace H2S and
CS2

-------
                                                    TABLE IV-1 (continued)

                                                  INDUSTRIAL STEAM-STRIPPERS
Column Type
Height
(feet)
Diameter
(feet)
   Flow Rates (Ib/hr)
  Feed         Bottoms
               Inlet Concentration    Outlet Concentration
Trays
Trays*
Trays1"
Packed*


Packed
 44
 24.83
 30
 17


 42
  2.5
  2.5
  1.5


  3.5
                    28,579
 41,897
 57,000
0-5,000
119,000
               28,906
 41,669
 55,961
0-5,000
121,000
35 ppn Benzene
4,220 ppn MNB
12,440 ppn Na Salts

IX Methylene
 chloride
0.13% Chlorobenzene
0.00001% Octa-
 decylamine
5.22% NaCl

0.35% TOC
1.66% Methylene
 chloride
0.091% Chlorobenzene
800-1,000 ppm Vinyl
 chloride

0.197% TOC
0.158% BOD
0.011% Vinyl Chloride
0.56% Dichloroethane
0.172% Other Organic
 chlorides
0 ppm Benzene
800 ppm MNB
12,300 ppm Na Salts

0.015% Methylene
 chloride
0.0025% Chloro-
 benzene
5.59% NaCl
0.008% TOC
0.009% Methylene
 chloride
0.0007% Chloro-
 benzene

<10 ppm Vinyl
 chloride

0.095% TOC
0.112% BOD
<0.0001% Vinyl
 chloride
<0.0002% Dichloro-
 ethane
0.017% Other Organic
 Chlorides

-------
ro
u>
                                                           TABLE IV-1  (continued)



                                                         INDUSTRIAL STEAM-STRIPPERS
Column Type
Packed
Trays*
Trays*
Height
(feet)
28
53
35
Diameter
(feet)
3.5
4
4
Flow Rates
Feed
112,500
60,000
52,700
(lb/hr)
Bottons
115,000
NA
51,533
Inlet Concentration
0.32% TOC
0.004% Vinyl Chloride
0.56% Dichloroethane
3.3 ppn 0/G
1.59 ppn Phenol
750-1,000 ppn TOC
<10-1,000 ppm BOD
2% "H.C."
"(hydrocarbon?)"
Outlet Concentration
0.07% TOC
<0.0005% Vinyl
chloride
0.021% Dichloro-
ethane
2.4 ppa 0/G
1.99 ppn Phenol
10-100 ppn TOC
40-300 ppn BOD
50-260 ppn H.C.
       * With recycle.

-------
                 Steam requirement (each pollutant)
                 Vapor-liquid equilibrium ratio
                 Activity coefficient (deviation from ideal-
                solution behavior)
COST PARAMETER:  Diameter of the column
COST CURVE SCALE
FACTOR:          Number of columns
                 For two or more operating columns (plus a
                 spare), multiply by (number of columns/2)08
                 Number of trays
RESIDUES:        Distillate is decanted; water phase is returned
                to column; organic phase  is  recovered  or
                incinerated.
MAJOR            Feed tank, carbon steel*
EQUIPMENT        Distillation columns with sieve trays, carbon
                steel*
                 Feed preheater, carbon steel*
                 Condensers,  carbon steel*
                 Accumulator/decanter,  carbon steel*
                 Organic-phase pumps
                 Water-phase recycle pumps
                 Column feed pumps
                 Bottom pumps

* Stainless steel if feed is corrosive or has high salt levels.

c.   Steam-stripper Operations at Plant 12003.   Plant  12003  can
operate  up to eight  different  steam-strippers to  reduce  VOC
concentrations reaching the  plant's  sewer system.   The strippers
are located throughout  the plant within production  buildings, or
at central solvent recovery operations  in  other buildings.  Steam-
stripping enables the  plant to meet a  POTW  requirement that the
concentration of explosive vapors in the plant sewer  pipes does not
exceed 40 percent of the lower explosion limit (LEL).  The LEL is
monitored in each production area with a  flame-thermocouple sensor.
If the solvent vapor concentration exceeds 30 percent of the LEL,
gas samples  are  automatically taken  and analyzed  by GC.   The
stripped wastewater  is  combined with sanitary and  other process
wastewater  in  a  pretreatment  system,   which  consists  of  oil
skimming, pH adjustment, and flow equalization.

The recovered solvents from the stripping  operations are currently
stored for disposal by contract hauling.   Plant personnel informed
EPA that they were considering using some of the recovered solvents
as  fuel  for an incinerator.   EPA representatives  visited Plant
12003  during the week of May  23-27, 1983,  and sampled the influent
and effluent from a packed column stripper and a steam distillation
flash tank.

d.  Packed  Column  Steam-stripper.  Five days of operating data from
a packed column steam-stripper, used to remove methylene chloride
from wastewater at Plant 12003, are shown in Table IV-2.  In
                               124

-------
addition to methylene chloride, analysis by plant personnel
confirmed that  methanol,  diethyl ether,  and pyridine were  also
present in the wastewater.  The stripper operates approximately
12  hours a  day,  five  days  a  week.    During periods  of  low
production,  the stripper  is  shut down,  and wastewater is allowed
to accumulate.  When the  stripper resumes operation,  it  operates
continuously for several days.

The major portion of the  feed to the stripper is wastewater from
a batch chemical-synthesis operation.   The feed is pumped to the
underground settling tank shown in  Figure IV-2.   In the  settling
tank,  the wastewater  separates  into  two  layers:     immiscible
methylene  chloride;  and  an  aqueous  solution  saturated  with
methylene chloride which also contains small amounts of methanol,
diethyl ether, pyridine,  and other  solvents listed in Table IV-2
footnotes.  The  immiscible  methylene chloride  is  pumped off the
bottom of the settling tank to a spent-solvent holding tank.  The
aqueous solution  is  pumped  to the stripper  feed tank.   The feed
rate to the column is controlled by  an automatic flow valve on the
discharge side of the feed pump.

The wastewater is pumped through an influent filter  and a preheater
before  it  enters  the  top  of  the  column  through  a  liquid
distributor,  which  is a special  pipe  outlet that  serves  to
uniformly wet the  tower  packing.    The  10-inch-diameter column
contains one 19-foot section packed with  1-inch-diameter, stainless
steel, pall rings.   Steam  is injected  through a  sparger in the
bottom of the stripper.  The overhead vapors from the stripper are
condensed and recycled to the underground settling tank.

Results of  five days of  sampling are  shown in Table  IV-2.   The
average  influent concentration of  methylene chloride was 8,800
mg/1.   The  column influent  also contains high concentrations of
inorganic salts.  According  to plant personnel, the influent and
effluent  filters  shown in Figure IV-2  were installed to prevent
fouling in the feed preheater. The  average  effluent concentration
of  methylene  chloride was 6.9 mg/  when  the  column was  operated
close  to  the  design  specifications  of  98°C  overhead  vapor
temperature.  This corresponds to greater than 99-percent removal
of methylene  chloride  in  the packed column stripper.   The packed
column  was seemingly  operating  under  unstable  conditions,  as
indicated by  a  drop in the  temperature  of overhead vapors below
85°C,  during  10  of  the  40  overhead temperature  readings taken
during sampling.

e.   Steam Flash Tank.   Five days of operating  data from a steam
flash  tank used to strip toluene from  wastewater  at Plant 12003
are shown in Table IV-3.   In addition to toluene,  analysis by plant
personnel confirmed that methanol, ethanol, acetone, isopropanol,
MEK, and  diethyl  ether were  also present in the wastewater.  The
flash tank normally operates  seven hours  a  day, five days a week.
                               125

-------
                                                                 TABLE IV-2


                                  METHYLENE CHLORIDE REMOVAL IN PACKED COLUMN STEAM STRIPPER AT PLANT 12003
                                                         OPERATING DATA FOR 5/23/83
to
ON
Sample
Number

1
2
3
4
5
6
7
8
Feed Temp.
f°C)

87
86
86
86
85
85
85
84
Composite of influent samples
Average of
Average of
all effluent datum
Overhead
Temp.

97
98
94
89
89
86
84
84
1-8
points
effluent datum points obtained
Bottoms
Temp.
C°C)

104
102
101
102
102
102
102
101


under normal
Feed Rate
(gpm)

9.6
8.9
9.0
9.0
9.0
9.0
9.0
9.0


operating conditions
Stream Rate
flbs/hr)

160
160
150
150
150
150
155
155



Methylene
Influent
NA1
NA
NA
NA
NA
NA
NA
NA
8,250


Chloride
'!)
Effluent
0.926
5.10
4.94
3.00
1.99
5.70
22. 802
38.05*
NA
10.31
3.61
       1 NA means not analyzed.


       2 Effluent concentrations under upset conditions,  overhead  temperature  <85°C.

-------
                                                           TABLE IV-2 (continued)


                                  HETHYLENE CHLORIDE  REMOVAL IN PACKED COLUMN STEAM STRIPPER AT PLANT 12003
                                                         OPERATING DATA FOR 5/24/83
to
•vj
Sanple
Number

9
10
11
12
13
14
15
16
Composite
Average of
Feed Temp.
(°0

84
84
83
85
84
84
84
84
of influent samples
all effluent datum
Overhead
Temp.
(°C)

87
89
86
90
89
86
87
85
9-16
points
Bottoms
Temp.
(°C)

101
101
100
101
101
101
101
101


Feed Rate
(gpm)

8.7
9.0
8.9
8.9
9.0
9.0
9.0
9.0


Stream Rate
(Ibs/hr)

150
154
155
150
150
150
150
150


Methylene Chloride
(•8/1)
Influent
NA1
NA
NA
NA
NA
NA
NA
NA
225 2

Effluent
3.90
8.36
20.60
4.07
10.70
20.30
4.80
7.87
NA
10.08
       1 NA means not analyzed.


       2 This datum point is suspect.  Plant 12003 collected duplicate samples and reported an average influent methylene
         chloride concentration of 10,305 ng/1.

-------
to
oo
                                                           TABLE IV-2 (continued)


                                  METHY1ENE CHLORIDE REMOVAL IN PACKED COLUMN STEAM STRIPPER AT PLANT 12003

                                                         OPERATING DATA FOR 5/25/83
Sample
Number

17
18
19
20
21
22
23
24
Composite
Average of
Average of
Feed Temp.
CO

85
85
85
85
85
82
83
83
of influent samples
all effluent datum
Overhead
Temp.
(°O

97
90
88
85
84
83
83
83
17-24
points
effluent datum points obtained
Bottoms
Temp.
(°C)

102
102
102
102
102
100
101
UK


under normal
Feed Rate
(KP«)

8.3
9.5
8.5
8.5
8.5
8.5
UK5
UK


operating conditions
Stream Rate
(Ibs/hr)

150
150
150
150
150
150
152
155



Hethylene Chloride
	 (mg/1)
Influent
NA1
NA
NA
NA
NA
NA
NA
NA
7,000


Effluent
1.72
1.63
3.60
14.25
39. 302'3
138. O2'4
110. O2
60. 802
NA
46.2
5.30
       1 NA means not  analyzed.


       2 Effluent concentrations under upset  conditions, overhead temperature <85°C.


       3 0.132 mg/1 of 1,1-dichloroethylene was detected in effluent sample number 21.


       4 0.193 mg/1 of 1,1-dichloroethylene and 0.302 mg/1 of 1,2-dichloropropene were detected in effluent sample number 22.


       5 UK means unknown.

-------
                                                           TABLE IV-2 (continued)


                                  METHTLEHE CHLORIDE REMOVAL IN PACKED COLUMN STEAM STRIPPER AT PLANT 12003
                                                         OPERATING DATA FOR 5/26/83
to
vO
Sample
Number

25
26
27
28
29
30
31
32
Average
Average
Overhead
Feed Temp. Temp.
(«C) (°C)

84
84
83
82
82
81
83
83
of all datum points
of effluent datum points

89
86
84
83
83
82
93
89

obtained
Bottoms
Temp.
(°C)

102
101
101
101
101
101
102
102

under normal
Feed Rate Stream Rate
(gpm) (Ibs/hr)

8.3
8.3
8.3
8.3
8.3
8.3
7.3
8.3

operating conditions

149
149
150
150
152
152
150
155


Methylene Chloride
(.*/!)
Influent
11,200
9,900
9,100
9,400
10,200
11,800
10,000
12,000
10,450

Effluent
10.1
22.851
57. 502
115. OO2
59. 902
127. OO2
3.18
3.73
49.9
10.0
       1 0.211 mg/1 of 1,1,1-trichloroethane was detected in effluent sample number 26.


       2 Effluent concentrations under upset conditions, overhead temperature <85°C.

-------
                                                  TABLE  IV-2  (continued)

                          METHYLENE CHLORIDE REMOVAL  IN PACKED COLUMN STEAM STRIPPER AT PLANT  12003
                                                OPERATING DATA FOR 5/27/83
Sample
Number

33
34
35
36
37
38
39
40
Composite
Average of
Feed Temp.
(°C)

85
85
85
84
84
84
84
84
of influent samples
all effluent datum
Overhead
Temp.
(°C)

90
90
95
90
89
90
88
88
33-40
points
Bottoms
Temp.
(°C)

102
102
102
102
102
102
102
102


Feed Rate
(*pm)

8.5
8.5
8.5
8.3
8.1
8.0
8.0
8.0


Stream Rate
(Ibs/hr)

150
150
154
154
154
152
160
170


Methylene Chloride
(me/1)
Influent
NA1
NA
NA
NA
NA
NA
NA
NA
9,500

Effluent
7.20
4.04
4.27
1.47
1.62
2.63
7.83
15.80
NA
5.61
NA means not analyzed.

-------
                                            VEMr TO f HISSIOIIS
                                            COMIROl
COOIINO
WATER
                                                                                           STRIKER
                                                                                           ir OIA.
                                                                                           rsSMURINSI
                                                                                           If PACKED HEIGHT
HflNVIEME
CHIORIDE
CONIAMINATEO
WASIEWATEH
                                                                                                             STEAM
                                                                                                VENT
                                                                                                MEIHVIEHE
                                                                                                CHIOHIOE
                                                                                                10 SIONA6E
                                                                       STMHtED
                                                                       WASTEWATER
                     FIGURE IV-2   PACKED COLUMN STEAM STRIPPER AT PLANT 12003.

-------
                                                                 TABLE IV-3


                                       TOLUENE REMOVAL IN STEAM DISTILLATION FLASH TANK AT PLANT 12003
                                                 OPERATING DATA FOR 5/23, 5/24, AND 5/25/83
u>
K)
Date

5/23/83

5/24/83

5/25/83

Sample
Number

1
2
Composite 1 & 2
3
4
Composite 3 & 4
5
6
Composite 5 & 63
Toluene (mg/1)
Influent
NA1
NA
320.5
NA
NA
494.0
NA
NA
550.0
Effluent
1.11
0.86
NA
1.46
0.385
NA
2.590
0.538
NA
Methylene
Chloride (mg/1)
Influent
NA
NA
7.46
NA
NA
7.05
NA
NA
6.150
Effluent
ND2
0.10
NA
0.134
0.695
NA
0.390
0.338
NA
Tank Overhead
Temp. Temp.

99 95
99 98

99 99
100 98

100 102
101 103

Bottoms Feed
Temp. Rate
(°C) (gmp)

99 12
100 14

100 18
100 18

97 9
100 9

       1 NA means not analyzed.


       2 ND means not detected.


       1 2.970 mg/1 of chloroform was detected in influent composite sample on 5/25/83.

-------
                                                            TABLE  IV-3  (continued)

                                        TOLUENE REMOVAL IN STEAM DISTILLATION  FLASH TANK AT PLANT 12003
                                                      OPERATING DATA  FOR 5/26  AND 5/27/83
U)
LJ
Date
5/26/83
5/27/83

Sample
Number Toluene (mg/1)
Influent
t 2
7 ' 635.0
83 580.0
9 NA5
10 NA
Composite 9 & 106 4,300
Effluent
229.0
27.2
2.79
3.38
NA
Methylene
Chloride (mg/1)
Influent
31.50
5.10
NA
NA
8.570
Effluent
1.740
ND4
1.21
1.59
NA
Tank Overhead
Temp . Temp .
94
96
97
96

91
98
97
97

Bottoms
Temp.
95
99
97
98

Feed
Rate
(*np)
16
16
14
14

        1 3.15 mg/1 of chloroform was detected  in influent  sample  number  7.   1.01  mg/1  of  chloroform and  0.245 mg/1  of benzene
          were detected in effluent sample number 7.

        2 Effluent concentrations under upset conditions, overhead temperature  91°C.

        3 0.975 mg/1 of 1,1,1-trichloroethane,  2.85 mg/1 of chloroform, and  0.915  mg/1  of  benzene  were  detected  in influent
          sample number 8.

        4 ND means not detected.

        5 NA means not analyzed.

        6 9.20 mg/1 of methyl chloride was detected in  influent  composite sample on 5/27/83.

-------
Wastewater  from batch  pharmaceutical  processes,  a vacuum  pump
system,  and steam  ejectors  is accumulated  in two  5,000-gallon
settling  tanks,  as  shown in  Figure  IV-3.    A connecting  line
maintains the liquid height at the same level in both tanks.   The
accumulated  wastewater  separates  into   two  liquid   layers:
immiscible toluene, and an aqueous solution  of toluene and small
amounts of methanol, ethanol,  acetone,  isopropanol,  MEK,  diethyl
ether, and  other solvents listed  in Table IV-3 footnotes.   The
immiscible  toluene  flows  by gravity to a spent-solvent  holding
tank.  The  aqueous  solution  is pumped  through two  preheaters and
enters the top  of the 500-gallon flash tank  through a spray nozzle.
Toluene is stripped from the wastewater  by steam, which is injected
through a sparger in the  bottom of the flash tank.   The overhead
vapors are partially condensed and introduced to a condensate drum.
The  liquid  condensate   is  recycled   to   the  settling  tanks.
Uncondensed vapors from the condensate  drum enter a scrubber where
they are absorbed in previously uncontaminated cooling water.  The
scrubber water is recycled to the  settling  tanks, and the scrubbed
vapors are vented to an emissions control system.

As  shown in  Table IV-3,  the  concentration  of toluene  in the
influent to the flash tank ranged  from  320.5  to 4,300 mg/1.   It is
suspected that the high influent concentration of 4,300 mg/1 on May
27 was caused  by a  low liquid  level  in the settling tanks.  This
probably resulted in a portion  of  the immiscible toluene being fed
to the  column, along  with the miscible solution of  toluene and
water.  The effluent concentration of toluene ranged from 0.39 to
229.0 mg/1. The high effluent concentration of 229.0 mg/1 occurred
on May  26 when  the tank operated under upset conditions.   The
temperature of the overhead vapors  during the upset  period was
91 eC; the  average  temperature  of the  overhead vapors  during the
rest  of  the week  was  99°C.    The average influent  and effluent
concentrations  for the five-day  period were  516  and  4.5 mg/1,
respectively,  excluding the  upset periods.   This  corresponds to
greater than 99 percent removal of toluene in the flash tank.

f.  Data Applicability. The  vapor-liquid equilibrium relationship
of  an  organic  compound  in  wastewater  forms  the  basis  for
determining its removability by steam-stripping.  The magnitude of
the vapor-liquid equilibrium constant  serves as a  measure of the
theoretical removal effectiveness.

The vapor-liquid equilibrium constant,  or  K-value,  is defined as
the ratio of the equilibrium mole fraction of  an organic compound
in the  vapor  phase, y,, to its equilibrium  mole fraction in the
wastewater phase, x,:
                               134

-------
U)
Ol
    SPENT SOLVENT
    STORAGE TANK
                                                            irmrrti
                                                            NASIfWATEM
                                       FEEOntlHEAUKI .
                              ffEAM
VENT TO
EMISSIONS CONTROL
                                                                 VENT TO
                                                              A EMISSIOM CONTROL
                                                          *S
                                                      CONDENUTI
                                                      OHOM
                                                      IM8AL

                                        lAMTLINO



                                      (NORMAUV ClOIEM
              mo     T
              riMr     INFIUENT MMTLINO fOINT
                     *-
                                                                                                        ICRUIIEH
                                                                                                                


-------
The vapor-liquid equilibrium constant can be  calculated  from the
following equation:
            P
                                                              it i it
where Y,  is  the activity coefficient of the organic  compound "i
in the wastewater; P,,, is the vapor pressure of the pure substance
at the steam-stripper  operating  temperature;  and P  is  the total
pressure.   This  expression,  which holds for low  pressures,  is a
simplified form of the  rigorous thermodynamic equation.  Following
is a list of vapor-liquid equilibrium constants calculated by Hwang
and  Fahrenthold  for  aqueous  solutions  of  toluene,   benzene,
methylene chloride, and chloroform:(14)

Compound                     Average K-Value at 100"C & 1 Atm

Toluene                                   1,156
Benzene                                   1,215
Methylene Chloride                          941.4
Chloroform                                  635.5

The  suggested limits  in  Section VIII  of the  Final Development
Document for  benzene are based  on the  performance  of  the steam
distillation  flash  tank in removing toluene  from pharmaceutical
process  wastewater at  Plant 12003.    The  suggested  limits for
chloroform are based on the performance of the packed  column steam-
stripper in removing methylene chloride from pharmaceutical process
wastewater  at Plant 12003.   In both cases, the use  of identical
limits is justified by these similarities between the vapor-liquid
equilibrium constants.

3.  Carbon  Adsorption

Adsorption  is defined as the adhesion  of  dissolved  molecules to
the surface of solid  bodies with which  they are in contact.  Two
properties make granular activated carbon (GAC) particles effective
and economical adsorbents.   First,  they have a high surface area
per unit volume, which results in faster, more complete adsorption.
Second, they have a high hardness value, which lends  GAC particles
to reactivation  and repeated use.

The  adsorption  process  typically  is  preceded  by preliminary
filtration  or  clarification to  remove  insolubles.    Next, the
wastewater  is  placed in contact with carbon so adsorption can take
place.  Normally, two or more beds are used so that adsorption can
continue while a depleted  bed  is reactivated.   Reactivation is
accomplished  by heating the carbon between 870"C and  980°C  (1600°F
and  1800°F) to volatilize and oxidize  the adsorbed  contaminants.
Oxygen in the furnace is normally controlled at less than 1 percent
                                136

-------
to avoid loss of carbon by combustion.  Contaminants may be burned
in an afterburner.

Carbon adsorption is primarily designed to remove dissolved organic
material from wastewater, although it can to some extent
remove chromium, mercury, and cyanide.  The technical and economic
feasibility  of  ACA  technology  is discussed in "Treatability of
Priority Pollutants in Wastewater  by Activated Carbon"  (S. T. Hwang
and P. Fahrenthold; US EPA, 1979).(14)

The  potential  use  for  this  technology by the  pharmaceutical
industry  is limited.   Concentrations of most toxic  pollutants
(i.e., metals, VOCs, and cyanide)  characteristic of pharmaceutical
wastewater  are  generally reduced more effectively  and with less
cost  by  the   previously  discussed  technologies,   or  through
biological  treatment,  than by ACA.   Phenols, the  other group of
pollutants  found in pharmaceutical wastewater, are biodegradable,
and their  concentrations can  be  reduced by  advanced  biological
treatment.    Carbon  adsorption  is  particularly  applicable  in
situations  where  organic material  in  low  concentrations,  not
amenable to treatment by other technologies,  must be removed from
wastewater.

