PHARMACEUTICAL
I
DUSTRY
Hazardous Waste Generation,
Treatment, and Disposal
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This report has been reviewed by the U.S. Environmental Protection Agency
and approved for publication. Approval does not signify that the contents
necessarily reflect the views and policies of the U.S. Environmental
Protection Agency, nor does mention of commercial products constitute
endorsement by the U.S. Government.
An environmental protection publication (SW-508) in the solid waste
management series,
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PHARMACEUTICAL INDUSTRY
Hazardous Waste Generation, Treatment, and Disposal
This final report (SW-508) describes work performed
for the Federal solid waste management program
under contract no. 68-01-^2684
and is reproduced as received from the contractor
U.S. ENVIRONMENTAL PROTECTION AGENCY
1976
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TABLE OF CONTENTS
Page
List of Tables vii
List of Figures xi
1.0 EXECUTIVE SUMMARY 1
1.1 INTRODUCTION 1
1.2 PURPOSE OF THE STUDY 1
1.3 STUDY APPROACH 2
1.4 CHARACTERIZATION OF THE PHARMACEUTICAL INDUSTRY 2
1.5 WASTE CHARACTERIZATION 3
1.6 TREATMENT AND DISPOSAL TECHNOLOGY 5
1.7 TREATMENT AND DISPOSAL COSTS 5
2.0 CHARACTERIZATION OF THE U.S. PHARMACEUTICAL INDUSTRY 11
2.1 CHARACTERIZATION OF THE INDUSTRY BY FUNCTION 11
2.2 BREAKDOWN OF THE PHARMACEUTICAL INDUSTRY BY
SIC CODES 12
2.3 DOMESTIC SALES OF THE U.S. PHARMACEUTICAL INDUSTRY 13
2.4 HISTORICAL GROWTH OF THE U.S. PHARMACEUTICAL
INDUSTRY 16
2.5 ROLE OF RESEARCH AND DEVELOPMENT IN GROWTH OF
THE U.S. PHARMACEUTICAL INDUSTRY 19
2.6 PHARMACEUTICAL CONSUMPTION-RECENT TRENDS 22
2.7 PHARMACEUTICAL INDUSTRY OUTLOOK FOR 1975-1980 23
2.8 NUMBER OF PHARMACEUTICAL PLANTS AND EMPLOYMENT
IN THE INDUSTRY 25
3.0 WASTE CHARACTERIZATION IN THE PHARMACEUTICAL INDUSTRY 31
3.1 SELECTION AND APPLICATION OF HAZARDOUS WASTE
CRITERIA 31
3.1.1 Background Information for the Selection of
Hazardous Wastes 31
3.1.2 Selection of Criteria for Classification of Potentially
Hazardous Substances from the Pharmaceutical Industry 32
3.1.3 Application of the Classification Scheme to Categorize
Wastes from the Pharmaceutical Industry as Priority
I or Priority II Potentially Hazardous Wastes 36
iii
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TABLE OF CONTENTS (Continued)
Page
3.0 WASTE CHARACTERIZATION IN THE PHARMACEUTICAL INDUSTRY
(Continued)
3.2 WASTE GENERATION DATA DEVELOPMENT 38
3.2.1 Approach to the Problem of Obtaining Valid Industry
Hazardous Waste Data 38
3.2.1.1 Wastes from Research and Development
Installations 42
3.2.1.2 Wastes from the Production of Active
Ingredients 43
3.2.1.2.1 Synthetic Organic Medicinal Chemicals 44
3.2.1.2.2 Inorganic Medicinal Chemicals 48
3.2.1.2.3 Fermentation Products (Antibiotics) 49
3.2.1.2.4 Botanicals 53
3.2.1.2.5 Medicinals from Animal Glands 58
3.2.1.2.6 Biologicals 60
3.2.1.3 Pharmaceutical Preparations 63
3.2.1.4 U.S. Pharmaceutical Industry Process Wastes and
Projections to 1977 and 1983 66
3.2.1.4.1 Annual Waste of Pharmaceutical
Industry 66
3.2.1.4.2 Typical Types of Pharmaceutical
Hazardous Wastes and Their
Properties 74
3.2.1.4.3 Projections of Pharmaceutical Proc.ess
Wastes to 1977 and 1983 74
DATA SOURCES FOR SECTION 3.1 80
DATA SOURCES FOR SECTION 3.2 85
4.0 TREATMENT AND DISPOSAL TECHNOLOGIES 87
4.1 BACKGROUND 87
4.2 DESCRIPTION OF PRESENT TREATMENT AND DISPOSAL
TECHNOLOGIES 87
IV
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TABLE OF CONTENTS (Continued)
Page
4.0 TREATMENT AND DISPOSAL TECHNOLOGIES (Continued)
4.2.1 Present Treatment/Disposal Technologies for General
Process Wastes (Hazardous and Non-hazardous) 87
4.2.2 Present Treatment/Disposal Technologies for Waste
Solvents 96
4.2.3 Present Treatment/Disposal Technologies for Organic
Chemical Residues 101
4.2.4 Present Treatment/Disposal Technologies for Potentially
Hazardous High Inert Content Wastes (Such as Filter Cakes) 103
4.2.5 Present Treatment/Disposal Technologies for Heavy
Metal Wastes 104
4.2.6 Present Treatment/Disposal Technologies for Returned
Goods and Reject Material from Formulation 104
4.2.7 General Description of Treatment and Disposal Tech-
nologies 106
4.3 ANALYSIS OF ON-SITE/OFF-SITE DISPOSAL METHODS 114
4.4 SAFEGUARDS USED IN DISPOSAL 115
4.5 TREATMENT AND DISPOSAL TECHNOLOGY LEVELS AS
APPLIED TO LAND-DESTINED HAZARDOUS WASTE STREAMS
FROM THE PHARMACEUTICAL INDUSTRY 115
4.5.1 Treatment and Disposal Levels for Halogenated and
Non-Halogenated Waste Solvents 118
4.5.2 Treatment and Disposal Levels for Organic Chemical
Residues 120
4.5.3 Treatment and Disposal Levels for Potentially Hazardous
High Inert Content Wastes, Such as Filter Cakes 122
4.5.4 Treatment and Disposal Levels for Heavy Metal Wastes 126
4.5.5 Treatment and Disposal Levels for Returned Goods and
Reject Materials from Formulation 127
GENERAL BIBLIOGRAPHY - SECTION 4.0 130
5.0 COST ANALYSIS 133
5.1 BACKGROUND 133
5.2 SUMMARY OF COSTS FOR CONTROLLED TREATMENT
AND DISPOSAL OF LAND-DESTINED HAZARDOUS WASTES 133
5.3 RATIONALE AND REFERENCES USED IN COST ESTIMATING 133
5.4 COSTS FOR TREATMENT AND DISPOSAL OF HAZARDOUS
WASTES 138
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TABLE OF CONTENTS (Continued)
Page
5.0 COST ANALYSIS (Continued)
5.4.1 Research and Development 138
5.4.2 Production of Active Ingredients (SIC 2831 and 2833) 138
5.4.3 Formulation and Packaging (SIC 2834) 142
APPENDIX A - DESCRIPTION OF HAZARD GRADES 155
APPENDIX B - PROPERTIES OF HAZARDOUS CONSTITUENTS -
EXPLANATION OF SPECIAL TERMS 161
GLOSSARY OF TERMS 175
VI
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LIST OF TABLES
Table No. Page
1.5 Estimates of Pharmaceutical Industry Generated Wastes for
1973, 1977 and 1983 6
1.6 Technology Levels for Disposal and Treatment of Pharmaceutical
Industry Process Wastes 8
1.7A Perspectives on the Pharmaceutical Industry: Hazardous Waste
Treatment and Disposal Costs 9
1.7B Perspectives on the Pharmaceutical Industry: Cost Impact of
Hazardous Waste Treatment and Disposal 10
2.3A Shipments of Ethical and Proprietary Products 13
2.3B Estimated Domestic Sales of Ethical Pharmaceutical Products 15
2.3C Facilities by Sales and Geographic Location 17
2.5 Ranking of Research Categories by Number of Compounds
Under Study 22
2.6 Number of Prescriptions Filled at Retail Pharmacies 24
2.8A Estimated Number of Pharmaceutical Plants (SIC 2831, 2833,
and 2834) Total Number of Plants and Those with More
Than 100 Employees 26
2.8B Number of Employees 27
3.1.2A Summary of Hazard Evaluation Criteria 34
3.1.2B Biological Functions and Toxicities of Selected Elements 35
3.1.3A Priority I Hazardous Wastes 37
3.1.3B Characterization of Typical Waste Solvents or Still Bottoms
Containing the Listed Chemicals 37
3.1.3C Typical Toxicities of Pharmaceutical Active Ingredients
as Measured by Oral LDggOn Mice and Rats 39
3.2.1.2.1 Estimated Average of Chemical Wastes Generated in Organic
Medicinal Chemical Production 46
3.2.1.2.3 Typical Antibiotic Production Plant (Procaine Penicillin G) 50
3.2.1.2.4.1 Typical Plant for Producing Botanical Medicinals (Plant
Alkaloids) 55
3.2.1.2.4.2 Typical Plant for Producing Botanical Medicinals
(Stigmasterol for Hormone Synthesis) 56
3.2.1.2.5 Typical Plant for Producing Medicinals from Animal Glands
(Insulin) 60
3.2.1.4.1A Pharmaceutical Industry Waste Generation Estimate for 1973 68
3.2.1.4.1B Distribution of Pharmaceutical Industry Waste Generation (1973) 70
3.2.1.4.1C Estimated Distribution of Waste Generated by the Pharmaceutical
Industry in 1973 73
3.2.1.4.2 Summary of Typical Types of Pharmaceutical Hazardous Waste
Materials 75
VII
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LIST OF TABLES (Continued)
Table No. Page
3.2.1.4.3A Estimates of Pharmaceutical Industry Generated Wastes for 1973,
1977 and 1983 76
3.2.1.4.3B Projected Distribution by State of Wastes Generated by the
Pharmaceutical Industry in 1977 78
3.2.1.4.3C Projected Distribution by State of Wastes Generated by the
Pharmaceutical Industry in 1983 79
4.2.2 Waste Solvent Disposal Methods 98
4.2.3 Organic Chemical Residue Disposal Methods 101
4.2.4 High Inert Content Wastes Disposal Methods 103
4.2.5 Heavy Metal Waste Disposal Methods 104
4.2.6 Disposal Methods for Returned Goods and Reject Material 105
4.2.7A Functions and Waste Types of Currently Used Hazardous
Waste Treatment and Disposal Processes 107
4.2.7B Waste Treatment Processes Used to Separate a Waste Destined
for Land Disposal 108
4.3 Analysis of On-Site/Off-Site Disposal Methods 116
4.4 Use of Safeguards in Disposal Operations 117
4.5.1A Treatment and Disposal Technology Levels for Non-Halogenated
Waste Solvents 119
4.5.1B Treatment and Disposal Technology Levels for Halogentated
Waste Solvents 121
4.5.2 Treatment and Disposal Technology Levels for Organic
Chemical Residues 123
4.5.3A Treatment and Disposal Technology Levels for Potentially
Hazardous High Inert Content Wastes 124
4.5.3B Treatment and Disposal Technology Levels for Potentially
Hazardous High Inert Content Wastes 125
4.5.4 Treatment and Disposal Technology Levels for Heavy Metal
Wastes 128
4.5.5 Treatment and Disposal Technology Levels for Potentially
Hazardous Returned Goods and Reject Material from Formulation 129
5.2A Perspective on the Pharmaceutical Industry: Treatment and
Disposal Costs Per Unit of Hazardous Waste 134
5.2B Perspective on the Pharmaceutical Industry: Hazardous
Waste Treatment and Disposal Costs 135
5.2C Perspectives on the Pharmaceutical Industry: Cost Impact
of Hazardous Waste Treatment and Disposal 136
5.3A Cost of Transporting Wastes 137
5.3B Contract Disposal Charges for Hazardous Wastes 137
5.3C Capital Investment for Industrial Solid Waste Incineration 140
Vlll
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LIST OF TABLES (Continued)
Table No. Page
5.4.2.1A Treatment and Disposal Costs: Active Ingredient Production;
Organic Medicinal Chemicals Waste Stream — Non-Halogenated
Waste Solvent 143
