EPA-340/1-80-016
      Enforceability Aspects for
RACT for the Chemical Synthesis
       Pharmaceutical  Industry
                       by

              T. Briggs, C. Harvey, J. McClure,
                  and R. Pollard-Cavalli

                PEDCo Environmental, Inc.
                  11499 Chester Road
                 Cincinnati, Ohio 45246
                 Contract No. 68-01-4147

                    Task No. 128



              EPA Project Officer: John R. Busik

               Task Manager: Robert L King
                    Prepared for

          U.S. ENVIRONMENTAL PROTECTION AGENCY
               Office of General Enforcement
            Division of Stationary Source Enforcement
                 Washington DC 20460

                    January 1981

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                                  DISCLAIMER


     This report was  furnished to the U.S. Environmental Protection Agency by
PEDCo  Environmental,   Inc.,   in  fulfillment  of  Contract  No.  68014147.   The
contents of this report are reproduced herein as received from the contractor.
The opinions,  findings,  and  conclusions expressed are those of the author and
not necessarily those of the U.S. Environmental Protection Agency.

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                                    CONTENTS
 1     Introduction

       Background of RACT
       Purpose and Scope of Report

 2     Industry Characterization

       Overview of Pharmaceutical Industry
       Process Description of Synthetic Pharmaceutical Industry
       Geographical Distribution of Synthetic Pharmaceutical Industry

 3    Control Techniques and Factors Affecting Enforcement

       Summary of RACT Regulations
       Control Technologies
       Factors Affecting Enforcement

4    Recommendations For Further Investigation

       Determining VOC Emissions
       Clarifying the Bubble Concept
       Extending Compliance Schedules

Appendix A
Appendix B
Page

   1

   1
   1
   2
   2
   9

  13

  13
  14
  16

  19

  19
  19
  19

A-l
B-l
                                      m

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                                    TABLES
Number

  1


  2
Distribution of Synthetic Pharmaceutical Manufacturing
 Plants by EPA Regions

Distribution of Synthetic Pharmaceutical Manufacturing
 Plants by States
Page

  10


  11
                                      IV

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                                  ACKNOWLEDGMENT
     This report was prepared under the direction of Mr. Thomas C. Ponder, Jr.
The  project  manager  and  principal  investigator  was  Dr. Terry M. Briggs.
Principal authors were Dr. Terry Briggs, Ms. Cynthia Harvey, Mr. Jack McClure,
and  Ms.  Roberta Pollard-Cavalli.    Task Manager  for  the  U.S.  Environmental
Protection Agency was Mr. Robert L. King.

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                                    SECTION  1

                                  INTRODUCTION
BACKGROUND OF  RACT

     The Clean Air Act Amendments of  1977  (CAAA)  required each state to report
compliance status  with  National Ambient Air  Quality  Standards  (NAAQS) to the
U.S.  Environmental  Protection  Agency  (EPA).   Attainment  and  nonattainment
areas of major pollutants  in each state were  listed in the Federal Register on
March 3, 1978.  According  to CAAA, nonattainment  areas must achieve compliance
with NAAQS by December 31, 1982, with  some possible extensions to 1987.  Those
industries in  areas  where standards for a particular pollutant  are not being
met will  be  required to apply  Reasonably  Available  Control  Technology (RACT)
under the  State  Implementation Plans  (SIP).  The  RACT  requirements  are based
on the lowest emission limit that a particular source is capable of meeting by
the application of control technology  that is reasonably available in terms of
technological and economic feasibility.

     The RACT  requirements for control of hydrocarbon emissions are explained
in  the  Control Technique  Guidelines   (CTG)  series.  It is  necessary to limit
hydrocarbon  emissions  in order to reduce  photochemical  oxidant  levels.   With
respect to the  pharmaceutical  industry, RACT is  applicable  to  those manufac-
turing plants  using  synthesis  processes that emit more than 15 pounds per day
of volatile organic compounds (VOC).
PURPOSE AND SCOPE OF REPORT

     A  current  survey  of operating plants  that  manufacture synthetic pharma-
ceutical s in  oxidant nonattainment areas is necessary  for  the  enforcement of
RACT and  for  long-range planning of the programs and resources of EPA's Divi-
sion of Stationary Source  Enforcement (DSSE),  regional, and local  programs.

     There has been little previous regulation of air pollution control activ-
ity in  this  industry.   The first phase of this study was to compile an inven-
tory of the  pharmaceutical  manufacturing plants that use synthesis processes.
The inventory includes  plant  demographic data, a categorization of the indus-
try by major synthetic  pharmaceutical  product groups, and emission and control
information.

     As background for  results  of this survey, Section 2 presents an industry
process description and  a review of the RACT  requirements.   An evaluation of
proposed  regulations  to  identify  enforceability  problems  is presented  in
Section 3; conclusions  and recommendations are given in Section 4.

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                                    SECTION 2

                             INDUSTRY CHARACTERIZATION


 OVERVIEW OF PHARMACEUTICAL  INDUSTRY

      The  pharmaceutical  manufacturing  industry encompasses  the manufacture
 purification,^ packaging of chemical materials to be used as medication for
 humans  or animals.   The broad  range  of  industry products  includes  natural
 substances  from plants  or animals,  chemically modified  natural  substances,
 synthetically  made organic  chemicals,  metal-organics,  and  wholly  inorganic
 materials.   Production  activities  of  the   pharmaceutical   industry  can  be
 grouped into the following categories:

 Chemical synthesis - The manufacture of pharmaceutical  products by
      chemical  synthesis.

 Fermentation - The production and separation of medicinal chemicals such
      as antibiotics and vitamins  from microorganisms.

 Extraction - The manufacture of botanical  and biological  products by the
      extraction of organic chemicals from vegetative materials or animal
      tissues.

 Formulation and packaging -  The formulation of bulk Pharmaceuticals into
      various  dosage forms  such as  tablets,  capsules,  injectable  solu-
      tions,  ointments,  etc., that can be taken by the patient immediate-
      ly and in  accurate amount.

      Pharmaceutical  manufacturers use many VOC  either  as raw materials or as
 solvents.   The  Pharmaceutical Manufacturers Association (PMA)  obtained  from 26
 member  companies their estimates  of the 10 VOC's that were purchased in larg-
 est  volumes.   According  to  the data obtained,  about 73  percent of all emis-
 sions  reported  are from  the  chemical  synthesis  group.   Therefore   EPA is
 considering only the chemical synthesis group  for regulation of VOC emissions
PROCESS DESCRIPTION OF SYNTHETIC PHARMACEUTICAL INDUSTRY

     Most^drugs are prepared today by chemical synthesis.  The Effluent Guide-
lines Division  of  the EPA has compiled a comprehensive data base, which indi-
 • SSon    °f Pharmaceutica"l Plants manufacturing products by chemical synthe-
sis, 80 percent of all  operations are batch processes, 8 percent are continu-
ous, and 12 percent are semicontinuous.

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     The basic
welded  bottom
driven  agitator  and an  internal
steel or glass-lined carbon steel,
either cooling water or  steam.   Vessels
ent sizes, with  capacities
accessories,  these  vessels
reaction  vessel  for the batch process  is  a mixing tank with a
and a  clamped-on top.   It  is usually  equipped with  a  motor-
                   baffle.   The tank, made  of  either stainless
                    has a carbon steel outer shell  suitable for
                          of this type are made in  many differ-
                                                 With suitable
                                                  including the
                            ranging from 0.02 to  11 m3 or more.
                            can be used  in  many different ways
mixing,  boiling,  and chilling of solutions.  With  addition of a condenser, a
complete reflux operation is possible; vacuum operation  is  also possible.  The
tanks  can  also be  used for  solvent  extraction and crystallizing operations.

     The  manufacture  of  synthetic Pharmaceuticals consists  of  using  one or
several  of  these  vessels  to perform the various  needed  operations, usually in
the   following   sequence:    (a) reaction   (sometimes   multiple  reactions);
(b) product  separation; (c)  purification;  and (d) drying.   Following a speci-
fic  recipe,  the   reactor  operator  or  computer-controlled  mechanism  blends
reagents; adjusts the  flow rate of cooling water, chilled water, or steam; and
pumps the reactor contents into other similar vessels.   At appropriate process
steps, solutions are pumped through filters or centrifuges into solvent recov-
ery headers or into waste sewers.

     The  vessels   and  their  auxiliary  equipment are  usually  combined  into
independent process  units;  a large pharmaceutical plant may contain many such
units.   Each  unit may be  suitable for the manufacture of many different phar-
maceutical intermediary and final compounds.  Dedicated  equipment is used only
for extremely high-volume production.

     A 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 of this  compound to satisfy its projected sales  demand.   Campaigns are
usually tightly scheduled,  with  detailed coordination extending from procure-
ment of raw materials to packaging and labelling of the product.  For variable
periods  of  time,  therefore,  a process unit actively manufactures  a specific
compound.  At the  end of  each campaign, the  same equipment and personnel are
used to  make  a  completely different product, utilizing  different raw materi-
als, executing a different formula, and creating different wastes.

     Figure 1 shows  a typical flow  diagram for  a batch synthesis  operation.
At the start  of a production cycle, the  reactor  is  usually washed and steri-
lized.   In  this example,  solid  reactants  and solvent are  charged to  a batch
reactor equipped with a condenser (which is usually water-cooled), and VOC may
be produced  as  products or  byproducts.   Any  remaining  unreacted solvent  is
removed by distillation.  When the reaction and solvent removal are complete,
the product  is  transferred  to a  holding tank,  in which  it undergoes three to
four washes of  water or solvent  to remove  any  remaining reactants  and bypro-
ducts.   The  solvent  used  to wash may  also be  evaporated from  the  reaction
product.   The  crude  product may  then  be  dissolved  in another solvent and
transferred to  a  crystallizer for  purification.   After crystallization, the
solid material  is centrifuged  from the remaining solvent.   In the centrifuge,
the product  cake  may  be  washed  several  times  with water  or solvent.   Tray,
rotary,   or  fluid-bed  dryers  may  then  be used  for  final   product  finishing.

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      Organic  chemicals  are  used  as raw materials  and solvents;  solvents are
 responsible  for the predominant VOC emissions  from production.   Almost every
 pharmaceutical  process  reaction step requires  a  solvent  chemical  to dissolve
 reactants and  to  bring  them into close proximity with each other.  A solvent
 also aids in process heat transfer and temperature control.

      The synthetic pharmaceutical  'industry uses a wide variety of reaction and
 purification solvents, including water.   Benzene and toluene, stable compounds
 that do  not  easily react,  are the most often  used organic solvents. .Similar
 compounds such  as xylene,  cyclohexane,  and pyridine  are  also  used.   Chlori-
 nated hydrocarbons  are  used occasionally in purification  operations,  but are
 rarely used as reaction  solvents.

      Each operation of the  chemical  synthesis  process may  be a  source of VOC
 emissions  which  vary widely within  and  among  operations, depending on  the
 amount and type of VOC  used, the  manufacturing equipment,  and the  size of the
 operation.   Because of  the  wide  variation,  typical  emission  rates for  each
 operation cannot be calculated.   The  CTG,  however,  establishes  an  approximate
 ranking  of emission sources, as  shown  below.  The first four sources generally
 account  for  most of the  emissions  from a plant.

      Dryers

      Reactors

      Distillation  units

      Storage  and transfer

      Filters

      Extractors

      Centrifuges

      Crystal!izers

      Applicable  controls for  these emission sources  include  condensers, scrub-
bers, and carbon adsorbers.   Use of incinerators  is expected to be  limited to
a few specific applications.  Storage and transfer emissions can be  controlled
by  vapor return lines,  vent condensers, conservation vents,  vent  scrubbers
pressure  tanks, and carbon adsorbers.  Floating roofs may be feasible controls
for large storage tanks.

Dryers

      Dryers  remove  most  of  the  remaining  solvent from a  centrifuged or fil-
tered product.   Solvent  is  evaporated  until an acceptable level  of dryness is
reached    Evaporation  is  accelerated by  applying heat  and/or vacuum  to  the
solvent-laden product  or by  blowing warm  air around  or through  it.  Because
many  products  degrade under severe  drying conditions,  the amount  of  heat
vacuum,   or warm  air  flow  must be  carefully  controlled.   Several  types  of

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dryers  are used  in  synthetic drug  manufacture,  including tray,  rotary,  and
fluid bed  dryers.

     A  typical  tray  dryer  consists of  a rectangular chamber  containing  two
carts with support  racks.   Each rack carries a  number  of shallow trays that
are  loaded with the product to  be dried.  Heated air is circulated within the
chamber.

     A  rotary  or tumbler dryer  consists of a revolving cylindrical or conical
shell supported in a horizontal or  slightly inclined position.  Rotary dryers
may  be  operated  under  vacuum or  with hot air  circulation.   Rotation of  the
dryer tumbles  the product to enhance  solvent evaporation and may also perform
a blending function.

     A  fluid  bed  dryer  evaporates solvent by forcing heated  air through  the
wet material.   Typically, a large pan  loaded with the product is placed inside
the dryer, where air  is blown through  the bottom of the pan.  The air agitates
or fluidizes the product.   Some product particles may be entrained in the gas
stream.    They   are captured  by  a  fabric filter and  returned to  the dryer.

     A  dryer  is  a  potentially  large  emission   source.    Emission rates  are
highest  at the  beginning  of the  cycle  and lowest  at  the end  of the cycle.
Dryer size,  number  of  drying  cycles per  year,  and the  amount and  type  of
solvent  evaporated per cycle  affect  the total  emissions.   Emissions  from  an
air  dryer  are  normally greater  than those from a vacuum dryer, mainly because
emissions from the air dryer are dilute and more difficult to control.