The  equipment  necessary  for  an  activated  carbon  adsorption
treatment system  consists of a preliminary  clarification and/or
filtration  unit to remove the  bulk  of suspended solids,  two or
three columns packed with activated carbon,  and pumps and piping.
When on-site regeneration is used, a furnace, quench tanks, spent
carbon tank, and  reactivated  carbon  tank are generally required.
Contract  regeneration  at  a  central  location  is  a  frequent
commercial practice, particularly if  carbon use  is less than 1,000
Ib/day.  An example of an ACA unit is shown in Figure IV-4.

Carbon adsorption systems are  compact, will tolerate variations in
influent  concentrations  and  flow rates,  and  can be  thermally
desorbed to recover the carbon for reuse.  Economic application of
carbon  adsorption is  limited to the removal  of low  pollutant
concentrations. Competitive adsorption of non-target constituents,
as well  as  blinding by  suspended  solids,  can be  a  source  of
interference.

Pilot  plant  studies recently  conducted by EPA  evaluated  the
performance   of   ACA   treatment  technologies   using   actual
pharmaceutical plant wastewater to consistently achieve reductions
in effluent COD.(18)   The two ACA  treatment technologies evaluated
were (1)  PAC enhancement  of an activated sludge system; and (2)  GAC
treatment of plant secondary effluent.
Conclusions from the biological treatment study are as follows:

    o   Effluent    soluble    chemical    oxygen    demand   (SCOD)
        concentrations were significantly reduced by the addition
        of  PAC  to  the  feed to activated sludge  treatment.
                               137

-------
                                                     SURFACE
                                                     WASH
                                                        CARBON
                                                        BED SURFACE
CARBON  _
INLET &  D
OUTLET-
                                                 -»-G RAVEL

                                                 -—FILTER BLOCK
                                                    WATER OUTLET
                          FIGURE  IV-4

                          CAS BON  ADSORPTION UNIT
                              138

-------
         Effluent SCOD concentrations were reduced by 44,  54,  68,
         and 67 percent of the control plant effluent SCOD
         concentrations when adding 208, 496, 827, and  1,520
         mg/1 PAC, respectively.   The control pilot plant reduced
         SCOD concentrations  from 8.6 to 10.2 percent of feed TCOD,
         whereas the PAC unit reduced  the  SCOD  concentrations to
         5.6 percent of feed TCOD  (208 mg/1  PAC)  to  2.8 percent
         (1,520 mg/1 PAC).

    o   The sludge volume  index  (SVI)  of  the mixed liquor solids
        was improved by the addition of PAC.

    o   Denitrification developed  in  the  final  clarifier of both
        units  containing  PAC,   causing  some  solids  to  float.
        Denitrification was not apparent in the control unit.

    o   A  viscous floating mass  of mixed liquor  solids  (VFMLS)
        developed  in both PAC units  near the end of the tests.
        The VFMLS  was very cohesive and  difficult to redisperse
        in water.   The VFMLS did not  appear  in the  control unit
        during  these  tests.   The  PAC/activated  sludge  process
        cannot be recommended as a reliable treatment process for
        this wastewater until the cause of the VFMLS is identified
        and   adequate   safeguards   against  its  occurrence  are
        demonstrated.

Conclusions from the GAC study are as follows:

    o   The  combination of  biological treatment  and  GAC  could
        remove  96 percent of  the  raw waste TCOD.   This  is 22
        percent  above  the currently  required  BPT  level  of 74
        percent removal.

    o   Carbon usage was  found to be  a function  of  the effluent
        SCOD  concentration.   Carbon usage rates  determined from
        the pilot study are summarized  in  the following table.

    Design effluent  SCOD, mg/1    300         400         500

    Carbon usage, kg/1,000
     (lb/1,000 gal)

    Run No. 2               2.6 (21.3)   2.1  (17.5)  1.6(13.6)


    o   The  removal of specific  organics  as measured  by  GC is
        directly related to the removal of SCOD by GAC treatment.

D.  END-OF-PIPE TREATMENT

In-plant treatment processes  are used to treat specific pollutants
in segregated wastestreams; EOP technologies usually are designed
                               139

-------
to treat  a number of pollutants in a  plant's  overall wastewater
discharge.  The types and/or stages of EOF treatment are primary,
biological,  and  tertiary.    Depending  on  the  nature  of  the
pollutants  to  be  removed,  and the degree of  removal  required,
various combinations of the available technologies are used.

As in the case of in-plant treatment,  the 308 Portfolio data base
was the principal source of information for identifying the use
of EOF treatment by the pharmaceutical  industry.  This information
was requested in both 308 Portfolio mailings.  As a cross-check for
accuracy  and  completeness,   the   308  Portfolio  responses  were
compared to information available  from  the  other data bases. Table
IV-4 summarizes the EOF technologies identified by the various data
bases, along with the number of plants that use each process.

1.  Primary Treatment

Primary treatment,  a form  of  physical/chemical treatment, refers
to those  processes  that  are  nonbiological  in nature.   Primary
treatment  involves  (1) the screening  of the  influent  stream to
remove  large  solids,   and   (2)  gravity  separation  to  remove
settleable solids and  floating  materials.   Commonly used primary
treatment technologies  in  the pharmaceutical  industry are coarse
solids   removal,   primary   sedimentation,    primary   chemical
flocculation/clarification, and dissolved air flotation.

In a  1984  field study of  a  wastewater treatment  system  at an
organic chemicals facility, 10-15 percent of the influent toluene
volatilized in the primary system.

2.  Biological Treatment

Biological  treatment  is   the  principal   method  by  which  many
pharmaceutical manufacturing  plants are  now  meeting existing BPT
regulations.  Although  it  is  discussed as  a  single  EOF treatment
alternative, biological treatment  actually encompasses  a variety
of specific technologies (e.g.,  aerated lagoons, activated sludge,
trickling  filters,  and rotating  biological contactors  [RBCs]).
Because numerous publications  are  available describing all aspects
of  the  operations  (i.e.,  advantages,  limitations,  and  other
pertinent  facts),   these  specific  treatment  processes  will  be
discussed in only moderate detail  herein.   Although each process
has unique characteristics,  all   are  based  on one  fundamental
principle:  the reliance  on  aerobic and/or  anaerobic biological
microorganisms for the removal of oxygen-demanding compounds.

Although the primary purpose of  biological  treatment is usually to
reduce  the  overall  oxygen  demand  of  wastewater,  biological
treatment can also remove some specific toxic compounds.  The major
mechanisms for removal of toxic chemicals are as follows:
                               140

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                                      TABLE IV-4

                          SUMMARY OF EOF TREATMENT PROCESSES
                                   (DATA BASE:   308)


EOF Technology	      Number of Plants

Equalization                                                             62

Neutralization                                                           80

Primary Treatment

     Coarse Settleable Solids Removal                                    41
     Primary Sedimentation                                               37
     Primary Chemical Flocculation/Clarification                         12
     Dissolved Air Flotation                                              3

Biological Treatment

     Activated Sludge                                                    52
       o  Pure Oxygen                                                     1
       o  Powered Activated Carbon                                        2
     Trickling Filter                                                     9
     Aerated Lagoon                                                      23
     Waste Stabilization Pond                                             9
     Rotating Biological Contactor                                        1
     Other Biological Treatment                                           2

Physical/Chemical Treatment

     Thermal Oxidation                                                    3
     Evaporation                                                          6

Additional Treatment

     Polishing Ponds                                                     10
     Filtration                                                          17
       o  Multimedia                                                      7
       o  Activated Carbon                                                4
       o  Sand                                                            5
     Other Polishing                                                     17
       o  Secondary Chemical Flocculation/Clarification                   5
       o  Secondary Neutralization                                        5
       o  Chlorination                                                   11
                                       141

-------
    o   Biodegradation  of the  chemical  into simpler  compounds.
        In  some  cases,  the compounds produced may be  more toxic
        than  the chemicals degraded.  Chlorinated compounds are
        often difficult to degrade.

    o   Adsorption of the chemical onto biological solids.  Heavy
        metals and  large hydrophobic organic compounds  are most
        readily  adsorbed.   The  sludge  containing  these  toxic
        solids must be properly treated prior to disposal.

    o   Air-stripping to the atmosphere of VOCs in those processes
        that  include aeration  (e.g.,  activated  sludge).   High
        concentrations of TVOs in the wastewater may generate air
        pollution problems near the treatment facility.

The fate of pollutants in biological treatment systems depends on
a  number  of complex  and interrelated  factors  that include the
design of the treatment  system,  its operation and maintenance, the
physical/chemical properties of  the individual pollutants, and the
physical/chemical properties of  the wastestream as a whole.  These
factors are often highly site specific.

None the less, in open biological treatment systems, volatilization
is expected to predominate over biodegradation and adsorption for
many  of the  ITD-listed  VOCs.    In  support  of this  hypothesis,
Petrasek  reported  a strong  correlation  between the Henry's law
constant  and  the fraction  of  priority  pollutants  found  in the
activated sludge off-gass.(18)

Henry's law constant is the relative equilibrium concentration of
a  compound  in air  and  water  at  a  constant  temperature  and is
defined by the following equation:

        K =  _P
              S

    where

        K = Henry's law constant, m3x atmosphere mole"1
        P = compounds vapor  pressure in atmospheres
        S = compounds solubility in water in moles per cubic meter

The constant is  an  expression of  the equilibrium distribution of
a  compound  between  air  and  water.    The  constant  indicates
qualitatively the volatility of a compound and is frequently used
in equations that attempt to predict "stripping"  of a compound from
aqueous  solution.     Increasing  values   of  the  constant  favor
volatilization as  a fate  mechanism  and  indicate amenability to
steam- or air-stripping.  Henry's law constants for selected VOCs
are shown in Table  IV-5. The  toxic compounds frequently present in
industrial  wastes   can  inhibit  or  upset biological  processes.
Acclimation, however, can produce strains of  organisms which are
                               142

-------
                                    TABLE IV-5
                        HENRY'S LAW CONSTANTS FOR SELECTED
                            VOLATILE ORGANIC COMPOUNDS
voc
   Henry's Law
    Constants
(atmos.m3 mole 1)
acroleia
acrylonitrile
benzene
bromome thane
chlorobenzene
chloroform
chlorome thane
cyclohexane
1 , 1-dichloroethane
1 ,2-dichloroethane
1 , 1-dichloroethene
trans- 1 ,2-dichloroethene
diethylamine
ethyl benzene
methylene chloride
methyl mercaptan
tetrachloroethene
tetrachlorome thane
toluene
trichloroethene
1,1, 1-trichloroethane
vinly acetate
vinyl chloride
xylenes
0.000077
0.0000666
0.00555
0.22
0.00393
0.00339
0.0368
0.16
0.00545
0.00110
0.0150
0.00532
0.00011
0.00644
0.00319
0.00385
0.0287
0.0302
0.00593
0.0117
0.00492
0.000594
0.036
0.00612
(15°C)
(15°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(50°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
(25°C)
Source:  Reference No.  19.
  5.87.23T
  0082.0.0
                                    143

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tolerant  to  normally toxic  substances.    Nonetheless,  once  the
specialized  strain  is established,  major  changes in  wastewater
composition or concentration  can kill the acclimated organisms and
cause   breakdown   or   upsets   in   the    treatment   process.
Reestablishment of  a suitable microbial  population can  require
months.

An aerated lagoon is one  example of a treatment facility that uses
aerobic biological processes.  It  is essentially a stabilization
basin to which air is added, either  through diffusion or mechanical
agitation.   The  air provides the oxygen  required  for  aerobic
biodegradation of the organic waste.  If properly designed, the air
addition will provide sufficient mixing to maintain the biological
solids in suspension so they can be  removed in a secondary sedimen-
tation tank.   After  settling,  sludge may be recycled  to the head
of the lagoon to ensure the presence of  a properly acclimated seed.
When operated  in this manner,  the  aerated lagoon is  analogous to
the activated sludge process.  The  viable biological  solids level
in an aerated lagoon is low when  compared to that of  an activated
sludge unit.   The aerated lagoon relies  primarily on detention time
for the breakdown and removal of  organic matter;  aeration periods
of three to eight days or more are  common.

The activated sludge process is also an  aerobic biological process.
The basic process components include an  aerated biological reactor,
a clarifier for separation of biomass,  and a piping arrangement to
return separated biomass to the biological  reactor.  The aeration
requirements are similar  to  those  of  an aerated  lagoon,  in that
aeration provides the necessary oxygen for aerobic biodegradation
and mixing to  maintain the biological  solids  in  suspension.  The
available activated sludge processes that are used in the treatment
of  wastewater  include   conventional,  step,  tapered,  modified,
contact-stabilization, complete-mix, and extended aeration.

A trickling  filter is a  fixed-growth  biological system  where a
thin-film biological slime develops and coats the surfaces of the
supporting medium as wastewater makes contact.  The film consists
primarily of bacteria, protozoa, and fungi that feed on the waste.
Organic  matter  and  dissolved oxygen are  extracted,  and  the
metabolic  end products are  released.   Although very  thin,  the
biological slime layer  is anaerobic at the  bottom,  resulting in
the generation of  hydrogen sulfide, methane, and organic acids.
These materials cause the slime to periodically  separate (slough
off) from the supporting medium and be carried through the system
with the hydraulic flow.   The sloughed biomass must be removed in
a clarifier.

Trickling filters are classified by hydraulic or organic loading
as "low rate"  or "high rate."  Low-rate  filters  generally have a
hydraulic loading rate of 1  to 4 million gallons/acre/day (or an
organic loading rate  of  300  to 1,000 Ibs.  BOD5/acre-feet/day), a
depth of  6  to 10 feet,  and no recirculation.  High-rate filters
                               144

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have a hydraulic loading rate of 10 to 40 million gallons/acre/day,
an organic loading rate of 1,000 to 5,000 Ibs. BOD5/acre-feet/day,
a depth  of  3 to 10 feet, and a recirculation rate of 0.5 to  4.0.
High-rate filters can be single- or two-stage.  The medium material
used  in  trickling filters must be  strong and durable.   The  most
suitable medium in both the low and high-rate  filters is crushed
stone or gravel graded  to a  uniform  size.

The  RBC process consists of a series  of disks  constructed of
corrugated plastic plates and mounted on a horizontal shaft.
These disks are placed in a tank with a contour bottom and immersed
to approximately 40 percent  of the diameter.  The  disks rotate as
wastewater  passes through the tank,  and a fixed-film biological
growth,  similar to that on trickling  filter media, adheres to the
surface.  Alternating exposure to the wastewater and  the oxygen in
the  air  results  in biological  oxidation of  the  organics  in the
wastes.  Biomass sloughs off (as in the trickling filter)  and is
carried  out  in  the  effluent  for gravity  separation.    Direct
recirculation  is not generally practiced with rotating biological
disks.

Three  other  biological  treatment  techniques  not  specifically
mentioned  in   this  section use  either aerobic   or  anaerobic
biodegradation or both:  stabilization ponds,  anaerobic lagoons,
and  faculative  lagoons.   In faculative lagoons,  the  bacterial
reactions include both  aerobic and anaerobic decomposition.

Besides  the  direct utilization  of  these treatment  processes,
biological treatment also encompasses two other approaches; in  this
report,  they  are  referred  to as  biological enhancement  and
biological   augmentation.     Generally,   these  variations  are
accomplished  by:   (1)  modifications made  in the  conventional
biological treatment itself,  or (2)  conventional processes combined
into a multi-stage system.  Examples of biological  enhancement are
pure  oxygen  activated sludge and biological  treatment  with  PAC.
Biological augmentation could be trickling filter/activated sludge,
activated  sludge/RBC,   aerated  lagoon/  polishing  pond,  or  any
combination  of  two or more  conventional biological  treatment
processes.

The differences in performance due  to  the number of  biological
treatment stages used rest on the applicability  of plug-flow/back-
mix effects.    A true plug-flow system   (e.g.,  a  narrow  channel
lagoon)   approaches  equivalence  to  an  infinity of stages  if  the
food/microorganism  (F/M) ratio  is  maintained.   This  tends to
beneficially maximize the availability of nutrients,  a function of
the concentration of biodegradable  pollutants.   A fully back-mixed
system   (as  an  activated  sludge   unit   tends  to   be)   operates
throughout at  its exit  concentration.    It  is thus a  distinct,
finite stage incremental from any stage before or after it.

In practice, these distinctions are not clearcut.   Since there is
some back-mixing even in a channel lagoon, separations of units or
even of  cells  within  one unit may be beneficial.  Also,  in most
mixed systems,  the concentration gradient established  is sufficient

                               145

-------
for  some  increase in  the  effective nutrient  concentration and,
consequently, the optimum microorganism concentration.

In many systems,  design  factors  other  than  the  concentration-
induced driving  force  may overshadow the  concentration gradient
and prevent simple performance correlation.

Comprehensive consideration of the criteria affecting bioreaction
performance suggests the following to be significant:

    o   influent  concentration of  pollutants

    o   resistive characteristics  of the BOD  pollutants  and the
        resultant  K  value   (i.e.,  how   easily  the   BOD  is
        biodegraded)

    o   presence   of  potential   interfering  pollutants   (e.g.,
        constituents toxic to the  microorganisms)

    o   bioreaction  characteristics  and  concentration  of  the
        microorganisms present

    o   dissolved oxygen content and distribution at least to the
        point of  adequate 02 availability

    o   sludge recycle as it may affect microorganism availability
        and character, as represented by the F/M ratio

    o   contact  efficiency  of pollutants and  microorganisms,  as
        may  be  induced  by  agitation,  flow  pattern, and  mixed
        liquor volatile suspended  solids (MLVSS)

    o   availability and balance of nutrients, including nitrogen
        and phosphate

    o   required  target effluent

    o   temperature  (e.g., seasonal effects)

The proper design of biological systems in addition to developing
optimum operating criteria,  must  also consider how much  of the
system's  potential  capacity  will  be  used  so  that an  optimum
modification approach  will  be  available.    The most economical
approach may be simple  adjustments  of operating variables to fully
exploit existing  capacity.    The  adjustments  may  require  minor
changes  such as  increasing agitation,  power  input, or  sludge
recycle rate or, at the extreme,  the addition of an independently
functioning system.  In many cases,  the  optimum upgrade may be a
combination of existing component  units  integrated with balanced
new units.  This is likely to result in a system complex dictated
in part by performance  requirements,  and  in part  by  equipment
already in place.  Some examples  of typical augmented biological
configurations are shown in Figure IV-5.
                               146

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BPT System
                                       FIGURE IV-5
                        EXAMPLES OF AUGMENTED BIOLOGICAL SYSTEMS
                                   Activated Sludge
                                                                               Effluent
                                                                            Sludge Disposal
BPT System
                             Rotating  Biological Contactors
                                                                                Effluent
                                                                            Sludge Disposal
BPT System
                                       Polishing Pond
                                                                                Effluent

-------
Biological treatment  systems are mainly  intended to  reduce the
level of the  traditional  pollutants BOD and COD.   However,  some
priority pollutants may be removed incidentally.

Biological treatment removal efficiency  is a function of treatment
intensity, detention  time,  and system  characteristics  such  as
bioreaction  rate constant,  biomass  concentration,  and  biomass
contact efficiency.  The configuration of the system is important
since  it  affects  these factors,  but the  effectiveness  is not
necessarily benefitted by splitting the bioreaction into a number
of steps.   In a  plug-flow  (i.e.,  non-backmixed)  system, there is
a continuation of reaction  and  little inherent  effect of staging
as in  certain separation techniques  and driving  force systems.
Reaction rate advantages  in a back-mixed system  may  accrue from
staging, but these must be evaluated for a specific system in the
context of  microorganism availability,  contact  efficiency,  and
other factors.

Economic  concerns  often  dictate  a  design that uses  (1)  one
biotechnique in preference to others,  (2) more than one technique
as the  reaction  progresses  (e.g.,  activated sludge and trickling
filter), or (3) various arrangement configurations. However, these
design  choices   are   highly   site-   and  waste-specific,   and
generalizations  should  be avoided  in the comparison  of systems
andthe choice of a particular treatment configuration.

3.  Pollutant Treatability and/or Removal

Information on the  treatability of  ITD-listed VOC pollutants was
obtained in the recent sampling  program conducted  at Plants 12236,
99999, and 12204.  Influent  and  effluent streams from each plant's
activated sludge wastewater  treatment plant were sampled for two
consecutive  24-hour periods.   The following paragraphs present
information on pollutant reduction by comparing the two-day average
influent and effluent concentrations.   The observations noted are
general in nature because the data are from a very short sampling
period, which  may or may  not represent typical  treatment plant
performance.

a.   Plant 12236.   Plant  12236  is  a  direct-discharging facility
providing primary and  secondary (activated  sludge)  treatment for
its wastewater.   The treatment plant appeared well-operated during
the recent sampling visit,  achieving average effluent BOD5 and TSS
levels  of  22 and 26  mg/1,  respectively.   These  effluent levels
represent average  BODjj  and  TSS  reductions of 99  and  86 percent,
respectively (Table IV-6).

Effluent wastewater concentrations  of VOCs  were consistently low
(i.e., less than 174 ppb,  or at  below  detectable levels), with the
exception of  approximately  1 ppm of  2-hexanone  for one day (see
Table IV-6).  Analytical  results for  the dewatered sludge sample
indicate that several pounds of VOCs can leave the plant with the
sludge  (see Table 111-19).
                               148

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                                      TABLE IV-6

                          AVERAGE WASTEWATER POLLUTANT LEVELS
                               ITD/RCRA SAMPLING PROGRAM
                                      PLANT 12236
Compounds
Volatile Organics (pg/£)
carbon tetrachloride*
methylene chloride*
toluene*
acetone
2-bexanone
Semivolatile Organics (UK/£)
None detected
Metals fug/*)
chromium*
nickel*
zinc*
aluminum
barium
boron
calcium
iron
magnesium
manganese
sodium
titanium
vanadium
Miscellaneous (ug/£)
cyanide*
Conventional Pollutants (mg/£)
BODS
TSS
oil and grease
Nonconventional Pollutant (mg/£)
COD
Primary
Influent**

<10
5,247
<10
928
<50



22
20
140
147
105
108
51,600
145,000
1,740
1,080
1,620,000
105
107

nr

1,817
432
6

2,250
Final
Effluent**

22
92
10
134
562



11
<40
34
<100
<50
<100
57,700
4,890
1,390
239
1,530,000
<50
<50

27

22 (182)***
62 (309)***
19

390(585)****
Percent
Removal


98
—
86
—



50
..
76
TBDL
TBDL
TBDL
—
97
20
78
6
TBDL
TBDL

--

99
86
--

83
*    Priority pollutant.

**   Flow-weighted average of two 24-hour composite samples.

***  BPT annual average effluent levels assuming an annual average influent BODS
     level of 1,817 mg/£.

**** BPT annual average effluent level assuming an annual average influent COD
     level of 2,250 mg/£

nr   No value reported due to matrix interference.

TBDL To below detection limit.
4.89.90T
0114.0.0
                                            149

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No information  on  the removal of semivolatile  organic compounds
(SVOCs) from  wastewater is available, as  none  were found  to be
present above the analytical detection limits.  However, analytical
results for the grab sample of the dewatered sludge indicate that
bis(2-chloroethyl)ether and n-octadecane may  tend  to concentrate
in the sludge (see Table 111-19).