5.4.2.1B Treatment and Disposal Costs: Active Ingredient Production;
Organic Medicinal Chemicals Waste Stream — Halogenated Waste
Solvent 144
5.4.2.1C Treatment and Disposal Costs: Active Ingredient Production;
Organic Medicinal Chemicals Waste Stream: Potentially Hazardous
High Inert Content Wastes 145
5.4.2.1D Treatment and Disposal Costs: Active Ingredient Production;
Organic Medicinal Chemicals Waste Stream — Organic Chemical
Residues 146
5.4.2.3A Active Ingredient Production; Fermentation Products; Penicillin
Waste Stream - Waste Solvent Concentrate (50% Solids) 147
5.4.2.3B Treatment and Disposal Costs: Active Ingredient Production;
Fermentation Products; Penicillin Waste Stream — Waste
Solvent Concentrate (50% Solids) 148
5.4.2.4A Treatment and Disposal Costs: Active Ingredient Production;
Botanicals; Alkaloids Waste Stream — Aqueous Solvent with
Solids (30% Solvent, 20% Water, 50% Solids) 149
5.4.2.4B Treatment and Disposal Costs — Active Ingredient Production;
Botanicals; Alkaloids Waste Tream — Halogenated Waste
Solvent 150
5.4.2.4C Treatment and Disposal Costs: Active Ingredient Production;
Botanicals; Alkaloids Waste Stream — Non-Halogenated Waste
Solvent 151
5.4.2.5 Treatment and Disposal Costs: Active Ingredient Production;
Drugs from Animal Sources; Insulin Waste Stream — Aqueous
Alcohol with Organic Solids (25% Alcohol, 25% Solids, 50%
Water) 152
5.4.2.6 Treatment and Disposal Costs: Active Ingredient Production;
Biological Products; Plasma Protein Fractions
Waste Stream — Aqueous Solvent 153
5.4.3 Treatment and Disposal Costs: Formulation and Packaging
(Finished Pharmaceutical Preparations) Waste Stream —
Returned Goods and Reject Material 154
IX
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LIST OF FIGURES
Figure No. Page
2.3A Estimated Domestic Sales at Manufacturers' Level of Ethical
Products 14
2.3B Industry Concentration of Domestic Ethical Sales 18
2.5 Research and Development Expenditures for Ethical Products 20
2.8A Number of Plants 28
2.8B Number of Plants (> 100 Employees) 29
2.8C Pharmaceutical Employment Trends by SIC Codes 30
3.2.1.2.1 Typical Synthetic Organic Medicinal Chemical Process 45
3.2.1.2.3 Representative Process for Antibiotic Production (Procaine
Penicillin G) 51
3.2.1.2.4.1 Representative Process for Botanical Medicinals (Plant
Alkaloids) 54
3.2.1.2.4.2 Representative Process for Botanical Medicinals (Stigmasterol
for Hormone Synthesis) 57
3.2.1.2.5 Representative Process for Medicinals from Animal Glands
(Insulin) 59
3.2.1.2.6 Diagrammatic Representation of Method 6 Blood Fractionation 62
3.2.1.3A Pharmaceutical Tablet Production 64
3.2.1.3B Pharmaceutical Capsule Production 65
3.2.1.3C Pharmaceutical Ointment Production 67
4.2.1.5 Solid Waste Disposal Facilities in Puerto Rico 95
5.3A In-Plant Storage and Landfill Charges 139
5.3B General Industrial Solid Waste Incineration — Capacity Ranges
and Investment Costs 139
5.3C General Industrial Solid Waste Incineration Operating Costs 139
XI
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1.0 EXECUTIVE SUMMARY
1.1 INTRODUCTION
This report is the result of a study commissioned by the U.S. Environmental Protection
Agency (EPA) to assess "Hazardous Waste Generation, Treatment and Disposal in the
Pharmaceutical Industry." This industry study is one of a series sponsored by the Office of
Solid Waste Management Programs, Hazardous Waste Management Division. The studies
were conducted for information purposes only and not in response to a Congressional
regulatory mandate. As such, the studies serve to provide EPA with: (1) an initial data base
concerning current and projected types and quantities of industrial wastes and applicable
disposal methods and costs; (2) a data base for technical assistance activities; and (3) a
background for guidelines development work pursuant to Sec. 209, Solid Waste Disposal
Act, as amended.
The definition of "potentially hazardous waste" in this study was developed based
upon contractor investigations and professional judgment. This definition does not neces-
sarily reflect EPA thinking since such a definition, especially in a regulatory context, must
be broadly applicable to widely differing types of waste streams. Obviously, the presence of
a toxic substance should not be the major determinant of hazardousness if there were
mechanisms to represent or illustrate actual effects of wastes in specified environments.
Thus, the reader is cautioned that the data presented in this report constitute only the
contractor's assessment of the hazardous waste management problem in this industry. EPA
reserves its judgments pending a specific legislative mandate.
1.2 PURPOSE OF THE STUDY
The study had four basic objectives:
1. to determine the nature and quantities of hazardous wastes originating from
the pharmaceutical industry (1973) and to project these wastes to 1977 and
1983;
2. to determine the current treatment and disposal practices within the indus-
try;
3. to examine improved control technologies which could be applied to reduce
hazards presented by the wastes; and
4. to calculate the cost of implementing three levels of control technology in a
typical hypothetical or existing plant. The three levels of technology are:
Level I - Technology currently applied by typical facilities;
Level II — Best technology currently employed; and
Level III — Technology necessary to provide adequate health and environ-
mental protection.
1
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1.3 STUDY APPROACH
Our study consisted of four interrelated tasks:
1. Industry characterization (Section 2.0);
2. Waste characterization (Section 3.0);
3. Treatment and Disposal Technology (Section 4.0); and
4. Cost Analysis (Section 5.0).
Since no Federal law (except the Federal Insecticide, Fungicide and Rodenticide Act, Public
Law 92-516) has yet been passed requiring industry to obtain and report data on non-radio-
active hazardous wastes destined for land disposal, we had to obtain the voluntary coopera-
tion of companies that represented a significant portion of the pharmaceutical industry.
Fortunately, the Pharmaceutical Manufacturers Association (PMA) supported the planned
attempt to obtain useful information on which EPA's Office of Solid Waste Management
Programs could base part of its future planning' and programs. The PMA Environmental
Control Committee lent us its support and assisted in obtaining the cooperation of several
major pharmaceutical producers.
Because the industry had never had to report detailed composition of waste streams,
we realized that mailing of questionnaires would not produce usable information. We there-
fore chose to conduct in-depth interviews and plant inspections at the plants of the cooper-
ating companies. We visited the principal production facilities of companies which repre-
sented an estimated 27 percent of the total U.S. sales of ethical Pharmaceuticals and an even
higher percentage of active ingredient production of the industry. All 14 facilities we visited
had multiple plants and multiple operations, so that in all we surveyed more than 35 com-
ponent plants. Good representative information was obtained on research and development
(R&D), fermentation, biological products, organic synthesis, extraction of animal glands,
and formulation and packaging operations in the United States, including Puerto Rico. We
checked the information we received in the interviews and by letter and confirmed it with
the companies. We then extrapolated the collected data to obtain information applicable to
the entire industry.
During the course of the study we also visited eight landfills and four contractors that
were treating wastes, principally by incineration. We also interviewed 11 contractors by tele-
phone to confirm information obtained fr6m plant visits.
1.4 CHARACTERIZATION OF THE PHARMACEUTICAL INDUSTRY
For this report we found it advantageous to characterize the industry by function as well
as by SIC codes. The main function of the pharmaceutical industry is to provide delivery of
active therapeutic substances in stable, useful dosage forms, such as tablets, injectables,
capsules, and the like. However, the overall pharmaceutical industry can be considered to have
four functional sections:
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1. Research and Development (R&D) — The function of R&D is to discover new
drugs and to develop and improve formulations of these and older drugs.
2. Production of Active Ingredients — This stage involves the production of the
basic active drugs in bulk form.
3. Formulation and Packaging — Bulk drugs are formulated into dosage forms,
such as tablets, ointments, syrups, injectable solutions, and the like, that can be
taken or used by patients easily and in accurate amounts.
4. Marketing and Distribution — To get Pharmaceuticals to doctors, hospitals,
pharmacies, and ultimately to the patient or consumer, Pharmaceuticals are
promoted by pharmaceutical companies and distributed either directly or
through wholesalers. Pharmaceuticals promoted by advertising directly to the
consumer are called "proprietary Pharmaceuticals" and those advertised to the
medical, dental and veterinary professions are called 'ethical Pharmaceuticals."
The U.S. Department of Commerce has divided the pharmaceutical industry into three
SIC codes: 2831, 2833, and 2834. SIC 2834 (Pharmaceutical Preparations) is essentially the
same as the Formulation and Packaging function described above. SIC 2833 covers the major
portion of bulk active ingredient manufacture. SIC 2831 covers a group of products which
were formerly regulated by the Division of Biologies Standards in the National Institute of
Health and not by the Food and Drug Administration. Because the manufacturing and isola-
tion procedures are similar to those in SIC 2833 (Medicinals and Botanicals), the SIC 2831
(Biological Products) operations are combined with SIC 2833 for the purposes of this study.