Reactors

     A  typical  batch reactor is made  of stainless steel  or glass-lined carbon
steel.   The  tank  is  usually jacketed to permit  temperature  control  of reac-
tions.  Generally, each is equipped with a vent,  which may discharge through a
condenser.  Batch  reactors may also be used as mixers, heaters, holding tanks,
crystal!izers,  and evaporators.

     Reactor emissions  may stem from  the following:  (a)  displacement of  air
containing VOC  during reactor charging;  (b) evaporation of solvent during the
reaction  cycle  (reaction byproduct  gases act as VOC carriers  in many opera-
tions);   (c) venting  of  uncondensed VOC  from  an  overhead condenser  during
refluxing;  (d)  purging  of vaporized  VOC remaining  from  a solvent wash;  and
(e) opening of  a reactor during a reaction cycle to take samples or determine
reaction endpoints.

     Emissions   may  be greater  when  a  reactor is  operated under  pressure
because   the pressure must be relieved  between  cycles.   This may  be  done  by
venting  directly  to  the atmosphere or through a  condenser.   When the reactor
is vented  through an overhead  condenser,  care  must be taken  not to  overload
the  condenser   by relieving  reactor  pressure  too  rapidly.    The number  of
batches   or annual throughput  will  affect  total  emissions from  the  reactor.

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 Distillation Units

      Distillation is  performed  by either of two principal methods.  The first
 method  is  based on  production  of  a  vapor by boiling  the  liquid mixture and
 condensing the vapors without allowing any liquid to return to the still   The
 second method is based on the return of part of the condensate to the still so
 that the returning  liquid  is brought into intimate contact with the vapors on
 the way to the condenser.   Either of these methods may be conducted as a batch
 or continuous operation.

      Distillation may be performed  in batch reactors,  in small  stills attend-
 ant to  reactors,  or  in  larger  distillation  columns  such as may  be  used for
 waste solvent  recovery.   The largest  distillation columns  in  pharmaceutical
 plants process around 3200  kg/h (7000 Ib/h) of feed material.   The distilla-
 tion condensers used to  recover  evaporated solvents may emit VOC.

 Storage  and Transfer

      Volatile organic compounds  are stored  in tank farms,  in 55-gallon drums
 and sometimes in process holding  tanks.   Capacities of storage tanks  in  tank
 farms  range  from  about  20,000  to 110,000 liters  (5,000 to  30,000  qallons)
 Most are horizontal  tanks,  although  vertical  tanks also  are used.   Process
 cA™9  tanks are  Sma11er> with  capacities  from 2,000 to 20,000  liters  (500 to
 5,000  gallons).   In-plant transfer of  VOC  is done  mainly by  pipeline,  but  also
 may be done manually.  Raw materials are delivered  to the plant  by tank truck
 rail car, or in  55-gallon drums.

     Emissions  of VOC from storage  tanks are  from  working losses  or breathing
 losses    The amount  of loss  depends on  the type of VOC stored, size of tank
 type of  tank,  diurnal  temperature  changes, and  tank throughput.

 Filters

     Generally,  filtration  is used  to remove  solids  from  a liquid,  whether
 these  solids are product, process intermediates,  catalysts,  or carbon  parti-
 cles  (eg    from  a  decoloring  step).   The  normal  filtration  procedure is
 simply to  force or draw the  mother  liquor  through a filtering medium.  After
 nitration, the retained solids  are removed from the filter medium  for further
 processing.   Pressure  filters, such  as shell and leaf filters, cartridge fil-
 ters, and plate and  frame filters, are commonly used.   Atmospheric and  vacuum
 filters are used in some applications.

     Enclosed  pressure filters  normally do  not emit  VOC during  a filtering
 operation.   The  filtered liquid  is  sent to a  receiving tank.   Emissions  can
 occur when  a filter  is opened to remove collected solids.  Emissions can also
 occur if  the  filter  is purged before cleaning.  The purge gas entrains evapo-
 rated solvent and probably is vented through the receiving tank.

     Highest VOC emissions are from  vacuum drum filters,  in  which solvent is
pulled through  a precoated  filter drum.   Potential  emissions are significant
both at  or near  the  surface of the drum  and from  the  ensuing  waste stream

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 Extraction

      Extraction  is used  to separate components  of liquid mixtures  or solu-
 tions.   This process  is  based on differences  in solubilities  of the compon-
 ents;  i.e.,  a solvent  is  used that will preferentially combine with one of the
 components.  The resulting mixture is made  up  of the extract,  which contains
 the  preferentially dissolved material,  and  the raffinate, which is the resid-
 ual  phase.

      The  pharmaceutical  industry  generally utilizes  two  kinds  of solvent
 extraction.   In  the   first,  the extraction takes place within  the reactor.
 Solvent is added to the vessel, and the mixture is  agitated until the material
 to  be extracted  is  dissolved.   The mixture  is then  allowed  to separate into
 two  phases,  and  the  bottom layer  is  drawn  off  and transferred to  a second
 vessel.

      The  second  type  of extraction takes place  in a vertical column.  A sol-
 vent is  made to  flow  through  the liquid mixture.  Either-the  solvent or the
 mixture  is  dispersed  before  entering the column;  this  increases contact and
 promotes  the extraction  process.   Further extraction efficiency may be gained
 by using  a packed column.

      Emissions  from  batch  extraction  stem  mainly  from  displacement of vapor
 while  solvent  is pumped into the extractor  and  while the vessel is purged or
 cleaned after  extraction.   Some VOC also may be  emitted while the liquids are
 being  agitated.   Column  extractors  may emit VOC  during filling or emptying of
 the  column   or  during  extraction.   Emissions  also occur  through  associated
 surge  tanks.   Significant amounts of solvent may be  emitted  from these tanks
 because of working losses as the tank is repeatedly filled and emptied during
 the  extraction process.

 Centrifuges

      Centrifuges  are   used  to  remove  intermediate or  product  solids  from  a
 liquid  stream.    Center-slung,  stainless  steel,  basket centrifuges  are  most
 commonly  used.   When  the centrifuge is started,  liquid  slurry  is pumped into
 it.   An  inert  gas, such as nitrogen, is sometimes  introduced into the centri-
 fuge  to  avoid  the buildup of an explosive atmosphere.  The liquid is strained
 through small basket perforations, and solids are retained in the basket.   The
 solids are  then  scraped  from  the  sides  of the  basket; they are unloaded by
 being  scopped through  a hatch on top of the centrifuge or dropped through the
 bottom into receiving  carts.

     A large potential source  of VOC emissions  is the  open-type centrifuge,
which permits large quantities  of air to contact and evaporate  solvents.   The
trend is toward complete enclosure of the centrifuge.   If an inert gas blanket
 is used,  it  will be  a transport vehicle for solvent vapor.   This vapor may be
vented directly  from   the  centrifuge  or from a process  tank  receiving mother
 liquor.

     The solids are still wet with solvent and are a source of emissions while
being  unloaded  and transported  to  the  next process step.  A bottom unloader
can  minimize this problem  if the solids  are transferred to  a  receiving  cart

                                       8

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 through
 solids.
a closed  chute and the  receiving  cart is covered while transporting
 Crystal!izers

      Crystallization  is  a means  of  separating  an  intermediate or final product
 from  a liquid solution.   This is  done by creating a  supersaturated solution,
 one in which the  desired compounds  will  form crystals.  Supersaturation may be
 achieved  in three  ways:   (1) if solubility of the solute increases strongly
 with   temperature,  a  saturated solution  becomes  supersaturated by  simple
 cooling;  (2)  if  solubility  is  relatively independent  of temperature, super-
 saturation  may be  attained  by  evaporating  a  portion  of the solvent; (3) if
 neither  cooling nor evaporation is  desirable,  supersaturation  may be induced
 by adding a third component  to form  a  mixture  in which  the solute  is consider-
 ably  less soluble.

      Crystallization  by  cooling  a solution will generate little VOC"emission.
 Crystallization by  solvent  evaporation increases the potential for emissions.
 Emissions  are  significant  if evaporated solvent  is  vented directly  to the
 atmosphere.  More frequently,  the solvent is  passed through  a  condenser or a
 vacuum jet.
GEOGRAPHICAL DISTRIBUTION OF SYNTHETIC PHARMACEUTICAL PLANTS

     It  is  estimated  that 800 to 1200 plants in the United States manufacture
pharmaceutical products, of which 140 use synthesis processes.  The 140 plants
are scattered through 30 states and Puerto Rico and are located in all ten EPA
regions.

Geographical Distribution

     More than 41 percent of the plants in the synthetic chemical industry are
located  in  EPA  Region  II.   New Jersey  and New  York have 27  and  23 plants,
respectively,  and  each plant  is  in a nonattainment  area  for oxidants.   Only
the 8 plants in Puerto Rico are in attainment areas.

     EPA Region  V  has 27 plants,  24 of which  are in nonattainment areas, and
Illinois has the majority with 15.   Of 18  synthetic  pharmaceutical  plants in
EPA Region  III,  12 are in Pennsylvania.  Sixteen  of  the plants in Region III
are in nonattainment areas.

     The  remaining 37 plants  (26  percent  of  the  total)  are located in the
other seven  EPA regions, with distribution  ranging from 1 plant each in Re-
gions VIII  and X  to  10 plants in Region IV.   Of these 37 plants, 11 are in
attainment areas for oxidants, and 26 are in nonattainment areas.

     Table 1 shows  the breakdown of  plants  by EPA region; Table 2 shows the
breakdown by state.  Appendix A provides a listing of all synthetic pharmaceu-
tical  plants, designating  county, air  quality control region, and attainment/
nonattainment area status.  These  plants produce a variety of  synthetic chemi-
cals.   Appendix B lists most of the  companies and their synthetically  manufac-
tured products.

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TABLE 1.  DISTRIBUTION OF SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                            BY EPA REGIONS

Region
I
II
III
IV
V
VI
VII
VIII
IX
X
Total s

Total
4
58
18
10
27
5
9
1
7
1
140
Number of plants
Attainment
0
8
2
6
3
1
4
0
0
0
24
Nonattainment
4
50
16
4
24
4
5
1
7
1
116
                                   10

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TABLE 2.   DISTRIBUTION OF SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                               BY STATE
State
Alabama
Arkansas
California
Colorado
Connecticut
Delaware
Florida
Georgia
Illinois
Indiana
Iowa
Kansas
Kentucky
Louisiana
Mary! and
Massachusetts
Michigan
Mississippi
Missouri
New Jersey
New York
North Carolina
Ohio
Pennsylvania
Tennessee
Texas
Virginia
Washington
West Virginia
Wisconsin
Puerto Rico
Number of plants
Attainment
0
1
0
0
0
0
1
2
0
3
1
0
0
0
0
0
0
1
3
0
0
1
0
0
1
0
1
0
1
0
8
Nonattainment
1
0
7
1
3
1
0
0
15
1
0
2
1
1
1
1
5
0
3
27
23
0
1
12
3
3
0
1
2
1
0
                                  11

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Projected Growth

     The  economic outlook for the pharmaceutical  industry  is generally posi-
tive. ^  Although  some  patent expirations  and governmental  efforts  at  cost
containment  may  threaten  the industry,  the  profitability of  developing new
products will foster the industry's interests.

     In all  probability,  growth  in dollars will  exceed  growth  in unit volume
by several percent.   Dollar sales should escalate by more than 10 percent per
year and  possibly by as much as  12  percent.  Based on a compounded rate of 12
percent,  the  U.S.  market will grow from $9.3 billion in 1978 to more than $18
billion in 1984. This assumes an annual inflationary impact of 5 to 6 percent.

     The  projected  growth  outlook  provides  a  strong  argument  for  smaller
companies  to actively  seek  acquisition  and  merger  situations.   The larger
companies would  likely  be  advised to alter their operations  to include joint
ventures  and  licensed  products.   Leading  companies  could  have  difficulty
generating from internal sources the sales volume required merely to keep pace
with market growth.
                                       12

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                                    SECTION 3

                         CONTROL TECHNIQUES AND FACTORS
                              AFFECTING ENFORCEMENT


 SUMMARY OF RACT REGULATIONS


      On the basis of the  control  technology specified in the  CTG,  EPA  devel-
 oped a model  regulation  affecting  emission sources of  facilities manufacturing
 synthesis  Pharmaceuticals.   The regulation applies to  all  sources  of VOC  such
 as  reactors,  distillation  units, dryers,  storage  and transfer operations,  fil-
 ters,  crystallizers,  and centrifuges,  that emit 15 Ib/day  or more.   Pharmaceu-
 tical  production  activities excluded  from the  regulation  are fermentation
 extraction of  organic chemicals from  vegetable  materials or animal tissues
 and formulation and packaging of the product.


      The owner or operator of  a facility  manufacturing synthetic  pharmaceuti-
 cals  must  reduce VOC emissions  by  adding  suitable controls  or applying main-
 tenance practices, discussed in the following  paragraphs.


     Where surface condensers are to be used as the control device,  the  outlet
 gas  temperature  must not  exceed  the  following  values (all  vapor pressures
 measured at 20°C):


           -25°C  when  condensing VOC of vapor  pressure greater  than  40 0
           kPa  (5.8 psi).


           -15°C  when  condensing VOC of vapor  pressure greater  than  20.0
           kPa  (2.9 psi).


           0°C  when  condensing  VOC  of  vapor pressure  greater than  10 0
           kPa  (1.5 psi).


           10°C  when  condensing   VOC of vapor  pressure greater than 7.0
           kPa  (1.0 psi).