Reduction of  the  metals detected  at levels  significantly  above
analytical detection  limits was very good with the  exception of
calcium,  magnesium,   and  sodium,   which  incurred  little  or  no
reduction (see Table IV-6).

b.  Plant 99999.   This  plant  is an  indirect discharger providing
activated sludge  pretreatment  for  wastewater.    The  wastewater
treatment plant at this site  consists of  pH adjustment with lime
or HgSO,,  equalization,  and a step-feed activated sludge  system
followed  by  degasification  and  sedimentation.   The  hydraulic
detention of the  treatment   system  (excluding equalization)  is
approximately 8.5 hours.  The low detention time is due primarily
to the high  recycle rate  (5:1).   The equalization, aeration, and
degassing tanks are covered and the  off-gasses  are vented to the
power boilers.  The treatment plant appeared to be operating well
during the recent sampling visits; however, treated effluent BOD5.
levels were significantly higher than the long-term average levels
previously reported for this plant.
                             Wastewater Comparison
                             Flow
                             (mad)
          BOD5
          fma/1)
           TSS
            (ma/11
Combined Influent

  1975-76 Data
  ITD/RCRA Sampling

Treated Effluent

  1975-76 Data
  ITD/RCRA Sampling
0.65
0.7
0.65
0.7
3,000
2,700
  120
  365
950
940
500
248
During the sampling program,  VOCs were very effectively removed by
their  activated sludge treatment  plant.    Based on  the two-day
averages, VOCs  were reduced  better than 99 percent,  or to below
detectable levels (Table IV-7).   It is important  to note that this
plant  operates  degassing  tanks  between the  aeration  basin and
secondary clarifiers, which may aid in the air-stripping of these
VOCs.

Observed reductions of  SVOCs were not as significant as for the
VOCs because influent concentrations were generally low  (see Table
IV-7).   The  single grab sample  of  the  thickened waste activated
                               150

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                                     TABLE IV-7

                         AVERAGE WASTEWATER POLLUTANT LEVELS
                              ITD/RCRA SAMPLING PROGRAM
                                     PLANT 99999
Confounds
Aeration
Influent**
Pretreated
Effluent**
Percent
Removal
Volatile Organics  (ug/l)

acrylonitrile*                          68
chloroform*                          6,537
ethylbenzene*                          330
•ethylene chloride*                  8,523
toluene*                             4,241

acetone                            465,130
2-butanone (HER)                       371

Semivolatile Organics (pg/Jt)

benzidine*                             103
bis(2-ethylhexyl) phthalate*           <10
2-chloronaphthalene*                    38
4-chloro-3-methylphenol*                74
3,3-dichlorobenzidine*                  44

N-nitrosodi-n-propylamine*             <20
alpha-terpineol                          7
dipbenyl ether                           7
2-methylnaphthalene                    <10
n-dodecane                             <10
n-eicosane                             103
n-hexacosane                            95
p-cresol                                 9

Pesticides/Herbicides (pg/Jt)

BHC, alpha*                             <4
BHC, beta*                              <4
TEPP                                 2,063

Metals (Mg/1)

arsenic*                                17
chromium*                               27
copper*                                440
nickel*                                 SO
selenium*                               14
silver*                                1.1
zinc*                                  150

aluminum                             2,700
bariua                                  69
boron                                   87
calcium                            165,000
cobalt                                   2
iron                                 2,350
magnesium                           19,000
•anganese                               97
sodium                             915,000
titanium                                58
vanadium                                 8

Miscellaneous Priority
Pollutants (pg/i)
cyanide*
      16
                        <50
                         25
                        <10
                         73
                        340
                        <50
                        160
                         11
                         42
                        <10
                        <50

                         21
                        498
                         13
                        231
                        3.1
                       0.66
                        484
                         12
                         24
                         43
                         22
                        4.2
                         <1
                         40

                        818
                         33
                         90
                     98,500
                         <4
                        690
                     17,500
                         43
                    715,000
                        100
                          2
     <20
                    TBDL
                    99.6
                    TBDL
                    99.1
                    TBDL

                    99.9
                    TBDL
                    TBDL
                                       TBDL
                      77
                      29
                      11
                      90
                      56
                      70
                    TBDL
                      73

                      70
                      52

                      40
                    TBDL
                      71
                       8
                      56
                      22

                      75
  TBDL
                                     151

-------
                               TABLE IV-7  (continued)

                         AVERAGE WASTEVATER POLLUTANT  LEVELS
                              ITD/RCRA SAMPLING PROGRAM
                                     PLANT 99999
Aeration
Compounds Influent**
Conventional Pollutants (mg/£)
BODS
TSS~
oil and grease
Nonconventional Pollutant (ng/£)
COD
2,700
940
47
7,200
Final
Effluent**
365
248
16
1,450
Percent
Removal
86
74
66
80
*  Priority pollutant.
** Flow-weighted average of two 24-hour composite samples.
                                     152

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                                  . .  the wastewater  treated











       -~'  sodium.                        ,,_^^ina  facility

1975-76 Data
ITD/RCRA Sampling
1975-76 Dattea
ITD/RCRA  Sampling
1.2
2.0
1.2
o n
1,200
1,700
146
360
2,000
1,500
320
260
                                                      effectively
removed through
                                        t
                                 syste,n at Plants  ^ e£fl  nt of
 sludges (see

                                                    wastewater
                                                               is
                                153

-------
                                            TABLE IV-8
                                          Raw
                                      Jfiitewater**
      acrolein*
      benzene*
      chloroform
      1,1-dichloroethane*
     toluene*
     M.l-trichloroethane*

     acetone
     diethyl ether
     vinyl acetate
   phenol*

   Metals  <>ft/»2

   cadmium*
   chromium*
  copper*
  selenium*
  zinc*

  aluminum
  barium
  calcium
  iron
 •agnesium
 •anganese
 •odium

 Conventional

BODS
TSS~
oil and grease
                                             39
                                             13
                                           349
                                         4,771
                                         2,256
                                            46

                                        93,562
                                        8,703
                                           52
                                          <100
                                                         Pretreated
                                                          Effluent**
    <50
     16
     57
     16
     13
  2,705
  3,952
    32

58,314
 7,732
    33
                  Percent
                  Removal
TBDL

  84


 43

 30

 38
 11
 37
2
14
163
6
294

2,480
127
273,000
2,610
35,900
470
324,000

1,700
1,500

<5
51
5
154

1,290
84
254,000
878
22,700
193
250,000

360
260

TBDL
TBDL
69
17
48
50
34
7
66
37
59
23
79
83
 COD
                                     3,900
                           1,1

**  r,rf.0rltT pollutant.
                  average of two 24-hour
                                                         800
                                         co^osite sample,.
                                                                          79
                                    154

-------
grab sample of    ,
concentrate in      "»^ sludge indicate that phenol nav tend to
Reductions of th*» m*+ ,   ^

                           ™ "                      «~
                                             =
          ff-           v^

           ••
                    - --- "' *- nQI_a
               'AL
 er a plant is a direct dl^S""1 "ethod us«>
Charger to POTWs"or a  zJ?87*r to su'face
 > determining which t«Sn?, *1."°har9ar ca"
   xng waste discharge.  Table TO f  are *1Ost
   >haritiaceutical  nanuf.,5.   •    ? sumiarizes

    '  Process  wastewater              171' *°r
              '
                                         r      is,
                      5ach plant's individual ^     ,able  was
                       osed Development          0881 ne
                           percent
                                                 Plants

-------
Methods of Discharge
Direct Only
sss sa
                                TABLE IV-9

                        SUMMARY OF WASTEWATER DISCHARGES


                              Number of Plants
                                  the Industt
                       «.*•-•
   C\_ U w A w*» • - —	
   Total Direct Dischargers


 SlSHsr^^MS,
 n Total Indirect Dischargers

   SUBTOTAL
 Zero Dischargers

   TOTAL
  Note:
41
 7
_4
52

264
 20
  1
285

337

127

464
                                                      Number of Plants
                                                      KY Siibcategories^
                                                      A    !T~~£
6
2
1
9

24
 4

28
                                                       37
4   16   24
4    5    4
1    2   _3
9   23   31

54   77   216
 7   10  13
          1
61   87  230
                                                       37    70  UO  261

                                                        0     9  _26  109
      79  136  370
        plants.
              FATE OF W.STEVATEK AT OO DiSCHARGE PUMS (TOTAL
  Dischar
   No Process Wastewater
   Contract Disposal
   Deep Well Injection
   Evaporation
   Land Application
   Ocean Dumping
   Recycle/Reuse
   Septic System
   Subsurface Discharge
   No Data

   TOTAL
                                   Zero
                                Dischargers
                                   96
                                    7
                                    0
                                    7
                                    5
                                    1
                                    2
                                    5
                                    2
                                     2.

                                   127
                                                      Direct
                                                      w/Zero
                    1
                    2
                    1
                    1
                    2
                    0
                    1
                    0
                    0
                                                                    Indirect
                 0
                 6
                 1
                 3

-------
latest data base  discharge to POTWs.   One plant also has  minor
direct discharges, and another 20 use zero discharge techniques for
some of  their smaller wastestreams.   Almost  27  percent of  the
manufacturing  plants use   only  zero  discharge  methods  (e . g. ,
contract  disposal,   evaporation,   ocean   dumping,   or  complete
recycling),  or  do   not  generate  process  wastewater  requiring
disposal?   Seventy-six  percent  of  the   zero  dischargers  were
classified as  such  because they generated no  process wastewater
requiring disposal.

1.  other Zero Wastewater Discharge or Disposal Methods

Other methods used to reduce or eliminate VOCs discharges include
incineration, deep well injection, off-site treatment,  and contract
hauling.  These methods all have potential  application, but usually
to a specific waste  source, or under carefully studied  and assessed
conditions.    a.    incineration.   Gaseous  or liquid  solvents,
flammable liquids, solids,  tars,  residues,  or low-volume hazardous
wastes  can be incinerated.   Combustion at  high  temperatures to
break down toxic  materials may be performed in properly designed
incinerators, with or without auxiliary fuel, depending on the BTU
value of the material being burned.   However  additional scrubby
or  particulate removal may  be required on  the gaseous products
released  from the incinerator  (boiler) .

b    Deep wgll infection.   This  approach has  been  used,  but now
carries critical legal connotations for protection of any adDacent
aquifers contacted.  Some states  completely Prohibit such disposal
EPA is developing  guidelines  on this  under PL 93-523, covering
potentially hazardous wastewater.
 c.  nff-site Tre^^P.nt and/c^ rontr^.t Hauling.  Of f -site treatment
 to  a central treatment facility mutually owned or operated,  either
 by  pipeline  or  truck  transport,  may  provide  more  economical
 treatment than an on-site facility.   Pretreatment may be required
 depending on raw waste composition.

 Contract hauling to another site may be applicable t ior small volume
 waste  generators.  However, this approach  really only shifts the
 impact from one site to another.

-------
section X  describes the procedures  used to estimate  compliance
costs ror individual plants.   Costs were estimated for each plant
S??h  wastewater discharge.   Section  XI  presents the  economic
impacts on individual plants.

-------
            VI.  ECONOMIC CHARACTERISTICS AND OUTLOOK

One major source of pharmaceutical industry information  is the data
collected by the U.S. Bureau of the Census.  The Census divides the
pharmaceutical industry into three  groups:   Biological Products,
such as blood derivatives and vaccines (SIC 2831);  Medicinals and
Botanicals, such as products extracted from animal organs and plant
material (SIC 2833);  and Pharmaceutical Preparations, mainly final
products (SIC 2834).

A.  INDUSTRY CHARACTERISTICS

From 1977  to  1982, the U.S.   pharmaceutical  industry  as  a whole
grew  in  terms  of  both  value  of  shipments  and  numbers  of
establishments and employees.  However,  not all SIC groups making
up the industry grew  during this  period.  The  largest of the three
pharmaceutical SIC groups is Pharmaceutical Preparations.   During
the  1977  to  1982  period,  this  SIC group declined in terms  of
numbers of companies, establishments and employees; the other two
SIC  groups   grew   in   size  during   the   same   time   period.
Establishments in  the pharmaceutical industry tend to be relatively
specialized, with between  83  percent and 90  percent of  the 1982
production at pharmaceutical plants being pharmaceutical products
in a single SIC group.  Likewise,  most Pharmaceuticals are produced
by pharmaceutical establishments, as indicated by coverage ratios
that range from 75 percent  to  96  percent.  Coverage ratios measure
the  percentage of pharmaceutical products that are produced by
pharmaceutical plants.  The rest is produced  by plants that were
not primarily  pharmaceutical plants.  Table VI-1  is a  summary of
the industry's characteristics.   These  data  are discussed below.

1.  Numbers of Companies, Establishments, and Employees

The Census of Manufactures is conducted by the U.S. Bureau of the
Census on an establishment basis.  Each establishment is classified
in the particular industry  (4  digit SIC group)  that accounts for
its major product (i.e.  the value of that product exceeds in value
its shipments of products in any other industry).  A  single company
may own establishments  in several industries.   Therefore, the total
number  of companies  in the  pharmaceutical  industry  cannot  be
estimated  by  summing  the  number of companies in  each  of  the
relevant SIC groups.  However, the  data can  be used to determine
the relative size of each group and changes over time.

Pharmaceutical Preparations is the largest of the three  SIC groups,
with 579  companies owning establishments  in  the  industry.   The
other two  groups  are about the  same size:   Biologicals  had 277
companies  in  1982  and  Medicinals had 208  companies.   During the
1977-82 period, the smallest  SIC  groups  grew the fastest while the
largest actually declined in terms of number  of companies.
                               161

-------
                                       TABLE VI-1

                         PHARMACEUTICAL INDUSTRY CHARACTERISTICS
SIC 2831
Biologicals

Number
Number

of
of
Number of
(1,000)
Average
Size of

Companies
Establishments
Employees
Employment
Establishments
Value of Shipments
($ million)
1977
249
310
15.7
51
899
1982
277
367
23

.1
63
2,254
SIC 2833
Medicinals &
Botanicals
1977
154
177
14

.4
81
1,890
1982
208
227
17

.7
78
3,391
SIC 2834
Pharmaceutic
Preparatio
1977
655
756
als
ns
1982
579
686
126.4 125.0
167
182
11,459 19,062
Average Shipment
  per Plant
 ($ million)               2.9        6.1      10.7        14.9      15.2       27.8

New Capital
  Expenditures
($ million)
Specialization*
Coverage**
35
93%
73%
98
90%
78%
124
82%
68%
284
83%
75%
419
86%
97%
868
89%
96%
Source:  1977 and 1982 Census of Manufactures, U.S.  Department of Commerce, Bureau of
         the Census.

*  Specialization Ratio:  The ratio of primary products  (i.e., product in same SIC
   group as plant's SIC) shipments to total product  shipments (primary and secondary)
   for the establishments.

** Coverage Ratio:  The ratio of primary products shipped by establishments classified
   in the industry (SIC group) to the total shipments of such products that are shipped
   by all manufacturing establishments, wherever classified.
                                          162

-------
A similar picture results if SIC groups are described in terms of
number of establishments.   SIC  2834 is the largest group, with 686
establishments; this  number declined from  756 between  1977  and
1982.  The smallest group,  SIC  2833, grew at the fastest rate from
177 establishments in 1977 to 227 establishments in 1982.

In terms  of number of  employees,  SIC  2834  continues to  be  the
largest.  While employment fell slightly (about 1 percent) between
1977 and  1982,  the decline  was not as great  as the  decline in
number of firms or establishments.  As a  result, the average number
of employees per  plant rose  from 167 to 182, which is over twice
as large as plants  in the  other two  groups.  The total number of
employees grew in the  other two SIC groups, and the average number
per establishment increased in SIC 2831.

2.  Value of Shipments

The order of these three SIC groups changes slightly if ranked in
terms of value of shipments.  The largest is SIC 2834, the second
largest group  is SIC 2833,  and SIC 2831  is the  smallest,  even
though shipments for SIC 2831 grew at the fastest rate  in the 1977-
82 period.  The average shipments per establishment in 1982 ranged
from $6.1 million in SIC 2831 to $27.8 million in SIC 2834.

3.  New Capital Expenditures

The industry group with the fastest growing shipments  in the 1977-
82 period,  SIC  2831,  had  the largest increase in  new capital
expenditures.  The rate of increase in shipments  for the other two
groups  was  about the  same  and  their  rates of increase  in  new
capital expenditures  paralleled these  rates.   The high  rate of
capital expenditures  in SIC 2831  is  consistent with  its large
increase in number and size of establishments.

4.  Specialization and Coverage

These three SIC groups tend to  be highly specialized;  i.e., plants
concentrate on  producing  products  in their  own industry segment
(SIC group) .    The  establishments  in  SIC 2833  tend  to  be  less
specialized than those in the other two SIC groups.  The coverage
ratio measures the  percent of the products in this industry made
by plants in this industry,  again measured on the basis of 4-digit
SIC  group.    For  Pharmaceutical  Preparations,  the  coverage is
extremely high; for the other two SIC groups, about 75 percent of
the product is produced by plants in the industry.

B.  OUTLOOK

Historically, the pharmaceutical industry  has  been characterized
by  its intensive  research  and  development efforts,  aggressive
marketing,  higher  than   average  profit  margins,  multinational
nature, and its high degree of involvement with regulatory agencies
such as the Food  and  Drug Administration.   These characteristics
                               163

-------
remain basically unchanged in recent years. While the amount spent
on R&D remains high,  fewer companies are heavily involved in basic
R&D work;  and while  their profit margins have  returned to their
previous high levels, 1985 saw a  substantial drop in profit rates.

Pharmaceutical industry shipments are  expected to continue to grow
through 1991.  However,  two factors will slow the rate of increase
in the value  of  shipments:   1) the market  share for generic, and
thus lower priced, prescription drugs  is expected to increase, and
2) the  market share for  new  drugs  with higher  unit  values  is
expected to decrease. Pharmaceutical  industry exports will benefit
from the  expected further decreases  in the value  of  the dollar,
which will make  U.S.  Pharmaceuticals cheaper  than otherwise for
foreign buyers.

1.  Value of Shipments

In  the  U.S.   Census of  Manufactures, value   of  shipments  are
presented  for   all   the   products   produced   by  pharmaceutical
establishments   (Industry  Data),  and  for  all  Pharmaceuticals
regardless of  where  produced (Product Data).   As  shown in Table
VI-2, the data are very similar.  Data are presented  in terms of
current dollars,  and in constant 1982 dollars,  which  removes the
influence of inflation.

Total  industry  shipments,  measured  in constant  dollars,  have
continued  to  grow over the  1972 to  1986  period.   However,  the
overall rate of growth has declined.   For Biological Products, the
value of  shipments in constant dollars declined during the 1984-
1986 period, with a rebound expected  in 1987.   The growth rate of
Medicinals and Botanicals  has steadily declined  from 1972 to 1986,
with  a  small  rebound  expected   in   1987.    The   largest  group,
Pharmaceutical Preparations,  was  the slowest growing group and had
a declining growth rate between  1972  and 1984.  Since 1984, the
growth rate has increased slightly over its rate of growth in the
preceding five years.

The product data presents a similar picture except for Biological
Products, which continued to grow during the 1984-86 period.  The
value of Medicinal and Botanical product shipments got between 1984
and 1986 in real terms while declining in current dollars because
the prices of these  goods fell during this period  due to intense
price pressure from  foreign producers.

2.  Trade Data

Both exports and  imports  of  Pharmaceuticals have  been increasing
over the 1972 to 1987 period.  However, imports have been growing
faster than exports,  and the  rate of increase for imports has been
growing while the rate of  increase for exports has been declining.
The net  result for  Pharmaceuticals overall  is that  exports are
expected to barely exceed  imports in 1987.  Table VI-3 presents the
trade data.
                               164

-------
                 TABLE VI-2

VALUE OF SHIPMENTS - PHARMACEUTICAL INDUSTRY
  (in Millions of dollars except as noted)
                                             Percent Change
                                             Compound Annual

Industry Data
Value of Shipments
(current dollars)
2831 Biological
Products
2833 Medicinal &
Botanicals
2834 Pharm. Prepar-
ations
Value of Shipments
(1982 dollars)
2831 Biological
Products
2833 Medicinal &
Botanicals
2834 Pharm. Prepar-
ations
Product Data
Value of Shipments
(current dollars)
2831 Biological
Products
2833 Medicinal &
Botanicals
2834 Pharm. Prepar-
ations
1984
28,967
2,669
3,410
22,888
25,796
2,626
3,613
19,558
26,869
2,779
3,398
20,692
1985
31,443
2,773
3,435
25,235
26,209
2,549
3,758
19,902
28,961
2,995
3,337
22,629
1986 1987
33,426
2,881
3,410
27,135
26,681 22,170
2,591 2,635
3,870 3,990
20,220 20,545
31,118
3,245
3,313
24,560
1972-84
11.3
18.2
17.2
10.2
4.1
11.8
10.4
2.7
11.1
15.5
12.9
10.4
1979-84
10.9
17.4
7.7
10.7
2.7
12.9
5.5
1.2
11.1
14.4
3.2
12.4
1984-86
7.4
3.9
0.0
8.9
1.7
-0.7
3.5
1.7
7.6
8.1
-1.3
9.0
                       165

-------
                                 TABLE VI-2 (continued)

                      VALUE OF SHIPMENTS - PHARMACEUTICAL INDUSTRY
                        (in Millions of dollars except as noted)
                                                                   Percent Change
                                                                   Compound Annual

Value of Shipment
(1982 dollars)
2831 Biological
Products
2833 Medicinal &
Botanicals
2834 Pharm. Prepa-
rations
1984

23,861

2,734

3,630

17,497
1985

24,377

2,784

3,683

17,910
1986 1987 1972-84

24,970 25,560 3.9

2,875 2,950 9.2

3,795 3,910 6.4

18,300 18,300 2.9
1979-84 1984-86

2.9 2.3

10.0 2.6

1.2 2.3

2.4 2.3
Source:   U.S.  Department of Commerce,  1987  U.S.   Industrial  Outlook.   January 1987,
         p.  17-2.
                                             166

-------
                                       TABLE VI-3

                          TRADE DATA - PHARMACEUTICAL INDUSTRY
                        (in millions of dollars  except as  noted)
                                                                   Percent Change
                                                                   Compound Annual


1984
1985
1986
1987
1972-84
1979-84
1984-86
Industry Data
Value
2831
2833
2834
Value
2831
2833
2834
of Imports
Biological
Products
Medicinal &
Botanicals
Pharm. Prepar-
ations
of Exports
Biological
Products
Medicinal &
Botanicals
Pharm. Prepar-
1,665
77
1,341
247
2,637
456
1,497
684
1,896
163
1,517
216
2,671
516
1,465
691
2,359
169
2,028
162
2,839
603
1,625
611
3,020
180
2,700
140
3,085
700
1,800
585
17
21
16
26
13
18
13
11
.3
.7
.1
.7
.4
.7
.1
.7
15
53
12
34
10
9
8
15
.5
.5
.5
.2
.0
.1
.4
.1
21
32
26
-17
5
15
6
-5
.9
.8
.2
.2
.3
.3
.3
.1
       ations

Net Trade Balance
  (Exports Minus
   Imports)

  2831 Biological
       Products

  2833 Medicinal &
       Botanicals

  2834 Pharm. Prepar-
       ations
972      775

379      353
156
437
-52
475
 480      65

 434     520


-403    -900


 449     445
Source:  U.S. Department of Commerce, 1987 U.S.  Industrial Outlook, January 1987,
         p. 17-2.
                                               167

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The trade  situation varies across the  SIC groups.   The  fastest
growth rates for both exports and imports have been experienced by
Biological Products.  The  net result  is a  growing positive trade
balance over the 1984 to 1987 period.   The opposite  case  is true
for Medicinals  and  Botanicals.    Their growth  rates  have  been
slower, and the  net trade  balance  has turned negative.   This is
particularly important  for the  overall picture  since  Medicinals
and Botanicals  comprise more than half of U.S.  pharmaceutical
exports and 80  percent to 90 percent of imports.  In 1987,  imports
are expected to equal one and half times exports.  While the trade
balance for Pharmaceutical  Preparations  is  expected to continue to
be positive in  1987,  the value  of both exports  and  imports have
declined during the 1984-87 period.