While the Department of Commerce indicated a 1972 total of 1058 plants in the United
States manufactured pharmaceutical products, only 416 of those plants had 20 or more
employees. These 416 plants were distributed as follows: SIC 2834 - 302 plants, SIC 2831 -
60 plants, and SIC 2833 — 54 plants. Employment in these three SIC categories in 1972*
totaled approximately 130,000. Estimated U.S. domestic sales of ethical Pharmaceuticals in
1973* were approximately $5.5 billion and sales of proprietary Pharmaceuticals were about
$1.9 billion.
1.5 WASTE CHARACTERIZATION
The largest tonnage of process wastes currently being landfilled comes from the produc-
tion of antibiotics by fermentation. In the fermentation industry the antibiotics are produced
* Employment figures are based on Census of Manufactures data which are published every five years (the last
being 1972), whereas sales figures have been estimated by ADL utilizing U.S. Department of Commerce data
for 1973 and other sources.
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as by-products of the growth of microorganisms (molds and bacteria). During operations to
recover the antibiotics, the microorganisms are filtered off, usually with the addition of an
inorganic filter aid, such as diatomaceous earth. This discarded product is usually called
"mycelium."
Because mycelium wastes consist only of cells of organisms, filter aid and residual
nutrients, the product is not considered hazardous. However, due to the large quantities pro-
duced by a typical fermentation plant and the tendency of the mycelium to emit odors on
decomposition, the waste can be a nuisance if not properly handled. The fermentation industry
likewise produces a high BOD effluent stream, similar to that produced in the brewing
industry, that must be treated in an activated sludge system. Neither the mycelium waste nor
the biological sludge from treatment of the effluent streams contains significant quantities of
hazardous materials.
Hazardous wastes are produced during the recovery of antibiotics in the form of waste
solvents and still bottoms. These solvents are usually nonhalogenated and are relatively non-
toxic, but they are hazardous due to their flammability.
The production of organic medicinal ingredients represent the major source of hazard-
ous wastes and a significant source of nonhazardous wastes. Of the roughly 90,700 metric
tons of organic medicinals (excluding antibiotics) produced in the United States in 1973,
only about 34,000 metric tons were produced by the pharmaceutical industry itself. The
remainder was produced by closely allied suppliers to the industry. Production of organic
medicinals resulted in wastes consisting of filter cakes, carbon, filter paper, sewage process
sludge, unrecoverable halogenated and nonhalogenated solvents, and still bottoms.
Wastes produced by the packaging and shipping sections of the industry are mostly glass,
paper, wood, rubber, aluminum, and the like, that are discarded. We estimate only a small
fraction of 1 percent of this material to be active pharmaceutical ingredient. We further
estimate that 75,000 metric tons of this rubbish is disposed of in regular municipal landfills,
along with cafeteria wastes, office wastes, and the like.
Goods returned to the pharmaceutical producer are received by the formulation and
packaging section of the industry. We estimate that the approximately 10,000 metric tons of
returned goods consist of approximately 85% glass, paper, water, and the like. Of the remaining
15% solids, the active ingredient may range from 100% down to approximately 1%. Because of
the low concentration of active ingredient in many products and the low toxicity of the active
ingredients, the resulting mix of materials disposed of on land is considered nonhazardous.
However, a small number of compounds, such as mercurials, controlled drugs, and the like, are
segregated and treated by environmentally acceptable methods.
The only hazardous waste of major concern produced in sufficient quantity from R&D
installations is waste solvents (1500 metric tons). Because of the generally flammable nature
and the wide variety of solvents in the mixed solvents disposed of, all of these materials are
considered hazardous. Many of the R&D personnel are scattered in small groups throughout
the industry, but some companies may employ from 200 to over 2000 researchers at a single
location. 4
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We classified waste streams from the various industry segments as hazardous or
nonhazardous according to criteria explained in Section 3.1.2. Estimates of waste quantities
are summarized in Table 1.5.
We expect quantities of both nonhazardous and hazardous wastes to increase in propor-
tion to production in the future with no significant effect of air and water guidelines for 1977
and 1983. We estimate production will increase only at a 3% compounded annual rate from
1973 to 1977 due to the present energy shortages and economic recession. We anticipate
economic recovery and the passage of national health insurance will take place in 1976. There-
fore, we expect production and concomitant wastes to increase at an annual compounded rate
of 7% from 1977 to 1983. Waste projections for 1977 and 1983 are also included in Table 1.5.
Approximately 244,000 metric tons of land-destined process wastes (on a dry basis)
were produced by the pharmaceutical industry in 1973. The amount of hazardous wastes is
about 25 percent of the total waste, or 61,000 metric tons in 1973. The total wastes are
expected to grow to nearly 400,000 metric tons per year and hazardous wastes to 100,000
metric tons per year by 1983.
1.6 TREATMENT AND DISPOSAL TECHNOLOGY
Approximately 85 percent of total wastes and 60 percent of hazardous wastes are esti-
mated to be treated and disposed of by contractors. Of the total wastes, ADL estimates that 60
percent, or 150,000 metric tons, are finally disposed of on land. About 9 percent, or 5,600
metric tons of the hazardous wastes, are finally disposed of on land. These percentages reflect
the extensive use of incineration, both on-site and by contractors off-site, by the pharma-
ceutical industry. Where possible, materials are recovered for reuse. Also secure chemical land-
fills and encapsulation are being used now — and will most probably be used in the future — for
the disposal of heavy metal wastes and the like, which are too dilute or contaminated for re-
covery, and general process wastes of a nonhazardous nature.
In the disposal of a major portion of hazardous wastes generated in the pharmaceutical
industry, Level I technology will be adequate for Level II and Level III also. This is true for
those wastes such as solvents and organic chemical residues that, are presently disposed of
by incineration. Some other pharmaceutical wastes that are presently landfilled, such as
returned goods and rejected product and high inert content wastes, such as filter cakes, may
require incineration to meet Level II and III criteria.
The heavy metal wastes or high inert content wastes, such as filter cakes, that contain
heavy metals and are presently landfilled, may require further treatment to meet Level II and
Level III criteria.
Table 1.6 presents a summary of the treatment and disposal technology levels for pharma-
ceutical industry process wastes determined to be hazardous.
1.7 TREATMENT AND DISPOSAL COSTS
We have calculated costs for "end-of-pipe" treatment and disposal of each hazardous
pharmaceutical waste. These costs do not include charges for in-process changes made to
5
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TABLE 1.5
ESTIMATES OF PHARMACEUTICAL INDUSTRY GENERATED WASTES FOR 1973, 1977 AND 1983*
(All Figures in Metric Tons Per Year)
Industry Segment
R&D
Solvent
Total R&D
SIC Code 2833: Production of Active Ingredients
Organic Medicinal Chemicals (34,000 Metric Tons/Yr)
Biological Sludge (from wastewater treatment)
High Inert Content (filter aid, carbon)
Contaminated High Inert Content (i.e., filter aid and solvent)
-^ Organic Chemical Residues (tars, mud, still bottoms)
Halogenated Solvent
Non-Halogenated Solvent
Heavy Metal Wastes
Zinc Compounds
Arsenic Compounds
Chromium Compounds
Copper Compounds
Mercury Compounds
Total for Organic Medicinal Chemicals
Rounded to:
Inorganic Medicinal
Heavy Metals (i.e., selenium waste)
Antibiotics (by Fermentation, 10,000 Metric Tons/Yr)
Mycelium (plus filter aid and sawdust)
Biological Sludge
Waste Solvent Concentrate
Total for Antibiotics
Rounded to:
Botanicals (Plant Alkaloids, 2,000 Metric Tons/Yr Plant Material)
Wet Plant Material
Aqueous Solvent Concentrate
Halogenated Solvent
Non-Halogenated Solvent
Total for Plant Alkaloids
Botanicals (Plant Steroids. ISO Metric Tons/Yr Stigmasterol)
Fused Plant Steroid Ingots
1973
Non-Hazardous
Dry Basis Wet Basist
-
47,600 476,000
3,400 6,800
-
51,000 482,800
51,000 480,000
-
75,000 300,000
35,000 350,000
1 1 0,000 650,000
1 1 0,000 650,000
2,000 4,000
Hazardous
Dry Basis
1,500
1,500
1,700
13,600
3,400
23,800
2,200
450
20
4
1
45,175
45,000
200
12,000
12,000
12,000
720
60
120
Wet Basis1
1,500
1,500
3,400
1 3,600
3,400
23,800
2,200
450
20
4
1
46,875
47,000
200
12,000
12,000
12,000
850
60
120
2,000
4,000
750
900
1,030
1977
Non-Hazardous
Dry Basis
-
53,600
3,800
-
57,400
57,000
-
84,400
39,400
123,800
124,000
2,250
Wet Basis*
-
536,000
7,600
_
543,600
540,000
-
338,000
394,000
732,000
730,000
4,500
Hazardous
Dry Basis
1,900
1,900
1,900
15,300
3,800
26,800
2,500
500
22
4
1
50,827
51,000
225
13,500
13,500
14,000
810
70
140
Wet Basis*
1,900
1,900
3,800
15,300
3,800
26,800
2,500
500
22
4
1
52,727
53,000
225
13,500
13,500
14,000
960
70
140
2,250
840
4,500
840
1,020
1,170
1983
Non-Hazardous
Dry Basis
-
80,400
5,700
-
86,100 -
86,000
-
127,000
60,000
187,000
190,000
3,400
Wet Basis*
-
804,000
1 1 ,400
—
815,400
815,000
-
508,000
600,000
1,108,000
1,100,000
6,800
Hazardous
Dry Basis
2,700
2,700
2,900
23,000
5,700
40,000
3,700
750
35
6
1
76,092
76,000
350
20,000
20.000
20,000
1,200
100
200
Wet Basis*
2,700
2,700
5,800
23,000
5,700
40,000
3,700
750
35
6
1
78,992
79,000
350
20,000
20,000
20,000
1,400
100
200
3,400
1,000
6,800
1,000
1,400
1,700
-------
TABLE 1.5 (Continued)
1983
Industry Segment
MedicinaIs from Animal Glands (8,000 Metric Tons Glands/Yr)
Extracted Animal Tissue
Fats or Oils
Filter Cake (Containing protein)
Aqueous Solvent Concentrate
Total Medicinals from Animal Glands
Total for Production of Active Ingredients (SIC Code 2833)
SIC Code 2831: Biological Products
Aqueous Ethanol Waste from Blood Fractionation
Antiviral Vaccine
Other Biologicals
Total for Biological Products
SIC Code 2834: Pharmaceutical Preparations
Returned Goods
Contaminated or Decomposed Active Ingredient
Totals for All Industry Segments
Rounded to:
Non-Hazardous
Dry Basis
7,500
350
250
8,100
172,000
-
-
10,000
10,000
181,850
182,000
Wet Basis*
7,500
350
500
8,350
1,143,000
-
-
1 0,000
1 0,000
1,153,000
1,153,000
Hazardous
Dry Basis
800
800
59,000
250
3OO
200
750
500
500
61,650
62,000
Wet Basis*
1,600
1,600
62,000
600
300
200
1,100
500
500
65,100
65,000
Non-Hazardous
Dry Basis
8,400
400
280
9,080
193,000
-
-
11,300
11,300
204,300
204,000
Wet Basis*
8,400
400
560
9,360
1,285,000
-
-
11,300
11,300
1,836,300
1,836,000
Hazardous
Dry Basis
900
900
67,000
280
350
225
855
600
600
70,445
70,000
Wet Basis*
1.8OO
1,800
70.0OO
680
350
225
1,255
600
600
73,755
74,000
Non-Hazardous
Dry Basis
12,500
600
420
13,520
294,000
-
-
17,000
17,000
311,000
310,000
Wet Basis*
12,500
6OO
840
13,940
1 ,937,000
-
-
17,000
17,000
1,954,000
1 ,954,000
Hazardous
Dry Basis
1,350
1,350
99,000
400
500
350
1,250
900
900
103,850
104,000
Wet Basis*
2,700
2,700
103,000
1,000
500
350
1,850
900
900
108,450
108,000
* Source: Arthur D. Little, Inc., estimates.