          25°C  when  condensing  VOC of vapor  pressure greater than 3.5
          kPa  (0.5 psi).


     The regulation  for  air dryers  and production equipment  exhaust  systems
states reduction  of the  VOC emissions  by at least 90  percent if emissions are
at least 150 kg/day (330  Ib/day).  Otherwise, emissions shall  be reduced to 15
kg/day (33  Ib/day).


     The owner  or operator of  the  facility must  also  provide  a vapor  balance
system or equivalent control  that is at least 90 percent efficient in reducing

                                       13

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VOC emissions  from  truck or rail car deliveries to  storage  tanks with capaci-
ties greater than  7500 liters (2000 gallons) that  store  VOC with vapor pres-
sures  greater  than  28.0 kPa  (4.1  psi) at  20°C.   Installation  of  pressure/
vacuum  conservation vents  set  at ±0.2  kPa  is also  required on  all  storage
tanks that  store VOC with vapor pressures greater  than  10.0 kPa (1.5 psi) at
20°C.

     All  centrifuges,  rotary vacuum  filters, and other  filters having  an
exposed liquid surface must be enclosed if the liquid exerts a total  VOC vapor
pressure of 3.50  kPa (0.5 psi)  or more  at 20°C.   Covers must be installed on
all  in-process tanks  that  contain  VOC.   All  observed leakage  of running or
dripping VOC is  to be corrected the first time the equipment is off-line long
enough to repair the source of leak.

     Final  compliance  is  by December  31,  1982.    The  owner or  operator  may
propose  an  alternative compliance schedule  before  September 15,  1980.   These
dates assume promulgation  on July 1, 1980.  Final compliance for the alterna-
tive schedule  must be achieved as quickly as possible and 'before the date for
attainment of  photochemical oxidant standards.

     Continuous  monitoring  of the following parameters  is  required  if add-on
control  equipment  is  used:   exhaust  gas temperature  of  all  incinerators,
temperature rise across a catalytic incinerator bed, and breakthough of VOC on
a  carbon  adsorption unit.   States may require  other  continuous monitoring or
recording devices  and  also  may request an emissions  test  to show compliance
with this regulation.   Test procedures must be consistent with the EPA Guide-
line Series document,  "Measurement Of Volatile Organic Compounds.


CONTROL TECHNOLOGIES

     The  model regulation  for  control  of VOC emissions from  manufacture of
synthesis Pharmaceuticals  is based on control techniques specified in the CTG
document.  Briefly,  these techniques specify the use of condensers, scrubbers,
carbon adsorption systems,  incinerators, or a combination of controls.

Condensers

     Condensers are  widely  used  to recover solvent  from reactors,  distillation
units,  extractors,  separators,  and dryers.  In a  surface condenser,  the most
common  type,  heat  is  transferred across a tube wall  that  separates the vapor
and  coolant.   The  coolant is not contaminated with the condensed  VOC; thus it
may  be directly reused.  The type of coolant depends on  the degree of cooling
required  and  is usually either  water or  brine.   Freon may  be  used to provide
lower cooling  temperatures.

     Condensation begins when the air/vapor temperature  is  low  enough that the
vapor  pressure of  the VOC  is  equal  to  its  partial  pressure.   The  point at
which  condensation  first  occurs is called  the dew  point.  As  the  vapor is
cooled further, condensation continues and the partial pressure  stays equal to
the  vapor pressure.   The less volatile  a  compound, the  lower  the amount that
can  remain vaporized at a -given  temperature.
                                        14

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      When the solvent  vapor  concentration is high, condensation is relatively
 easy; condensers are a less  attractive control option when  the gas stream is
 dilute or  far from saturation.   In such  cases,  considerable  cooling  is  re-
 quired to condense  the VOC.   .Condenser performance  (lower  temperature  limit)
 may also be  limited  if one of the  condensables  freezes.   Frozen water  or  VOC
 on the condenser tubes  or walls renders them ineffective  as  heat transfer sur-
 faces.   The  CTG  outlines a method  of  estimating the removal efficiency of  a
 condenser.                                                              J

 Scrubbers

      Scrubbers are designed to provide  intimate  contact  between the scrubbing
 liquid and  the   gaseous  pollutant  which  promotes mass  transfer between  the
 phases.   The liquid absorbs the  gas because of the preferential  solubility of
 the gas  or  gases  in  the liquid.   Absorption is  important  in  the  pharmaceutical
 industry  because  many VOC's or  other chemicals  used are soluble  in water  or in
 caustic  or  acidic solutions.   Scrubbers  are  of  the  venturi,  packed tower
 plate or tray tower,  and spray  tower  types.   Scrubbing  is  applied to reduce
 emissions  from reactors,  distillation  equipment,  process  and storage tanks
 centrifuges,  filters, crystal!izers,  dryers,  and  fugitive sources.

     Jhe  VOC  concentration  in a scrubber exhaust  is related to the equilibrium
 partial  pressure of the  DoHutant(s)  in  the scrubbing  medium.   For a given
 unit,  overall scrubber efficiencies  are  influenced  by intimacy  of contact
 between  gas  and  liquid, operating temperature, concentration of the pollutant
 in  the  gas  stream, concentration  of the  pollutant  in  the  liquid scrubbing
 medium, and gas and liquid flow rates.              '

 Carbon Adsorbers

     Activated carbon  adsorption  has been  found  effective  in controlling VOC
 emissions  because many organics  are easily adsorbed onto  activated carbon
 Because the  adsorbed  compounds  have practically  no vapor pressure at ambient
 temperatures,  a   carbon adsorption   system  is particularly  suited  to streams
 with low VOC concentrations.

     Activated carbon for  adsorption of organic vapors should  have  a sponqe-
 like  structure with  a  large internal surface area  (500  to  1000 m2/g)   Pores
 within the  carbon structure should  be  about the  size of the  molecules  to  be
 adsorbed.  Activation of  the  carbon consists of subjecting  it to steam and/or
 air at high temperatures to remove strongly adsorbed hydrocarbons by oxidation
 or desorption.

     A carbon  adsorption  system initially removes almost 100 percent of a VOC
 contaminant; then,as saturation of  the  carbon progresses  through the bed the
 VOC will break through  the bed into the  system exhaust.  At or before break-
 through,  the carbon must  be regenerated and  another  adsorption  cycle must  be
 started.   During  regeneration  the  VOC are desorbed with steam, warm air,  inert
 gas, or vacuum.   Stripped  vapors  are usually condensed or adsorbed.   Possible
VOC emission points are condensate  receivers, water (condensed steam) drains
and wastewater treatement basins.                                             '
                                       15

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     The  amount of material adsorbed  on  a carbon bed depends  on  the type of
activated carbon used; the VOC characteristics; the VOC concentration; and the
temperature, pressure,  and  humidity of the system.  Overall VOC removal effi-
ciencies  depend on  the system design.  Units  can  be designed and operated at
removal efficiencies  well  above 90 percent.   Carbon  adsorbers  can be used to
control VOC  with boiling points up to 250°C and concentrations ranging from 1
ppm  to 40 percent.   Maximum inlet temperature  of the  VOC-containing stream
should not exceed 140°C.

Incinerators

     Incinerators and afterburners  oxidize VOC in waste  gases  to  form carbon
dioxide and water.  The two types of vapor incinerators in use are thermal and
catalytic.

     A thermal  incinerator  depends  on direct  flame  contact  and high tempera-
tures  to  burn  the  combustible  materials.  Supplemental  fuel  is  required to
combust dilute  VOC streams.   Factors that influence  the efficiency  of  com-
bustion are  temperature, degree  of mixing, residence time  in  the combustion
chamber,  and type  of  VOC combusted.   Destruction  efficiency  increases as the
VOC concentration or the operating temperature is increased.

     A catalytic  incinerator  preheats a contaminated waste stream to a prede-
termined temperature  (usually lower than in thermal incineration) and promotes
further oxidation  by   contacting  the  VOC with a catalyst.   The efficiency of
catalytic  incineration  is  a function  of the surface  area of  the  catalyst,
catalyst  type,  uniformity  of gas flow through the  bed,  VOC type,  oxygen con-
centration, volume  of gas  per unit of catalyst,  and operating temperature of
the  unit.   Periodic  catalyst  replacement is  required  because  efficiency de-
creases with use of  the unit.   In addition, some  compounds may poison the
catalyst and render it ineffective.   The efficiency of a catalytic incinerator
depends strongly on the amount  of  the catalyst  in the  unit.   Because of the
high catalyst volume  required for very high conversion (>98 percent) catalytic
incineration is generally uneconomical.

     Incinerators are  not widely used to control vapor organic emissions from
synthesis  drug  production.   The primary  reasons  are  high  operating costs,
variability of  waste  gases  that would be ducted to an incinerator, and opera-
tion by batch processes.   Fluctuating flows and VOC concentrations may hamper
safe and efficient operation.  Heat recovery is impractical because the incin-
erators would be  relatively small  and would generally  run less than 24 hours
per  day.   In addition,  some  compounds such as  chlorinated  organics, amines,
and sulfinated organics can corrode the incinerator.


FACTORS AFFECTING ENFORCEMENT

     Problems related  to enforcement  and compliance with the model regulation
include the exemption  of  certain  manufacturing  processes,  the  provisions
regarding source size,  determination  of compliance schedules, and application
of the bubble concept.
                                       16

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      The  model  regulation  specifically exempts  fermentation,  extraction  of
 organic chemicals from  vegetable  materials or animal tissues, and formulation
 and  packaging processes.   The  regulation  indicates  that manufacturers  of
 pharmaceutical products  by  chemical  synthesis emit most of  the VOC  in  the
 industry,  but many VOC  are also used and emitted  by the exempted pharmaceuti-
 cal manufacturing processes.   In  fact,  many pharmaceutical  companies use more
 than one manufacturing process at the same facility over the course of a year
 Sources should not be allowed to control VOC emissions from  chemical  synthesis
 operations at a  facility  that operates such  processes for  3 months  and  to
 exempt VOC emissions  from  other processes  that might operate 9 months.   State
 permit review may solve this problem.

  _    Recent guidance  for OAQPS has begun to clarify the source size provision
 The criterion of 15  Ib  or  more of VOC  emission per  day applies to each vent
 and not the process  equipment (i.e.,  each reactor,  distillation  unit,  dryer'
 storage and process tank, VOC  transfer,  filter,  crystallizer,  centrifuge).   It
 does not apply to the total of emissions  from  all  the sources in a  manufac-
 turing process.   The  new guidance  covers  vents from  storage tanks,  centri-
 fuges,  and filters having an exposed liquid surface.

      However,  for  further clarification  it  should be  reworded  to  apply only  to
 sources that  emit  15  Ib  per day after  the application of air pollution control
 equipment.  This  concept also  agrees  with  the  recent redefinition of  "poten-
 tial  to emit" in the  case  of  Alabama  Power.  A  policy  statement  is planned  by
 OAQPS  on this  subject.   Many  sources are  already  equipped  with  state-of-art
 air emission  controls, and mass VOC emissions may  already be below the  exclu-
 sion  level.

     Determining  compliance with the regulation will be  difficult because the
 only methods currently available to  measure VOC  emissions are by solvent usage
 and/or  by  correct control equipment  operations.  The  test methods cited  in the
 model  regulation are  not applicable  to the  emissions  associated with the batch
 operations  predominant in  this industry; these  emissions are intermittent and
 highly  variable,  and  often occur at  low velocities  and low concentrations.
 The  use of alternative  methods such  as  calculations  and  audits  should  be
 defined  as acceptable.  Another problem is  that  testing and  monitoring re-
 quirements  specify that VOC breakthrough on a carbon  bed  is to be continuously
 monitored.  The equipment for  the low  level of detection  required can  be quite
 expensive.

     The  regulation  should  somewhere describe a  vapor balance  system  for
 reducing  emissions during  VOC  deliveries.   The type  of delivery specified
 should  not eliminate any form  of transportation such  as barging.

     Meeting the  compliance schedules  may pose a problem for the pharmaceuti-
 cal industry.   Determining compliance status and defining a compliance program
 for  a  major synthesis  pharmaceutical  plant  will be a  lengthy  task.   Such a
plant  contains hundreds of  pieces  of equipment,  each of which may  be a VOC
emission source.   Moreover, a single  source can be  used for  many processes,
with wide variations in the magnitude of emissions.   Simply defining the scope
of the compliance effort will be a major undertaking.   Compliance efforts that
 require  a  process modification must also  be approved  by the Food  and Drug
Administration and  thus will  require  additional time  to meet the compliance

                                       17

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schedule.   The model  regulations provide  for compliance  schedule  modifica-
tions, but specific guidance for this industry is needed.

     Because  most synthetic pharmaceutical  plants contain  numerous  sources,
the bubble  concept will  be  beneficial  to the industry  in  complying  with VOC
regulations.   It  may  be advantageous to allow more  stringent controls on the
large sources  and less  stringent controls on the smaller sources.   All uncon-
trolled VOC emissions must be quantified, however, before  the bubble concept
can be applied.
                                       18

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                                    SECTION 4

                    RECOMMENDATIONS FOR FURTHER INVESTIGATION


      Areas where further investigation could facilitate the enforcement of VOC
 regulation by  regional,  state,  and  local  agencies  include determining  VOC
 emissions, clarifying the bubble  concept,  and extending compliance  schedules.


 DETERMINING VOC  EMISSIONS

      Emissions  in the  synthetic  pharmaceutical industry vary greatly  because
 of  the nature  of batch operations  and also  because  many chenvical  synthesis
 plants may also  produce  pharmaceutical  products by  fermentation and  extraction
 of  organic materials  using  the  same  process equipment.   Emissions  (particu-
 larly those subject to control  by  the  VOC  regulations)  usually vary  from month
 to month and from year to year.  Guidelines  should  be established for a method
 of determining potential and controlled emissions.