3.  Profits

Up until 1985,  profit rates for  pharmaceutical companies remained
very  high and  continued  to exceed  the  profit rates  of  both
chemicals and allied products and  manufacturing  in  general.   As
shown in Table VI-4,  in the 4th quarter of 1985,  profit rates in
both chemicals and allied products  and in Pharmaceuticals dropped
precipitously,   while  manufacturing  in  general  experienced  a
significant but much  smaller drop  in  profits.   However,  based on
data for the other  quarters  of  1985 and the  first half  of 1986,
profit  rates  regained  their  traditionally  high levels.    The
conclusion that profit  rates have  rebounded is  further supported
by examining second  quarter 1987 earnings,  which are higher than
1986  second  quarter  earnings   for  many  large pharmaceutical
companies.  For example, out of a  sample  of 17  large drug firms,
14 had higher earnings in the 2nd quarter of 1987 than they had in
the 2nd quarter of 1986.  In addition, total 2nd quarter earnings
for all  17 firms  were  16  percent above  total  earnings  in  2nd
quarter 1986 (22) .

The overall  forecast is  that the  pharmaceutical industry will
continue to be  very profitable,  in spite  of  growing competition
from  domestic  producers  of  generic  drugs  and  from  foreign
producers.  The rate of growth of value of shipments (measured in
terms of  constant  dollars)  has  slowed substantially in  the past
three  years,   as  compared to  the  preceding  decade  or  more.
Likewise, the net balance of trade  has declined to the point where
the value of imports almost equals  the value of exports.  However,
the profit  levels  for  the industry  have  maintained  their high
levels,  when  compared  to  manufacturing  in  general.    These
continuing high profit rates  are dependent  on  drug  companies'
ability to  introduce new drugs that  tend  to be  high  priced and
their  ability  to  raise  prices  overall.    In  comparison  to
hospitalization,  drugs  are  an  economically efficient  form  of
treatment and so  are better able than health care  in  general to
raise their prices.
                               168

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                    TABLE  VI-4



             AFTER-TAX RATES  OF  PROFIT
Profit per Dollar of
                                       Profit on Stockholders'
Year
(4th
Quarter)
1972
1973
1974
1975
1976
1977
1978
1979
1980
1981
1982
1983
1984
1985
1986 (2nd
Quarter)
Source:
h?aj.w*> \ w*.** w>0 /
Chemicals and
Allied All
Pharmaceuticals Products Manufacturing
10.1
10.7
12.2
10.7
12.6
11.7
11.3
11.9
11.3
12.4
14.6
14.1
12.6
2.8
12.9
U.S. Federal
Mining, and
6.3
6.9
8.3
7.6
7.5
6.7
7.7
7.0
6.3
6.7
4.8
5.2
5.2
1.5
7.0
Trade Commission,
Trade Corporations
4.4
4.6
5.7
5.1
5.3
5.3
5.6
5.3
4.8
4.3
2.8
4.4
4.1
3.4
4.7
Quarterly
, various
Chemicals and
Allied All
Pharmaceuticals Products Manufacturing
18.3
17.7
15.9
15.6
16.5
17.4
17.0
17.9
16.9
18.6
21.3
21.8
19.3
4.3
19.6
Financial Report
issues.
12.8
14.4
14.8
15.2
12.8
13.8
16.3
15.3
13.3
13.3
8.8
11.1
10.4
3.1
14.9
11.5
13.4
13.2
13.1
13.1
14.4
16.1
15.7
14.1
12.0
7.2
12.0
11.0
9.3
12.2
for Manufacturing


                           169

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         VII.   PRODUCT GROUPS - DESCRIPTION AND OUTLOOK

The value of pharmaceutical final products grew faster in the 1977-
82 period than they did in the 1972-77 period  (measured in current
dollars).  An exact comparison cannot be made due to a creation of
a new category  of  products  (diagnostic substances)  by  the Bureau
of the Census.  However,  the compound annual rate of growth in the
earlier period  was approximately  9.4  percent as opposed  to 12.4
percent in the later period.    During  the 1977-82  period,  three
groups of  products grew much faster  than the overall  industry:
products affecting  the cardiovascular system,  products affecting
parasitic and infectious diseases, and products for veterinary use.
At the same time,  preparations for the skin,  and blood and blood
derivatives grew  at a much lower rate  than  Pharmaceuticals  in
general.  Detailed  descriptions of the major product groups follow.
All are final products and all but two of these product groups are
part of SIC 2834.   The last two groups on  the list (blood and blood
derivatives for human  use,  and  active  and passive immunization
agents)  are  part  of SIC  2831.    The  remaining  Pharmaceuticals
products  included   in  SIC  2831  and  SIC 2833 are  intermediate
products used as inputs for final products.   Table VII-1 presents
information  on the  value  of shipments  for  each  product  group
discussed.

A.  PREPARATIONS AFFECTING NEOPLASMS.  ENDOCRINE SYSTEM AND METABO
LIC DISEASES

This group includes a fairly diverse collection of pharmaceutical
products.   Shipments of  $1,724  million  were recorded  in  1982,
accounting for  9.9   percent of the  final products  shown in Table
VII-1.  Value  of shipments  for this group increased 13.9 percent
percent annually, while pharmaceutical shipments overall grew 12.4
percent annually.   In addition, this was substantially higher than
its 7.9 percent growth rate in the 1972-77 period.

Hormones accounted  for nearly 85  percent  of total group shipments.
Secreted by the endocrine glands (thyroid, pituitary,  gonads, and
others) and present only in minute quantities, natural hormones
regulate  the   body's  metabolic   activities.     Hydrocortisone,
androgens,  estrogens,  and progestogens  are  examples  of  steroid
hormones.  Corticotropin and  insulin are nonsteroidal hormones.
Hormone shipments  increased at a rate of about 15   percent a year
between 1977 and 1982.   Ten out  of  the  200 most prescribed drugs
in 1980 were  oral contraceptives.  Topical and systemic corticoids
(used as anti-flammatory agents)  account for 17  percent of group
shipments and show an average  annual increase  of 9.6  percent from
1977  to  1982.   Insulin and  antidiabetic  agents had  shipment
increases above the industry average.

To  summarize,   this  product group  has   exhibited  a higher than
average  rate   of  increase  in  shipments  in  years  1977-82.   In
contrast during the preceding  five years  its growth  rate was lower
than the industry average.
                               170

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                                       TABLE VII-1

                   PHARMACEUTICAL FINAL PRODUCTS - VALUE OF SHIPMENTS
                           BY ALL PRODUCERS (current dollars)


                                     Value of Shipments            Compound Annual Rate
                                     (Million of Dollars)          of Change (Percent)
   Product Class	1972	1977	1982	1972-77     1977-82

Preparations affecting            615         900       1,724        7.9         13.9
neoplasms, endocrine
system and metabolic
disease

Preparations affecting          1,636       2,231       4,003        6.4         12.4
central nervous system
and sense organs

Preparations affecting            400         751       1,938       13.4         20.9
cardiovascular system

Preparations affecting            561         896       1,580        9.8         12.0
respiratory system

Preparations affecting            746       1,074       1,410        7.6         13.6
digestive and genito-
urinary systems

Preparations affecting            344         621         825       12.5          5.9
the skin

Vitamins, nutrients and           587       1,302       2,093       17.3         10.0
hematinics

Preparations affecting            948       1,285       2,592        6.3         15.1
parasitic and infectious
diseases

Preparations for                  214         354         811       10.6         18.0
veterinary use

Blood and Blood deriva-           126         243         361       14.0          8.2
tives for human use
                                          171

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                                 TABLE VII-1  (continued)

                   PHARMACEUTICAL FINAL PRODUCTS  -  VALUE  OF SHIPMENTS
                           BY ALL PRODUCERS  (current  dollars)
                                     Value of Shipments             Compound Annual Rate
                                     (Million of Dollars)           of Change (Percent)
Product Class
Active and passive immu-
nization agents and
therapeutic counterparts
Total, incl. last group
Total, excl. last group
1972
89
6,266
6,177
1977
126
9,783
9,657
1982
*
*
17,337
1972-77
7.2
9.3
9.4
1977-82
.'.
*
12.4
* Change of definition in 1982 makes comparison not possible.

Source:  U.S. Census of Manufactures, various years.
                                          172

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B. PREPARATIONS AFFECTING CENTRAL NERVOUS SYSTEM AND SENSE ORGANS

The largest of all groups, the value  of  shipments for this group
accounted  for  23 percent  of shipments  for all  product  groups.
Shipments increased 12.4 percent annually from 1977 to reach $4,003
million in  1982.   Important subgroups are  internal  narcotic and
nonnarcotic analgesics and  antipyretics, psychotherapeutic agents,
Central Nervous System (CNS)  stimulants,  sedatives and hypnotics,
anesthetics, and eye and ear preparations.

Analgesics reduce awareness of pain without  loss of consciousness;
antipyretics help lower body  temperature.  The narcotic analgesics
include morphine and its derivatives, synthetic morphine-like drugs
and synthetic moieties of morphine molecules.  While shipments of
narcotic analgesics were nearly  unchanged between 1977 and 1982,
nonnarcotic  analgesics   (including  aspirin,   phenacetin,   and
acetaminophen)  had 1982 shipments of $1,744 million with an average
annual  increase  since 1977  of 18.5   percent.   Aspirin,  aspirin
combinations  and  other  salicylates  yielded  $558  million  in
shipments.   While the narcotic  analgesics  require prescriptions
(referred to as ethical drugs), most of the  nonnarcotic analgesics
do not  (referred to as proprietary drugs).  Also included in this
group are the nonhormonal antiarthritics.

Amphetamines, a  major subgroup  of CNS stimulants,  typically are
used  to   reduce  fatigue   or   appetite    (anti-obesity  drugs).
Amphetamine  shipments  decreased   during  the  1977-82  period.
Stimulants as a whole had constant shipments over this period.

Sedatives  and  hypnotics  (sleep  inducing agents)  shipments  fell
during  the  1982-87  period.    This  was  due   in  part  to  the
introduction of  a number of  new  nonbarbiturate drugs in the late
1970s.

General and local anesthetic  shipments grew  12.8  percent annually
from  1977  to reach  $161  million  in 1987.   Most  of  the growth in
this subgroup has been in general anesthetics.

In  summary, the largest  product  group in  terms  of value  of
shipments  has  experienced a growth rate equal  to that  for all
pharmaceutical products in years 1977-82.   This is in contrast to
the preceding  five  years  when this product group had the lowest
growth rate (6.4  percent annually).

C.  PREPARATIONS AFFECTING THE CARDIOVASCULAR SYSTEM

This  group of  products  had the  highest  increase  in  rate  of
shipments of all eleven groups,  with an annual rate of increase
of 20.9  percent.  Total  1982 shipments were $1,938 million, while
1977  shipments  were  $751  million.    This  drug market  appears
promising  because  a  number  of   new   drugs  with   far-ranging
possibilities,  notably calcium and beta blockers,  have  entered the
market in recent years.
                               173

-------
 Anticoagulants   are  agents  that   delay   or  counteract   blood
 coagulation and are used to reduce or prevent blood clot formation
 within blood vessels.   Shipments  in  1982  were  valued at  $103
 million,   having   grown  24.2    percent  annually  since   1977.
 Hypotensives  help   control  hypertension   and   its   effects,
 particularly high  blood pressure.  The  major hypotensives contain
 rauwolfia  compounds derived  from  an herb.    Data  for total  1982
 shipments  of hypotensives  is  not available.

 Vasodilators induce smooth and cardiac muscle relaxation and  dilate
 the  blood  vessels.   Shipments  in  1982  were estimated at  $339
 million, having increased  16.8  percent annually since  1977.
 The last major subgroup includes vasopressors, antiarrhythmics and
 antiheparin agents.  Vasopressors constrict  blood vessels and thus
 raise  blood pressure.   Antiarrhythmics help the irregular,  rapid
 heartbeats  known as arrhythmias (a potentially fatal condition for
 those with weak or diseased hearts) .  The beta and calcium blockers
 are perhaps the most  important  new drugs in this group.  Calcium
 blockers prevent calcium and minerals from entering muscle tissues
 and thus ease the  pain of angina.  Calcium blockers  have fewer side
 effects than beta blockers,  which try  to  influence the  hormonal
 system  that can speed  up  the heart and other  organs'  action  in
 times  of  stress.   Shipments in 1982  for  this subgroup were  $801
 million, with a growth  rate  of  31.9  percent annually,  from  1977
 to 1982.

 In summary,  this  product group has  been  experiencing very  rapid
 growth  in  shipments.   It was the  second  fastest growing product
 group  in the 1972-77  period  and  the fastest growing group  in  the
 1977-82 period.

 D.  PREPARATIONS AFFECTING THE RESPIRATORY SYSTEM

 This product group's  shipments increased 12.0   percent  annually
 from  1977  to 1982,  slightly below  the overall  pharmaceutical
 industry average of 12.4 percent.   With 1982 shipments of  $1,580
 million,   this   group   accounted   for  9.1   percent   of   all
 Pharmaceuticals.  Cold preparations,  both ethical and proprietary,
 nose drops,  lozenges, nasal  decongestants  and antihistamines  are
 included  in  this  product  group.    Cold   preparations  include
 combinations  of antibiotics,  nasal decongestants, antihistamines,
 analgesics,  and bioflavanoids.   Bronchial  dilators,  agents that
 open the  lungs,  bronchi,  and bronchial  tubes  making breathing
 easier, and cough  preparations, both  narcotic (those with  codeine)
 and  nonnarcotic,   had   shipment  increases  greater   than   the
pharmaceutical industry  average.  Antihistamines  are complex amines
that prevent the  buildup of  histamines in  body tissues and  are
typically used for treatment of allergenic diseases.  They are also
used in nasal and ophthalmic decongestants,  sleep inducers,  and
antipruritics (for relief of itching).

E.  PREPARATIONS AFFECTING THE DIGESTIVE AND  GENITO-URINARY SYSTEMS
                               174

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This product group accounted  for  $1,410  million  dollars in value
of  shipments  in  1982   and   represented 8    percent  of  total
pharmaceutical product shipments.   Antacids,  the largest subgroup
in  this category,  with  $417 million  in 1982  shipments,  have
experienced a  growth rate of  6.8   percent annually  since 1977.
Antacids  reduce  excess  gastric  acidity  by  several  methods:
neutralization; buffering; a combination of absorption, buffering
and partial neutralization; or ion-exchange.   Sodium bicarbonate,
sodium citrate, sodium acetate, magnesium oxide, calcium carbonate,
and  aluminum  hydroxide  gel  are  common active ingredients  in
antacids.   Antacids are  mainly  proprietary  drugs.   For  both
antacids and laxatives there  is intense competition and the rising
costs  for  advertising will become  an important factor  in sales
growth  in the  near  future.   Phenolphthalein,  castor oil,  dioctyl
sodium, and calcium  sulfosuccinates are all active ingredients in
laxatives.  Antispasmodics and anticholinergenics  are drugs that
relax involuntary (smooth) muscles and help relieve discomfort from
peptic ulcers  and asthma.

Diuretics,  agents that  promote  urine   excretion,  have  been  an
important growth market.   Data for  1982  are  not available due to
confidentiality.   While  diuretics  increase  urine,  sodium,  and
chloride excretion, many  also promote potassium excretion.  Perhaps
the  biggest area  for sales  growth  is   with  "potassium  sparing"
diuretics.  A number  already exist, with others slated for  release.

F.  PREPARATIONS AFFECTING THE SKIN

The value of shipments for this group increased  only  5.9  percent
annually between 1977 and 1982. Dermatological preparations, used
for treatment  of skin disorders, represented 60  percent  of group
shipments and  increased  only 4.7 percent annually.   Other drugs
contained in this group are hemorrhoidal  preparations and  external
analgesics.

G.  VITAMINS.  NUTRIENTS AND HEMATINIC PREPARATIONS

This group  had 1982  shipments  of  $2,093  million  and  accounted for
12 percent of total pharmaceutical product shipments.  This group's
shipments  have  been increasing  strongly since the  1960s;  the
average annual growth in  shipments  from  1977  to  1982  was 10.0
percent and from 1967 to 1977 was 13.4   percent.

Vitamins are  necessary  in small quantities for  normal metabolism
and are most often marketed as dietary supplements.   They  are also
used medicinally to  prevent or treat  disease.  Most  of
vitamin production is by chemical  synthesis.   Bulk vitamins are
formulated  either  as pills or capsules and are frequently used by
the animal  feed and  food additive industries.  From  1977  to 1982,
multivitamin shipments increased  annually at  13.9  percent.

H.  PREPARATIONS AFFECTING PARASITIC  AND INFECTIOUS  DISEASES
                                175

-------
 Included in this group are amebicides, anthelmintics, antibiotics,
 tuberculostatic  agents,  antimalarials,  sulfonamides,  antifungal
 preparations, antibacterials,  and antiseptics.   In terms of total
 1982, shipments, this was  the second largest group,  with $2,592
 million.   The  growth rate for value  of shipments  slowed  to 6.3
 percent  annually from  1972   through  1977,  but  jumped to  15.1
 percent in the  1977-82 period.  Over 70  percent of total shipment
 value was  due  to shipments of antibiotics in 1977.   Comparable
 figures are not available for  1982.

 Broad and medium spectrum antibiotics  (not including penicillin)
 grew at an annual rate  of  15.1  percent;  this  subgroup includes
 ^etracycline and its derivatives, erythrocin, cephalosporins and
 chloramphenicol.    Cephalosporins  have  seen  a  number  of  new
 developments in  recent  years.   They  are  substances  chemically
 related to penicillins but have a broader spectrum of activity and
 lower acute toxicities than penicillins.  Penicillin shipments grew
 at a slower rate of  7.1  percent annually.   Most  likely,  shipments
 will continue to grow at a slow  rate as more and more  pathogens
 become  resistant to penicillin.    However, a number of  popular
 antibiotics  are semi-synthetic  penicillins;  the  precursor  to
 penicillin is produced by fermentation and then chemically altered
 to increase effectiveness.

 Sulfonamides,  or sulfa  drugs, have  been  gradually replaced  by
 antibiotics in treating bacterial infections, but shipments growth
 rate (18.2  percent annually) is above the group average.  They are
 used   in  _  diuretics,    hypoglycemics,   and    hemotherapeutics.
 Antibacterials and antiseptics have shown slow growth from 1977 to
 1982 (6.0  percent annually) but represent only 8  percent of value
 of shipments  for the group  in  1977.

 I.   PREPARATIONS  FOR VETERINARY USE

 This group  includes all health,  vitamin  and  nutrient products
 formulated  for veterinary use.   There  were over $811  million worth
 of shipments  in  1982 representing 4.7  percent of total  shipments
 for all  product  groups.   Average  annual growth from 1977 to  1982
 (18.0  percent) was  much higher than for Pharmaceuticals overall.

is	BLOOD AND BLOOD  DERIVATIVES FOR HUMAN USE

Included in this group are whole human blood, blood plasma,  normal
blood serum,  and  other blood fractions.   Total shipments in  1982
were $361 million, or only 2 percent of  all Pharmaceuticals.  The
growth rate for this group, at 8.2 percent,
was below the industry average.

£*	PREPARATIONS FOR ACTIVE AND PASSIVE IMMUNIZATION AND THERAPEU
    TIC COUNTERPARTS

Comparable product value  data  are not available  for 1982 due to
                               176

-------
changes  in  Census  Bureau  definitions.    However,  total  1977
shipments for this group were only $126 million,  having shown a
average annual increase of 7.2 percent  since 1972.  A slow growth
rate in the subsequent period is expected.  Toxoids, antigens, and
viral  vaccines   are  used  in  active  immunization.    An  active
immunization agent alerts the body's immunological defense system
and  causes  it to  form  antigens  and antibodies  to deal with a
possible  future  pathogen.    Passive  immunization agents,  like
antitoxins, help the  body  deal with  a  pathogen that has breached
the  body's  defenses.   Antivenins, antitoxins,  immune globulins,
and immune serums are agents of passive immunization.
                               177

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        VIII.  FINANCIAL ANALYSIS OF PHARMACEUTICAL FIRMS

The following  section describes the  financial  condition  of  the
pharmaceutical industry  based  on recent data from publicly-held
pharmaceutical companies.  This analysis focuses on publicly-held
companies  for several  reasons.   First,  the  data are  readily
available and are appropriate for the level  of  detail  needed for
this preliminary  analysis.   Second,  these  companies  provide  a
reliable preliminary  assessment of  the industry.   Publicly-held
pharmaceutical companies form the majority of  the industry in terms
of both total  sales  and number of establishments.   Based  on the
industry data  previously  collected  by EPA  (under  authority  of
Section 308  of the  Clean Water Act), 93  publicly-held companies
owned 279 establishments, while the 152 private firms  owned only
185 pharmaceutical establishments.

For this analysis, six years of financial  data  from 43 publicly-
held companies were  obtained from  Standard  and  Poors COMPUSTAT
Services.   In most cases,  this  data covered  the years  1981-1986.
In a few cases, the data  were for an earlier period, such as 1979-
84.

A.  RATIO ANALYSIS

Financial ratios  are  frequently used to  identify companies with
operating and/or  financial difficulties.   Since the  ratios  are
calculated using  data available from  balance  sheets  and  income
statements, they are widely applicable.   This makes it  relatively
easy to  compare   industries  and to compare  companies  within  an
industry.

Four types of ratios  are presented, which measure profitability,
liquidity,  solvency,  and leverage.    For  most  ratios,  there  are
"rules of thumb" which can be used to determine whether the company
is  financially healthy.   In  addition,  pharmaceutical  industry
ratios are  available  from Robert Morris Associates  (RMA),  based on
information  collected  from commercial loan  applications.   These
ratios were used  for  comparison  purposes:  RMA ratios were used to
judge whether the sample used is representative, and the rules of
thumb were  used  to  determine  if  the companies  are  better  off
financially than manufacturing companies in general.

B.  PROFITABILITY

The  first   financial   question  usually  asked   concerns  the
profitability of  the  operation.  In this analysis, profitability is
measured in two ways, return on total assets  and return on sales.
The return on total assets measures how effectively the operation
is being managed.  Since  RMA measures this in  terms of  profit
before taxes, the before tax measure  is used here.  Based on 94
drug company loan applications during 1985-1986,  as reported by
RMA, median profits before taxes were  8.4 percent  of total assets.
For these same companies, the upper quartile  profit rate was 19.3
                               178

-------
percent  and  the  lower  quartile rate  was  1.7  percent of  total
assets. For the 43 companies in our sample and shown in Table VIII-
1, average profitability over six years ranged from a high of 53.0
percent  (Mylan  Laboratories)  to a low of -1.70 percent  (A.   H.
Robins).   The  median profitability for the  43  companies  is 11.6
percent.   In general,  these companies  have been somewhat more
profitable than those included  in  the RMA sample.   There appears
to be no relationship between size of company (as measured in terms
of total assets)  and the profitability of the company.   Both the
most profitable and  the least profitable  are among  the smallest
companies.