Wet weight estimates are given for all wastes. The two wastes that typically have the highest moisture content are biological sludge and
mycelium from fermentations. Where the wet waste estimates are the same as on the dry basis, the waste is usually disposed of with only
a minor amount of moisture. However, disposal practices vary from plant to plant, depending on the form in which the waste is produced.
-------
TABLE 1.6
TECHNOLOGY LEVELS FOR DISPOSAL AND TREATMENT OF PHARMACEUTICAL INDUSTRY PROCESS WASTES*
Treatment and Disposal Technology
Industry Segment Level I Level II Level III
R&D
Solvent Incineration
Animals Incineration
Heavy metals Recovery
Active Ingredient Production
— Organic Medicinal Chemicals
Non-halogenated waste solvent Incineration
Halogenated waste solvent Incineration
High inert content wastes
— containing flammables only Landfill or incineration Incineration
— containing heavy metals or corrosives Landfill Secure chemical landfill* »
Heavy metal wastes Secure chemical landfill** Level I and recovery Recovery and engineered storage
Organic chemical residues Incineration *
Inorganic Medicinal Chemicals
Heavy metal wastes Chemical landfill*** Secure chemical landfill*** *
Fermentation Products
oo
Waste solvent concentrate Incineration
— Botanicals
Aqueous solvent Incineration
Halogenated waste solvent Incineration
Non-halogenated waste solvent Incineration
— Drugs from Animal Sources
Aqueous alcohol Incineration
— Biologicals
Aqueous alcohol Incineration
Antiviral vaccines Incineration
Other biologicals (toxoids, serum) Incineration
• Pharmaceutical Preparations
Returned goods and reject material Landfill Incineration
*Neutralize waste or precipitate heavy metal prior to placing in landfill.
**Convert heavy metal to most insoluble form and place in drum prior to placing in landfill.
***Waste is dilute; therefore, Level II technology will involve a more secure landfill rather than a recovery operation.
Source: Arthur D. Little, Inc.
-------
minimize or to change the hazardous nature of the wastes. More detailed analyses are given
in Section 5.0. Table 1.7A and 1.7B summarize generalized costs of treatment and disposal
systems either currently in use or recommended for future use in pharmaceutical production
facilities. Because typical plants were used to develop an estimate of the total industry cost
of treatment and disposal of hazardous wastes, the total industry costs should be taken only
as an indication of the order of magnitude of such costs rather than as the outcome of a
detailed industry survey of the costs. Issues such as site specific costs, different products or
product mixes, local disposal rates, and available disposal methods were not included in this
estimate.
TABLE 1.7A
PERSPECTIVES ON THE PHARMACEUTICAL INDUSTRY:
HAZARDOUS WASTE TREATMENT AND DISPOSAL COSTS*
Total Annual Costs, $000**
1973 1977 1983
Product Category
• Bulk Active Ingredient
Organic Medicinal Chemicals 3,800 4,295 6,140
Inorganic Medicinal Chemicals* — — —
Fermentation Products 1,440 1,620 2,300
Botanicals 165 180 260
Drugs from Animal Sources 115 130 180
Biologicals 50 60 85
• Pharmaceutical Preparations 15 40 50
Partial Total"1" 5585 6325 9015
*0ne hazardous waste cost is included in organic medicinal chemicals.
**December 1973 dollars.
+ Excludes R&D costs.
Source: Arthur D. Little, Inc.
-------
TABLE 1.7B
PERSPECTIVES ON THE PHARMACEUTICAL INDUSTRY:
COST IMPACT OF HAZARDOUS WASTE TREATMENT AND DISPOSAL*
Estimated Hazardous Waste
Control Cost as Percent of Price*
Product Category
• Bulk Active Ingredient
Price
Level
$/kg
Level I
Level II
Level III
Organic Medicinal Chemicals 22
Inorganic Medicinal Chemicals**/ —
Fermentation Products 44
Botanicals ***
Drugs from Animal Sources ***
Biologicals ***
0.2% 0.22% as Level 11
0.34% as Level I as Level I
< 0.1 as Level I as Level I
* Manufacturers selling price in the case of pharmaceutical preparations; value of sales,
that is, the net selling value FOB plant or warehouse, or delivered value, whichever
represents the normal practice for bulk activity ingredient.
** Representative data not available because most inorganic medicinal ingredients that
might produce a hazardous waste are purchased from the chemical industry.
*** Data not available; the selling price of many of these products is stated in terms of
biological activity.
Source: Arthur D. Little, Inc.
10
-------
2.0 CHARACTERIZATION OF THE U.S. PHARMACEUTICAL INDUSTRY
2.1 CHARACTERIZATION OF THE INDUSTRY BY FUNCTION
The pharmaceutical industry can be described or characterized in several ways, depend-
ing on the needs of the particular study. For purposes of this report, we found it
advantageous to break down the industry along functional lines in addition to classifying it
by SIC codes.
The main function of the pharmaceutical industry is to provide delivery of active
therapeutic substances in stable, useful dosage forms. Thus it may be distinguished from the
chemical industry, the function of which is to synthesize various chemicals which may be
useful in a variety of applications. It is true that the pharmaceutical industry may integrate
vertically and become involved in the synthesis of active ingredients, but its major function
is to prepare the tablets, injectables, ointments, capsules, and the like, to provide what is
needed, where it is needed, and when it is needed.
The production and sale of Pharmaceuticals may be outlined in a four-step series:
1. Research and Development: New drugs are discovered and developed by
research laboratories (principally those of the pharmaceutical industry itself,
but also those of government and educational institutions). After clinical
trials and government approval, the drugs are ready for general production
and sale.
2. Production of Active Ingredients: At this stage, the basic active drugs used in
medicine are produced in bulk. These drugs can be categorized according to
their principal ingredients as follows:
a. organic medicinal chemicals (such as aspirin), inorganic medicinal chem-
icals (such as magnesium sulfate), fermentation products (such as peni-
cillin and tetracycline), botanicals (such as quinine), and drugs from
animal sources (such as insulin); and
b. biological products, including vaccines (such as smallpox vaccine),
toxoids (such as tetanus toxoid), serums (such as tetanus antitoxin),
and products from human blood (such as plasma).
3. Formulation and Packaging: The basic drugs, which are manufactured in
bulk, are formulated into various dosage forms such as tablets, ointments,
syrups, lotions, injectable solutions, and the like, that can be taken by
patients easily and in accurate amounts. The formulated products are pack-
aged in appropriate containers.
11
-------
4. Pharmaceutical Marketing and Distribution: To get the Pharmaceuticals to
doctors, hospitals, pharmacies, and ultimately to the patient or consumer,
they are promoted by the pharmaceutical companies and distributed either
directly by the companies or through wholesalers. Pharmaceuticals promoted
by advertising directly to the consumer are called "proprietary pharmaceu-
ticals" and those advertised to the medical, dental, and veterinary profes-
sions are called "ethical Pharmaceuticals."
The larger, established pharmaceutical companies engage in all four functions - re-
search, production, formulation, and marketing - although these may be carried out by
separate divisions, often located many miles apart. Other companies, however, specialize in
only one phase, such as producing medicinal chemicals in bulk or in formulating pharmaceu-
tical products from purchased raw materials.
2.2 BREAKDOWN OF THE PHARMACEUTICAL INDUSTRY BY SIC CODES
The drug industry as defined by the U.S. Department of Commerce actually consists of
three industries, consisting of producers of biological products, medicinal chemicals and
botanical products, and pharmaceutical preparations. Under the 1972 SIC system, the three
industry codes are assigned as follows:
• SIC 2831—Biological Products: Establishments primarily engaged in the
production of bacterial and virus vaccines, toxoids and analogous prod-
ucts (such as allergenic extracts), serums, plasmas, and other blood
derivatives for human and veterinary use.
• SIC 2833—Medicinals and Botanicals: Establishments primarily engaged in
(1) manufacturing bulk organic and inorganic medicinal chemicals and
their derivatives; and (2) processing (grading, grinding, and milling) bulk
botanical drugs and herbs. Also included in the industry are establish-
ments primarily engaged in manufacturing agar-agar and similar prod-
ucts of natural origin, endocrine products, manufacturing or isolating
basic vitamins, and isolating active medicinal principals, such as alka-
loids, from botanical drugs and herbs.
• SIC 2834-Pharmaceutical Preparations: Establishments primarily engaged in
manufacturing, fabricating, or processing drugs in pharmaceutical prep-
arations for human and veterinary use. Most of the products of these
establishments are finished in the form intended for final consumption,
such as ampuls, tablets, capsules, vials, ointments, medicinal powders,
solutions, and suspensions. Products of this industry consist of two
important lines, namely (1) pharmaceutical preparations promoted pri-
marily to the dental, medical, or veterinary professions; and (2) phar-
maceutical preparations promoted primarily to the public.
12
-------
While there is no SIC code for Research and Development, the other SIC codes —
2831, 2833, and 2834 — can be fitted into the functional classification of the industry.
SIC 2834 (Pharmaceutical Preparations) is essentially the same as the Formulation and
Packaging function described in Section 2.1.
SIC 2831 (Biological Products) has many manufacturing and isolation procedures
similar to those in SIC 2833 (Medicinals and Botanicals). Therefore, for purposes of this
study, we combined plant operations of both SIC 2831 and 2833 under Production of
Active Ingredients.
2.3 DOMESTIC SALES OF THE U.S. PHARMACEUTICAL INDUSTRY
Total dollar volume of shipments for ethical products and proprietary products by the
three sectors, according to Census Bureau figures, rose nearly 8% per year between 1954 and
1972, increasing from $2.05 to $7.54 billion, as shown in Table 2.3A.