 CLARIFYING THE BUBBLE CONCEPT

      The bubble  concept  is beneficial  to the chemical synthesis pharmaceutical
 industry.   Clarification is  needed on an  overall  control  efficiency that can
 be  applied plantwide for  application of  the bubble concept.   Presently the
 control strategies  for  reduction of VOC emissions  from air dryer and produc-
 tion  equipment  exhaust  systems require 90 percent  reduction  if  VOC emissions
 are at least  150 kg/day or require control  to 15 kg/day if VOC emissions are
 less  than  150  kg/day.   A standard  percentage  reduction  applicable  to  the
 emission sources in the plant would enhance application of the bubble concept.


 EXTENDING  COMPLIANCE SCHEDULES

     Process modifications may delay compliance or extend the time required to
 install add-on controls  because the Food and Drug Administration must approve
all  modifications.   Some  guidance should  be  prepared for  situations  where
compliance will  be delayed by process modifications.  A standard method should
be established for obtaining extensions required by the need for FDA approval
                                       19

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                                  APPENDIX A

                        SYNTHETIC PHARMACEUTICAL PLANTS
                                  BY LOCATION
     This appendix provides a listing of all synthetic pharmaceutical plants,
first in a table by region; then in a table by state.  The county and attain-
ment/nonattainment area status is given.
                                     A-l

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                      TABLE A-l.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                      IN REGION I
State
Connecticut
Maine
Massachusetts
New Hampshire
Rhode Island
Vermont
Total s
No. of plants
3
0
1
0
0
0
4
Plants in
attainment areas
0
0
0
0
0
0
0
Plants in
nonattainment areas
3
0
1
0
0
0
4
                         A-2

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                      TABLE A-2.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                       BY STATE
Name and location
Connecticut
CPC International
Wallingford
Pfizer, Inc.
Groton
Sterling Drug, Inc.
Glenbrook
Massachusetts r ".
Astra Pharmaceutical
Worcester
County

New Haven
New London
Fairfield

Worcester
AQCR

42
41
43

118
Status

Nonattainment
Nonattainment
Nonattainment

Nonattainment
                         A-3

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                       TABLE A-3
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                     IN REGION II
State
New Jersey
New York
Puerto Rico
Virgin Islands
Total s
.No. of plants
27
23
8
0
58
Plants in
attainment areas
0
0
8
0
8
Plants in
nonattainment areas
27
23
0
0
50
                          A-4

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                                   TABLE A-4.
             OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                                    BY STATE
Name and location
NEW JERSEY
Aceto Chemical Company, Inc
Carlstadt
American Cyanamid
Bound Brook
Beecham, Inc.
Piscataway
Ciba Geigy Corporation
Summit
CPC International
Lyndhurst
CPC International
Newark
Diamond Shamrock Corp.
Harrison
Ganes Chemicals, Inc.
Carlstadt
Ganes Chemicals, Inc.
Pennsville
Gulf Oil Corporation
Berkeley Heights
Hexcel Corporation
Lodi
Hoffman-LaRoche, Inc.
Belvidere
Hoffman-LaRoche, Inc.
Nutley
Hummel Chemical Company
South Plainfield
Merck and Company, Inc.
Hawthorne
Merck and Company, Inc.
Rahway
Miles Laboratories, Inc.
Clifton
County

Bergen
Somerset
Middlesex
Union
Bergen
Essex
Hudson
Bergen
Salem
Union
Bergen
Warren
Essex
Middlesex
Passaic
Union
Passaic
AQCR

43
43
43
43
43
43
43
43
45
43
43
151
43
43
43
43
43
Status

Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
(continued)
                                      A-5

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TABLE A-4.  (continued)
            OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                                   BY STATE
Name and location
NEW JERSEY (continued)
Napp Chemicals, Inc.
Lodi
N. L. Industries, Inc.
Bayonne
Norda, Inc.
Newark
Rhone-Paul enc, Inc.
New Brunswick
Richardson-Merrell , Inc.
Phillipsburg
Southland Corporation
Great Meadows
Squibb Corporation
New Brunswick
Stauffer Chemical Company
Edison
Sterling Drug, Inc.
Trenton
Tenneco Chemicals, Inc.
Garfield
NEW YORK
Accurate Chemical and Scientific
Corporation
Hicksville
Aceto Chemical Company, Inc.
Flushing
Aceto Chemical Company, Inc.
Long Island City
American Cyanamid
Pearl River
American Lecithin Company
Woods ide
County

Bergen
Hudson
Essex
Middlesex
Warren
Warren
Middlesex
Middlesex
Mercer
Bergen

Nassau
New York
New York
Rock! and
Queens
AQCR

43
43
43
43
151
151
43
43
161
43

43
43
43
43
43
Status

Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment

Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
 (continued)
                                       A-6

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 TABLE  A-4.   (continued)
             OPERATING  SYNTHETIC  PHARMACEUTICAL  MANUFACTURING  PLANTS
                                    BY  STATE
Name and location
NEW YORK (continued)
Arenol Chemical Corporation
Long Island City
Atomergic Chemetals Corp.
Plainview
Bristol-Myers Company
Syracuse
Ciba Geigy Corporation
Suffern
DDR Pharmaceutical Corporation
Cop i ague
Eastman Kodak Company
Rochester
E. I. DuPont De Nemours and Co. , Inc.
Garden City
General Foods Corporation
White Plains
Heterochemical Corporation
Valley Stream
Hexagon Laboratories, Inc.
Bronx
Nepera Chemical Co. , Inc.
Harriman
Norton-Norwich Products, Inc.
Norwich
Pennwalt Corporation
Buffalo
Pfizer, Inc.
Brooklyn
Polychemical Laboratories, Inc.
Bronx
RSA Corporation
Ardsley
County

New York
Nassau
Onondaga
Rock! and
Suffolk
Monroe
Nassau
Westchester
Nassau
New York
Orange
Chenango
Erie
New York
New York
Westchester
AQCR

43
43
158
159
43
160
43
43
43
43
161
163
162
43
43
43
Status

Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattai nment
Nonattainment
Nonattainment
(continued)
                                      A-7

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TABLE A-4.  (continued)
            OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                                   BY STATE
Name and location
NEW YORK (continued)
RSA Corporation
Bronx
Sterling Drug, Inc.
Rensselaer
PUERTO RICO
Abbott Labs
Barceloneta
E. I. DuPont Oe Nemours and Company
Carolina
Eli Lilly and Company
Carolina
Merck and Company, Inc.
Barceloneta
Norton-Norwich Products, Inc.
Manati
Smith Kline
Guyana
Squibb Corporation
Humacao
Upjohn Company
Arecibo
County

New York
Rensselaer









AQCR

43
161

244
244
244
244
244
244
244
244
Status

Nonattainment
Nonattainment

Attainment
Attainment
Attainment
Attainment
Attainment
Attainment
Attainment
Attainment
                                      A-8

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                      TABLE A-5.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                     IN REGION III
State
Delaware
Maryland
Pennsylvania
Virginia
West Virginia
Washington, D.C.
Totals
No. of plants
1
1
12
1
3
0
18
Plants in
attainment areas
0
0
0
1
1
0
2
Plants in
nonattainment areas
1
1
12
. 0
2
0
16
                         A-9

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                                  TABLE A-6.
            OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                                   BY STATE
Name and location
DELAWARE
ICI Americas, Inc.
Newark
MARYLAND
Becton, Dickinson, Inc.
Baltimore
PENNSYLVANIA
American Home Products
Paol i
Beecham, Inc.
Myerstown
Carroll Products, Inc.
Philadelphia
Glyco Chemicals, Inc.
Williamsport
Koppers Company, Inc.
Petrol i a
Merck and Company, Inc.
Danville
Pharmachem Corporation
Bethlehem
Ruetgers-Nease Chemical Co. , Inc.
State College
Smith-Kline Corporation
Philadelphia
Smith-Kline Corporation
Swedeland
Tyler Corporation
Tamaque
West Chemical Products
Eighty Four
County

New Castle

Baltimore

Chester
Lebanon
Philadelphia
Lycomi ng
Butler
Montour
Northampton
Centre
Philadelphia
Montgomery
Schuylkill
Washington
AQCR

45

115

45
196
45
195
197
195
151
195
45
45
151
197
Status

Nonattainment

Nonattainment

Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattai nment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
(continued)
                                      A-10

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TABLE A-6.  (continued)
            OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                                   BY STATE
Name and location
VIRGINIA
Merck and Company, Inc.
Elkton
WEST VIRGINIA
American Cyanamid
Willow Island
Monsanto Company
Nitro
Union Carbide
Charleston
County

Rockingham

Pleasants
Kanawha
Kanawha
AQCR

226

179
234
234
Status

Attainment

Attainment
Nonattainment
Nonattainment
                                     A-11

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                      TABLE A-7.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                     IN REGION IV
State
Alabama
Fl ori da
Georgia
Kentucky
Mississippi
North Carolina
South Carolina
Tennessee
Total s
No. of plants
1
1
2
1
1
, 1
0
3
10
Plants in
attainment areas
0
1
2
0
1
1
0
1
6
Plants in
nonattainment areas
1
0
0
1
0
0
0
2
4
                          A-12

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                      TABLE A-8.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                       BY STATE
Name and location
ALABAMA
Degussa Corporation
Theodore
FLORIDA
SCM Corporation
Gainesvil le
GEORGIA
Dow Chemical U.S.A.
Gainesville
Merck and Company, Inc.
Albany
KENTUCKY
Diamond Shamrock Corporation
Louisville
MISSISSIPPI
Sterling Drug, Inc.
Gulfport
NORTH CAROLINA
Burroughs Wellcome Company
Greenville
- TENNESSEE
Chattem, Inc.
Chattanooga
Eastman Kodak
Kingsport
Syntex Corporation
Newport
County

Mobile

Alachua

Hall
Dougherty

Jefferson

Harrison

Pitt

Hami 1 ton
Sullivan
Cocke
AQCR

5

49

57
59

78

5

168

55
207
207
Status

Nonattainment

Attainment

Attainment
Attainment

Nonattainment

Attainment

Attainment

Nonattainment
Nonattainment
Attainment
                         A-13

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                      TABLE A-9.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                      IN REGION V
State
Illinois
Indiana
Michigan
Minnesota
Ohio
Wisconsin
Totals
No. of plants
15
4
6
'o
1
1
27
Plants in
attainment areas
0
3
0
0
0
0
3
Plants in
nonattainment areas
15
1
6
0
1
1
24
                          A-14

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                                  TABLE A-10.
            OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                                   BY STATE
Name and location
ILLINOIS
Abbott Laboratories
North Chicago
A. E. Staley Manufacturing
Decatur
Chemtek Laboratories
AT sip
Dawe's Laboratories, Inc.
Chicago Heights
Douglas Laboratories, Inc.
Chicago Heights
G. D. Searle and Company
Skokie
Henkel Corporation
Kankakee
I no lex Corporation
Park Forest South
Lonza, Inc.
Mapleton
Minnesota Mining and Manufacturing
Company
Cordova
North American Philips Corporation
Waukegan
Organics, Inc.
Chicago
Pfanstiehl Laboratories, Inc.
Waukegan
Revlon, Inc.
Kankakee
Vitamins, Inc.
Chicago
INDIANA
Eli Lilly and Company
Lafayette
County

Lake
Macon
Cook
Cook
Cook
Cook
Kankee
Will
Peoria
Rock Island
Lake
Cook
Lake
Kankakee
Cook

Tippecanoe
AQCR

67
75
67
67
67
67
67
67
65
69
67
67
67
67
67

84
Status

Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattai nment
Nonattainment
Nonattainment
Nonattainment

Attainment
(continued)
                                      A-15

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TABLE A-10.  (continued)
            OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                                   BY STATE
Name and location
INDIANA
International Minerals and Chemical
Corporation
Terre Haute
Pfizer, Inc.
Terre Haute
Reilly Tar and Chemical Corporation
Indianapolis
MICHIGAN
Anderson Development Company
Adrian
Dow Chemical U.S.A.
Midland
Hexcel Corporation
Zeeland
Hoffman- LaRoche, Inc.
Muskegon
Upjohn Company
Kalamazoo
Warner-Lambert Company
Holland
OHIO
Sterling Drug, Inc.
Cincinnati
WISCONSIN
Oscar Mayer and Company
Madison
County

Vigo
Vigo
Marion

Lenawee
Midland
Ottawa
Muskegon
Kalamazoo
Ottawa

Hamilton

Dane
AQCR
.„
84
84
80.