The  second measure  of  profitability is  return on  sales,  i.e.,
profits as a percentage of  sales.   Based on loan applications in
1985-86 from 94 drug companies,  as  reported by RMA, median profits
before taxes were 6.1 percent of sales.   For the 43 publicly held
companies  in  the  sample and  shown in Table  VIII-1,  the average
profitability over  six  years ranged from  a  high  of  37.4 percent
(Mylan Laboratories) to a low of -4.03 percent  (Sceptre Resources
Inc.).   The  median  profitability  for  the  43  companies is 11.83
percent.   As with return on assets,  these companies are somewhat
more profitable than those in the RMA sample.  Again, there is no
relationship between size and profitability.

C.  LIQUIDITY

Liquidity  ratios  measure the  firm's  ability to meet its maturing
short-term  obligations.   This  is  particularly  relevant to  a
financial officer when evaluating whether  or  not a company should
borrow more money.   The most commonly  used measure of  short-term
solvency is the current ratio.   This  ratio is computed by dividing
current assets by current liabilities, and it indicates  the extent
to which the claims  of short-term creditors  are covered by assets
that can be converted to cash in a roughly corresponding period.
The  rule  of  thumb for a healthy liquidity position  is a current
ratio of 2.0,  i.e.,  current  assets,  including inventory, are twice
current liabilities.  This  allows the company to cover its current
liabilities without  liquidating all current  assets.  Based on RMA
data, the  current ratio for pharmaceutical  companies had a median
value of  1.9, with  an upper quartile of  3.5 and a lower quartile
of  1.4.  The  average  current  ratio  for  our 43  publicly-held
companies  ranged  from a high of 6.2  (Bolar Pharmaceutical Co.) to
a low of  1.7  (Abbott Laboratories).   The median current ratio is
2.32.  Pharmaceutical companies generally are in a strong position
visa-vis  liquidity,  and  the  publicly-held  companies  are  in  a
particularly strong  position.

A second liquidity ratio commonly used  is the quick ratio, or acid
test.   This  is a more  conservative measure  in that  it does not
include  inventories  in current  assets.  Since  inventories  are
usually the least liquid of a firm's current assets, they are most
likely to be sold at a loss in the event  of  liquidation.  The
                               179

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                       TABLE VIII-1




FINANCIAL RATIOS  OF 43  PUBLICLY OWNED PHARMACEUTICAL FIRMS

1
2
3
4
5
6
7
8
9
10
11
12
oo 13
0 14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Company Name
Abbott Laboratories
Alza Corp.
American Cyanamid
American Home Products
American Hospital Supply
Astra Corp.
Baxter Travenol Lab
Becton, Dickinson & Co.
Bio-Rad Laboratories
Block Drug
Bolar Pharmaceutical Co.
Bristol-Myers Co.
Carter-Wallace, Inc.
Chattem, Inc.
Cooper Companies, Inc.
Del Laboratories, Inc.
Dexter Corp.
Forest Laboratories, Inc.
ICN Pharmaceuticals, Inc.
Johnson & Johnson
Key Pharmaceuticals, Inc.
Lee Pharmaceuticals
Lilly (Eli) & Co.
Marion Laboratories
Merck & Co.
Monsanto Co.
Mylan Laboratories
North American Biological
Pfizer, Inc.
Reid Rowel I
Total
Assets
(Million $)
3,042.25
71.24
3,252.87
3,184.87
1,877.21
1.47
3,569.71
1,210.27
65.05
240.23
33.11
3,234.13
280.66
48.76
410.75
61.12
424.34
55.03
167.37
4,667.43
97.57
9.59
3,610.76
181.07
4,295.04
7,015.36
38.91
8.41
4,167.59
11.28
Net
Sales
(Million $)
3,024.
29.
3,641.
4,611.
2,829.
2.
2,452.
1,146.
80.
247.
30.
4,080.
345.
58.
275.
83.
585.
30.
55.
6,113.
96.
17.
3,144.
228.
3,412.
6,648.
55.
26.
3,801.
10.
12
82
16
08
03
52
72
96
49
87
38
47
68
69
98
40
88
63
81
56
33
86
97
99
44
11
02
92
38
87
Profits
Before Taxes
as Percent of
Total
Assets
19.
9.
7.
35.
12.
7.
5.
8.
5.
12.
30.
22.
12.
9.
3.
9.
11.
11.
0.
15.
17.
17.
20.
22.
17.
6.
52.
0.
17.
9.
72
25
44
54
45
55
34
92
69
70
41
80
44
50
29
23
61
12
88
50
52
52
90
75
90
67
96
56
34
04
Sales
19.84
22.10
6.64
24.55
8.26
4.40
7.78
9.41
4.60
12.31
33.15
18.07
10.10
7.89
4.89
6.76
8.41
19.98
2.65
11.83
17.74
9.40
24.00
17.99
22.53
7.04
37.46
0.17
19.01
9.38
Current
Ratio
1.65
3.96
1.92
3. 12
2.32
1.49
1.86
2.31
2.28
2.55
6.22
2.48
2.34
2.12
2.34
2.38
2.16
4.70
3.18
2.44
2.70
2.49
1.94
2.37
1.97
2.00
5.54
1.91
2.05
3.23
Financial Ratios
Quick
Ratio
0.92
3.24
1.29
2.10
1.21
0.50
1.00
1.36
1.14
1.29
3.68
1.65
1.45
1.25
1.53
1.21
1.21
3.51
2.21
1.39
1.38
1.41
1.12
1.58
1.33
1.17
3.23
0.96
1.19
2. 11
Beaver" s
Ratio
0.40
0.35
0.25
1.02
0.33
0.23
0.24
0.26
0.11
0.44
1.92
0.51
0.32
0.22
0.21
0.16
0.23
0.67
0.12
0.47
0.42
0.33
0.48
0.59
0.50
0.36
1.50
0.32
0.32
0.36
Leverage
Ratio
1.00
4.71
1.04
0.61
0.71
1.23
2.62
0.96
1.90
0.46
0.13
0.58
0.72
0.73
0.90
1.88
1.48
0.46
1.41
0.79
1.19
0.79
0.68
0.51
0.80
1.72
0.53
1.32
1.04
0.76

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00
                                                   TABLE VIII-1  (continued)




                                   FINANCIAL  RATIOS OF 43 PUBLICLY OWNED  PHARMACEUTICAL  FIRMS



31
32
33
34
35
36
27
38
39
40
41
42
43


Company Name
Revlon Group, Inc.
Robins (A.H.) Co.
Rorer Group
Sceptre Resources Ltd.
Scherer (R.P.)
Schering-Plough
Smithkline Beckman Corp.
Squibb Corp.
Sterling Drug, Inc.
Syntex Corp.
Upjohn Co.
Warner-Lambert Co.
Zenith Laboratories, Inc.
Total
Assets
(Million $)
951.36
597.84
515.50
153.29
185.01
2,567.28
3,176.66
2,136.96
1,478.14
1,085.05
2,239.95
2,769.51
35.23
Net
Sales
(Million $)
973
604
490
19
182
1,939
2,956
1,777
1,843
873
2,038
3,200
42
.25
.10
.79
.98
.23
.22
.77
.66
.62
.24
.12
.65
.59
Profits
Before Taxes
as Percent of
Total
Assets
2.10
-1.70
12.10
-0.53
8.29
10.60
21.56
12.12
17.85
16.09
11.46
8.44
16.61

Sales
2.05
-1.68
12.70
-4.03
8.41
14.03
23.16
14.57
14.31
20.00
12.59
7.30
13.73
Current
Ratio
2.13
3.05
2.05
2.06
2.12
1.67
1.88
2.15
2.47
2.23
2.05
1.78
2.93
Financial Ratios
Quick
Ratio
1
2
1
2
1
1
1
1
1
1
1
1
1
.19
.14
.27
.06
.34
.06
.31
.34
.63
.56
.15
.01
.59
Beaver' s
Ratio
0.15
0.10
0.27
0.11
0.14
0.21
0.49
0.36
0.35
0.45
0.29
0.18
0.49
Leverage
Ratio
1.02
-4.74
-1.81
3.19
0.57
0.86
1.29
0.80
0.70
0.69
0.91
1.63
0.77
   Source:   Meta Systems, Inc.  calculations  based  on  financial  data  obtained  from Compustat Services,  Inc.

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common rule of thumb for a healthy  financial position  is a quick
ratio of  1.0;  i.e., cover all  current liabilities with current
assets not including inventories.  Based on RMA data, quick ratios
for pharmaceutical  firms are generally strong.   The median ratio
is 1.1,  with an upper quartile of 2.1 and a lower quartile of 0.6.

The quick ratios for our 43 publicly-held companies also tend to
be strong.   The  average  ratios  range from a high  of  3.68 (Bolar
Pharmaceutical Co.) to a low of 0.50  (Astra Corp.)  with a median
quick ratio of 1.34.

Taken together, the two liquidity ratios indicate that only one of
these 43 companies has potential liquidity problems and two other
companies are  borderline.   There are  10  companies with current
ratios  below 2.0.    However,  seven  of these  have quick ratios
greater than 1.0 and thus  are not interpreted to  have liquidity
problems.   One  company  (Astra Corp.)  clearly  has a  potential
problem, with a current ratio of 1.49  and a quick  ratio of 0.50.
It is the smallest  company in the sample  and has a profitability
rate below the median.   The next smallest  company (North American
Biological)  is borderline in terms of liquidity (current ratio of
1.91 and quick  ratio of 0.96) .  This  company has a more significant
problem in  terms  of its very small  average  profits.    The other
company with borderline  liquidity problems  (Abbott Laboratories
with a current ratio of 1.65 and a  quick  ratio  of  0.92) has very
high profits.

D.  SOLVENCY

Beaver's Ratio is designed to assess the short-term solvency of a
firm.   It  has been found  to be  a good  predictor of business
bankruptcy,  although recent literature has been  critical of this
test.   The  ratio  compares internally generated cash  flow (net
income  after  taxes plus depreciation)  to total   debt  (current
liabilities  plus  long-term debt).   Generally,  if the  ratio is
greater than 0.2, the firm is judged to be solvent.  If the ratio
is less  than 0.15,  the firm is judged to be insolvent.   Ratios
between  0.15  and   0.2  indicate   that   solvency/insolvency  is
uncertain.  RMA does not calculate Beaver's Ratio.

Beaver's Ratio was calculated for  each  of the  43 publicly-held
companies in our sample.   The values ranged from  a high of 1.92
(Bolar Pharmaceutical  Co.) to a low of 0.10 (A. H. Robins Co.).
The median  value  is a healthy  0.35.   Further indication of the
general  health of  this  industry  is that  only five  of  the 43
companies have a Beaver's Ratio of less than 0.15,  and three have
a ratio between 0.15 and 0.20.

E.  LEVERAGE

Leverage ratios compare the amount of funds supplied by  the owners
of the company to the amount of funds provided by the firm's
                               182

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creditors.  For several reasons, creditors are less willing to loan
money when  the debt  equity ratio is high.   First,  if  the owners
provide only a small  proportion of total financing, then the risks
of the enterprise are borne mainly by the creditors.  Likewise, if
the firm earns more on the borrowed funds than it pays in interest,
the return  to the owner  is magnified.   However if  it earns less,
then the differential must  be made up from the owner's share of the
profits.  In times of economic downturns, firms with low leverage
ratios have less  risk of loss.  There are no rules of thumb for
debt-equity  ratios,  since  the amount of leverage  desirable  is a
function of the industry's  operating characteristics. Based on RMA
data, the median debt-net worth ratio for pharmaceutical firms was
1.2, with an upper quartile of 0.4 and a lower quartile of 3.1.

The average debt equity ratio for the 43 publicly-held firms ranged
from 0.13 (Bolar Pharmaceutical Co.) to 4.71  (Alza Corp.), with a
median value of 0.90.  Therefore,  these  43  firms have relatively
less debt than the sample  covered by RMA.  Two firms had negative
debt-equity ratios.   (A.  H. Robins and Rorer Group).  In the case
of  A.  H.  Robins,  this negative  value  is the  result  of negative
equity in two years and of  intangibles having a value greater than
equity in three years.  In the case of Rorer Group, this negative
value  is  due to  one year  when equity was negative combined with
several years when the debt equity ratio was very small.

F.  SUMMARY

In general, the financial condition  of pharmaceutical companies is
strong.   In a few cases, companies  have problems as indicated by
one or more of the ratios.  However, none of the companies  fail all
the ratios.  Companies with very high  debt  equity ratios and low
leverage  ratios may  have problems  raising significant amounts of
capital through borrowing.   For large companies, this might result
in their paying higher interest rates.   For  small companies, this
might  result  in  their not  being able to  raise the funds at all,
even at higher interest rates.
                               183

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            SECTION IX.  PHARMACEUTICAL PLANT PROFILE

The location  and  size  (both  in terms of employment and sales) of
464 pharmaceutical plants that might be covered by regulation are
described below.   This discussion supplements Section  II of the
Development Document,  which  presents information  on 465 plants.
Since that document was written,  one  plant has been removed due to
uncertainty about its status.   Therefore,  this  report presents
information on, and analyzes, 464 plants.

A.  GEOGRAPHICAL DISTRIBUTION OF THE INDUSTRY

Table IX-1 shows the geographical distribution of plants in terms
of number of plants, their sales, and their employment.   These data
were originally compiled for earlier analyses of the pharmaceutical
industry.  A  comprehensive list  of  464  pharmaceutical plants was
identified and data were gathered via Section 308 surveys conducted
in 1978 and 1979.   The employment data in Table IX-1 are  from those
surveys.  The  sales data  represent plant-level  sales in 1979, as
estimated by Economic Information Systems,  Inc.  and Meta Systems,
Inc.

In  terms of  number of  plants,  the  pharmaceutical  industry is
concentrated  in  EPA Region II  (with 36 percent  of  the plants),
followed by Regions V  (with 19  percent),  IV  (with  11 percent), III
(with  9  percent)  and  IX  (with 9  percent) .     The states  and
territories containing  the largest  number  of  plants  are:   New
Jersey  (with  16  percent  of the plants),   Puerto Rico  (with 10
percent), New York (with  9 percent),  and Illinois and  California
(with 8 percent each) .  While all EPA regions have some  plants, 12
states do not have any pharmaceutical plants.

The distribution of pharmaceutical sales  across regions  is similar
to the  distribution in  terms  of number  of  plants.   However,  the
plants in Region V tend to be much larger on  average,  and so Region
V accounts for over one-third of pharmaceutical  sales.  Region II
is sightly smaller with 33.5 percent  of sales.  Trailing these two
are Regions  IV (with 9  percent)  and IX  (with  7 percent) .   The
states with the largest pharmaceutical sales  are:   New Jersey (with
21 percent of  the sales), Indiana (with 13 percent), Illinois (with
12 percent) and Puerto Rico (with 11 percent).

Regions II and V are also  the most important in terms of number of
employees.  Region II  accounts for 39 percent and Region V for 32
percent of pharmaceutical employment.  The next  largest is Region
IV with only 12 percent of the employment,  followed by Regions IX
(6 percent)  and VI (5  percent) .  The  states  with  the greatest
pharmaceutical employment are:  New Jersey (with  21 percent of the
employment), Indiana (with 12 percent),  Illinois  (with 11 percent),
and New York and Puerto Rico (with 9 percent each).
                               184

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              TABLE IX-1

PHARMACEUTICAL PLANT PROFILE BY PLANT,
   SALES BY PLANT, SALES,  EMPLOYMENT
Location
REGION I
CT
ME
MA
NH
RI
VT
Total
REGION II
NJ
NY
PR
VI
Total
REGION III
DE
MD
PA
VA
WV
DC
Total
REGION IV
AL
GA
FL
MS
NC
SC
TN
KY
Total
REGION V
IL
IN
OH
MI
WI
MN
Total
Number of
Plants

7

7

1
1
16

75
43
46
2
166

2
6
27
7
2

44

3
6
8
2
12
3
10
5
49

38
17
14
14
4
4
91
% of
Total

1.51

1.51

0.22
0.22
3.45

16.16
9.27
9.91
0.43
35.77

0.43
1.29
5.82
1.51
0.43

9.48

0.65
1.29
1.72
0.43
2.59
0.65
2.16
1.08
10.57

8.19
3.66
3.02
3.02
0.86
0.86
19.16
Sales
($000)

138,198

120,493

22,613
11,663
292,967

3,570,921
150,422
1,861,798

5,583,141

18,600
67,281
304,218
304,218
57,002

751,319

6,024
182,832
135,782
197,000
502,520
72,682
419,179
31,781
1,547,800

2,079,952
2,187,365
553,433
1,088,433
54,874
25,058
5,989,115
% of
Total

0.83

0.72

0.14
0.07
1.76

21.43
8.90
11.17

33.50

0.11
0.40
1.88
1.83
0.34

4.51

0.04
1.10
0.81
1.18
3.02
0.44
2.52
0.19
9.3

12.48
13.12
3.32
6.53
0.33
0.15
35.98
Employ

324

584

73
33
1014

21,313
9,065
8,797

39,175

241
402
897
897
299

2,736

44
1,132
752
1,517
5,476
261
2,947
59
12,188

11,612
11,704
2,842
5,617
215
163
32,153
% of
Total

0.32

0.58

0.07
0.03
1.00

21.00
8.93
8.67

38.60

0.24
0.40
0.88
0.88
0.29

2.69

0.04
1.12
0.74
1.49
5.40
0.26
2.90
0.06
12.01

11.44
11.53
2.80
5.58
0.21
0.16
31.67
                 185

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                                 TABLE IX-1 (continued)

                         PHARMACEUTICAL PLANT PROFILE BY PLANT,
                            SALES BY PLANT, SALES, EMPLOYMENT
Location
REGION VI
AR
LA
OK
TX
NM
Total
REGION VII
IA
KS
MO
NE
Total
REGION VIII
CO
UT
WY
MT
ND
SD
Total
REGION IX
AZ
CA
NV
HI
Total
REGION X
AK
ID
OR
WA
Total
U.S. TOTAL
Number of
Plants

2
2

13

17

3
4
18
4
29

5
1




6

1
38
1

40



2
4
6
464
% of
Total

0.43
0.43

2.80

3.66

0.65
0.86
3.38
0.86
6.25

1.08
0.22




1.3

0.22
8.19
0.22

8.63



0.43
0.86
1.29
100.00
Sales
($000)

225,500
9,800

266,008

501,308

71,800
123,186
483,658
87,300
765,944

69,233
70,200




139,433

13,900
1,056,268
24,632

1,094,800



14,900
18,058
32,958
16,666,822
% of
Total

1.35
0.06

1.60

3.01

0.43
0.74
2.90
0.52
4.59

0.42
0.42




0.84

0.08
6.34
0.15

6.57



0.09
0.11
0.2
100.00
Employ

3,116
18

1,523

4,657

231
494
2,064
803
3,592

362
17




379

6
5,469
115

5,590



50
129
179
101,484
% of
Total

3.07
0.02

1.50

4.59

0.23
0.49
2.08
0.79
8.54

0.36
0.02




0.38

0.01
5.39
0.11

5.51



0.05
0.13
0.18
100.00
Source:  Meta Systems Inc. calculations based on EPA Section 308 Survey data (1978 and
         1979), and Economic Information Systems data (1979).
                                           186

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B.  PLANT SIZES

Plant sizes are measured in terms of both pharmaceutical sales in
1979 and pharmaceutical  employment.   Measured either  way,  there
are more small plants than  large plants,  as  shown in Table IX-2.
In terms of sales,  plants tend to be concentrated at the small end
of the scale.  Nearly one-quarter of the plants had sales of less
than $5 million,  and over one-half had sales under $20 million. At
the other end of the scale,  there are  21 plants  (5 percent)  with
sales between $200 and $499.9 million and only three plants (less
than 1 percent) with sales of $500 million or more in 1979.

A similar distribution  of sizes is found when plants  are ranked
according to number of pharmaceutical employment.  Nearly one-third
have less than 20 employees and about 60 percent have  less than 100
employees.   At the other  end of the  range,  53  plants  (over 11
percent) have 500 or more employees.
                               187

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                                  TABLE IX-2

                       PLANT SIZES: SALES AND EMPLOYMENT


Sales  ($ millions)	Number of Plants	Percent of Total

Less than 5                        111                             24
5-19.9                             177                             38
20-49.9                             79                             17
50-199.9                            69                             15
200-499.9                           21                              5
500 or greater                       3                              1
Missing data                       	4                              1

Total                              464                            100


Number of Employees

1-4                                 60                             13
5-19                                84                             18
20-99                              137                             30
100-499                            117                             25
500-2499                            47                             10
2,500 or more                        6                              1
Missing data                        13                              3

Total                              464                            100


Source:  Meta Systems, Inc., calculations  based on EPA Section 308 survey data
         (1978 and 1979)  and Economic Information Systems data (1979).
                                      188

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              X.  TREATMENT TECHNOLOGY AND COSTING

Control  technologies  for removing  pollutants  are  customarily
classified as in-plant and end-of-pipe.  In-plant control includes
source reduction and treatment technologies.  Based on information
presented in the Technical Support section of this document steam
stripping  is  effective for  removing volatile  organic  compounds
(VOC) such as benzene, toluene, methylene chloride, and chloroform.
These four VOCs are  the compounds  of concern in this preliminary
assessment.  One way  to apply steam stripping  is in-plant treatment
before VOC-bearing waste  streams  mix with nonprocess wastewater,
because the cost of steam stripping increases  with wastewater flow.
It is estimated that VOC-bearing wastewater is about 26 percent of
the process wastewater reported  in a  previous 308 Survey  (20).  In
addition, in-plant application of  steam stripping will remove more
and  discharge  less  of the  pollutant  loadings than  end-of-pipe
application of steam stripping.   Detailed study of plant specific
conditions may show that treatments other  than steam stripping are
less expensive  for  some plants.   But overall,  in-plant treatment
by steam stripping is applicable to most facilities, especially if
stripped VOCs  are reclaimed.   In  this preliminary  analysis,  the
treatment technology addressed  is  steam  stripping as an in-plant
treatment.

The  costs  of  steam stripping used in this  analysis were derived
using  data  from  "Proposed  Development  Document  for  Effluent
Limitations  Guidelines   and  Standards   for  the  Pharmaceutical
Industry Point  Source  Category" 1  (5) .   Costs were developed on a
plant-specific basis, using the 3-step process described below.

Step 1;  Regression  Analysis

In   this   step,   regression  analysis   is  used  to  estimate  a
relationship  between  treatment costs  and  wastewater   flowrate.
Information is  obtained from the Development Document cited above
for various flowrate sizes and costs.

Assumptions in  the Analysis;

1.   The  steam  stripping flowrate Q,  is assumed to  be 26 percent
     of  the  reported process wastewater  flowrate.    This  is an
     engineering estimate  that  reflects the  fact  that 26 percent
     of  the actual process flowrate  contains priority pollutants
     and  other pollutants  of  interest.