TABLE 2.3A
SHIPMENTS OF ETHICAL AND PROPRIETARY PRODUCTS*
($ Millions)
1954 1958 1963 1967 1972
Biological Products (SIC 2831) 66.6 63.8 167.3 220.6 481.1
Medicinals and Botanicals (SIC 2833) 281.0 322.3 434.0 593.8 782.6
Pharmaceutical Preparations (SIC 2834) 1,700.5 2,591.8 3,000.2 4,139.7 6,276.0
Total 2,048.1 2,977.9 3,601.5 4,954.1 7,539.7
* Source: U.S. Department of Commerce
During the comparable period, U.S. domestic sales for ethical products grew at a 9%
annual rate to $5.45 billion in 1973 from $1.00 billion in 1953, as shown in Figure 2.3A.
Proprietary pharmaceutical sales are estimated at $1.9 billion for 1973 compared to
approximately $0.4 billion in 1953. Prior to World War II, proprietaries outsold ethicals but
the tremendous increase in new active ingredients has led to a remarkably accelerated
growth of Pharmaceuticals under prescription and other Pharmaceuticals only promoted as
ethicals. We expect ethical Pharmaceuticals to continue to be the dominant factor in the
expanded markets of the future.
Table 2.3B shows the estimated domestic sales of ethical pharmaceutical products and
their growth rates by major therapeutic classes for selected years during the past decade.
Within these major categories, the growth rates have varied substantially — from a slight
decline in sulfonamides to a 19% growth for anti-arthritics. The most important factors
stimulating demand during the period were:
13
-------
6,000
5,000 -
4,000 -
c
o
to
CO
3,000 -
2,000 -
1,000
1955
1960
1965
Year
1970
Source: Arthur D. Little, Inc., estimates.
FIGURE 2.3A ESTIMATED DOMESTIC SALES AT MANUFACTURERS'
LEVEL OF ETHICAL PRODUCTS1"
14
-------
TABLE 2.3B
ESTIMATED DOMESTIC SALES* OF ETHICAL PHARMACEUTICAL PRODUCTS1"
($ millions)
Therapeutic Group
Analgesics
Antacids
Antiarthritics
Antibiotics
Antihistamines
Antiobesity Products
Antispasmodics
Ataraxics
Cardiovasculars
Cough and. Cold Preparations
Diabetic Therapy
Diuretics
Hematinics
Hormones
Muscle Relaxants
Psychostimulants
Sedatives
Sulfonamides
Vitamins and Nutrients
Others
Total
*At manufacturers' selling price.
**Preliminary estimates.
Source: Arthur D. Little, Inc., estimates.
1963
90
50
20
363
33
65
53
185
110
80
72
65
36
175
27
25
65
50
200
619
1967
160
65
63
458
35
82
70
315
200
125
99
96
36
300
35
48
66
48
225
840
1972
270
109
101
697
50
67
89
530
348
198
127
174
42
455
55
75
90
43
300
1,230
1973
292
113
110
730
50
71
92
575
387
223
130
200
41
490
60
79
86
47
325
1,349
1974**
310
118
125
760
52
80
97
615
425
250
140
225
43
525
67
85
90
52
340
1,411
Annual Growth
Rate (%) From
1963 to 1973
12
9
19
7
4
1
6
12
13
11
6
12
1
11
8
12
3
0
5
8
2,383
3,366
5,050
5,450
5,810
-------
• The introduction of several important new drugs (e.g., Indocin [anti-
arthritic] , Lasix [diuretic], oral contraceptives, Valium and Librium
[ataraxics]);
• Routine consumption of more drug products to control chronic illnesses and
geriatric deterioration;
• New medical techniques and other health care products; and
• Continued growth in private and public health insurance.
At the present time, more than 1000 companies are considered as pharmaceutical
firms because they sell drug products. Many are relatively small with annual sales less than
$1 million and they frequently service a limited geographic area. Many do not manufacture
their own products, but sell products to various drug outlets on a contract basis. They
represent a small part of total drug sales. The distribution of pharmaceutical facilities by
sales volume and geographical location is shown in Table 2.3C. Although sales data are not
available for some firms (those in columns headed "G"), these firms usually are small and
the numbers of facilities listed in columns headed "F" can be taken as indicative of the
numbers of facilities with more than $10 million worth of annual sales. An inspection of the
table indicates that only approximately 5 percent of the facilities in SIC codes 2831 and
2833 have sales greater than $10 million per year and only about 10 percent of the facilities
in SIC code 2834 are of that size.
The Pharmaceutical Manufacturers Association (PMA) estimates that perhaps 600 to
700 U.S. firms actually produce ethical products. Many of these firms are quite small. In
fact, the 110 members of the Pharmaceutical Manufacturers Association account for 95% of
industry sales of ethical Pharmaceuticals in this country. As shown in Figure 2.3B, this
figure can be broken down with the top 15 companies accounting for greater than 50% of
ethical sales and the top 40 companies accounting for 80% of domestic ethical sales.
Moreover, since many drug companies function as a division of a larger corporation, the top
40 companies actually represent 33 corporations.
The evolving environment for Pharmaceuticals suggests further concentration, with
balanced resources in manufacturing, marketing, and research/development essential for
successful participation in the expected growth. The industry leaders today possess the
balanced resources necessary for success in the future. Because the barriers are substantial,
probably few new pharmaceutical firms will be established.
2.4 HISTORICAL GROWTH OF THE U.S. PHARMACEUTICAL INDUSTRY
Historically, drug companies started as drugstores established to provide drugs to the
public, but gradually they became more involved in preparing formulations for local
physicians. The druggist ran a one-man show and acted as purchasing agent, production
16
-------
TABLE 2.3C
FACILITIES BY SALES AND GEOGRAPHIC LOCATION*
IV Alabama
X Alaska
IX Arizona
VI Arkansas
IX California
VIII Colorado
1 Connecticut
III Delaware
III District of Columbia
IV Florida
IV Georgia
IX Hawaii
X Idaho
V Illinois
V Indiana
VII Iowa
VII Kansas
IV Kentucky
VI Louisiana
1 Maine
III Maryland
1 Massachusetts
V Michigan
V Minnesota
IV Mississippi
VII Missouri
VIII Montana
VII Nebraska
IX Nevada
1 New Hampshire
II New Jersey
VI New Mexico
II New York
IV North Carolina
VIII North Dakota
V Ohio
VI Oklahoma
X Oregon
III Pennsylvania
II Puerto Rico
1 Rhode Island
IV South Carolina
VIII South Dakota
IV Tennessee
VI Texas
VIII Utah
1 Vermont
III Virginia
X Washington
III West Virginia
V Wisconsin
VIM Wyoming
National Totals
Region Totals
1
II
III
IV
V
VI
VII
VIM
IX
X
A
2
1
3
1
1
2
1
1
1
1
1
1
1
1
1
5
1
25
2
1
2
3
3
6
2
1
4
1
Key:
B
2
5
1
3
4
2
3
1
2
1
1
1
1
3
5
1
1
1
1
4
1
2
46
0
8
4
11
6
4
4
1
7
1
A
B
C
SIC 2831
Biologicalt
C D E F
1 411
1 1
1 1
3
1
1 1 1
1
1 2
1
1
1
1
2 1
2 2 1
1 5
1
1
1
3
1
1
1
2
1
14 24 9 5
0110
3710
3 120
4021
0211
0 200
1 412
1 200
1411
1 100
($1,000)
$ 0 - $ 99.9
$100- $499.9
$500 - $999.9
SIC 2833
Medicinali and Botanicals
G
3
2
1
12
4
2
3
2
10
4
1
5
1
1
3
1
2
1
2
1
1
6
1
1
4
3
8
2
4
91
2
7
9
13
20
11
9
4
14
2
A
1
9
1
1
3
4
1
1
1
1
1
1
2
1
2
1
2
4
4
1
5
2
3
52
3
6
2
3
15
7
4
3
9
0
B C
1
11 7
1
4 1
3 1
1
7
1
1
2
1 1
1
4
2
2
1 2
9 4
7 6
2
1
3
6
7 1
1
4
80 26
7 1
16 10
7 2
7 2
19 0
10 1
2 2
0 1
12 7
0 0
D E
4 2
3 1
1
4 1
1
1
1
2 1
5 2
3
2 1
27 8
4 1
7 3
0 0
1 0
7 2
0 0
1 0
0 0
4 2
3 0
F G
1 24
1
2 4
1
1
4
26
5
1
2
I 1
1
1
1 4
1
2 11
2 22
1 23
3
3
1
1
11
3
3
1
1 6
1
2
3
11 171
3 9
3 45
0 15
0 12
1 42
1 9
2 12
0 2
1 24
0 1
A
5
2
18
5
2
11
7
15
5
3
1
1
1
3
14
11
5
2
9
1
1
7
37
4
13
1
1
14
1
1
2
11
2
6
5
4
231
20
44
25
33
53
15
14
3
18
6
SIC 2834
Pharmaceutical Preparations
B
2
1
23
1
6
12
5
20
4
2
3
3
6
8
6
6
3
10
2
13
42
4
5
2
2
14
2
1
1
1
10
1
2
4
3
2
232
18
55
24
31
43
15
14
3
24
5
C
1
17
3
1
8
1
1
1
2
3
3
1
4
1
8
12
1
3
2
6
1
5
1
1
1
B8
4
20
9
3
17
5
6
3
18
3
D
1
1
18
1
4
2
1
9
3
17
4
3
4
2
2
2
3
2
5
2
25
29
2
1
1
1
10
1
3
7
4
170
7
54
15
17
31
11
14
1
19
1
E
2
1
1
2
1
1
1
1
3
1
8
3
1
5
1
32
1
11
6
3
7
2
0
0
2
0
F
1
a
2
2
7
3
1
2
4
3
15
16
1
2
7
2
1
3
80
4
31
13
3
16
1
3
0
9
0
G
2
4
3
57
6
5
3
6
7
34
9
7
4
3
4
3
8
10
5
7
24
6
1
68
71
10
14
2
2
24
1
4
15
20
1
6
3
2
8
469
14
139
38
54
80
29
41
7
62
5
A
7
1
3
30
1
7
2
14
8
21
6
4
3
1
2
5
16
13
6
2
11
1
2
2
9
42
4
18
2
1
16
1
1
2
21
4
6
6
7
308
26
51
29
39
71
28
20
7
31
7
B
2
4
39
2
10
18
9
29
5
2
4
4
3
2
9
9
11
9
6
11
3
25
54
7
6
5
3
21
2
2
1
1
21
1
2
5
3
8
358
26
79
35
49
68
29
20
4
43
6
State Total
C
1
25
5
1
2
5
8
1
2
1
3
3
3
1
6
1
14
19
1
3
3
9
1
6
2
1
1
128
5
33
14
9
17
6
9
5
26
4
D
1
1
26
2
7
2
1
9
4
21
4
4
5
2
3
4
4
3
5
5
29
39
2
2
1
4
10
1
1
3
9
1
6
221
12
68
16
18
40
13
19
3
27
5
E
5
1
1
1
4
1
1
1
3
1
3
1
10
5
1
1
5
1
1
1
1
49
3
15
8
5
10
2
1
0
5
0
F
1
10
4
2
1
7
3
1
1
2
6
6
1
17
17
1
2
7
2
2
3
96
7
34
13
4
18
2
7
0
11
0
G
5
6
4
93
11
9
6
10
13
70
18
9
9
3
7
2
7
10
16
6
8
37
7
1
91
100
14
17
4
3
39
4
7
19
34
2
8
5
2
15
731
25
191
62
79
142
49
62
13
100
8
($1,000,000)
D
E
F
G
$ 1 -
$ 5 -
$10 r-
$4.9
$9.9
over
Not Available
f Source: Arthur D. Little, Inc., estimates based on data from Dun & Bradstreet.