125
122
122
122
125
122

79

240
Status

Attainment
Attainment
Nonattainment

Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment

Nonattainment

Nonattainment
                                     A-16

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                      TABLE A-11.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                     IN REGION VI
State
Arkansas
Louisiana
New Mexico
Oklahoma
Texas
Totals
=^======
No. of plants
1
1
0
0
3
5
===^=^=====^==^
Plants in
attainment areas
1
0
0
0
0
	 1
'
Plants in
nonattainment areas
0
1
0
0
3
4
                         A-17

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                                  TABLE A-12.
            OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                                   BY STATE
             Name and location
   County
AQCR
    Status
ARKANSAS
     Diamond Shamrock Corporation
      Van Buren
LOUISIANA
     Monsanto Company
      Luling
TEXAS
     Dow Chemical U.S.A.
      Freeport
     E. I. DuPont De Nemours and Co., Inc.
      Beaumont

     Union Carbide Corporation
      Texas City	
Crawford
St. Charles
Brazoria
Jefferson
Galveston
 17
106
216
106
216
Attainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
                                      A-18

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                      TABLE A-13.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                     IN REGION VII
State
Iowa
Kansas
Missouri
Nebraska
Totals
No. of plants
1
2
6
0
9
Plants in
attainment areas
1
0,
3
0
4
Plants in
nonattainment areas
o
2
3
0
5
                          A-19

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                      TABLE A-14.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                       BY STATE .
Name and location
IOWA
Salisbury Labs
Charles City
KANSAS
Daitom, Inc.
Kansas City
North American Phillips Corporation
Kansas City
MISSOURI
American Cyanamid
Hannibal
Mallinckrodt, Inc.
St. Louis
Monsanto Company
St. Louis
Syntex Corporation
Springfield
Syntex Corporation
Verona
West Chemical Products, Inc.
Kansas City
County

Floyd

Wyandotte
Wyandotte

Marion
St. Louis
St. Louis
Greene
Lawrence
Jackson
AQCR

89

94
94

137
70
70
139
139
94
Status

Attainment

Nonattainment
Nonattainment

Attainment
Nonattainment
Nonattainment
Attainment
Attai nment
Nonattainment
                          A-20

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                      TABLE A-15.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                    IN REGION VIII
State
Colorado
Montana
North Dakota
South Dakota
Utah
Wyomi ng
Totals
No. of plants
1
0
0
0
0
0
1
Plants in
attainment areas
0
0
0
0
0
0
0
Plants in
nonattainment areas
1
0
0
0
0
0
1
                          A-21

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                      TABLE A-16.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                       BY STATE
Name and location
COLORADO
Shell Chemical Company
Denver
County

Denver
AQCR

36
Status

Nonattainment
                         A-22

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                      TABLE A-17.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                     IN REGION IX

State
Arizona
California
Hawaii
Nevada
American Samoa
Guam
Totals

No. of plants
0
7
0
0
0
0
7
Plants in
attainment areas
0
0
0
0
0
0
0
Plants in
nonattainment areas
0
7
0
0
0
0
7
                         A-23

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                      TABLE A-18.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                       BY STATE
Name and location
CALIFORNIA
Alameda Laboratorties
Los Angeles
Beckman Instruments, Inc.
Palo Alto
Belport Company, Inc.
Camari 11 o
Hill Brothers Chemical Company
City of Industry
ICI Americas, Inc.
Pasadena
International Rectifier Corporation
Long Beach
Minnesota Mining and Manufacturing
Company
Northridge
County

Los Angeles
Santa Clara
Ventura
Los Angeles
Los Angeles
Los Angeles
Los Angeles
AQCR

24
30
24
24
24
24
24
Status

Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
Nonattainment
                           A-24

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                      TABLE A-19.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                      IN REGION X
State
Alaska
Idaho
Oregon
Washington
Total s
No. of plants
0
0
0
1
1
Plants in
attainment areas
0
• o
0
0
0
Plants in
nonattai nment areas
0
0
0
1
1
                         A-25

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                      TABLE A-20.
OPERATING SYNTHETIC PHARMACEUTICAL MANUFACTURING PLANTS
                       BY STATE
Name and location
WASHINGTON
Stansbury Chemical Company, Inc.
Seattl e
County

King
AQCR

229
Status

Nonattainment
                           A-26

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                                  APPENDIX B

                        SYNTHETIC PHARMACEUTICAL PLANTS
                         BY TYPE OF CHEMICAL PRODUCED
     This appendix provides a listing of synthetic pharmaceutical  plants  and
their synthetically manufactured products.
                                     B-l

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                               ABBOTT LABORATORIES
                         NORTH CHICAGO, ILLINOIS  60064
 Ammonium heparin
 Arsanilic acid
 Butabarbital
 Butabarbital, sodium
 Butyl aminobenzoate
 para-N.N-Dichlorosulfamylbenzoic acid
 Erythromycin
 Erythromycin lactobionate
 Erythromycin phosphate
 Erythromycin stearate
 Fumagi11i n
 Heparin
 Hydrochlorothiazide
 Lithium heparin
 Menadione
 Menadione  sodium bisulfite
 Methapyrilene fumarate
 Methapyrilene hydrochloride
 Pentobarbital,  sodium
 Pramoxine  hydrochloride
 Pentobarbital,  sodium
 Pramoxine  hydrochloride
 Sodium heparin
 Succinylcholine  chloride
 Thiopental,  sodium
 Tubocurarine chloride

 *Plant also manufactures  13 other chemicals.
Erythromycin
                              ABBOTT LABORATORIES
                        BARCELONETA, PUERTO RICO  00617
                 ACCURATE CHEMICAL AND SCIENTIFIC CORPORATION
                          HICKSVILLE, NEW YORK  11801
Hepari n
Metrizoate, meglumine
Metrizoate, sodium
*Plant also manufactures 27 other chemicals and products.
                                      B-2

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                            ACETO CHEMICAL CO.
                            FLUSHING, NEW YORK
     , INC.
      11368
 Thimerosal
 *Plant also manufactures 5 other chemicals.
                            ACETO CHEMICAL CO.,  INC.
                          CARLSTADT,  NEW JERSEY   07072
 Acetylglycol  sal icylate
 Ambutonium bromide
 Aminobenzoic  acid
 Butyl  aminobenzoate
 Ethyl  p-aminobenzoate
 Glyceryl  guaiacolate
 N-(2-Hydroxyethyl)  gentisamide
 Isobuty1-p-ami nobenzoate
 Salicylic acid,  3,3,5-timethylcyclohexyl
 Tetracaine hydrochloride
ester
*Plant  also manufactures  111  other  chemicals.
                           ACETO CHEMICAL CO.,  INC.
                       LONG ISLAND CITY, NEW  YORK   11101

Phenypropanolamine hydrochloride
Tolazoline hydrochloride

*Plant also manufactures 7 other chemicals.
                          ALAMEDA LABORATORIES, INC.
                        LOS ANGELES, CALIFORNIA  90001

Chlorpromaxine hydrochloride
Diphenoxylate
imipramine
Phendimetrazine bitartrate
Prochlorperazine, base
Pseudoephedrine hydrochloride
Trifluoperazine hydrochloride
Triprocidine hyrdochloride

*Plant also manufactures 13 other chemicals.
                                      B-3

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                           AMERICAN CYANAMID COMPANY
                        BOUND BROOKS, NEW JERSEY  08805

Beta naphthol
Diethylcarbamazine citrate
Dithiouracil
Salicylazosul fapyridine
Sulfabenzamide
Sulfachloropyrazine, sodium
Sulfadiazine
Sulfamerazine
Sulfamethazine
Sulfamethizole
Sulfapyridine
Thiouracil
Tridihexethyl chloride
Trihexyphenidyl hydrochloride

*Plant also manufactures 151 other chemicals and products.
                           AMERICAN CYANAMID COMPANY
                           HANNIBAL, MISSOURI  63401

Chlortetracycline

*Plant also manufactures 3 other chemicals.
                           AMERICAN CYANAMID COMPANY
                         PEARL RIVER, NEW YORK  10965

Chiortetracycli ne hydrochlori de
Cyanocobalamin (intrinsic factor concentrate)
Demeclocycline hydrochloride
Minocycline hydrochloride
Nystati n
Tetracycline hydrochloride
                           AMERICAN CYANAMID COMPANY
                         WILLOW ISLAND, WEST VIRGINIA

Chiortetracycli ne
Bis (m-nitrophenyl) disulfide
Choline bitartrate
Choline citrate
Choline dihydrogen citrate

*Plant also manufactures 27 other chemicals and products.
                                      B-4

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                       AMERICAN  HOME  PRODUCTS  CORPORATION
                           PAOLI,  PENNSYLVANIA  19301
 Ampicillin
 Ampicillin,  sodium
 Carphenazine maleate
 Cyclandelate
 Dicloxacillin,  sodium
 Ethoheptazine citrate
 Meperidine hydrochloride
 Nafcillin, sodium
 Norgestrel
 Oxazepam
 Oxethazaine
 Penicillin G, benzathine
 Penicillin G, potassium
 Penicillin G, proclaine
 Phenoxymethylpenicillin, potassium
 Promazine hydrochloride
 Promethazine  hydrochloride
 Sodium mercaptomerin
                           AMERICAN LECITHIN COMPANY
                           WOODSIDE, NEW YORK  11377
Lecithin
*Plant also produces 2 other types of products.


                         ANDERSON DEVELOPMENT COMPANY
                            ADRIAN, MICHIGAN  49221

m-Cresyl acetate

*Plani also manufactures 25 other chemicals and products.
                          ARENOL CHEMICAL CORPORATION
                       LONG ISLAND CITY, NEW YORK  11101
Methenamine mandelate
                                      B-5

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                       ASTRA  PHARMACEUTICAL  PRODUCTS,  INC.
                        WORCESTER, MASSACHUSETTS  01606
 Etidocaine
 Etidocaine  hydrochloride
 Lidocaine
 Prilocaine
 Prllocaine  hydrochloride
 Terbutaline sulfate
                        ATOMERGIC CHEMETALS CORPORATION
                          PLAINVIEW, NEW YORK  11803

Acetazolamide
Allopurinol
Amygpalin
Aspartic acid
Bisacodyl
Bupiyacaine
Calcium phytate
Carbetapentane citrate
Carisoprodol
Chlorobutanol
Chlorothiazide
Chlorpromazine base
Diazepam
Ferrous fumarate
Flurazepam hydrochloride
Hydrochlorothiazide
Hydroxyzine hydrochloride
lossorbide dinitrate
Lidocaine
Mefenamic acid
Mepivacaine
Oxazepam
Phenaceti n
Propylthiouracil
Terpin hydrate
Thimerosal
Vitamin B15, sodium salt
Vitamins (unspecified)

*Plant also manufactures 20 other chemicals and products.
                           BECKMAN INSTRUMENTS, INC.
                         PALO ALTO, CALIFORNIA  94304

Parathyroid hormone

*Plant also manufactures 51 other chemicals and products.
                                      B-6

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                             BECTON,  DICKINSON,  INC.
                           BALTIMORE,  MARYLAND  21201
 Indocyanine green
 Merbromin
 Phenolsulfonphthal ei n
 Sal icy!  alcohol

 *Plant  also manufactures  6  other chemicals.
                                  BEECHAM,  INC.
                          PISCATAWAY,  NEW JERSEY   08854
 Amoxicillin
 Ampicillin
 Carbenicillin
 Cloxacillin, sodium
 Dicloxacillin,  sodium
 Methicillin, sodium
 Ticarcillin
                                 BEECHAM, INC.
                        MYERSTOWN, PENNSYLVANIA   17067

Arsanilic acid
Piperazine monhydrocloride, neutral solution

*P1ant also manufactures 3 other chemicals.
                           THE BELPORT COMPANY, INC.
                         CAMARILLO, CALIFORNIA  93010

Epinephrine hydrpchloride (racemic)
Epinephrine (levo)
                             BRISTOL-MYERS COMPANY
                           SYRACUSE, NEW YORK  13201
Amikacin
Amikacin sulfate
Amoxicillin trihydrate
Ampicillin, sodium
Amp i c i11i n, tri hydrate
Butrophanol tartrate
Cephapirin
Cephapirin, sodium
Cloxacillin, sodium
Dicloxacillin, sodium
                                      B-7

-------
                       BRISTOL-MYERS COMPANY (CONTINUED)
Hetacillin
Hetacillin, potassium
Hydrof1umethi azi de
Kanamycin sulfate
Methicillin, sodium
Mitomycin C
Oxacillin, sodium
Phenethicillin, potassium
Phenoxymethyl penicillin, potassium
Pheny Hoi examine citrate
Rolitetracycline nitrate
Tetracycline
Tetracycline hydrochloride
Tetracycline pho'sphate complex
                            BURROUGHS WELLCOME CO.
                       GREENVILLE, NORTH CAROLINA

Allopurino
2-Amino-6-Benzylthiopurine
6-Anilinopurine
Bethanidine sulfate
Busulfan
Butoxamine hydrochloride
6-Carboxypuri ne
6-Chloropurine
6-Cyanopurine
2, 6-Diaminopurine
Diaveridine
Digoxin
6-Dimethylami nopuri ne
6-Iodopurine
Mercaptopurine
6-Mercaptopurine riboside
6-Methylmercatopurine
Pyrimethamine
Thoguanine
Thiopurino
Trimethoprim
Tripro!idine

*Plant also manufactures 1 other chemical.
27834
                                      B-8

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                             CARROLL PRODUCTS, INC.
                        PHILADELPHIA, PENNSYLVANIA  19132
 All antoin
 Allantoin N-acetyl DL-methionine
 Allantoin polygalacturonic acid

 *Plant also manufactures 7 other chemicals.
                                  CHATTEM, INC.
                             CHATTANOOGA, TENNESSEE

 Aminoacetic acid
 Dihydroxy aluminum aminoacetate
 Theophylline sodium gylcinate

 *Plant also manufactures 13 other chemicals.
                           CHEMLEK LABORATORIES,  INC.
                             ALSIP,  ILLINOIS  60658

 Calcium pantothenate  (racemic)
 Calcium pantothenate  (racemic)  calcium chloride  complex

 *Plant  also manufactures  1  other  chemical.
                            CIBA-GEIGY CORPORATION
                           SUFFERN, NEW YORK   10901

Acenocoumarol
Biscodyl
Carbamazepine
Chlorquinaldol
Chiorthalidone
Chiorthalidone and reserpine
Crotamiton
Desipramine
Dipyridamole
Heptabarbital
Imipramine hydrochloride
Oxyphenbutazone
Phenmetrazine hydrochloride
Phenylbutazone
Phenylbutazone (other ingredients)
Sulfinpyrazone
                                      B-9

