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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.
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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
-------
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
-------
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
-------
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
-------
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).
-------
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,
-------
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
-------
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
-------
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)
..
— - — ~
_ _ — —
_ _ — —
— — — —
_ -. — —
__
(a) Existing BPT, BODS, TSS, and COD
48 FR 49808, October 27, 1983.
4.89.90T
0048.0.0
-------
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
-------
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-
31
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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
-------
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
-------
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-
CMOMOFOHM-
IQlUfcNk-
ME IMVIENE CM OHM IE-
CARBON TETHACMOMJE-
CHLOHO8EN2ENE-
CHLOHOMETHANE-
aftOMOMETHAME-
AamOMTMLE-
TMOtOftOETHYLENE-
EIHVLElC OCHLOMIE-
METHANOL-
ACETOnc-
ETHYl ACElATE-
PYNUME-
I.4UKMAM:-
IO1AI XVIEM-6-
IE TRAM VONOFUHAN •
ETMYl ETHHt-
ACETOMTMLE •
nBUTVl ALCOHU.-
OOOMETMAK-
- MfeR-
OMETHnAMNE-
FOHMAL06HYI* -
ACE in CMiomiE-
CYOOKXAK-
f OAMC AOO-
WMf JHYl SULFOXIIE-
E1HVLENE OKI* -
OCTHVIAMMC-
lui OME IHVLFOHMAMtC-
ACEP»*NON£-
ACE1ALOEMYUE-
HHANOL7 OtOHO-
MEInYl MERCAPlAM-
iSOBUKt AlCOMfX.-
HVDMA^M -
VMVl ACf Ulf-
FUVUMAi-
METHVl METHACMALAlE*
J ' ! ' I '
XIX KXXXXXXXXXXXXXX^
X X XJ X KXXXXXXXXXXXX
1 xkxxxxxxxxxxVxxxM
XKXXXXXXXX^I
1 ^vXXXX>l
E3
S3
3
&OOOO&OOC
1 1 1 \ 1 1 1 1
XX\\XX\XX\XXXXX1
V\XXS\XX\VM
1
a
3
3
fc
i
2
X X X N X y^\X\\\\X\XX\XXX\XXXX\\\XXXX\XXXXX\X\XXJ
V V V V 1 / XxxxxxxxxxxxxxxVxxxxxxxxxxxxxxxxxxxxT
XXIX K\\\X\XXX\XX\\XX\\X\VS
VI KX\\V\\\\\XXXXXXX\X\XN
1 / NXXXXXXXXl
vXXXXXXXXI
CVXXXXXXX1
1 KxxxVN
KVVxxVi
NKXXX^
KXXXXM
Vvxxxl
XXXN
S3
S3
13
E3
3
D
3
3
3
3
1
n
I
m
i
e
1
*
^ CT [^1
RSj i/\ [S3
O «D >
lie
e e c
Q -< 2
CO O CO
m
I
O
3
m
o
Z
CO
: «
s g
^ §
-------
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* ^^ ^^ ^^
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MO O — — K> O W ff. O
<^f^ taC ^ «V«I^^P'^^ **
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*^ n
-
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N e
s?
S1?
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ii g
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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
-------
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
-------
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
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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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
. . 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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
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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
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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
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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
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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.
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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
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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.
-------
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.
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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
-------
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 $500 million or more in 1979.
A similar distribution of sizes is found when plants are ranked
according to number of pharmaceutical employment. Nearly one-third
have less than 20 employees and about 60 percent have less than 100
employees. At the other end of the range, 53 plants (over 11
percent) have 500 or more employees.
187
-------
TABLE IX-2
PLANT SIZES: SALES AND EMPLOYMENT
Sales ($ 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
-------
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
-------
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
-------
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 $20.8 million.
191
-------
TABLE X-l
CALCULATION OF ANNUALIZED COSTS FOR PLANTS WITH PROCESS WASTEWATER FLOW
(Plants ordered by Annualized Cost)
Line
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Process
Wastewater
Flow
(mud)
8.3160
2.9730
2.0250
1.8000
1.7000
1.6500
1.6350
1 . 4480
1.3000
1.2500
1.1700
1.1000
1.0920
1.0650
1.0400
1.0280
1.0070
0.9940
0.9000
0.8780
0.8500
0.7780
0.7400
0.7010
0.7000
0.5270
0.5000
0.5000
0 . 4640
0.4300
0.4250
0.4100
0.3870
0.3800
0.3800
0.3620
0.3500
0.3500
0.3400
0.2950
Capital
Cost
(S)
1,381,880
711,033
554,825
514,176
495,536
486,072
483,212
446,747
416,690
406,265
389,272
374,063
372,304
366,331
360,752
358,058
353,315
350,362
328,584
323,372
316,672
299,074
289,554
279,601
279,344
232,539
224,771
224,771
214,179
203,904
202,369
197,726
190,488
188,255
188,255
182,445
178,515
178,515
175,203
159,849
O&M
Cost
(S/yr)
2,605,781
1,172,961
870,703
794,650
760,173
742,766
737,520
671,183
617,311
598,806
568,848
542,257
539,194
528,820
519,161
514,507
506,332
501,252
464,06*
455,235
443,929
414,462
398,665
382,262
381,839
306,344
294,093
294,093
277,525
261,611
259,247
252,118
241,073
237,682
237,682
228.898
222,988
222,988
218,028
195,284
Monitoring
Fee
($/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
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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
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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
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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
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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
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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
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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
-------
ENVIRONMENTAL IMPACT ANALYSIS
215
-------
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
-------
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
-------
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
-------
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
-------
£*—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
-------
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.
-------
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
-------
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>
-------
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
-------
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.
-------
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
-------
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
-------
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
-------
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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