17
-------
Number of Firms/
Percent Sales
1200 Firms Total
Cumulative Percent of
Domestic Ethical Sales
V>OOO< 1090 Firms- 5%XXX>O
««
««
:••::••::••::••::•• 15 Firms - 52% ::••::••::••::••::••
100%
95%
80%
52%
Source: Arthur D. Little, Inc., estimates.
FIGURE 2.3B INDUSTRY CONCENTRATION OF DOMESTIC ETHICAL SALES*
18
-------
superintendent, salesman, and treasurer. Traditionally, the drug operation was a family
business, with the children taking an active role in the growing company. Because of this
structure of strong family ties, most drug manufacturers were quite secretive about their
businesses, and a strong relationship developed between the various companies. Several of
the families developed significant businesses and began to employ professional managers to
run their businesses profitably.
The drug industry was relatively small prior to World War II. Two distinct categories of
drugs were available in 1939 — proprietary and ethical products, with proprietary outselling
ethicals. Proprietaries were sold directly to the consumer, while ethicals were specified or
prescribed by doctors. Most products were designated by a house label; for example, Lilly
aspirin or Parke-Davis throat discs, and not by brand or trade names. The company name
was an important part of the product description. Most products were relatively unsophisti-
cated compared to those of today. Most of today's drugs were unknown, with rather simple
preparations used to treat conditions now treated with a variety of complex, highly selective
agents.
The principal activities of the larger drug companies did not vary considerably from
those of the one-man shop, with the essential duties being sales and manufacturing. The size
of the operation increased as the firms began selling nationally, and quality control
laboratories were installed primarily to ensure standardized production and a high-quality
image "house name" for the physician. The drug industry, as we now know it, came into
existence after World War II.
2.5 ROLE OF RESEARCH AND DEVELOPMENT IN GROWTH OF THE
U.S. PHARMACEUTICAL INDUSTRY
Much of the growth in ethical sales has resulted from new classes of compounds. The
ethical pharmaceutical field is characterized by a heavy commitment to the research and
development of significant new agents. Before 1950, traditional products like vitamins,
barbiturates, and laxatives accounted for most of the industry's growth. After 1950, the
heavy research investment begun during the war and continuing afterwards resulted in the
new product explosion of antibiotics, steroids, and tranquilizers. The industry's emphasis on
development of new products since then has produced an impressive array of effective
products.
Figure 2.5 shows that the research and development (R&D) budget for the ethical drug
industry has grown from $50 million in 1951 to $850 million in 1974. Traditionally, the
ethical drug industry spends about 9-10% of its worldwide sales dollars on research effort —
a higher percentage than in most other industries. Moreover, the R&D budget for specific
companies may be substantially higher. For example, Lilly had worldwide pharmaceutical
sales of $633.6 million in 1974, while its R&D spending was $93.3 million - nearly 15% of
sales. Industry sources indicate the following partial analysis of expenditures:
19
-------
900
1951
1955
1960
1965
1970
1974
Source: Pharmaceutical Manufacturers Association.
FIGURE 2.5 RESEARCH AND DEVELOPMENT EXPENDITURES FOR ETHICAL PRODUCTS"1"
'Government contract funds are not included nor is R&D funding for veterinary ethical
products.
20
-------
Modifying and/or improving existing products 29%
Biological screening and testing 18
Clinical testing 17
Synthesis and extraction 16
Process development, manufacturing work-up,
and quality control 10
Toxicology and safety evaluation _9_
99%
In general, we believe that about one-sixth of the current industry-wide R&D budget is
devoted to basic research and close to one-third to help existing products meet the FDA's
more stringent requirements on bioavailability, efficacy, safety, and so forth. Thus, slightly
more than one-half of the stated budget is devoted to new products.
In the past 30 years, almost 900 new active medicinal ingredients have been introduced
to the U.S. market, two-thirds originating in the United States. (These active medicinal
ingredients are unique compounds in terms of molecular structure. However, they may be
used as an active ingredient in varying concentrations or in conjunction with other active
ingredients in a number of different pharmaceutical products.) For the past decade, the
number of new entities introduced annually into the U.S. market has tended to decline. In
part, this decrease may be due to a trend in research to seek major breakthroughs for
treatment of the more intractable diseases. However, the increased time needed for testing
and meeting the FDA's regulatory requirements is an important factor. We estimate that the
time factor can run five to eight years and cost from $9 to $18 million. Only the leading
pharmaceutical companies have the money and research capacity needed to meet these
demands.
Table 2.5 ranks published research activities on compounds by therapeutic categories
to determine which research areas are currently of greatest interest. As future commercial
production will depend in part on the areas now being researched, these data should give
some indication of the future importance of various therapeutic classes. The 19 categories
listed represent nearly 75% of all the compounds currently being investigated. The types of
compounds under study suggest that there will be no drastic shift in the general types of
active medicinal ingredients in the next 10 years, nor in the general processes (such as
organic syntheses and fermentations) required to produce them.
R&D will be valued even more highly in the future, but it will also be more difficult to
develop significant new agents. Much of the work which could lead quickly to drug
discoveries has already been completed, and now investigators are concentrating on more
difficult subjects, such as developing a basic understanding of heart disease, cancer, con-
genital disease, and stroke — all difficult areas in which to achieve quick developments.
However, new breakthroughs in pharmacology will be forthcoming, involving not only new
classes of therapeutic drugs but also advances brought about by molecular biology, that is,
supplying missing or substitute chemicals in minute doses or in elaborate delivery systems in
order to correct aberrant metabolism.
21
-------
TABLE 2.5
RANKING OF RESEARCH CATEGORIES BY NUMBER OF
COMPOUNDS UNDER STUDYt
Percent of Total Number of
Category Compounds Under Study
Cardiovasculars 14
Psychotropic Drugs 9
Cancer Chemotherapy Agents 6
Antibiotics 6
Hormones 4
Antivirals 3
Analgesics 3
Antagonists/Antidotes 3
Muscle Relaxants 3
Anti-inflammatory Agents 3
Fungicides 3
Cholesterol Reducers 2
Enzyme Inhibitors 2
Diuretics 2
Bronchodilators 2
Antibacterials 2
Immunosuppressants 2
Anticoagulants 2
Antispasmodics 2
Others, each comprising less than
2% of the total compounds 27
Sources: Paul de Haen, Inc., and Arthur D. Little, Inc., estimates.
2.6 PHARMACEUTICAL CONSUMPTION - RECENT TRENDS
There is no simple unit of measure, such as millions of tablets or tons of chemicals,
which shows overall unit consumption of Pharmaceuticals. However, the trend of unit
consumption can be inferred from the number of prescriptions filled at retail pharmacies.*
* Retail pharmacies account for approximately 75% of all prescriptions, with hospitals and other institu-
tions accounting for the balance.
22
-------
Table 2.6 presents data on the number of prescriptions filled at retail pharmacies and shows
that from 1968 to 1973, the number of prescriptions filled at retail pharmacies rose at a 6%
compound annual rate to a total of 1.5 billion. New prescriptions rose at a somewhat higher
rate of 6.4% and refill prescriptions grew at a 5.6% rate. The higher rate of growth in new
prescriptions is primarily due to government restrictions on prescription refills for drugs that
are subject to abuse, and above average growth in prescriptions for antibiotics. These data
give a general indication of unit growth in drug consumption, but not a complete picture,
because various drugs are taken with different frequencies and in different quantities. If
anything, however, the growth rate is probably understated, since studies indicate that there
has been an increase in the size of the average prescription in terms of numbers of tablets,
capsules, and the like, per prescription.
2.7 PHARMACEUTICAL INDUSTRY OUTLOOK FOR 1975-1980
We expect the pharmaceutical industry to maintain a domestic dollar growth rate on
the order of 7-9% over the next five years, and that international growth will probably be
stronger in the near future. However, we believe that the production requirements of the
industry will become more important as unit consumption increases. The following factors
will be affecting the drug industry during this period:
• Enactment of an expanded program of National Health Insurance will be of
prime importance during this period. We expect National Health Insurance
to increase pharmaceutical sales and to boost drug consumption, particularly
over the long-term, when coverage is extended to outpatient drugs. However,
we do not anticipate legislation to be passed before 1976, with additional
time required before the program can be implemented smoothly.
• Price pressures are being, and will continue to be, exerted by the Govern-
ment. For example, HEW is currently assessing the maximum allowable cost
regulations which would have an adverse impact on the profitability of the
industry, particularly since the regulatory environment will encourage the
use of price-competitive, multi-source drugs.
• Several Congressional hearings are being held which are investigating various
practices of the pharmaceutical industry. For example, the Kennedy Health
Subcommittee investigated many of the established marketing techniques of
the industry, and we expect enforcement of related changes, particularly in
the use of sampling and in the regulation of the activities of the medical
representatives (detailmen). Such proposed curbs on promotional practices
of drug companies could have a slightly adverse effect for a limited period of
time.
• The -availability of new drugs has slowed significantly from the flood of
products introduced in the late 1950's and 1960's and is encouraging use of
older, established drugs.
23
-------
TABLE 2.6
NUMBER OF PRESCRIPTIONS FILLED AT RETAIL PHARMACIES1
Total Prescriptions
1968-1973
1973
1972
1971
1970
1969
1968
1967
to 1966
1965
1964
Millions
—
1532
1450
1351
1280
1197
1145
1069.
1055
967
857
Growth Rate %
6.0
5.7
7.3
5.5
6.9
4.5
7.1
1.3
9.1
12.8
—
New Prescriptions
Refill Prescriptions
Prescriptions
—
48
48
48
47
47
47
46
45
45
44
Millions
_
729
696
646
603
562
534
492
476
432
382
Growth Rate %
6.4
4.7
7.7
7.1
7.3
5.2
8.5
3.4
10.2
13.1
—
Millions
—
803
754
706
676
635
612
577
579
535
475
Growth Rate %
5.6
6.5
6.8
4.4
6.5
3.8
6.1
(0.4)
8.2
12.6
—
Source: National Prescription Audit
-------
2.8 NUMBER OF PHARMACEUTICAL PLANTS AND EMPLOYMENT
IN THE INDUSTRY
The latest available Census of Manufactures lists a total of 1058 establishments in 1972
for the SIC codes under evaluation. In addition, there were 42 plants in operation in Puerto
Rico in 1974. Overall, a total of approximately 1100 plants are currently producing drug
products in the United States and its territories. Most of these plants are small. Of the 1058
plants listed in the 1972 Census of Manufactures, in fact, only 416 had 20 or more
employees each. For this study it is noteworthy that in the important function of producing
organic chemical-active ingredients (SIC 2833), only 54 plants in the United States had 20
or more employees. Only 60 plants in the production of biologicals (SIC 2831) were in the
comparable category and 302 were of this size in the formulation and packaging sector (SIC
2834).