-------
                            CIBA-GEIGY CORPORATION
                           SUMMIT, NEW JERSEY  07901
Adiphenine hydrochloride
Benzonatate
Diazepam
Dibucaine
Dibucaine hydrochlon'de
Di i odohydroxyqui n
Dimethindene maleate
Glutethimide
Guanethidine sulfate
Hydra!azine
Hydrochlorothiazide
lodobrassid
lodochlorhydroxyqui n
Methrapone
Naphazoline hydrochlon'de
Nikethamide
Sodium carboxymethylcellulose
Sulfachloropyridazine, sodium
Syrosingopine
Tripelennamine
Tripelennamine citrate
Tripelennamine hydrochloride

*Plant also manufactures 2 other chemicals.
                            CPC INTERNATIONAL,  INC.
                           NEWARK, NEW JERSEY  07114
L-acetyle methadol
Bismuth subgallate
Bismuth subsalicylate
Calami ne
Candicidin
Codeine
Codeine hydrochloride
Codeine phosphate
Codeine sulfate
Diphenoxylate hydrochloride
Ethylmorphine hydrochloride
Glyceryl guaiacolate
Gramicidin
Hydrocodone bitartrate
lodoform
Meperidine hydrochloride
Methadone hydrochloride
Methocarbamol
Morphine alkaloid
Morphine hydrochloride
Morphine sulfate
                                      B-10

-------
                       CPC INTERNATIONAL,  INC.  (CONTINUED)
 Neomycin
 Neomycin palmitate
 Noscapine
 Noscapine hydrochloride
 Opium and derivatives
 Papaverine hydrochloride
 Sal icy!amide
 Thebaine
 Tyrocidine hydrochloride
 Tyrothricin

 *Plant also manufactures  18  other  chemicals.
                             CPC  INTERNATIONAL,  INC.
                              LYNDHURST, NEW JERSEY

Acetaminophen
Aloin
Berberine hydrochloride
Casanthranol
Diperodon hydrochloride
Hydrastine hydrochloride
Podophyllum
Potassium estrone sulfate
Proveratrine A
Proveratrine B
Reserpine

*Plant also manufactures 9 other chemicals and products.
                            CPt INTERNATIONAL, INC.
                        WALLINGFORD, CONNECTICUT  06492
Guaiacol
*Plant also manufactures 1 other chemical.
                                 DAITOM, INC.
                          KANSAS CITY, KANSAS  66106
Calcium pantothenate (dextro)
                                      B-ll

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                           DAWE'S LABORATORIES, INC.
                       CHICAGO HEIGHTS, ILLINOIS  60411
Choline chloride
Menadione sodium bisulfite
Vitamin D3

*Plant also manufactures 2 other chemicals.
                        DDR PHARMACEUTICAL CORPORATION
                           COPIAGUE, NEW YORK  11726
L-dopa

*Plant also manufactures 1 other product.
                              DEGUSSA CORPORATION
                           THEODORE, ALABAMA  36582

Methionine

*Plant also manufactures 4 other chemicals.


                         DIAMOND SHAMROCK CORPORATION
                          HARRISON, NEW JERSEY  07029

Vitamin D3

*Plant also manufactures 3 other chemicals and products.
                         DIAMOND SHAMROCK CORPORATION
                          LOUISVILLE, KENTUCKY  40218

Amino acids
Antibiotics (unspecified)
Calcium pantothenate (racemic)
Choline chloride
Vitamins (unspecified)

*Plant also manufactures 1 other product.
                         DIAMOND SHAMROCK CORPORATION
                          VAN BUREN, ARKANSAS  72956

B-alanine
B-alanine, calcium salt
Calcium pantothenate (dextro)
                                      B-12

-------
                           DOUGLAS LABORTORIES, INC.
                       CHICAGO HEIGHTS, ILLINOIS  60411
Vitamin A
Vitamin D2
Vitamin D3

*Plant also manufactures 2 other products.
                              DOW CHEMICAL U.S.A
                            FREEPORT, TEXAS  77541

Choline chloride
Piperazine, base
Piperazine dihydrochloride
Piperazine hydrochloride

*Plant also manufactures 96 other chemicals and products.
                              DOW CHEMICAL U.S.A.
                          GAINESVILLE, GEORGIA  30501
3,5-Dinitro-o-toluamide
Mietochlopramide
                              DOW CHEMICAL U.S.A.
                           MIDLAND, MICHIGAN  48640

Aspirin
Bromoform
3,5-Dinitro-o-toluamide
Metoclopramide
Phenyl sal icylate
Sal icy!ic acid
Sodium salicylate

*Plant also manufactures 146 other chemicals and products.
                            E.I.  Du PONT De NEMOURS
                            BEAUMONT, TEXAS  77704

Methionine, hydroxyanalogue, calcium salt

*Plant also manufactures 1 other chemical.
                                      B-13

-------
                            E.I. Du PONT De NEMOURS
                         GARDEN CITY, NEW YORK  11530
Hydrocodone bitartrate
Oxycodone hydrochloride
Oxymorphone hydrochloride
                            E.I. Du PONT De NEMOURS
                         CAROLINA, PUERTO RICO  00630
Anistotropine
                             EASTMAN KODAK COMPANY
                          ROCHESTER, NEW YORK  14613

D-a Tocopherol
D-a Tocopherol acetate
D-a Tocopherol acid succinate
Choline chloride
Phenolsulfonphthalei n

*Plant also manufactures 195 other chemicals and over 6000 organic chemicals.
                             EASTMAN KODAK COMPANY
                             KINGSPORT, TENNESSEE

Cellulose, oxidized

*Plant also manufactures 101 other chemicals and products.
                             GANES CHEMICALS, INC.
                         CARLSTADT, NEW JERSEY  07072

Aminophyll
Barbital
Barbital, sodium
Butabarbital
Butabarbital, sodium
Butalbital
Butalbital, sodium
Caffeine sodium benzoate
Dimenhydrinate
Diphenhydramine hydrochloride
Ethyl p-aminobenzoate
Glutethimide
Hexobarbital
Phendimethrazine tartrate
Phenobarbital
                                      B-14

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                        GANES CHEMICALS, INC.  (CONTINUED)
 Phenobarbital,  calcium
 Phenobarbital,  sodium
 Phentermine hydrochloride
 Phenlephrine
 Phenlephrine,  hydrochloride
 Phenlpropanolamine hydrochloride
 Potassium aminobenzoate
 Probenecid
 Propoxyphene hydrochloride
 Pseudoephedrine,  base
 Pseudoephedrine hydrochloride
 Pseudoephedrine sulfate
 Sodium aminobenzoate

 *Plant also manufactures  14 other chemicals.
                              GANES  CHEMICALS,  ING.
                         PENNSVILLE,  NEW JERSEY  08070

Glyceryl guaiacolalte
Phenylpropane!amine hydrpcfilpride

*Plant also manufactures  14 other chemicals.
Caffeine, natural
                           GENERAL  FOODS CORPORATION
                         WHITE PLAINS, NEW YORK   10625
                             GLYCO CHEMICALS, INC.
                       WILLIAMSPORT, PENNSYLVANIA  17701
Ichthammol
*Plant also manufactures 64 other chemicals.
                             GULF OIL CORPORATION
                      BERKELEY HEIGHTS, NEW JERSEY  07922
Benactyzine hydrochloride"
Dimethoxanate hydrochloride
Glyceryl guaiacolate
Mebutamate
Mephenesin
Nylidrin hydrochloride
                                      B-15

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                       GULF OIL CORPORATION (CONTINUED)
Phenformin hydrochloride
3-Quinuclipinol
Tybamate

*Plant also manufactures 33 other chemicals.
                              HENKEL CORPORATION
                           KANKAKEE, ILLINOIS  60901

D-a Tocopherol
D-a Tocopheryl acetate
D-a Tocopheryl acid succinate

*Plant also manufactures 46 other chemicals.
                          HETEROCHEMICAL CORPORATION
                        VALLEY STREAM, NEW YORK  11580

Menadione
Menadione dimethylpyrimidino! bisulfite
Menadione sodium bisulfite
Vitamin Ks                                      •

*Plant also manufactures 1 other chemical.
                          HEXAGON LABORATORIES, INC.
                            BRONX, NEW YORK  10475

Aspartic acid
Brompheniramine maleate
Cetylpyridinium chloride
Chlorpheniramine base
Chlorpheniramine gluconate
Chlropheniramine maleate
Dimenhydrinate
Diphenhydramine hydrochloride
Glyceryl gluaiacolate
Homatropine                               .   '  .
Homatropine hydrobromide
Homatropine methyl bromide
Methocarbamoc
Neostigmine bromide
Neostigmine methylsulfate
Pheniramine base
Pheniramine maleate
Phentermine
Phenylephrine hydrochloride
                                      B-16

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                      HEXAGON  LABORATORIES,  INC.  (CONTINUED)
  Prophylhexedrine
  Pyrilamine maleate
  Quinidine gluconate
  Quinidine sulfate
  Tropine

  *Plant also manufactures 10 other chemicals.
                               HEXCEL CORPORATION
                             LODI, NEW JERSEY  07644

 Benzalicorn urn chloride
 Centalicom'urn chloride
 Cetylpyridinium chloride

 *Plant also manufactures 17 other chemicals.
                               HEXCEL CORPORATION
                            ZEELAND,  MICHIGAN  49464

 N-Butyroy1-p-Aminophenol
 Dibenzylamine
 N-Lauroyl-p-Aminophenol
 N-Stearoyl-p-Aminophenol

 *Plant  also manufactures 22  other  chemicals.
                          HILL BROTHERS CHEMICAL CO.
                         CITY OF INDUSTRY, CALIFORNIA

Phenolphthalein

*P1ant also manufactures 3 other chemicals and products.
                            HOFFMAN-LA ROCHE, INC.
                         BELVIDERE, NEW JERSEY  07823
Ascorbic acid
Sodium ascorbate
Sulfamethoxazole
*Plant also manufactures 2 other chemicals.
                                      B-17

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                            HOFFMAN-LA ROCHE, INC.
                           NUTLEY, NEW JERSEY  07110

Acetyl sulfisoxazole
Apocarotenal
Biotin
Canthaxanthin
B-caroten
Chlordiazepoxide Hydrochlon'de
Chlorprothixene
Clidlnlum bromide
Dextromethorphan hydrobromide
Diazepam
L-dopa
Edrophonium chloride
5-Fluorouracil  -
Flurazepam
Ipronidazole
Isocarboxazid
Levorphanol tartrate
Menadiol sodium diphosphate                     ,
Methyprylon
Neostigmine bromide
Nicotinyl alcohol tartrate
Ormetoprim
D-panthenol
Panthenol (racemic)
Phenazopyridine hydrochloride
Phenindamine tartrate
Phytonadione
Pyridostigmine bromide
Pyridoxine hydrochloride
Riboflavin
Fiboflavin-51-phosphate, sodium
Sulfadimethoxine
Sulfisoxazole
Sulfisoxazole, sodium
Thiamine hydrochloride
Thiamine mononitrate
DL-ot Tocopherol
DL-a Tocopheryl acetate
Triclobisonium chloride
Vitamin A acetate
Vitamin A alcohol
Vitamin A palmitate

*Plant also manufactures 7 other chemicals and products.
                                      B-18

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                             HOFFMAN-LA ROCHE,  INC.
                            MUSKEGON, MICHIGAN   49442
 Dyclom'ne hydrochloride
 Thiphenamic hydrochloride
 *Plant also manufactures  21  other chemicals.
                            HUMMEL  CHEMICAL  COMPANY
                       SOUTH PLAINFIELD,  NEW JERSEY   07080

 Methapyrilene
 Methapyrilene  fumarate
 Methapyrilene  hydrochloride

 *Plant also manufactures 67 other  chemicals  and products.
                               ICI AMERICAS,  INC.
                            NEWARK, DELAWARE   19711

 Isosorbide dinitrate

 *Plant also manufactures 1 other product,


                               ICI AMERICAS, INC.
                          PASADENA, CALIFORNIA  91109

 Isosorbide dinitrate

 *Plant also manufactures 7 other products.
                                 INOLEX CORP.
                      PARK FOREST SOUTH, ILLINOIS  60466

Ammonium heparin
Bile acids, oxidized
Bile salts
Dehydrocholic acid
Epinephrine (levo)
Liver concentrate
Liver, desiccated
Pepsin
Sodium heparin
Trysin

*Plant also manufactures 7 other chemicals and products.
                                      B-19

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                   INTERNATIONAL MINERALS AND CHEMICAL CORP.
                          TERRA HAUTE, INDIANA  47808
Bacitracin
Bacitracin ( no timed icinal)
Bacitracin, zinc
Bacitracin, zinc (nonmedicinal)
Choline chloride
Hexetidine
Tromethami ne
                         INTERNATIONAL RECTIFIER CORP.
                             RACHELLE LABORATORIES
                         LONG BEACH, CALIFORNIA  90801
Chloramphenicol
Chlordiazepoxide
Chiortetracycli ne
Doxycycline
Oxytetracycline hydrochloride
Tetracycl i ne hydrochl on' de
                             KOPPERS COMPANY, INC.
                         PETROLIA, PENNSYLVANIA'  16050