2.   Influent concentration of pollutants  has no effect on overall
     costs.

3.   Annual  costs  are based on 300  days of plant operation.
     1This document was prepared for the regulatory analysis that
 supported  the promulgation of  Effluent Limitations,  Guidelines,
 New  Source Performance Standards,  and Pretreatment Standards  for
 the  Pharmaceutical  Industry.
                                189

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The first regression estimates the relationship between ca
pital costs  (CC)  and flowrate (Q) .   This analysis yields  the
equation  used to  compute  CC  for  all  plants  for which  process
wastewater flow is known.  The error term (E) is found
to  be negligible  and hence  is ignored  in the  analysis.   The
resultant equation is as follows:

    Ln (CC) =  [0.646 Ln  (Q) + 4.716 + E]
    Where Q is in gallons/day and CC is in dollars.

Similarly, the second regression analysis yields the relationship
between operating and maintenance costs  (O&M) and Q.  The equation
is as follows:

    Ln (O&M) = [-0.224 Ln  (Q) + 4.658 + E]
    Where Q is in gallons/day and O&M is in dollars/lOOO gallons.

Step 2;  Capital Costs Annualization

The annualized portion of capital costs is computed using a Capital
Recovery Factor (CRF). The CRF is obtained by using the following
equation:

    CRF = [i

    where  i = interest  rate = 10 percent
          n =  time period   =  5 years
    CRF =0.26
Step 3:  Annualized Costs Calculation

Annualized  costs  (AC)  represent  the  sum  of  annualized capital
costs,  O&M  and  monitoring  fee.    Monitoring  fee  is  the  cost
associated with sampling and analyzing VOCs concentration.  While
the Development Document  cited above provides no  data about the
monitoring  fee for  this industry,  the amount  of  $1,200 per year
per plant  is used here based  on experience  in  other industries
(such as Plastics  Forming and Molding) .  Thus,  the annualized costs
are obtained using the equation:

    AC = (CRF*CC) + MF  +   (O&M)
          where,  MF = Monitoring Fee =  $l,200/year

It is noted that the  regression analysis performed on the O&M and
Q  yields an  O&M cost  per  1,000  gallons.   This  cost  must  be
converted to  an  annual cost by multiplying the O&M  cost by the
wastewater  flowrate  in 300 days.  With this  conversion,  the O&M
costs are consistent with Capital Costs (CC).

To summarize, capital and O&M  costs  are estimated for each plant
with wastewater flow, using the regression equations developed in
Step 1.  The capital  costs are annualized using a CRF of 0.26.
                               190

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Then the annual  capital,  O&M and monitoring costs  are summed to
obtain the annualized costs  that  are  used in the economic impact
analysis (Section XI).  For example, the first plant in Table X-l
has  a  process wastewater flow of  8.316  mgd.    Steam stripping
applies to a flow of 2,162,160 gallons per day  (8.326 mgd x 0.26).
Substituting Q=2,162,160 gpd into the regression equations:

    Ln  (CC) = 0.646  Ln  (2,162,160) +  4.716 = 14.139
      or CC = $1,381,880

      and
    Ln  (O&M) = -0.224 Ln  (2,162,160)  + 4.658 = 1.391
      or O&M = $4.017/1000 gallons

For the entire year, the O&M costs are:

    4.017 X  (2,162,160/1000)  X 300 =  $2,605,781/yr

Thus annualized costs are:

     (0.26 X  1,381,880)  +  2,605,781 +  1200  =  $2,971,521/yr

This estimate of annualized  costs is  shown in the last column of
Table X-l.

For these 224 pharmaceutical  plants, total annualized cost is $34.6
million and total capital cost is $21.7  million.  Steam stripping
is a  relatively  expensive treatment  process  to  operate,  with an
annual O&M cost of $28.6 million for these 224  plants.  For the 49
pharmaceutical  plants  that   are  direct  dischargers,  the  total
annualized costs  is $13.8 million.    For the 175 plants that are
indirect dischargers, the total annualized cost  is  $20.8 million.
                                191

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                               TABLE X-l

CALCULATION OF ANNUALIZED COSTS FOR PLANTS WITH PROCESS WASTEWATER FLOW
                  (Plants ordered by Annualized Cost)
Line
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Process
Wastewater
Flow
(mud)
8.3160
2.9730
2.0250
1.8000
1.7000
1.6500
1.6350
1 . 4480
1.3000
1.2500
1.1700
1.1000
1.0920
1.0650
1.0400
1.0280
1.0070
0.9940
0.9000
0.8780
0.8500
0.7780
0.7400
0.7010
0.7000
0.5270
0.5000
0.5000
0 . 4640
0.4300
0.4250
0.4100
0.3870
0.3800
0.3800
0.3620
0.3500
0.3500
0.3400
0.2950
Capital
Cost
(S)
1,381,880
711,033
554,825
514,176
495,536
486,072
483,212
446,747
416,690
406,265
389,272
374,063
372,304
366,331
360,752
358,058
353,315
350,362
328,584
323,372
316,672
299,074
289,554
279,601
279,344
232,539
224,771
224,771
214,179
203,904
202,369
197,726
190,488
188,255
188,255
182,445
178,515
178,515
175,203
159,849
O&M
Cost
(S/yr)
2,605,781
1,172,961
870,703
794,650
760,173
742,766
737,520
671,183
617,311
598,806
568,848
542,257
539,194
528,820
519,161
514,507
506,332
501,252
464,06*
455,235
443,929
414,462
398,665
382,262
381,839
306,344
294,093
294,093
277,525
261,611
259,247
252,118
241,073
237,682
237,682
228.898
222,988
222,988
218,028
195,284
Monitoring
Fee
($/yr)
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
Annualized
Cost
($)
2,971,521
1,361,731
1,018,266
931,489
892,096
872,191
866,192
790,235
728,434
707,179
672,738
642,135
638,608
626,658
615,528
610,162
600,736
594,878
551,943
541,741
528,667
494,557
476,249
457,221
456,730
368,888
354,588
354,588
335,225
316,601
313,832
305,479
292,523
288,544
288,544
278,227
271,280
271,280
265,446
238,652
                                    192

-------
                         TABLE X-l (continued)

CALCULATION OF ANNUALIZED COSTS FOR PLANTS WITH PROCESS WASTEWATER FLOW
                  (Plants ordered by Annualized Cost)
Line
No.
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
Process
Wastewater
Flow
(mgd)
0.2820
0.2820
0.2820
0.2770
0.2600
0.2590
0.2400
0.2320
0.2230
0.2170
0.2100
0.2000
0.1900
0.1830
0.1800
0.1740
0.1700
0.1660
0.1660
0.1610
0.1600
0.1400
0.1400
0.1300
0.1270
0.1250
0.1250
0.1250
0.1180
0.1100
0.1070
0.1070
0.1040
0.1010
0.1010
0.1000
0.1000
0.1000
0.0900
Capital
Cost
($)
155,262
155,262
155,262
153,478
147,326
146,959
139,901
136,871
133,417
131,087
128,339
124,357
120,304
117,422
116,175
113,658
111,963
110,254
110,254
108,097
107,663
98,765
98,765
94,148
92,739
91,793
91,793
91,793
88,438
84,517
83,021
83,021
81,510
79,983
79,983
79,470
79,470
79,470
74,241
O&M
Cost
($/yr)
188,572
188,572
188,572
185,972
177,053
176,524
166,390
162,070
157,170
153,878
150,012
144,439
138,802
134,818
133,099
129,643
127,325
124,994
124,994
122,062
121,473
109,517
109,517
103,396
101,540
100,297
100,297
100,297
95,910
90,825
88,897
88,897
86,957
85,004
85,004
84,350
84,350
84,350
77,728
Monitoring
Fee
(S/yr)
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
Annualized
Cost
($)
230,730
230,730
230,730
227,660
217,118
216,492
204,496
199,377
193,565
189,659
185,068
178,444
171,739
166,993
164,946
160,826
158,061
155,279
155,279
151,778
151,075
136,771
136,771
129,432
127,204
125,712
125,712
125,712
120,440
114,321
111,998
111,998
109,659
107,303
107,303
106,514
106,514
106,514
98,513
                                     193

-------
                         TABLE X-l (continued)

CALCULATION OF ANNUALIZED COSTS FOR PLANTS WITH PROCESS WASTEWATER FLOW
                  (Plants ordered by Annualized Cost)
Line
No.
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
Process
Wastewater
Flow
Ongd)
0.0900
0.0890
0.0880
0.0850
0.0800
0.0800
0.0790
0.0760
0.0750
0.0640
0.0640
0.0630
0.0600
0.0600
0.0590
0.0560
0.0530
0.0520
0.0520
0.0490
0.0470
0.0450
0.0440
0.0420
0.0420
0.0400
0.0400
0.0400
0.0390
0.0380
0.0370
0.0370
0.0370
0.0370
0.0360
0.0350
0.0340
0.0340
0.0340
Capital
Cost
($)
74,241
73,707
73,171
71,550
68,802
68,802
68,245
66,560
65,993
59,566
59,566
58,963
57,134
57,134
56,517
54,643
52,734
52,089
52,089
50,127
48,796
47,444
46,760
45,376
45,376
43,968
43,968
43,968
43,255
42,535
41,808
41,808
41,808
41,808
41,075
40,334
39,586
39,586
39,586
O&M
Cost
($/yr)
77,728
77,057
76,384
74,356
70,939
70,939
70,249
68,170
67,473
59,660
59,660
58,935
56,745
56,745
56,010
53,787
51,537
50,781
50,781
48,493
46,950
45,392
44,607
43,025
43,025
41,427
41,427
41,427
40,621
39,810
38,995
38,995
38,995
38,995
38,175
37,349
36,518
36,518
36,518
Monitoring
Fee
($/yr)
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
Annualized
Cost
($)
98,513
97,701
96,887
94,430
90,289
90,289
89,453
86,929
86,082
76,573
76,573
75,689
73,017
73,017
72,119
69,402
66,649
65,722
65,722
62,916
61,022
59,107
58,142
56,196
56,196
54,226
54,226
54,226
53,232
52,231
51,224
51,224
51,224
51,224
50,210
49,189
48,161
48,161
48,161
                                 194

-------
                         TABLE X-l (continued)

CALCULATION OF ANNUALIZED COSTS FOR PLANTS WITH PROCESS WASTEWATER FLOW
                  (Plants ordered by Annualized Cost)
Line
No.
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
Process
Wastewater
Flow
(mgd)
0.0340
0.0340
0.0330
0.0330
0.0320
0.0310
0.0290
0.0290
0.0260
0.0250
0.0250
0.0230
0.0230
0.0220
0.0200
0.0200
0.0200
0.0200
0.0190
0.0180
0.0180
0.0170
0.0170
0.0160
0.0150
0.0140
0.0130
0.0120
0.0110
0.0100
0.0100
0.0100
0.0100
0.0100
0.0100
0.0100
0.0090
0.0090
0.0090
0 0080
Capital
Cost
($)
39,586
39,586
38,830
38,830
38,066
37,293
32,000
35,720
33,287
32,454
32,454
30,753
30,753
29,882
28,098
28,098
28,098
28,098
27,182
26,249
26,249
25,297
25,297
24,326
23,332
22,315
21,272
20,200
19,096
17,956
17,956
17,956
17,956
17,956
17,956
17,956
16,774
16,774
16,774
15,545
O&M
Cost
($/yr)
36,518
36,518
35,682
35,682
34,840
33,992
32,278
32,278
29,655
28,766
28,766
26,964
26,964
26,050
24,193
24,193
24,193
24,193
23,249
22,293
22,293
21,326
21,326
20,346
19,352
18,343
17,318
16,275
15,213
14,128
14,128
14,128
14,128
14,128
14,128
14,128
13,019
13,019
13,019
11,882
Monitoring
Fee
($/yr)
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
Annualized
Cost
($)
48,161
48,161
47,125
47,125
46,082
45,030
42,901
42,901
39,637
38,528
38,528
36,277
36,277
35,133
32,805
32,805
32,805
32,805
31,619
30,418
30,418
29,200
29,200
27,963
26,707
25,430
24,130
22,804
21,450
20,065
20,065
20,065
20,065
20,065
20,065
20,065
18,644
18,644
18,644
17,183
                                   195

-------
                         TABLE X-l (continued)

CALCULATION OF ANNUAL1ZED COSTS FOR PLANTS WITH PROCESS WASTEWATER FLOW
                  (Plants ordered by Annualized Cost)
Line
No.
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
Process
Wastewater
Flow
(mgd)
0.0080
0.0080
0.0080
0.0070
0.0070
0.0060
0.0060
0.0050
0.0050
0.0050
0.0050
0.0050
0.0050
0.0040
0.0040
0.0040
0.0040
0.0040
0.0040
0.0040
0.0030
0.0030
0.0030
0.0030
0.0030
0.0030
0.0020
0.0020
0.0020
0.0020
0.0020
0.0020
0.0020
0.0020
0.0020
0.0020
0.0020
0.0020
0.0010
0.0010
Capital
Cost
($)
15,545
15,545
15,545
14,261
14,261
12,909
12,909
11,475
11,475
11,475
11,475
11,475
11,475
9,934
9,934
9,934
9,934
9,934
9,934
9,934
8,249
8,249
8,249
8,249
8,249
8,249
6,348
6,348
6,348
6,348
6,348
6,348
6,348
6,348
6,348
6,348
6,348
6,348
4,057
4,057
O&M
Cost
($/yr)
11,882
11,882
11,882
10,712
10,712
9,050
9,505
8,251
8,251
8,251
8,251
8,251
8,251
6,939
6,939
6,939
6,939
6,939
6,939
6,939
5,550
5,550
5,550
5,550
5,550
5,550
4,052
4,052
4,052
4,052
4,052
4,052
4,052
4,052
4,052
4,052
4,052
4,052
2,366
2,366
Monitoring
Fee
($/yr)
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
Annualized
Cost
($)
17,183
17,183
17,183
15,674
15,674
14,110
14,110
12,478
12,478
12,478
12,478
12,478
12,478
10,759
10,759
10,759
10,759
10,759
10,759
10,759
8,927
8,927
8,927
8,927
8,927
8,927
6,927
6,927
6,927
6,927
6,927
6,927
6,927
6,927
6,927
6,927
6,927
6,927
4,637
4,637
                                  196

-------
                             TABLE X-l (continued)

    CALCULATION OF ANNUALIZED COSTS FOR PLANTS WITH PROCESS WASTEWATER FLOW
                      (Plants ordered by Annualized Cost)
Line
No.
199
200
201
202
203
204
205
206
207
208
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
TOTAL
Process
Wastewater
Flow
(mgd)
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0010
0.0003
53.8463
Capital
Cost
($)
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
4,057
1,864
21,745,960
O&M
Cost
($/yr)
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
2,366
930
28,608,532
Monitoring
Fee
(S/yr)
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
1200
267,600
Annualized
Cost
($)
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
4,637
2,621
34,612,716
Source:  Meta Systems,  Inc.  calculations based on data from Agency reports
                                      197

-------
                 XI.  ESTIMATED ECONOMIC IMPACTS

The  Clean Water Act  requires  that effluent  limitations  be both
technically and  economically achievable.   This section addresses
the  question  of whether regulations to control  the discharge of
certain VOCs are economically achievable by comparing the estimated
treatment costs for individual  plants to their estimated sales and
profits,  as  measures  of  the  industry's ability to  pay  for
treatment.

Compliance  costs  were  estimated  for  all direct  and  indirect
discharging plants for  which  flow data  are  available  (i.e.  228
plants) according  to  the  procedure discussed  in  Section X.  Zero
discharging  plants are  not included  since  they  will not have
additional treatment  costs.  Plant-specific impacts are measured
in two ways:  the ratio  of  annualized  compliance  costs  to sales,
and  the  reduction   in  profits  resulting  from  the  costs  of
compliance.

The  cost  to  sales ratio  gives  a  preliminary assessment  of  the
relative  impact  of the  regulation.  If the ratio  is  small, then
compliance costs are  small  in  relation to  sales  and so the plant
is likely to  be able to carry these costs.   The benchmarks that
distinguish small  impacts from large depend  on  profit  levels in
the industry.  The second measure,  reduction in profits, compares
the compliance costs to  the amount  of funds available to pay these
costs.  Both of these measures are worst case calculations in the
sense that they  assume  there will  be no  price increases to cover
all or part of the cost increases.

Both impact measures  require an estimate of plant-specific sales.
Since sales data are not available  for  five of the plants, impacts
are analyzed for 223  plants.  These include 48 direct dischargers
and 175 indirect dischargers.  Plants are also classified according
to their  production  processes.  There are four  basic production
processes:

    A)  Fermentation
    B)  Biological Extraction
    C)  Chemical Synthesis
    D)  Formulation

Each plant has one or more  of  these processes,  and subcategories
are  defined  in   terms   of combinations   of processes.     All
combinations of discharger status and subcategory are included in
the analysis,  except  for subcategory AB.   There is only one plant
in subcategory AB, and  it is  an indirect  discharger.   It  is  not
included in the  analysis  because flow  data are not available  for
this plant.   For  many  discharge/subcategory  groups,  all  of  the
plants are analyzed.  Table XI-1 presents  a comparison  of plants
analyzed to existing plants.
                               198

-------
                                  TABLE XI-1

            NUMBER OF PLANTS BY DISCHARGE STATUS AND SUBCATEGORIES:
                  ALL PLANTS AND PLANTS ANALYZED FOR IMPACTS
                                       Discharge Status
Subcat.
A
AB
ABC
ABCD
ABD
AC
ACD
AD
B
BC
BCD
BD
C
CD
D
E
Unknown
Total
Direct
All
Plants
2
0
0
1
0
3
1
1
2
2
0
3
13
2
22
0
0
52
Dischargers
Plants
Analyzed
2
0
0
1
0
3
1
1
2
2
0
3
10
2
21
0
0
48
Indirect
All
Plants
2
1
1
7
4
0
9
4
16
7
8
17
23
29
156
2
0
286
Dischargers
Plants
Analyzed
1
0
1
6
3
0
7
4
12
6
8
10
19
21
77
0
0
175
Zero
Dischargers
0
0
0
0
0
0
0
0
4
3
1
2
11
12
92
0
1
126
Source:  Meta Systems, Inc.   calculations, based on Section 308 survey data.
                                       199

-------
A.  COMPLIANCE COST TO SALES RATIO

The  first measure  of impact  is a  comparison  of each  plant's
annualized compliance cost to its sales,  using estimates of costs
and  sales  in 1979 dollars.   The cost estimation  procedures  are
described  in Section X  of this  report.   Sales  estimates  were
provided by Economic Information Systems  or were estimated by the
Agency on  the  basis of plant  employment and the  sales  at other
plants.2

Table XI-2  lists  the 228 plants  in  order of this cost  to sales
ratio expressed as a  percent.  The ratio could not be calculated
for  five of  the  plants  (marked *) ,  due to  missing sales  and
employment data.  Annualized  compliance  costs  as a percentage of
sales range from a high of 9.04 percent to a low of 0.01 percent.
The  median  for  all  plants  incurring  costs   is  0.15  percent.
Therefore, compliance costs for most plants are estimated to be a
very small proportion of their total revenues,  even assuming that
none of the costs  are passed on to consumers in the form of higher
prices.    However,  a  number   of  plants   will  experience  higher
compliance costs.   Thirteen plants,  or 5.8 percent of the plants,
are  estimated to  have  annualized  compliance  costs  equal to  2
percent or more of their sales, and 36 plants,  or 16.1 percent of
the  plants,  are  estimated  to have  compliance  costs equal to  1
percent or more of sales.

Since this preliminary analysis  assumes  that each plant will  use
the  same pollution control option, regardless of discharge status
or subcategory, treatment  costs are simply a function of wastewater
flow.  Therefore,  impacts  were  not analyzed to see if they differed
among subcategories and/or discharge type.
            estimates were  prepared  for earlier analyses.  For a
description  of   the   estimation   procedures,   see  Appendix  A:
Estimation  of  Pharmaceutical Plant  Sales,  Economic  Analysis of
Effluent Standards and Limitations for the Pharmaceutical Industry,
(21) EPA 440/2-83-013, September 1983.

                               200

-------
                              TABLE XI-2

PLANTS BY DISCHARGE STATUS, SUBCATEGORY AND ANNUALIZED COMPLIANCE COSTS
                        AS PERCENTAGE OF SALES
Plant
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Discharge
Status
I
I
I
D
D
I
I
D
I
I
I
D
D
D
DI
D
I
D
D
D
D
I
D
I
D
D
I
I
D
D
D
D
I
I
D
I
D
I
I
I
Subcategory
D
AD
BCD
C
AC
C
D
C
B
ACD
ACD
C
D
ABCD
D
C
C
D
D
AC
B
C
CD
CD
A
AC
CD
BD
C
ACD
A
D
CD
B
C
CD
AD
C
BD
C
Ratio of
Annual Cost
to Sales
(Percent)
9.04
6.91
5.03
3.42
3.26
3.12
3.11
2.79
2.77
2.71
2.67
2.65
2.19
1.85
1.85
1.75
1.71
1.60
1.53
1.51
1.48
1.40
1.39
1.38
1.35
1.30
1.20
1.15
1.12
1.07
1.06
1.05
1.03
1.02
1.02
1.01
0.94
0.94
0.82
0.81
                                     201

-------
                        TABLE XI-2 (continued)

PLANTS BY DISCHARGE STATUS, SUBCATEGORY AND ANNUALIZED COMPLIANCE COSTS
                        AS PERCENTAGE OF SALES
Plant
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
Discharge
Status
I
I
I
D
I
I
D
D
D
I
I
I
D
I
I
I
I
I
I
D
I
I
I
I
I
I
I
I
I
D
I
I
D
I
I
I
I
I
I
I
Subcategory
BC
C
ACD
D
C
BD
BD
C
D
D
D
D
D
D
D
D
B
AD
D
D
ABC
BCD
D
C
C
D
B
D
CD
BC
D
D
BD
BCD
C
CD
BCD
ABCD
C
B
Ratio of
Annual Cost
to Sales
(Percent)
0.79
0.75
0.73
0.72
0.70
0.69
0.68
0.60
0.59
0.55
0.53
0.51
0.50
0.47
0.45
0.45
0.44
0.43
0.42
0.39
0.38
0.36
0.36
0.35
0.35
0.35
0.34
0.33
0.33
0.32
0.32
0.31
0.31
0.31
0.31
0.30
0.29
0.29
0.28
0.27
                                     202

-------
                        TABLE XI-2 (continued)

PLANTS BY DISCHARGE STATUS, SUBCATEGORY AND ANMJALIZED COMPLIANCE COSTS
                        AS PERCENTAGE OF SALES
Plant
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
Discharge
Status
I
I
I
I
I
I
I
I
I
I
D
I
I
I
D
D
I
I
I
I
I
D
I
I
I
I
I
D
I
D
I
I
I
I
I
I
I
I
I
I
I
Subcategory
ACD
D
CD
D
B
AD
CD
BD
B
D
BD
D
B
B
CD
BC
D
D
C
CD
ABCD
C
D
D
C
CD
BD
D
ABCD
D
D
CD
CD
D
D
CD
D
ABCD
AD
CD
D
Ratio of
Annual Cost
to Sales
(Percent)
0.25
0.25
0.24
0.24
0.24
0.23
0.23
0.23
0.22
0.21
0.20
0.20
0.20
0.19
0.19
0.19
0.19
0.18
0.18
0.18
0.17
0.17
0.15
0.15
0.15
0.15
0.15
0.14
0.14
0.14
0.14
0.14
0.14
0.13
0.13
0.12
0.12
0.12
0.12
0.12
0.12
                                     203

-------
                        TABLE XI-2 (continued)

PLANTS BY DISCHARGE STATUS, SUBCATEGORY AND ANNUALIZED COMPLIANCE COSTS
                        AS PERCENTAGE OF SALES
Plant
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
Discharge
Status
I
D
1
I
I
I
I
I
D
I
I
I
I
I
I
I
I
D
D
I
I
I
I
I
I
I
D
D
I
I
DZ
I
I
I
I
I
I
I
I
I
Subcategory
ACD
D
D
BD
BC
D
ACD
BD
D
D
D
BD
C
D
B
ABCD
D
C
D
ABCD
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
B
CD
D
D
D
Ratio of
Annual Cost
to Sales
(Percent)
0.12
0.11
0.11
0.11
0.11
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.09
0.09
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.07
0.07
0.07
0.07
0.07
0.07
0.07
0.07
0.07
0.07
0.06
0.06
0.06
0.06
                                    204

-------
                        TABLE Xl-2 (continued)

PLANTS BY DISCHARGE STATUS, SUBCATEGORY AND ANNUALIZED COMPLIANCE COSTS
                        AS PERCENTAGE OF SALES
Plant
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
Discharge
Status
I
I
I
I
I
I
I
I
I
I
I
I
I
I
D
I
I
I
I
I
I
I
I
I
I
D
I
D
I
I
I
I
I
I
I
I
I
I
I
I
Subcategory
D
D
CD
ABD
D
BD
BC
D
CD
ABD
BCD
C
D
ACD
B
D
D
D
CD
C
BC
D
A
D
CD
C
C
D
D
D
BCD
BCD
CD
D
BD
D
C
D
D
BCD
Ratio of
Annual Cost
to Sales
(Percent)
0.06
0.06
0.06
0.06
0.06
0.06
0.06
0.06
0.06
0.06
0.06
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.03
0.03
0.03
0.03
0.03
0.03
                                     205

-------
                             TABLE XI-2  (continued)

     PLANTS  BY DISCHARGE  STATUS,  SUBCATEGORY AND ANNUALIZED  COMPLIANCE  COSTS
                             AS PERCENTAGE OF  SALES


Plant
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
NOTE:
Discharge Status:


Subcategory :





Discharge
Status
I
I
D
I
I
I
D
ID
I
I
I
D
I
I
I
I
I
I
I
I
I
I
D
I
D
D
D

I = Indirect Discharge
D = Direct Discharge
Z = Zero Discharge
A = Fermentation
B = Biological Extraction
C = Chemical Synthesis
D - Packaging
* = Insufficient Data


Subcategory
B
D
D
BC
D
D
D
D
D
D
BC
D
ABD
CD
D
D
D
D
C
D
D
D
C
D
C
C
D









Ratio of
Annual Cost
to Sales
(Percent)
0.03
0.03
0.03
0.03
0.03
0.03
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.01
0.01
0.01
0.01
0.01
0.01
*
-;,-
*
*
„!_









Source:  Meta Systems, Inc.  calculations based on EPA data.
                                        206

-------
B.  CHANGE IN PROFITS

The second measure  of regulatory impact estimates the  change in
profitability resulting  from  treatment compliance costs.   Since
operating cost data  for individual plants are not available at this
time,  plant-level profits are  estimated using company and industry
profitability rates.  The approach requires four steps.