Because Government data on a state-by-state basis were not complete at the time of
this study, we have estimated the number of pharmaceutical plants in some of the States
and Puerto Rico as shown in Table 2.8A. Totals of plants by EPA regions and for the
individual states are presented on the map in Figure 2.8A. The corresponding map for plants
with more than 100 employees is presented in Figure 2.8B. As may be observed in these
tables and figures, drug industry production is concentrated primarily in the northeastern
and north central regions, with relatively heavy involvement also in California. As designated
by EPA regions, these include Regions II (282 plants- 26% of total), Region V (215
plants - 20% of total), and Region IX (143 plants - 13% of total). It should be noted that
the new Puerto Rican facilities are incorporated into the total number of plants for
Region II. For the continental United States, Region II contains 240 plants (22% of total).
A further indication of the geographic concentration of the U.S. pharmaceutical
industry is the fact that five states have nearly 50% of all plants- New York (12%),
California (12%), New Jersey (10%), Illinois (7%), and Pennsylvania (6%). Not only is the
total number greater in these states, but the plants are also the largest in the industry. As
shown in Figure 2.8B, these five states and Puerto Rico contain nearly two-thirds of the
plants which have more then 100 employees.
An interesting observation from the Census data is that the total number of establish-
ments in the continental United States dropped from 1359 facilities in 1958 to 1058 in
1972 (a decrease of 22%), but establishments with more than 20 employees increased from
403 to 416 during the same period (an increase of 3%). This shift is a further indication of
the smaller producer disappearing from the industry with the larger manufacturers becoming
even more dominant factors.
The number of employees in the various sections of the pharmaceutical industry from
1947 to 1972 are listed in Table 2.8B and presented graphically in Figure 2.8C. The
industry employed a total of 129,300 workers in 1972, 67,400 of which were production
workers. During the period 1958 to 1972, total employment increased by 26%, while
production workers increased by 19%. This substantial increase in employment took place
during the period noted above in which total plants decreased - again an indication of the
concentration occurring within the industry.
25
-------
TABLE 2.8A
ESTIMATED NUMBER OF PHARMACEUTICAL PLANTS {SIC 2831, 2833, AND 2834)
TOTAL NUMBER OF PLANTS AND THOSE WITH MORE THAN 100 EMPLOYEES1"
EPA Region
IV
X
IX
VI
IX
VIII
I
III
III
IV
IV
IX
X
V
V
VII
VII
IV
VI
I
III
I
V
V
IV
VII
VIM
VII
IX
I
II
VI
II
IV
VIM
V
VI
X
III
II
I
IV
VIM
State
Alabama
Alaska
Arizona
Arkansas
California
Colorado
Connecticut
Delaware
District of Columbia
Florida
Georgia
Hawaii
Idaho
Illinois
Indiana
Iowa
Kansas
Kentucky
Louisiana
Maine
Maryland
Massachusetts
Michigan
Minnesota
Mississippi
Missouri
Montana
Nebraska
Nevada
New Hampshire
New Jersey
New Mexico
New York
North Carolina
North Dakota
Ohio
Oklahoma
Oregon
Pennsylvania
Puerto Rico
Rhode Island
South Carolina
South Dakota
Total Plants1
( 7)
0
( 8)
( 2)
134
( 15)
16
( 4)
0
28
18
0
0
78
26
16
12
( 5)
( 11)
( 3)
23
31
39
( 21)
( 8)
44
0
9
( D
0
112
0
128
( 18)
0
34
( 5)
( 9)
69
42
( 4)
( 6)
( 2)
% of Total2
#
0
*
#
12
1
1
#
0
3
2
0
0
7
2
1
1
»
1
*
2
3
4
2
*
4
0
#
*
0
10
0
12
2
0
3
*
*
6
4
#
*
*
Plants @
>100
Employees
0
0
0
0
18
1
6
0
0
1
3
0
0
13
9
3
1
0
0
0
2
2
10
2
1
10
0
2
0
0
45
0
26
5
0
5
0
1
19
16
0
2
0
% of Plants2
>100
Employees
0
0
0
0
8
*
3
0
0
#
*
0
0
6
4
1
#
0
0
0
*
*
5
*
*
5
0
#
0
0
21
0
12
2
0
2
0
#
9
7
0
#
0
26
-------
EPA Region State
TABLE 2.8A (Continued)
Total Plants1
IV
VI
VIII
I
V
VIII
Tennessee
Texas
Utah
Vermont
Virginia
Washington
West Virginia
Wisconsin
Wyoming
National Totals
Regional Totals
I
II
III
IV
V
VI
VII
VIM
IX
X
16
50
( 3)
0
( 16)
( 7)
( 3)
17
0
1100
54
282
115
106
215
68
81
20
143
16
% of Total2
1
5
#
0
1
*
*
2
0
Plants @
>100
Employees
7
4
1
0
3
0
0
1
0
% of Plants2
>100
Employees
3
2
*
0
1
*
*
*
*
5
26
10
10
20
6
7
2
13
1
219
8
87
24
19
40
4
16
2
18
1
4
40
11
9
18
2
7
*
8
1. Figures in parentheses are Arthur D. Little, Inc., estimates, based on 1967 Census of Manufactures and
Dun and Bradstreet 1974 data; all others from 1972 Census of Manufactures (Preliminary).
2. 'designates less than 1%.
Sources: Arthur D. Little, Inc., estimates and Census of Manufactures.
TABLE 2.8B
Number of Employees
SIC 2833
1947
1954
1958
1963
1967
1972
Total
2,987
3,965
3,692
5,800
7,400
9,800
Production
Workers
NA
NA
2,567
3,600
4,800
5,500
Total
13,097
11,541
10,246
8,100
8,400
8,700
Production
Workers
NA
NA
6,640
5,300
5,600
5,300
Total
65,143
76,555
82,000
85,100
102,000
110,800
Production
Workers
NA
NA
45,708
45,900
55,200
56,600
Total
81,227
92,061
95,938
99,000
117,800
129,300
Production
Workers
NA
NA
54,915
54,800
65,600
67,400
^Source: Census of Manufactures
-------
Ni
oo
Hawaii
0
Puerto Rico (II)
42
N.B.: Numbers in parentheses are Arthur D. Little, Inc., estimates; Roman numerals designate EPA regions.
^Sources: Arthur D. Little, Inc., estimates and Census of Manufactures, 1972 (preliminary).
FIGURE 2.8A NUMBER OF PLANTS1
-------
Alaska
0
to
VO
Hawaii
0
Puerto Rico (II)
16
N.B.: Roman numerals designate EPA regions.
Source: Arthur D. Little, Inc., estimates.
FIGURE 2.8B NUMBER OF PLANTS (> 100 EMPLOYEES)1"
-------
140,000
130,000 _
120,000 -
110,000
100,000
90,000
>. 80,000
_o
a
E
^ 70,000
-o 60,000
50,000
40,000
30,000
20,000
10,000
SIC 2834 Pharmaceutical
SIC 2833 Medicinal Chemicals and Botanical Products
SIC 2831 Biological
2834
2833
2831
2834
2834,2833,2831
2834
Production Employees
Total Employees
2833
Total Employees
— 2831
i I i i i i
Production Employees
1947
t
1954 1958
Source: Census of Manufactures
1963
1967
1972
FIGURE 2.8C PHARMACEUTICAL EMPLOYMENT TRENDS BY SIC CODES1"
30
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3.0 WASTE CHARACTERIZATION IN THE PHARMACEUTICAL INDUSTRY
3.1 SELECTION AND APPLICATION OF HAZARDOUS WASTE CRITERIA
3.1.1 Background Information for the Selection of Hazardous Wastes
In the studies covering various industries, the individual contractors were asked to:
". . identify and describe the wastes generated by each industry which pose a
potential health or environmental hazard upon final disposal. In performing his
analysis, the contractor should pay particular attention to wastes which contain
any of the following specific substances, or types of substances: asbestos, arsenic,
beryllium, cadmium, chromium, copper, cyanides, lead, mercury, halogenated
hydrocarbons, pesticides, selenium, and zinc. EPA believes these substances, on
the basis of initial analysis, to have the potential for producing serious public
health and environmental problems when contained in wastes for disposal. Other
wastes, believed by the contractor to be of a hazardous nature, such as car-
cinogens, should also be identified. "
To identify the wastes that pose a potential health or environmental hazard upon final
disposal, we had to develop a set of criteria to select the hazardous wastes generated by the
pharmaceutical industry. Whereas some industries have only a few well defined inorganic
substances to classify, the pharmaceutical industry manufactures or purchases an estimated
15,000 inorganic and organic chemicals to make its formulated pharmaceutical products.
Potential hazards of these chemicals range from essentially nonhazardous to highly hazard-
ous due to such characteristics as flammability or toxicity.
We studied other hazard classification schemes to assist in developing criteria for
selecting potentially hazardous and highly hazardous wastes generated in the pharmaceutical
industry, but found no universally applicable scheme for classifying the types of hazards and
the degree to which they are hazardous. Each classification scheme was selected to meet
specific needs. Industrial toxicologists selected criteria to assist them in handling the toxic
materials produced in industry, and public health toxicologists assembled criteria to assist
the physician in treating acute poisoning by various chemicals and commercial products.
Classification schemes designed to aid the physician in treating acute poisonings were
usually developed on the basis of LDS 0 values alone, while the industrial hygienist was often
more concerned with the toxicity of inhaled vapors, irritation to the skin, allergic reactions,
and flammability of products.
While none of the other systems have addressed the same problems that the Office of
Solid Waste Management Programs will face, the Coast Guard addressed a related problem in
the safe handling of materials in bulk water transportation. During 1965-66 the National
31
-------
Academy of Sciences (NAS) developed an initial evaluation system for the Coast Guard.* In
this system the substances were rated on a simple numerical scale of 0, 1, 2, 3 or 4,
indicating an increasing degree of hazard in each of 10 categories describing different types
of hazards (flammability, human toxicity, etc.). The publication was revised from time to
time;the current edition is dated 1970 with additions to September 22, 1972. Comments
were received from overseas sources including the Intergovernmental Maritime Consultative
Organization (IMCO), the Netherlands, and the United Kingdom, suggesting the need for
further extension and amplification of the guidelines to define the ratings more precisely.