Resorcinol

*Plant also manufactures 8 other chemicals and products.
                             ELI LILLY AND COMPANY
                         CAROLINA, PUERTO RICO  00630
Tobramtcin sulfate
                           ,  ELI LILLY AND COMPANY
                           LAFAYETTE, INDIANA  47902
Acetohexamide
N-Carbamoylarsanilic acid
Cephalexin monohydrate
Cephaloridine
Cephalothin
Cephalothin, sodium
Cyclopentamine hydrochloride
Dioxyline phosphate
Erythromycin
Ethi namate
Ethomoxane hydrochloride
                                      B-20

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                         ELI LILLY AND COMPANY (CONTINUED)

   nJ'  5"d1hydr0"4"OXO"1'3"d1oxo1o(4'5"9)cinno^ne-3-carboxyl1c  acid
  dl-4-(2-E3-(p-hydroxyphenl)-l-methylpropyi:amino)ethylcathechol,  hydrochloride
  Hygromycin  B
  Insulin
  Methadone hydrochloride
  Methapyrilene  hydroxybenzoylbenzoate
  Methimazole
  Methohexital,  sodium
  Nortripthyline
  Papaverine  hydrochloride
  Penicillin  G,  potassium
  Penicillin  G,  procaine
  Penicillin  G,  procaine  (nonmedicinal)
  Phenoxymethyl  penicillin
  Phenoxymethyl  penicillin,  potassium
  2-(3-phenoxypheny) propionic acid Gallium salt dihydrate
  Piperocaine hydrochloride
  Pyrrobutamine  hydrobromide
  Pyrrobutamine  phosphate
  Tylosin
  Vancomycin
  Vinblastine sulfate
  Vincristine sulfate

  *Plant also manufactures 46 other chemicals.
                                   LONZA, INC.
                            MAPLETON, ILLINOIS  61547
 Niacin
 Niacinamide
 *Plant also manufactures 184 other chemicals and products.
                               MALLINCKRODT,  INC.
                           ST.  LOUIS,  MISSOURI  63147
 Bismuth subgallate
 Bismuth subsalicylate
 Calcium gluconate
 Ethyl  ether (medicinal)
 lodoform
 Resorcinol
 Zinc phenolsulfonate
 lothalamic  acid
 Acetaminophen
"Amy! nitrate
                                       B-21

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                         MALLINCKRODT,  INC.  (CONTINUED)

 Codeine
 Codeine phosphate
 Codeine sulfate
 Dihydrocodeine bitartrate
 Diphenoxylate hydrochloride
 Ferric  hydrophosphate
 Ferrous fumarate
 Hydrocodone  bitartrate
 Magnesium  citrate
 Morphone sulfate
 Noscapine
 Oxycodone  hydrochloride
 Oxycodone  terephthalate
 Phenobarbital
 Thebaine
 Thymol  iodide

 *Plant  also manufactures 133 other chemicals and products.
                               MERCK & CO., INC.
                            ALBANY, GEORGIA  31701

Chlorothiazide
Hydrochorothiazide
Methyldopa
Probencid
Sulfanil amide

"'Plant manufactures 2 other chemicals and products.
                               MERCK & CO., INC.
                         DANVILLE, PENNSYLVANIA  17821

Dexamethasone
Dexamethasone phosphate
Ethopabate
Hydrocortisone acetate
Hydrocortisone phosphate
Methyldopa
Penicillin G, procaine (nonmedical)
Prednisolone-tert-butylacetate
Prednisolone phosphate
Riboflavin
Ronidazone
Sulindac
                                      B-22

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                                MERCK & CO., INC.
                             ELKTON, VIRGINIA  22827
 Amproll urn
 Carbidoda
 Cefoxitin
 Cyanocobalamin
 Nicarbazin
 Sulfaquinoxaline
 *Plant also manufactures 3 other products.
                                MERCK & CO.,  INC.
                            RAHWAY,  NEW JERSEY  07065
 Amitriphyline hydrochloride
 Anileridine hydrochloride
 Apomorphine hydrochloride
 Bethanechol  chloride
 Bismuth  formic iodide
 Cambendazole
 Carbachol
 Cocaine
 Codeine
 Cyclobenzapri ne
 Cyproheptadine hydrocholoride
 Dichlorphenamide
 Ethacrynic  acid
 Ethylmorphine  hydrochloride
 Gold sodium  thiomalate
 Hexaylcaine  hydrochloride
 Hexylresorcinol
 Hydrocodone  bitartrate
 Indomethacin
 Mecamylamine
 Metaraminol  bitartrate
 Methacholine chloride
 Methyldopate hydrochloride
 Metyrosine
 Monochloracetone
 Morphine
 Nalorphine hydrochloride
 Noscapine
Oxycodone hydrochloride
p-Pentoxyphenol
 Phthalysulfathiazole
 Phytonadione
 Protriptyline hydrochloride
Sulfabromomethazine, sodium
                                      B-23

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                               MERCK &  CO. ,  INC.
Thiabendazole
Timocol maleate
*Plant also manufactures 4  other chemicals and products.
                               MERCK & CO. , INC.
                         HAWTHORNE, NEW JERSEY  07507

Chioromercuriphenol
Mercuric sal icylate
Oxyquinoline
Oxyquinoline, citrate
Oxyquinoline, sulfate

*Plant also manufactures 13 other chemicals and products.
Methyldopa
                               MERCK & CO., INC.
                        BARCELONETA, PUERTO RICO 00617
                           MILES LABORATORIES, INC.
                              CLIFTON, NEW JERSEY
Pepsin

*Plant also manufactures 14 other chemicals.
Sodium heparin
                    MINNESOTA MINING AND MANUFACTURING CO.
                              RIKER LABORATORIES
                           CORDOVA, ILLINOIS  61242
                    MINNESOTA MINING AND MANUFACTURING CO.
                              RIKER LABORATORIES
                         NORTHRIDGE, CALIFORNIA  91324
Alkaveruir
Alseroxylone
Ammonium heparin
Calcium heparin
Chlophedianol hydrochloride
Deanol p-acetamidobenzoate
Lithium heparin
                                      B-24

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               MINNESOTA MINING AND MANUFACTURING CO.  (CONTINUED)
 Methenamine  hippurate
 Orphenadrine citrate
 Orphenadrine hydrochloride
 Sodium  hepan'n
                               MONSANTO  COMPANY
                            LULING,  LOUISIANA   70070

Acetaminophen

*Plant also manufactures 7  other chemicals and products.


                               MONSANTO  COMPANY
                          NITRO, WEST VIRGINIA 25143

Methionine, hydroxy analogue, calcium salt

*Plant also manufactures 20 other chemicals and products.


                               MONSANTO  COMPANY
                          ST. LOUIS, MISSOURI  63177

Aspirin
L-dopa
Methapyrilene fumarate
Methapyrilene hydrochloride
Phenacetin
Salicylic acid

*Plant also manufactures 20 other chemicals and products.
                         MORTON-NORWICH PRODUCTS, INC.
                           NORWICH, NEW YORK  13815

Aspirin
Furazolidone
Nifuralidone
Nihydrazone
Nitrofurantoin
Nitrofurazone

*Plant also manufactures 6 other chemicals.
                                      B-25

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Nitrofurantoin
                         MORTON-NORWICH PRODUCTS, INC.
                          MANATI, PUERTO RICO  00701
                             NAPP CHEMICALS, INC.
                            LODI, NEW JERSEY  07644
Aminobenzoic acid
Betaine hydrochloride
Bisacodyl
Calcium glutamate
Calcium succinate
Diiodohydroxyquin
Ethyl p-aminobenzoate
Glutamic acid hydrochloride
lodochlorhydroxyqui n
Lidocaine
Methionine
Orphenadrine citrate
Oxyquinoline
Oxyquinoline benzoate
Oxyquinoline sulfate
Phenylto!examine dihydrogen citrate
Phthalylsulfacetami de
Potassium glutamate
Propoxyphen hydrochloride
Resorcinol
Sodium caprylate
Sulfacetamide
Sulfacetamide, sodium
Sulfadiazine
Sulfaguanidine
Sulfamerazine
Sulfamethazine
Sulfanilamide
Sulfapyridine
Sulfathiazole
Sulfathiazole, sodium

*Plant also manufactures 10 other chemicals.
                           NEPERA CHEMICAL CO.
                           HARRIMAN, NEW YORK
 INC.
10926
Methenamine mandelate
Niacin
Niacinamide
                                      B-26

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                            NEPERA CHEMICAL CO.,  INC.

 Phenazopyridine hydrochloride
 Phenylpropanolamine hydrochloride
 Thonzylamine hydrochloride

 *Plant also manufactures 10 other chemicals.
                             N.  L.  INDUSTRIES,  INC.
                           BAYONNE,  NEW JERSEY   07002

 Zinc undecylenate

 *Plant also  manufactures  36  other  chemicals  and products.


                                   NORDA,  INC.
                           NEWARK,  NEW JERSEY   07114

 Chlorothymoc

 *Plant also  manufactures  46  other  chemicals  and products.


                          NORTH AMERICAN PHILIPS CORP.
                          KANSAS CITY,  KANSAS   66110

 Choline chloride

 *Plant also  manufactures  8 other chemicals and  products.


                          NORTH AMERICAN PHILIPS CORP.
                           WAUKEGAN, ILLINOIS   60085

 Calcium pantothenate (racemic) calcium chloride complex
                                ORGANICS, INC.
                           CHICAGO, ILLINOIS  60625

Adrenocorticotropin
Estrogenic substances, conjugated
Hormones, steroid type
Natural estrogenic substance
                                      B-27

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                               OSCAR MAYER & CO.
                            MADISON, WISCONSIN  53701
Pepsin
Sodium heparin
*Plant also manufactures 1 other chemical.
                             PENNWALT CORPORATION
                           BUFFALO, NEW YORK  14240
Calcium undecylenate
Zinc undecylenate
*Plant also manufactures 7 other chemicals.


                         PFANSTIEHL LABORATOTIES, INC.
                           WAUKEGAN, ILLINOIS  60085

L-Cysteine hydrochloride

*Plant also manufactures 73 other chemicals and products.
                                 PFIZER, INC.
                           BOOKLYN, NEW YORK  11206
Bacitracin
Calcium gluconate
Copper gluconate
Dihydrostreptomycin
Ferrous gluconate
Hydrocortisone
Magnesium gluconate
Oleandomycin
Potassium gluconate
Viomycin
                                 PFIZER, INC.
                          GROTON, CONNECTICUT  06340
Ascorbic acid
Benzthiazide
Caffeine, synthetic
Carbetapentane citrate
Doxyeyeline
Hydrocortisone
Hydroxyzine hydrochloride
Hydroxyzine pamoate
                                      B-28

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                            PFIZER,  INC.  (CONTINUED)

 Methacycline
 Neomycin
 Neomycin  sulfate  (nonmedicinal)
 Oleandomycin
 Oxyphencycl inline  hydrochloride
 Penicillin  G
 Penicillin  G, potassium
 Penicillin  G, procaine
 Penicillin  G, sodium
 Penicillin  0, sodium
 Phenethicillin, potassium
 Phenoxymethyl penicillin
 Polythiazide
 Procaine  hydrochloride
 Pyranthel pamoate
 Pyranthel tartrate
 Streptomycin
 Streptomycin (nonmedical)
 Tetracycline
 Tetrahydrozoline hydrochloride
 Troleandomycin
 Viomycin
 Vitamin A acetate
 Vitamin A alcohol
 Vitamin A palmitate

 *Plant also manufactures 21 other chemicals and products.
                                 PFIZER, INC.
                          TERRE HAUTE, INDIANA  47808

Cyanocobalamin
Oxytetracycline (nonmedicinal),
Streptomycin (nonmedicinal)

^Plant also manufactures 3 other chemicals.
                               PHARMACHEM CORP.
                        BETHLEHEM, PENNSYLVANIA  18018

Dextran

*Plant also manufactures 4 other chemicals and products.
                                      B-29

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                        POLYCHEMICAL LABORATORIES, INC.
                            BRONX, NEW YORK  10474
Acetylcholine chloride
Calcium levulinate
Calcium phytate
N-Carbamoylarsanilic acid
Chlorpheniramine maleate
Danthron
Diiodohydroxyquin
Diphenylhydantoin, sodium
Glycobiarsol
lodochlorhydroxyquin
Methenamine mandelate
Naphazoline hydrochloride
Oxyquineline hydrochloride
Oxyquinoline sulfate
Phtahlylsulfacetamide
Piperazine adipate
Piperazine citrate
Piperazine tartrate
Propy1thi ouraci1
Pyrilamine maleate
Sodium arsanilate
Thimerosal

*Plant also manufactures 10 other chemicals.
                          REILLY TAR & CHEMICAL CORP.
                         INDIANAPOLIS, INDIANA  46204
Niacin
Niacinamide
*Plant also manufactures 90 other chemicals and products.
                                 REVLON, INC.
                           KANKAKEE, ILLINOIS  60901

Adrenocorticotropin
Bile extracts
Chymotrypsin
Insulin
Oxytoci n
Trypsin

*Plant also manufactures 15 other products.
                                      B-30

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                               RHONE-POULENC,  INC.
                        NEW BRUNSWICK,  NEW JERSEY  08901
 Dimetridazole
 Glycol  monosalicylate
 Metronidazole

 *Plant  also  manufactures  11  other chemicals  and products.
                            RICHARDSON-MERRELL,  INC.
                         PHILLIPSBURG,  NEW JERSEY   08865

Azacyclonol  hydrochloride
Bismuth  subgallate
Chiorotrianisene
Dicyclomine  hydrochloride
Diethylpropion hydrochloride
Doxy!amine succinate

*Plant also  manufactures 117 other chemicals.
                                 R.S.A. CORP.
                           ARDSLEY, NEW YORK   10502

Acetylcholine bromide
Acetylcholine chloride
Acetylcholine iodide
Acetyl-p-methylcholine bromide
Acetyl-p-methylcholine chloride
Aspirin, calcium salt
Butyl aminobenzoate
Dibucaine hydrochloride
Diiodohydroxyquin
Guaiacol sal icylate
Hexamethonium chloride
Hexamethonium iodide
Hexylresorcino.l
4-Hydroxynicotinic acid
Isobuty1e-p-aminobenzoate
Methacholine chloride
Methenamine mandelate
Phenylbutazone, sodium salt
Propantheline bromide
Propyl aminobenzoate
Sal icy! alcohol
Tetracaine
Tetracaine hydrochloride
Tetraethylammonium chloride

*Plant also manufactures 297 other chemicals.
                                      B-31

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                      RUETGERS-NEASE  CHEMICAL COMPANY,  INC.
                       STATE  COLLEGE,  PENNSYLVANIA   16801
 Chiorami nophenami de

 *Plant also manufactures  18 other chemicals.
                             SALSBURY LABORATORIES
                           CHARLES CITY, IOWA  50616

Ammonium phenolsulfonate
Sali cylazos ulfapyri di ne
Sodium phenolsulfonate
Sulfanil amide
Sulfapyridine  .
Zinc phenolsulfonate

*Plant also manufactures 16 other chemicals.
                                SCM CORPORATION
                          GAINESVILLE, FLORDIA  32601

Acepromazine
Chiordiazepoxide
Chlorpromazine hydrochloride
5-Fluorouracil
Halothane
Promazine hydrochloride

*Plant also manufactures 60 other chemicals and products.
                              G. D. SEARLE & CO.
                            SKOKIE, ILLINOIS  60075
Aminophylcine
Dimenhydrinate
Estradiol
Ethisterone
Methyl testosterone
Spironolactone
Testosterone
Testosterone and esters
                            SHELL CHEMICAL COMPANY
                            DENVER, COLORADO  80201
2,2-Dichlorovinyl-0,0-dimethyl phosphate

*Plant also manufactures 5 other chemicals.