1.  Plant  profits  without   the   regulation   are  estimated  by
    multiplying  plant sales  by the appropriate ratio of profits
    before taxes to sales.   Plant sales are described  above and
    profit ratios are discussed below.

2.  Annualized  compliance costs are  subtracted from profits to
    estimate plant profits with the regulation.

3.  A new profit rate is calculated as the ratio  of profits with
    the regulation to sales.  Both steps 2 and 3 assume the plant
    is unable to pass on any  of the compliance costs in the form
    of higher prices.   By using profits before taxes,  it is not
    necessary to calculate  the impact on  tax  payments  resulting
    from compliance costs.

4.  Impact is measured as the change in profitability rate due to
    compliance costs.

Two sources of profitability rate data are used in this exercise.
Average before-tax profits to  sales ratios  are calculated for each
of the 43 companies for which income account data were collected.
(See the discussion in Section IX,  dealing  with financial ratios.)
The company's profitability rate is used for  each plant owned by
the company.  For plants not  owned by one of  these 43 companies,
the ratio of pharmaceutical before-tax  profits to sales, as pub-
lished by Robert Morris  Associates,  is used.   This  ratio is 6.1
percent.

The impacts  on  profits are  presented in Table XI-3.   This table
lists the 223 plants  analyzed,  ordered by the  percentage change
in profits  resulting  from the compliance  costs.   The table also
presents the plant's estimated  profit rates  without compliance
costs, and with  compliance  costs.   For  example,  the profits for
the 25th  plant  on  the  list  decline  from 6.10  percent  to 4.95
percent, which   is  an 18.91  percent  decline  in  their profits.
Profit changes range from a low of 0.08 percent to  a high of 148.14
percent.  The two plants with the greatest declines in profits both
have  negative  profits after  paying  compliance  costs,   and thus
declines in profits exceed 100 percent.  The median decline is 2.11
percent, as in a decline  in profit  rates  from 6.10 percent to 5.97
percent.  The impact on the majority of plants with costs is very
small.  However, 44 plants,  or 19.7  percent, have  a  decline in
profits of 10 percent or more.  For example, a 10 percent decline
would lower a 7.85 percent profit rate to 7.06 percent, or a profit
rate of 4.84 percent to 4.34 percent.
                               207

-------
             XI-3




EFFECT OF REGULATION ON PROFITS






          Profit As
Plant
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
rercentag(
Without
Regulation
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
0.17
6.10
6.10
6.13
4.73
6.10
6.10
6.10
6.10
; of Sales
With
Regulation
-2.94
-0.81
1.07
2.68
2.84
2.98
3.31
3.33
3.39
3.43
3.45
3.91
4.25
4.25
4.35
4.39
4.50
4.57
4.59
4.62
4.70
4.72
4.75
4.80
4.95
4.98
0.14
5.03
5.04
5.08
3.92
5.07
5.08
5.08
5.09
Percentage
Change
	 in Profits
-148.14
-113.32
-82.50
-56.05
-53.36
-51.19
-45.81
-45.47
-44.40
-43.85
-43.51
-35.85
-30.37
-30.30
-28.75
-28.00
-26.28
-25.10
-24.77
-24.34
-22.95
-22.58
-22.10
-21.33
-18.91
-18.36
-18.06
-17.60
-17.36
-17.19
-17.10
-16.86
-16.77
-16.74
-16.58
              208

-------
       XI-3 (continued)




EFFECT OF REGULATION ON PROFITS






          Profit As
Plant
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
Percentage
Without
Regulation
19.84
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
14.31
7.78
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
8.41
10.10
4.60
6.10
6.10
6.10
14.31
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
24.55
6.10
6.10
6.10
6.10
7.78
6.10
of Sales
With
Regulation
16.73
5.16
5.16
5.28
5.35
5.37
5.40
5.41
5.42
5.50
12.92
7.06
5.55
5.57
5.59
5.65
5.68
5.71
5.72
5.74
7.91
9.51
4.33
5.75
5.75
5.76
13.52
5.77
5.77
5.78
5.78
5.79
5.79
5.79
5.79
23.35
5.80
5.81
5.81
5.82
7.43
5.85
Percentage
Change
in Profits
-15.67
-15.48
-15.35
-13.52
-12.33
-11.97
-11.47
-11.36
-11.15
-9.87
-9.69
-9.23
-9.08
-8.73
-8.38
-7.44
-6.93
-6.40
-6.22
-5.98
-5.97
-5.84
-5.79
-5.75
-5.70
-5.55
-5.50
-5.47
-5.42
-5.28
-5.21
-5.09
-5.07
-5.03
-5.01
-4.90
-4.88
-4.83
-4.72
-4.61
-4.52
-4.17
               209

-------
       XI-3 (continued)




EFFECT OF REGULATION ON PROFITS






          Profit As
Plant
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
Percent
Without
Regulation
6.10
6.10
6.10
6.10
12.70
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
7.78
4.40
6.10
6.10
14.31
6.10
6.10
6.10
6.10
6.10
19.84
6.10
6.13
6.10
6.10
8.41
19.84
7.04
6.10
19.84
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
:age of Sales
With
Regulation
5.86
5.87
5.87
5.87
12.25
5.89
5.90
5.90
5.90
5.91
5.91
5.91
5.92
5.92
7.56
4.28
5.93
5.93
13.95
5.95
5.95
5.95
5.95
5.96
19.37
5.96
5.99
5.96
5.96
8.22
19.40
6.89
5.97
19.41
5.97
5.98
5.98
5.98
5.98
5.98
5.99
5.99
Percentage
Change
in Profits
-3.87
-3.79
-3.78
-3.70
-3.58
-3.46
-3.36
-3.33
-3.30
-3.20
-3.15
-3.09
-2.97
-2.92
-2.89
-2.80
-2.77
-2.75
-2.54
-2.54
-2.53
-2.51
-2.50
-2.37
-2.37
-2.37
-2.34
-2.31
-2.27
-2.24
-2.20
-2.19
-2.17
-2.15
-2.11
-2.02
-2.00
-1.96
-1.95
-1.90
-1.85
-1.82
             210

-------
       XI-3 (continued)




EFFECT OF REGULATION ON PROFITS






          Profit As
Plant
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
Percentage
Without
Regulation
13.73
6.10
6.10
2.05
6.10
6.10
6.10
14.31
6.10
14.31
6.10
6.13
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
14.57
6.10
6.10
6.10
6.10
6.10
6.10
6.13
6.10
6.10
6.10
6.10
6.10
6.10
6.10
6.10
14.03
6.10
6.10
6.10
6.10
of Sales
With
Regulation
13.48
5.99
6.00
2.02
6.00
6.00
6.00
14.07
6.00
14.07
6.00
6.03
6.00
6.00
6.01
6.01
6.02
6.02
6.02
6.02
6.03
14.39
6.03
6.03
6.03
6.03
6.03
6.03
6.06
6.04
6.04
6.04
6.04
6.04
6.04
6.04
6.04
13.89
6.04
6.04
6.04
6.04
Percentage
Change
in Profits
-1.80
-1.75
-1.72
-1.69
-1.69
-1.66
-1.66
-1.66
-1.65
-1.65
-1.64
-1.64
-1.63
-1.62
-1.52
-1.46
-1.38
-1.37
-1.33
-1.23

-1.22
-1.22
-1.20
-1.20
-1.18
-1.16
-1.14
-1.07
-1.07
-1.05
-1.04
-1.03
-1.03
-1.03
-1.02
-1.02
-0.98
-0.98
-0.98
-0.96
-0.95
               211

-------
       XI-3 (continued)




EFFECT OF REGULATION ON PROFITS






          Profit As
Plant
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
Percentage of
Without
Regulation
11.83
6.10
6.10
6.10
6.10
4.89
6.13
6.10
6.10
6.10
12.31
6.10
7.78
6.10
6.10
6.10
6.10
6.10
14.31
6.10
6.10
6.10
6.10
6.10
6.10
19.84
6.10
6.10
6.10
14.31
6.10
6.10
6.10
6.10
19.84
6.10
17.99
6.10
20.00
6.10
6.10
14.31
Sales
With
Regulation
11.72
6.04
6.05
6.05
6.05
4.85
6.08
6.05
6.05
6.05
12.21
6.05
7.72
6.05
6.05
6.05
6.06
6.06
14.21
6.06
6.06
6.06
6.06
6.06
6.06
19.72
6.06
6.07
6.07
14.23
6.07
6.07
6.07
6.07
19.74
6.07
17.91
6.07
19.93
6.08
6.08
14.26
Percentage
Change
in Profits
-0.94
-0.92
-0.87
-0.85
-0.85
-0.82
-0.82
-0.82
-0.78
-0.78
-0.77
-0.76
-0.76
-0.75
-0.75
-0.75
-0.69
-0.68
-0.67
-0.67
-0.66
-0.64
-0.63
-0.62
-0.60
-0.60
-0.58
-0.57
-0.56
-0.55
-0.52
-0.51
-0.50
-0.49
-0.48
-0.48
-0.46
-0.42
-0.37
-0.36
-0.36
-0.35
              212

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                               XI-3 (continued)

                        EFFECT OF REGULATION ON PROFITS


                                  Profit As
Plant
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
Percentage of
Without
Regulation
19.84
6.10
24.00
7.78
6.10
7.78
6.10
6.10
7.78
22.53
19.84
6.10
18.07
6.10
6.10
6.10
19.01
14.31
7.78
14.31
Sales
With
Regulation
19.77
6.08
23.92
7.76
6.08
7.76
6.08
6.08
7.76
22.47
19.79
6.09
18.04
6.09
6.09
6.09
18.98
14.29
7.77
14.30
Percentage
Change
in Profits
-0.34
-0.33
-0.32
-0.32
-0.32
-0.31
-0.27
-0.27
-0.26
-0.25
-0.25
-0.23
-0.19
-0.17
-0.14
-0.13
-0.13
-0.13
-0.09
-0.08
Source:   Meta Systems, Inc. calculations based on data obtained from EPA and
         Compustat Services, Inc.
                                      213

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C.  CONCLUSIONS

Both   of   the  impact  measures  support  the   conclusion  that
pharmaceutical manufacturing is  generally  a  healthy industry and
most  plants  would  experience  little   or no  impact  from  the
compliance  costs associated with  regulating VOCs.   The median
profit rate without additional  compliance costs is estimated to be
6.10 percent, and the median profit rate with compliance costs is
estimated to be 6.00 percent, a decline of 1.6 percent.   In terms
of  the ratio of  compliance  costs  to sales,  the median  is  0.15
percent; and 187 plants out of  the 223 analyzed have cost to sales
ratios of 1 percent or less.   However,  some plants may experience
significant impacts from this  level of  compliance  costs.   For 44
plants, out of the 223 analyzed, profits are estimated to fall by
10  percent  or  more  due  to  this  level  of  compliance  costs.
Likewise, 13 plants, out of the 223 analyzed,  are estimated to have
ratios of compliance costs to sales of 2 percent or more.   The 44
plants with the  largest estimated declines in profit include the
13 plants with the largest cost to sales ratios.

This analysis is  intended to provide a  general  assessment of the
potential impact of regulating VOCs.  A more comprehensive analysis
would  include  additional  data  and more  precise  impact  measures.
For example, this analysis was conducted using sales for 1979 and
compliance cost  estimates  in 1979  dollars.   Current plant-level
sales  data  would reflect  any  changes  in  product  mix  and price
changes that have taken place since 1979.   Likewise, the financial
ability of the  plant  to handle compliance costs could  be better
measured if plant-specific operating  costs were available.   For
many plants  in this analysis,  an  industry-wide profit rate was
used.     Additional  and  more  current  data  would  refine  the
assessments presented  here.    However,   it  is  expected that the
general conclusion, that these  compliance costs are affordable for
most plants, would be supported.
                               214

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ENVIRONMENTAL IMPACT ANALYSIS
             215

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                XII   ENVIRONMENTAL IMPACT ANALYSIS

The  environmental  impact  analysis  summarizes the  environmental
considerations for the pharmaceutical manufacturing industry.  The
environmental considerations include an industry profile, projected
and monitored human  health and aquatic life  impacts,  as  well as
pollutant effect levels and environmental  factors.   This section
is composed of three parts, a description of the methodology used
in the analysis, a list of the data sources, and a summary of the
environmental impacts.

A.  METHODOLOGY

The environmental impacts of both direct and indirect discharging
pharmaceutical  manufacturing  facilities were projected  using  a
simplified  dilution  analysis.    In  addition,  the  impacts  of
monitored  discharges  from 47  direct  and indirect  discharging
facilities were also evaluated.

1.  Assumptions   The  following  assumptions were  used  in  the
analysis:

    o    Industry-wide  average  pollutant concentrations were used
         to project instream concentrations.

    o    Background concentrations for  each pollutant  at the POTW
         and in  the receiving streams were  equal to zero.

    o    Complete  mixing of the discharge  flow  and  stream flow
         occurs  across  the  stream at the discharge point.

    o    The plant's process water and water discharged to the POTW
         were  obtained  from a  source  other  than the  receiving
         stream.

    o    Removal efficiency rates were  based on  removals expected
         for a well-operated POTW with secondary treatment.

    o    Pollutant  fate  processes  (e.g.,  sediment  adsorption,
         volatilization,  hydrolysis)  were  not considered.   This
         results in environmentally conservative (higher) instream
         concentrations.

2.  Projected Impacts of Direct Dischargers A simplified dilution
analysis  was  performed  for  22  of the   29  direct  discharging
pharmaceutical facilities  in subcategories A, B,  and  C (Appendix
N) .  Using industry-wide average pollutant concentrations, instream
concentrations were projected at current treatment discharge levels
and under low receiving stream flow conditions (Equation 1).

 Equation 1

  Instream    Pollutant    Concentration     (ug/1)    -
Plant Concentration fua/1)  x Plant Flow (MGD)
                             Plant Flow (MGD)  +  Stream Flow (MGD)

                               216

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Instream  pollutant concentrations  were  compared to  EPA  water
quality criteria or toxic effect levels  (reported in  the MDSD's
Toxics  Data  Base).   Water  quality  criteria  exceedances  were
determined   by  dividing   the   projected  instream   pollutant
concentrations by the EPA water  quality  criteria or  toxic effect
levels (except for acute aquatic life criteria, which were compared
directly to effluent levels).   A value greater than one indicated
an exceedance.

3.  Projected Impacts of Indirect Dischargers  The  environmental
impact on 26  POTWs and their  receiving streams  for 28  of the 130
indirect discharging pharmaceutical  facilities  (in subcategories
A, B,  and  C)  were also  evaluated.   A simplified  POTW model and
stream dilution  analysis were used  to project  receiving stream
impacts (Appendix 0) .  POTW influent and effluent concentrations
are shown in Equations 2 and 3.

  Equation 2

    POTW Influent Concentration  (ug/1) =
    Plant Concentration  (ug/l)x	Plant Flow  (MGD)	
                             Plant Flow  (MGD) + POTW Flow  (MGD)
  Equation 3

  POTW Effluent
  Concentration  (ug/1) =  POTW  Influent  (ug/1) x (1-Treatment
                    Removal Efficiency)
The  simplified dilution  model  predicts  the instream pollutant
concentrations  resulting  from  indirect   discharging  facilities
(Equation 4).

  Equation 4

   Instream    Pollutant    Concentration    (ug/1)    =
POTW Effluent Concentration fua/1) x POTW Flow  (MGD)
      POTW Flow  (MGD)  + Receiving Stream Flow (MGD)
Impacts on POTW operations were calculated in terms of inhibition
of POTW processes  and contamination  of POTW sludges.  Inhibition
of POTW  processes were  determined  by comparing  calculated POTW
influent levels  (Equation 2)  with inhibition levels,  which were
available for 12 volatile pollutants.  Sludge contamination could
not be  evaluated as no  values for  sludge  contamination for the
volatiles have been published. For pharmaceutical facilities that
discharge to  the same POTW,  their  individual  flows were summed
prior to calculating the POTW influent and effluent concentrations.

4.  Monitored Impacts of Direct and  Indirect Dischargers
The environmental impacts of current loadings, as monitored on 22
streams receiving direct discharges from pharmaceutical facilities
and  on  25  streams  receiving  discharges  from  pharmaceutical
facilities discharging to POTWs,  were also evaluated.  Impacts of
volatile pollutant loadings were assessed by comparing ambient
                               217

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 instream pollutant concentrations in STORET to EPA  water quality
 criteria or toxic effect  levels  (reported in MDSD's  Toxics  Data
 Base) .   Data were retrieved from 1980 to present and summarized as
 detected (unremarked, nonzero data)  or not detected (remarked,  zero
 data)  according to media type.  Pollutant  data for pharmaceutical
 facilities in the Permit Compliance System  (PCS)  with monitoring
 requirements or limitations were  also summarized.

 B.   DATA SOURCES

 The pharmaceutical  manufacturing  industry includes a  total of 52
 direct  discharging  facilities (29 in subcategories A,  B,  & C and
 23  in subcategory D)  and 285  indirect discharging  facilities  (130
 in  subcategories A,  B  & C  and  155  in  subcategory  D)  located
 throughout the  United States  and  Puerto  Rico.

 Preliminary plant and stream information was readily  available and
 sufficient to evaluate some of the direct and indirect  discharging
 facilities in subcategories  A, B, and C only.  Based  on initial
 review  of available  data  by  EPA, it was  apparent that  volatile
 organic compounds used  as process solvents were likely to be the
 pollutants of  concern.   Therefore,  the following  environmental
 analysis focuses on these  facilities  and pollutants.

 ij—Plant-Specific Data   Projected  pharmaceutical plant  and  POTW
 effluent flows  and projected plant pollutant loadings (Appendix P)
 were obtained  from  EPA's Industrial Technology Division  (ITD)  in
 October 1987.   The locations  of facilities and POTWs on receiving
 streams were obtained  from  the  Industrial  Facilities Discharge
 (IFD) data base (Appendix Q).   (It should be noted that the names
 of  the  POTWs were matched as well  as  possible with  the  information
 in  IFD; however, some POTWs may have  been incorrectly identified.)
 The USGS cataloging  and stream segment   (reach) numbers,  obtained
 from IFD,  were  used to obtain the receiving stream flow data  from
 the W.E.  Gates  study.   The W.E.  Gates  study contains  calculated
 average and low flow  statistics based on the best available  flow
 data  and  on drainage  areas  for reaches  throughout  the United
 States.

 2_.	POTW  Evaluations  POTW treatment efficiency removal rates  were
 developed from POTW removal data and  pilot  plant studies (Appendix
 R) .  The removal rates assumed that the evaluated POTWs were well-
 operated  and had at least secondary treatment  in place.

 Inhibition values were obtained from data published in  the Federal
 Guidelines,  state and Local  Pretreatment  Programs,  January  1977
 (EPA 430/9-76-Ol7a)  (Appendix 0).   No sludge contamination values
 were available  for this analysis.

lj—Monitoring  Data   Water quality  data were obtained from the
 STORET  Water Quality  File (March  1988).   Facility monitoring or
 limitations data were obtained  from  the  Permit Compliance System
 (March  1988).
                               218

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4.  Water Quality Criteria (WOO    The ambient  criteria  for  the
protection of  aquatic  life and human health  considerations were
obtained  from  EPA  criteria   documents.    Toxic  effect  levels
(reported in the MDSD's Toxics Data Base)  were used when criteria
values were not available  (Appendix S).

a.  Aquatic Life. Several WQC  values have been established for the
protection of freshwater aquatic life (acute and chronic criteria).
The  acute  value  represents  a maximum  allowable  1-hour  average
concentration  of  a pollutant  at any  time  and can be  related to
acute toxic effects on aquatic life.   The chronic value represents
the  average  allowable concentration,  over  a  4-day period,  of a
toxic pollutant  and can  be related to chronic  effects resulting
from long-term exposure to aquatic  life.  Freshwater criteria were
used since the facilities evaluated discharge to freshwater rivers
and streams.

b.  Human Health Criteria.  EPA established water quality criteria
values to  protect human  health  in terms of  a  pollutant's toxic
effects and  carcinogenic potential.   These WQC values have been
developed  for  two exposure routes:   (1)  ingesting the pollutant
both  through water  and  contaminated  aquatic organisms,  and  (2)
ingesting the pollutant through contamination  of aquatic organisms
only.  The values for ingesting  water and organisms were derived
by assuming a daily ingestion  of  two liters of water and 6.5 grams
of potentially contaminated fish  products.   Carcinogenicity values
were used to access the  potential  effects  on  human health when a
pollutant was  suspected of being carcinogenic to humans.