                                      B-32

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                                SMITHKLINE  CORP.
                        PHILADELPHIA,  PENNSYLVANIA   19101
Amphetamine  sulfate  (racemic)
Caramiphen edisylate
Chlorpheniramine maleate
Chlorpromazine, base
Chlorpromazine hydrochloride
Dextroamphetamine sulfate
Hydroxyamphetamine hydrobromide
Isopropamide  Iodide
Prochlorperazine, base
Prochlorperazine edisylate
Prochlorperazine maleate
Propy1hexedri ne
Triamterene
Trifluoperazine, base
Trifluoperazine hydrochloride
Trimeprazine  tartrate

*Plant also manufactures 8 other chemicals.
                               SMITHKLINE CORP.
                        SWEDELAND, PENNSYLVANIA  19479
Cefazolin
Cephradine
                               SMITHKLINE CORP.
                              GUYAMA, PUERTO RICO
Cimetidine
Cimetidine hydrochloride
                                SOUTHLAND CORP.
                       GREAT MEADOWS, NEW JERSEY

5-Chloro-8-Quinolinol
Diiodohydroxyquin
Oxyquinoline
Oxyquinoline benzoate
Oxyquinoline citrate
Oxyquinoline sulfate
Phenylpropanolamine hydrochloride
6-Methoxytetralone-1
5-nitroisophthalic acid
M-Ni tro-p-phenylenediami ne
4-Nitro-o-phenylenediamine

*Plant also manufactures 32 other chemicals.

                                      B-33
07838

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                                  SQUIBB  CORP.
                        NEW BRUNSWICK,  NEW JERSEY
                                     08903
 Amphotericln  B
 Bendrof1umethi azi de
 Diatrizoate,  meglumine
 Diatrizoate,  sodium
 Diatrizoic acid
 FTumethiazide
 Fluphenazine  hydrochloride
 Insulin
 lodipamide, meglumine
 lodipamide, sodium
 Neomycin
 Nystatin
 Nystatin (nonmedicinal)
 Penicillin G, potassium
 Penicillin G
 Procainamide
 Proparacaine
 Sincalide
 Thirostrepton
 Tri f1upromazi ne
 procaine (nonmedicinal)
hydrochloride
hydrochloride
*Plant also manufactures 2 other chemicals.
                                 SQUIBB CORP.
                             HUMACAO, PUERTO RICO
Cephradine
Halcinonide
Triamcinolone
Triamcinolone acetonide
Triamcinolone diacetate
Amphotericin B
Nystati n
Amoxicillin
Ampicillin
Ampicillin, trihydrate
Dihydroampicill in
                             A. E. STALEY MFG. CO.
                               DECATUR, ILLINOIS
Ami no acid mixtures
Inositol
Lecithin
                                      B-34

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                          STANSBURY CHEMICAL CO. , INC.
                               SEATTLE, WASHINGTON

 Ephinephrine
                               STERLING DRUG, INC.
                                CINCINNATI, OHIO

 Benzalkonium chloride
 Gentian violet
 Nalidixic acid
 Salicylic acid

 *Plant also manufactures 34 other chemicals.
                               STERLING DRUG,  INC.
                              RENSSELAER,  NEW  YORK

 Acetarsone
 Aminacrine
 Aminacrine  hydrochloride
 Arterenol hydrochloride (racemic)
 Arterenone
 Cetalkonium chloride
 Cinnamylephedrine  hydrochloride
 Danthron
 Diatrizoate, sodium
 Epinephrine bitartrate (levo)
 Ethacridine lactate
 Isoproterenol hydrochloride
 Levarterenol bitartrate, monohydrate
 Lidocaine
 Lidocaine hydrochloride
 Mafenide hydrochloride
 Mafenide hydrochloride
 Meperidine  hydrochloride
 Mepivacaine  hydrochloride
 dl-Metanephrine hydrochloride
 Metaraminol   bitartrate
 Nordefrin hydrochloride
 Norepinephrine
 Norepinephrine bitartrate
 dl-Normetanephrine hydrochloride
 Pepsin
 Phenacaine  hydrochloride
 Phenylalanine
 Phenylephrine
 Phenylephrine hydrochloride
 Primaquine phosphate
Quinacrine hydrochloride
                                      B-35

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                        STERLING DRUG, INC.  (CONTINUED)
Succinylcholine chloride
Tetracai ne
Tetracaine hydrochloride
Trihexyphenidyl hydrochloride
L-Tryptophan

*Plant also manufactures 17 other chemicals.
                              SYNTEX CORPORATION
                             SPRINGFIELD, MISSOURI

Allantoin
Betaine base
Calcium pantothenate (dextro)
Calcium pantothenate (racemic)

*Plant also manufactures 1 other chemical.
                              SYNTEX CORPORATION
                               VERONA, MISSOURI

B-Alanine
Bethine hydrochloride
Calcium pantothenate (racemic) calcium chloride complex
Choline bitartrate
Choline chloride
Choline dihydrogen citrate
Ethylenedi ami ne di hydroi odi de
Panto!actone

*Plant also manufactures 3 other chemicals.
                            TENNECO CHEMICALS, INC.
                             GARFIELD, NEW JERSEY

Phenyl sal icylate
Potassium guaicolsulfonate
Potassium sal icy!ate
Salicylic acid
Salicylsalicylic acid
Sodium salicylate

*P!ant also manufactures  16 other  chemicals.
                                       B-36

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                                 TYLER CORPORATION
                               TAMAQUA, PENNSYLVANIA
  Glyceryl  trinitrate
  Isosorbide dinitrate
  Mannitol  hexanitrate
  Pentaerythritol  tetranltrate

  *Plant  also manufactures  7  other  chemicals.
                             UNION  CARBIDE  CORPORATION
                                TEXAS CITY, TEXAS
 Piperaine, base
 Piperazine, derivatives
 *PTant also manufactures 43 other chemicals.
                               THE UPJOHN COMPANY
                               KALAMAZOO, MICHIGAN

 Chlorphenesin
 Colestidol
 Cortisone
 Cortisone acetate
 Cytarabine
 Cytarabine hydrochloride
 Diflorasone diacetate
 Diphenadione
 Ephedrine hydrochloride
 Ephedrine sulfate
 Erythromycin
 Erythromycin stearate
 Estradiol  cypionate
 Ethisterone
 Fluorocortisone  acetate
 Flurometholone
 9-of-Fluroprednisolone acetate
 Fluoxymesterone
 Fluprednisolone
 Hydrocrotisone
 Hydrocortisone acetate
 Hydrocortisone cypionate
 Hydrocrotisone hemisuccinate
 Hydrocortisone sodium succinate
 lla-Hydroxypregn-4-ene-3,20-dione
 17a-Hydroxyprogesterone
Hydroxyprogesterone caproate
 Lincomycin hydrochloride
Medroxyprogesterone acetate
                                      B-37

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                        THE UPJOHN COMPANY (CONTINUED)

Melengestrol acetate
Sot-Methyl predni sol one
Methylprednisol one acetate
Methylprednisol one sodium succinate
Methyl testosterone
Mibolerone
Neomycin sulfate
Novobiocin
Novobiocin calcium
Novobiocin sodium
Prednisol one
Prednisol one acetate
Prednisone
Progesterone
Prostaglandins
Spectinomycin dihydrochloride
Spectinornycin sulfate
Tetracyclone hydrochloride
Tolazamide
Tolbutamide

*Plant also manufactures 15 other organic chemicals.
                              THE UPJOHN COMPANY
                             ARECIBO, PUERTO RICO
Clindamycin
Clindamycin palmitate
Clindamycin phospate
Ibuprofen
Lincomycin
                                VITAMINS, INC.
                               CHICAGO, ILLINOIS
7-Dehydrocholesterol
Vitamin D2
Vitamin D3
                                VITAMINS, INC.
                            MICHIGAN CITY, INDIANA

Ergosterol

*Plant also manufactures 4 other organic chemicals.
                                      B-38

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                             WARNER-LAMBERT COMPANY
                                HOLLAND,  MICHIGAN

 Ami tn'pty line
 Amodiaquin
 Amodiaquin hydrochloride
 Bisacodyl
 Bromodiphenhydramine  hydrochloride
 Carbromal
 Chiordiazepoxide
 Diphenhydramine hydrochloride
 Diphenylhydantoin
 Diphenylhydantoin,  sodium
 Ethosuximide
 Ethyl-p-ami nobenzoate
 Ketamine  hydrochloride
 Meclofenamic  acid
 Mefenamic  acid
 Methsuximide
 Oxolinic acid
 Oxytocin
 Phensuximide
 Pheny1propanolamine hydrochloride
 Prazepam
 Procainamide  hydrochloride
 Procaine hydrochloride
 Propylhexedrine
 Sal icy!salicylic acid
 Thiamycal, sodium
 Vasopressin

 *Plant also manufactures 18  other chemicals.
                         WEST CHEMICAL PRODUCTS, INC.
                           EIGHTY FOUR, PENNSYLVANIA
Phenbthiazine
*Plant also manufactures 3 other chemicals.
                         WEST CHEMICAL PRODUCTS, INC.
                              HAMILTON, NEW YORK

Dry cow injectable antibiotics
Lactating cow injectable antibiotics
                                      B-39

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                         WEST CHEMICAL PRODUCTS, INC.
                             KANSAS CITY, MISSOURI

Ethylenedianrine dihydroiodide

*Plant also manufactures 2 other organic chemicals.
                                      B-40

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                                    TECHNICAL REPORT DATA
                             (Please read Instructions en the reverse before completing)
 1. REF
              -80-016
                                                            3. RECIPIENT'S ACCESSION NO.
 4. TITLE AND SUBTITLE

   Enforceability Aspects for RACT  for the Chemical
   Synthesis  Pharmaceutical Industry
            5. REPORT DATE

              January  1QR1
            6. PERFORMING ORGANIZATION CODE
 7. AUTHOR(S)
   T. Briggs,  C.  Harvey, J. McClure,
   R. Pollard-Cavalli
            8. PERFORMING ORGANIZATION REPORT NO.

             PN 3570-3-K
 9 PERFORMING ORGANIZATION NAME AND ADDRESS
   PEDCo Environmental, Inc.
   11499 Chester Road
   Cincinnati,  Ohio  45246
            10. PROGRAM ELEMENT NO.
            11. CONTRACT/GRANT NO.
              68-01-4147
              Task No.  128
 12. SPONSORING AGENCY NAME AND ADDRESS
    U.S. Environmental  Protection Agency
    Division of  Stationary Source Enforcement
    Washington,  D.C.   20460
            13. TYPE OF REPORT AND PERIOD COVERED

                Final	"	
            14. SPONSORING AGENCY CODE
  5. SUPPLEMENTARY NOTES
   Project Officer:   John R. Busik
      Task Manager:   Robert L.  King
 6. ABSTRAC1
               Reasonably available control  technology (RACT) requirements  apply to
    pharmaceutical  manufacturing plants  using synthesis processes that  emit more
    than Ib  pounds  per day of volatile organic compounds (VOC) located  in  photo-
    chemical oxidant nonattainment areas.   There are 140 operating pharmaceutical
    plants that  use chemical  synthesis processes in the 10 U.S. Environmental  Pro-
    tection Agency  regions; 116 of these are  located in. nonattainment areas.   A
    current survey  of the operating synthetic pharmaceutical manufacturing  plants
    is necessary for the enforcement of  RACT  and for long-range planning of EPA
    regional,  and local  programs and resources.   This report provides an inventory
    of the operating synthetic pharmaceutical  manufacturing plants, an  industry
    tnTmndP^T?^-"'  V6^ 
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