Criteria for suspected or actual carcinogens  have been developed
in terms of  three  lifetime risks (risk levels of 10's,  10"8,  and
10"7.   Criteria at a risk level of 10"6  were  chosen  for  this
analysis.    This  risk  level  indicates   a  probability  of   one
additional  case of  cancer for every 1,000,000  persons exposed.
Toxic  effects criteria  for noncarcinogens are based  on bodily
disfunction, such  as damage to the liver.

C.   SUMMARY  OF ENVIRONMENTAL IMPACTS

Receiving stream  impacts  were evaluated for 22 direct and 28
indirect pharmaceutical  facilities in subcategories A, B, and C.

1.   Projected  Impacts  of  Direct  Discharging Facilities  A total of
22 direct facilities discharging 15 volatile organics to 22  stream
segments were  evaluated.   At low receiving  stream  flow, pollutant
instream  concentrations   were  projected to exceed human  health
(water and organisms)  criteria in  86  percent  (19 of the total  22)
of the receiving stream segments at current conditions  (Table XII-
1).  A total of 8  pollutants  (all  known or  suspected carcinogens)
were projected to exceed  water quality criteria using a target risk
level of 10"* for the carcinogens (Tables XII-1 and XII-2) .

None  of the  volatile pollutants were  projected to exceed aquatic
life criteria  or  toxic effect  levels  (Tables XII-1 and XII-2).
                                219

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£*—Monitored Impacts of Direct Discharging Facilities Five of the
22 streams receiving discharges from 22 facilities were monitored
for volatile pollutants  (Table  XII-3).   Nine of the 15 evaluated
pollutants were detected in water,  tissue,  or sediments in  four of
the five  stream segments  (Tables  XII-3  and XII-4).  Two  of the
pollutants exceed human health criteria in three of the five stream
segments  using  a  target  risk  level  of  10*  for  the carcinogens
(Table XII-3 and  XII-4).   None  of  the volatile pollutants exceed
aquatic life  criteria or  aquatic  life  toxic effect levels.   In
addition,  eleven  of the  evaluated pollutants were  monitored or
limited for 36 percent of the facilities in PCS (8 of 22)  (Tables
XII-3 and XII-4).

3-s—Projected  Impacts of Indirect Discharging Facilities  Receiving
stream impacts were evaluated for 26 POTWs  receiving discharges of
28 indirect pharmaceutical facilities.    A total  of  21  volatile
pollutants discharging to 25 receiving streams were evaluated.  At
low receiving stream flow, pollutant instream concentrations were
projected to exceed human health (water and organisms) criteria in
60 percent (15 of  the  total  25)  of the  receiving stream segments
at current conditions (Table XII-5).   Six pollutants  (all known or
suspected carcinogens)  were  projected  to  exceed water  quality
criteria  using  a  target  risk level  of  10"8  for  the carcinogens
(Tables XII-5 and  XII-6).   None of the volatile  pollutants were
projected to exceed aquatic  life criteria  or toxic effect levels
(Tables XII-5  and XII-6).

Impacts to  POTW  operations  were  also  evaluated.   At  current
conditions,  no inhibition of  POTW treatment processes is projected
for the   12 volatile  pollutants  which  have inhibition  values.
Sludge contamination could not be evaluated as no values for sludge
contamination  from volatile pollutants have been published.
                               220

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                                                                 TABLE  XII-1
                             SUMMARY OF VOLATILE ORGANICS  AND  RECEIVING STREAMS  WITH PROJECTED HUMAN HEALTH AND
                                          AQUATIC LIFE  IMPACTS AT  LOW FLOW UNDER CURRENT CONDITIONS
                                                DIRECT  DISCHARGERS (Subcategory  A,  B,  and C)
                                                                                                          Percent of
Projected
Discharge of
Pollutants
Known or
Suspected
Carcinogen
Human Health or
Aquatic Life
Criteria
Available*
Pollutants
Evaluated
Receiving
Streams
Evaluated
Receiving
Streams with
Exceedances
Number
Pollutants
Projected
To Exceed
Criteria
       Human Health Impacts

       Volatile O.rganics                     24

       Aquatic Life '.Impacts {Chromic)

       Volatile ©rganics                     24
16**
22
              21
15
              14
22
            22
86 (19/22)
N)
NJ
       NOTE:  Projections were based on simplified dilution analysis  assuming industry-wide average pollutant concentrations.
          C = Carcinogen, M = Mutagen, T = Teratogen
         *Criteria or toxic effect levels were available or estimated.   Human health criteria (water and organisms) at a risk level of
          10 6 for carcinogens.
        •^Criterion for halomethanes has been derived for an entire class  of compounds.   EPA does not state that each chemical in the
          class is a carcinogen.
         aAll known or suspected carcinogens.

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                                           TABLE XII-2

                         SUMMARY  OF VOLATILE ORGANICS  PROJECTED TO EXCEED
                           CRITERIA AT LOW FLOW UNDER  CURRENT CONDITIONS
                           DIRECT DISCHARGERS  (Subcategory A, B, and C)
Pollutant
Average
Effluent
Pollutant
Concentration
(M8/2)
Water Quality
Criteria3 (pg/J?)
Human Aquatic
Health Life
(W&O) (Chronic)
Number of
Exceedances
Human Aquatic
Health Life
(W&O) (Chronic)
Known or
Suspected
Effects
Volatile Organics
Benzene
Bromodichlorome thane
Chloroform
Chloromethane
1 ,2-Dichloroethane
1 , 1-Dichloroehtene
Methylene chloride
Tetrachloromethane
94.8
1.3
63.2
52.1
83.7
90.0
631.7
25.3
0.66
0.19
0.19
0.19
0.94
0.033
0.19
0.4
265
...
1,240
27,500
20,000
2,400
9,650
352
10
4
12
11
7
19
19
7
C(A)/T
C
C(B9)/M
C(NIOSH-X)
C(B,)/M
C(CJ
C(B,)
2.
*™ GtiJrt jri
NOTE:

Total No. of Facilities - 22
Total No. of Receiving Streams - 22
  For pollutants without EPA criteria, toxic effect levels, reported in the MDSD's
k Toxics Data Base or estimated using environmental factors, were used.
  Criterion for halomethanes has been derived for an entire class of compounds.  EPA
  does not state that each chemical in the class is a carcinogen.
W&O = Ingesting water and organisms.
  C = Carcinogen (CAG designation, if available, or other specified group designation).
  M = Mutagen, T = Teratogen
CAG - A   = Human carcinogen
      B~  = Probable human carcinogen
      C   = Possible human carcinogen
NIOSH - x = Potential carcinogen
                                          222

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                                                             TABLE  XII-3

                                            SUMMARY OF MONITORED RECEIVING STREAM IMPACTS
                                      DIRECT AND INDIRECT DISCHARGERS  (Subcategory A,  B, and C)















Receiving Receiving
Type of
m. j j*s_ v —
Discharge
Direct 22
Indirect
Facilities
Evaluated
22 15 5
26-POTWs 25
9
21
Streams Pollutants Streams
Evaluated Evaluated Monitored
4
6
3 8
8435

Receiving
Streams
with
Detected Detected
Pollutants Pollutants


Receiving
Streams
with
Pollutants
Exceeding
Criteria



Facilities
with
Monitoring
Requirements
or Limitations


28-Facilites
   NOTE:  Receiving stream water quality data was obtained from STORET, 1980 to present (March 1988)
          Facility information was obtained from the Permit Compliance System (March 1988).

   f Human health criteria (water and organisms) at a risk level of 10 6 for carcinogens.
     28 Facilities discharging to 26 POTWs.
N>

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                                        TABLE XII-4

                          SUMMARY OF MONITORED POLLUTANT IMPACTS
                       DIRECT DISCHARGERS  (Subcategory A,  B,  and C)
Number of
Pollutant Facilities in PC:
Acrolein
Benzene
Bromodichlorome thane
Chloroform
Chlorome thane
Dibromochlorme thane
1 ,2-Dichloroethane
1 , 1-Dichloroehtene
Ethylbenzene
Methylene Chloride
Tetrachloroethene
Tetrachlorome thane
Toluene
1 , 1 , 1-Trichloroethane
Trichloroethene
NOTE:
Ph a v*m •a/-»^ii^^^'»l *r*41^*-«'«»

4
2
5
1
2
2
1

4

1
2
1


.
Observations
in Storet
Sa Detected Not Detected

W*, T

W*
T


T
T
W

T
W
W


w,
S
w,
s,
w,
w,
w,
w,
w,
w,
s,
w,
w,
s,
s,


S, T

S, T
T
S
S, T
S, T
S, T
S
S
T
S, T
S
T
T


Known or
Suspected
Effects0

C(A)/T
C
C(B2)/M
C(NIOSH-X)
C
C(B2)/M
C(C)

C(B2)
C(B2)
C(B2)/M


C(B2)/M


  Pharmaceutical facilities with monitoring or limits data in the Permit Compliance
  System (March 1988).

  STORET data 1980 to present.  Detected = Unremarked or nonzero data.
  Not Detected = Remarked or zero data.  Information is reported for the
  following sample media: S = Sediment, W = Water, and T = Tissue.

  Criterion for halomethanes has been derived for an entire class of compounds.  EPA
  does not state that each chemical in the class is a carcinogen.

* Exceeds human health criteria for ingesting water and organisms (R = 1E-6).

C = Carcinogen (CAG designation, if available, or other specified group designation).
M = Mutagen, T = Teratogen

CAG - A  = Human carcinogen
      B2 = Probable human carcinogen
      C  = Possible human carcinogen
NIOSH-X  = Potential carcinogen
                                       224

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                                                                   TABLE XII-5

                               SUMMARY OF VOLATILE ORGANICS AND RECEIVING STREAMS WITH PROJECTED HUMAN HEALTH AND
                                            AQUATIC LIFE IMPACTS AT LOW FLOW UNDER CURRENT CONDITIONS
                                                 INDIRECT DISCHARGERS (Subcategory A, B, and C)
                                                                                                           Percent of
Projected
Discharge of
Pollutants
Known or
Suspected
Carcinogen
Human Health or
Aquatic Life
Criteria
Available*
Pollutants
Evaluated
Receiving
Streams
Evaluated
Receiving
Streams with
Exceedances
Number
Pollutants
Projected
To Exceed
Criteria
K)
M
Ul
        HUMAN HEALTH IMPACTS

        Volatile Organics                     24

        AQUATIC LIFE IMPACTS (CHRONIC)

        Volatile Organics                     24
16**
22
              21
21
              21
25
            25
60 (15/25)
        NOTE:  Projections were based on simplified dilution analysis assuming industry-wide average pollutant concentrations.
           C = Carcinogen, M = Mutagen, T = Teratogen
          *Criteria or toxic effect levels were available or estimated.  Human health criteria (water and organisms) at a risk level of
           10 6 for carcinogens.
         **Criterion for halomethanes has been derived for an entire class of compounds.  EPA does not state that eac'h chemical in the
           class is a carcinogen.
           All known or suspected carcinogens.

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                                            TABLE XII-6

                         SUMMARY OF VOLATILE ORGANICS PROJECTED TO EXCEED
                           CRITERIA AT LOW FLOW UNDER CURRENT CONDITIONS
                           INDIRECT DISCHARGERS (Subcategory A, B, and C)
                       Average
                       Effluent
                       Pollutant
                     Concentration
Pollutant
  POTW
Treatment
Efficiency
             Water Quality
            Criteria0 (pg/1)
                      Number of
                      Exceedances
Human
Health
(W&O)
 Aquatic
  Life
(Chronic)
Human
Health
(W&O)
 Aquatic
  Life
(Chronic)
Known or
Suspected
 Effects
Volatile Organics0
Benzene
Chloroform
Chloromethane
1,2-Dichloroethane
1 , 1-Dichloroethene
Methylene chloride
971.8
264.1
2,091.4
760.5
30.6
5,925.8
0.98
0.83
0.90
0.88
0.84
0.95
0.66
0.19
0.19
0.94
0.033
0.19
265
1,240
27,500
20,000
2,400
9,650
2(2)
10(9)
15(14)
5(5)
7(6)
16(15)
C(A)/T
C(B )/M
C(NTOSH-X)
C(B )/M
C(CJ
C(B2)
NOTE:

Total No. of POTWs - 26
Total No. of Facilities - 28
Total No. of Receiving Streams - 25
,  Concentration discharged from pharmaceutical industry.
  For pollutants without EPA criteria, toxic effect levels, reported in the MDSD's Toxics Data
  Base or estimated using environmental factors, were used.
  Criterion for halomethanes has been derived for an entire class of compounds.  EPA does not
  state that each chemical in the class is a carcinogen.
( ) = Number of receiving streams.
  C = Carcinogen (CAG designation, if available, or other specified group designation).
  M = Mutagen, T = Teratogen
CAG - A   = Human carcinogen
      B~  - Probable human carcinogen
      C   = Possible human carcinogen
NIOSH - x = Potential carcinogen
                                                 226

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A.  Monitor^ TTnnacts of Tndustrial Pi scharqincf Facilities Six of
the 25 streams receiving discharges from pharmaceutical facilities
discharging to POTWs were monitored for volatile pollutants (Table
XII-3).   Eight  of  the 21  evaluated  volatile pollutants  were
detected in water, tissue,  or sediments in four of the six stream
segments (Tables XII-3 and  XII-7).  Three of the pollutants exceed
human health criteria in three of  the six stream segments using a
target risk level of 10"8 for  carcinogens  (Tables XII-3 and Xii-7).
None  of  the volatile pollutants exceed aquatic  life criteria or
aquatic  life toxic  effect  levels.   In  addition,  eight  of the
evaluated pollutants were  monitored  or limited for 19 percent of
the POTWs in PCS  (5  of  26)  (Tables XII-3 and XII-7).
                                227

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                                       TABLE XII-7

                         SUMMARY OF MONITORED POLLUTANT IMPACTS
                      INDIRECT DISCHARGERS  (Subcategory A, B, and C)
                                                                             Known or

Number of _ Observations in Storet Suspected
Pollutant Facilities in PCS" Detected Not Detected Effects1"
Acrolein
Acrylonitrile
Benzene
Bromodichlorome thane
Chlorobenzene
Chloroethene
Chloroform
Chlorome thane
1 , 1-Dichloroe thane
1,2-Dichloroethane
1 , 1-Dichloroethene
Ethylbenzene
Methylene Chloride
1,1,2, 2-Tetrachloroethane
Tetrachloroethene
Tetrachlorome thane
Toluene
Tribromome thane
1,1, 1-Trichloroethane
1 , 1 ,2-Trichloroe thane
Trichloroethene
NOTE:


1

1

2


2


1



2

1

1

Pharmaceutical facilities with monitoring
System (March 1988).
STORET data 1980 to present
Not Detected = Remarked or
following sample media: S =
Criterion for halomethanes

. Detected =
W, S, T
W, S, T
W, S, T
W, S, T
W, S, T
W, S, T
W*, S, T
W, S, T
W, S, T
W, S, T
W, S, T
W, S, T
W*, S, T
W, S, T
W*, S T
W, S, T
T W, S
W, S, T
W, S T
S W, T
W, S T


C(B2)/M/T
C(A)/T
C

C(A)/M
C(B2)/M
C(NIOSH-X)

C(B2)/M
C(C)

C(B2)
C(C)
C(B2)
C(B2)/M

C

C(C)
C(B2)/M

or limits data in the Permit Compliance

Unremarked or nonzero data
zero data. Information is reported for
Sediment, W =
Water, and T = Tissue.
has been derived for an entire class of
does not state that each chemical in the
class is a carcinogen.


the

compounds . EPA

* Exceeds human health criteria for ingesting water and organisms (R = 1E-6).

C = Carcinogen (CAG designation, if available, or other specified group designation).
M = Mutagen, T = Teratogen

CAG - A  = Human carcinogen
      B2 = Probable human carcinogen
      C  = Possible human carcinogen
NIOSH-X  = Potential carcinogen
                                           228

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                        XIII.   REFERENCES

1.  PEDCo Environmental submittal to the U.S.  EPA,  "The Presence
    of   Priority  Pollutant   Materials   in   the   Fermentation
    Manufacture of Pharmaceuticals", no date.

2.  PEDCo Environmental submittal to the U.S.  EPA,  "The Presence
    of  Priority  Pollutants  in the  Extractive  Manufacture  of
    Pharmaceuticals", October 1978.

3.  PEDCo Environmental submittal to the U.S.  EPA,  "The Presence
    of  Priority  Pollutants  in  the  Synthetic  Manufacture  of
    Pharmaceuticals",  March 1979.

4.  U.S. EPA, "Development Document  for Final Effluent Limitations
    Guidelines, New Source Performance Standards and Pretreatment
    Standards  for the Pharmaceutical Manufacturing  Point Source
    Category", EPA 440/1-83/084, September 1983.

5.  U.S.  EPA,   "Development   Document  for   Proposed  Effluent
    Limitations Guidelines, New Source  Performance  Standards and
    Pretreatment  Standards for the  Pharmaceutical  Manufacturing
    Point Source  Category", EPA 440/1-82/084,  November 1982.

6.  U.S.  EPA,   "Control   of   Volatile   Organic  Emissions  from
    Manufacture   of  Synthesized  Pharmaceutical  Products",  EPA
    Office  of Air Quality Planning  and  Standards,  450/2-78-029,
    December  1978.

7.  Letter   dated  August  18,   1986,   from  Thomas   X.  White
    (Pharmaceutical Manufacturers Association)  to David Beck (U.S.
    EPA, OAQPS, RTF, NC).

8.  U.S.  EPA, "Industry  Fate  Study",  Report No.  600/2-79-175,
    August  1979.

9.  E.G. Jordan  Co., "Pretreatment Standards  Evaluation for the
    Pharmaceutical  Manufacturing Category", Report to  the U.S.
    EPA, Contract No. 68-01-6675, August 1983.

10. Windholz, M., et. al.,  "The Merck  Index,"  Merck & Co., Inc.,
    Rahway, NJ. tenth edition,  1983.

11. Treybal,  R.E.,   Mass  - Transfer Operations. Third Edition.
    McGraw-Hill Book Company, New York, NY, 1980.

12. McCabe,  W.L., and  J.C.  Smith,  Unit Operations  oj: Chemical
    Engineering.  Third Edition.  McGraw-Hill  Book  Company,  New
    York, NY, 1976.

13. Peters, M.S., and K.D. Timmerhaus, Plant Design and  Economics
    for  Chemical  Engineers.   Second Edition.  McGraw-Hill  Book
    Company,  New  York, NY, 1968.
                               229

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14. Hwang,  Seong  T.,  and Fahrenthold,  Paul,  "Treatability of the
    Organic Priority  Pollutants by Steam Stripping", presented at
    A.I.Ch.E. meeting, August 1979.

15. Chemical  Engineers Handbook.  4th  Edition.  McGraw-Hill Book
    Company, New  York, NY, 1963.

16. U.S.EPA, "Proposed Development Document for Effluent
    Limitations Guidelines and Standards for the
    Pesticides Point Source Category",  EPA 440/1-82/079-b,
    Washington, D.C., November 1982.

17. U.S.EPA,"Proposed Development Document for Effluent
    Limitations Guidelines and Standards for the  Organic
    Chemicals and Plastics and Synthetic Fibers Point Source
    Category", EPA 440/1-83/009-6, Washington, D.C.,  February
    1983.

18. Petrasek, A.,  et.al.,  "Removal and Partitioning  of Volatile
    Organic Priority  Pollutants",  Proceedings  of the Ninth U.S.-
    Japan Conference  on  Sewage Treatment Technology,  EPA 600/9-
    85/014,  Water  Engineering Research  Laboratory,  U.S.  EPA,
    Cincinnati, OH, May 1985, pp. 559-591.

19. U.S. EPA, "Treatability Manual, Volume I - Treatability Data",
    Office  of Research  and  Development,  Washington,  D.C.,  EPA
    600/2-82-OOla, February 1983.

20. Communication with technical contractor.

21. U.S.  EPA,  "Economic  Analysis  of  Effluent  Standards  and
    Limitations for  the  Pharmaceutical Industry",  EPA 440/2-83-
    013, September 1983.

22. The Wall Street Journal,  Friday, August 7,  1987, p.6.
                               230

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                    XIV.   GLOSSARY OF ACRONYMS
AC
ACA
ANPR
BAT
BCT
BMPs
BOD
BOD5
BPT
CC
CNS
COD
CRF
CWA
DSE
DSS
E
EOF
EPA
F/M
GAG
GC
HSWA
IFD
ITD
LEL
MDSD
MEK
MF
MGD
MLVSS
MS
NPDES
NRDC
NSPS
OAQPS
O&M
PAC
PCS
PEDCo
PMA
POTWS
PSES
PSNS
Q
RBC
RCRA
R&D
RMA
RSKERL/ADA
Annualized Cost
Activated Carbon Adsorption
Advance Notice of Proposal Rulemaking
Best Available Technology
Best Conventional Technology
Best Management Practices
Biochemical Oxygen Demand
Five-Day Biochemical Oxygen Demand
Best Practical Technology
Capital Costs
Central Nervous System
Chemical Oxygen Demand
Capital Recovery Factor
Clean Water Act
Domestic Sewage Exclusion
Domestic Sewage Study
Error Term
End-of-Pipe
U.S. Environmental Protection Agency
Food/Microorganism Ratio
Granular Activated Carbon
Gas Chromatography
Hazardous and Solid Waste Amendments of 1984
Industrial Facilities Discharge
Industrial Technology Division
Lower Explosion Limit
Monitoring and Data Support Division (EPA)
Methyl Ethyl Ketone
Monitoring Fee
Million Gallons Per Day
Mixed Liquor Volatile Suspended Solids
Mass Spectrometry
National Pollutant Discharge Elimination System
Natural Resources Defense Council
New Source Performance Standards
Office of Air Quality Planning and Standards
Operating and Maintenance Costs
Powdered Activated Carbon
Permit Compliance System
PEDCo Environmental, Incorporated
Pharmaceutical Manufacturers Association
Publicly Owned Treatment Works
Pretreatment Standards for Existing Sources
Pretreatment Standards for New Sources
FLowrate
Rotating Biological Contactor
Resource Conservation and Recovery Act of 1976
Research and Development
Robert Morris Associates
Robert S. Kerr Environmental Research Laboratory at
Ada, Oklahoma
                               231

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SCOD           Soluble Chemical Oxygen Demand
SIC            Standard Industrial Classification
SVI            Sludge Volume Index
SVOCs          Semivolatile Organic Compounds
TCLP           Toxicity Characteristic Leaching Procedure
TEPP           Tetraethylpyrophosphate
TOC            Total Organic Carbon
TSS            Total Suspended Solids
TTVOs          Total Toxic Volatile Organics
TVOs           Total Volatile Organics
VFMLS          Viscous Floating Mass of Mixed Liquor Solids
VOCs           Volatile Organic Compounds
WQC            Water Quality Criteria
                               232

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