Thus in 1974 the NAS submitted a revised publication, "System for Evaluation of the
Hazards of Bulk Water Transportation of Industrial Chemicals," which brought the grade
classifications for human toxicity and aquatic toxicity into agreement with grade classifica-
tions developed by IMCO and one hazard category (effect on amenities) was dropped. The
suggested classification scheme now has nine hazard categories as follows: (1) fire, (2) skin
and eyes, (3) vapor inhalation, (4) gas inhalation, (5) repeated inhalation, (6) human
toxicity, (7) aquatic toxicity, (8) water reaction, and (9) self reaction. The same rating scale
of 0, 1, 2, 3 and 4 was retained and used for all hazard categories.
We also examined the IMCO system which was developed by the Joint Group of
Experts on the Scientific Aspects of Marine Pollution to review the environmental hazards
of transporting substances besides oil. In contrast to the NAS system which has nine
categories of hazards, the IMCO system has only five categories: (1) bio-accumulation, (2)
damage to living resources, (3) oral intake hazard to human health, (4) skin contact and
inhalation hazard to human health, and (5) reduction of amenities.
3.1.2 Selection of Criteria for Classification of Potentially Hazardous Substances from
the Pharmaceutical Industry
Classification of materials as hazardous or nonhazardous is an arbitrary process.
Whether or not a substance is hazardous depends on its quantity, concentration, location,
and the species affected. Even air and water can be hazardous in certain situations. For
example, air injected into a vein may cause a fatal air embolism. Likewise water can be fatal
if too much water gets into the lungs by blocking access of air to the lungs and seriously
disrupting the ionic balance of the blood. On the other hand, a substance such as
hydrochloric acid, which can be fatal if ingested in concentrated form, can also be beneficial
in dilute solutions for patients who have a deficiency of normal hydrochloric acid secretions
in the stomach.
Despite the difficulties of developing a universally applicable scheme for grading
hazardous materials, materials with the highest potential for environmental damage and
human hazard can be identified for various handling or disposal techniques. Theoretically,
such a classification scheme should take in all possible hazards. In observing the pragmatic
"Described in NAS publication No. 1465, "Evaluation of the Hazard of Bulk Water Transportation of
Industrial Chemicals - A Tentative Guide."
32
-------
approaches taken by IMCO, NAS-Coast Guard, and the Hazardous Substances Branch of
EPA's Office of Water Planning and Standards, it is apparent that firm decisions had to be
made to eliminate or exclude certain hazard categories. For example, effects on amenities
was eliminated in the 1974 NAS proposed system and bio-accumulation was not included as
a hazard category. Likewise, the IMCO scheme did not include consideration of flamma-
bility in its hazard ratings, presumably because it is concerned with dumping of materials
from ships on the high seas where toxicity is a more important consideration than
flammability.
Because of the wide range of hazards considered in the NAS scheme, and because of
the extensive data that had been collected for the scheme, we proposed that the 1974
modification suggested to the Coast Guard by NAS be used as a basis for evaluating the
hazards of materials for disposal on land. Initially, we suggested classifying substances which
fell into hazard grades 3 and 4 in any category of the NAS scheme as highly hazardous and
those in grades 1 and 2 as moderately hazardous as shown in Table 3.1.2A. Another
contractor (TRW, Inc.) suggested expansion of the NAS-Coast Guard classification to
include bio-accumulation to toxic levels and addition of substances that are carcinogenic,
(oncogenic, teratogenic, or mutagenic. Since the classification scheme developed for this
(preliminary study of hazardous wastes would not bind EPA to the same criteria, the Office
|of Solid Waste Management Programs, ADL, and TRW agreed that both contractors would
!use the expanded classification scheme for the pharmaceutical and organic chemical indus-
jtries, but with a modification involving the water pollution hazards. The criteria for highly
hazardous wastes were retained and, therefore, included any substances falling into hazard
i grades 3 or 4 in any category of the NAS classification scheme. Criteria for moderately
hazardous wastes included any substance falling in grades 1 or 2 in any category, except that
under the "water pollution" heading substances falling in grade 1 were considered non-
hazardous unless they presented a hazard upon collection. We thus have nine graded criteria
to use in making preliminary judgments in evaluating the hazard of a given material. In
addition, bio-concentratable materials are raised to the next higher hazard classification and
suspected carcinogens* are rated as Grade 4, highly hazardous. A summary of the classifica-
tion criteria is presented in Table 3.1.2A with the boundaries between the three hazard
classifications (highly hazardous, moderately hazardous, and essentially nonhazardous)
delineated by heavy lines. A more detailed explanation of the criteria for hazard grades in
each of the nine categories is given in Appendix A.
When one attempts to apply the classification scheme developed above to a specific
industrial situation, other precautions must be observed. The problems of quantity and
concentration arise immediately when we consider the inorganic chemicals (heavy metals
and fluorides, for example) that are usually considered to be toxic. The assumption that any
exposure to a toxic chemical is harmful at any dose is erroneous; for many chemical
substances a deficiency is known to be every bit as injurious as an excess.
Several examples illustrate that substances can be nutritional at one level and toxic at
another. For example, fluorine is essential for life (Table 3.1.2B) and is a demonstrated
growth factor in rats. A fluorine deficiency leads to tooth decay, but in slight excess this
*Does not include list of "suspected carcinogens" published by NIOSH in the Federal Register, 48,
No. 121, pp 26,390-26,496, June 23, 1975. NIOSH is asking for information on the carcinogenicity of
compounds on this list. oo
-------
TABLE 3.1.2A
SUMMARY OF HAZARD EVALUATION CRITERIA
Etsentially
1 Priority II
Moderately Hazardous
Priority !•
Highly Hazardous
Hazard Categories
G 1 II III IV V VI
R
A Fire Health Water 1
« n
g E Skin and Vapor Gas Repeated | Human
3 Eyes Inhalation Inhalation Inhalation Toxicity
T>
» Not
£ Applicable
o 0 All not All not
Non-combust- described described OSHA> LD50>
iWe below below 1000 ppm 5000 mg/kg
1
FPcc > 140° F Corrosive Depressants, All not OSHA LD50
(60°C) to eyes asphyxiants described 100-1000 ppm 500-5000 mg/kg
below
I
i
2 FPcc
100°F-140°F Corrosive LC50 LC50 OSHA LD50
(37.8° -60°C) to skin 200-2000 ppm 200-2000 ppm 10-100 ppm 50-500 mg/kg
3 (37.8°C) LD50
FPcc < 1 00° F 20-200 mg/kg
BP>100°F 24-hr, skin LCSO 50^200 ppm LC50 OSHA LDSO
„ (37.8°C) contact or 0.5-2 mg/K 50-200 ppm 1-10 ppm 5-50 mg/kg
| 4 (37.8°C)
FPcc<100°F LD50<20mg
BP < 100°F 24-hr, skin LCSO < 50 ppm
(37.8°C) contact or<0.5mg/K LC50<50ppm OSHA<1ppm LDso<5mg/kg
VII VIII IX
'Dilution Reaction
Aquatic 1 Water 1
Toxicity Reaction Serf-Reaction
Insignif.
Hazard
T Lm > 1 000 mg/K No appreciable
self-reaction
TLm e.g., CI2 May polymerize
1 00- 1 000 mg/e with low heat
evolution
'^ Contamination
may cause
e.g., NH3 polymerization;
TLm no inhibitor
10-100 mg/K required
May polymerize;
requires
TLm 1-10 mg/K e.g.. Oleum stabilizer
Self-reaction
may cause
explosion or
TL < 1 mg/K e.g., S03 detonation
'Priorities are discussed in Subsection 3.1.3
Note: Bio-concentratable materials are raised to next higher hazard classification. Suspected carcinogens are rated as Grade 4.
-------
TABLE 3.1.2B
BIOLOGICAL FUNCTIONS AND TOXICITIES OF SELECTED ELEMENTS
Element Biological Function*
Hydrogen Constituent of water and organic
compounds
Boron Essential in some plants; function
unknown
Carbon Constituent of organic compounds
Nitrogen Constituent of many organic
compounds
Oxygen Constituent of water and organic
compounds
Fluorine Growth factor in rats; possible
constituent of teeth and bones
Sodium Principal extracellular cation
Magnesium Required for activity of many
enzymes
Silicon Shown essential in chicks; pos-
sible structural unit in
diatoms
Phosphorus Essential for biochemical synthesis
and energy transfer
Sulfur Required for proteins and other
biological compounds
Chlorine Principal extracellular anion
Potassium Principal cellular cation
Calcium Major component of bone; required
by some enzymes
Vanadium Essential in lower plants; certain
marine animals and rats
Chromium Essential in higher animals; related
to action of insulin
Manganese Required for activity of several
enzymes
Iron Most important transition metal ion
essential for hemoglobin and
many enzymes
Cobalt Required for activity of several
enzymes; in vitamin Bj 2
Copper Essential in oxidative and other
enzymes and hemocyanin
Zinc Required for activity of many
enzymes; deficiency causes
anemia
Selenium Essential for liver function
Molybdenum Required for activity of several
enzymes
Tin Essential in rats; function
unknown
Iodine Essential constituent of thyroid
hormones
Toxldty"
Used in insecticides and rat poisons;
fluorides are protoplasmic poisons,
removing essential body calcium inter-
fering with enzyme reactions causing
death from respiratory or cardiac failure
High plasma levels can result in respira-
tory depression and death
Quite toxic, especially as V20S dust
Carcinogenic in rats and mice; industrial
exposure has resulted in dermatitis, skin
ulcers, liver injury, and lung cancer.
Industrial exposure to dust has resulted in
a neurological syndrome and a pneumonitis
Excessive doses have caused severe symptoms
and a high proportion of deaths, especially
in children; actdosts, cardiovascular
collapse and tissue damage to the gastro-
intestinal tract, liver and kidneys
Produces polycythemia, nephritis, etc.
Excessive doses damage liver, kidneys,
capillaries, and central nervous systems
Relatively nontoxic to mammals; yet causes
illness due to inhalation of Zn compounds
High toxicity, similar to Te and As; Even
natural levels cause serious disease (blind
staggers) in cattle; inhibits enzyme
function
lodism in some persons; irritation of
mucous membranes and gastrointestinal tract
'from E. Frieden, Scientific American, Vof 227, No. 1, p 52 (July 1972).
"from J.R. DiPatma (ed.), Drill's Pharmacology in Medicine, (3rd ed.), McGraw-Hill
Book Co., New York (1965). ^ c
-------
same element produces an unsightly mottling of tooth enamel. In large excess it is a very
dangerous poison — the active ingredient, in fact, in some insecticides and rat poisons.
Another example is zinc. Many enzymes require this element yet it can be an industrial
health hazard and has been responsible for fish kills. The list of chemical elements essential
to life is growing fast. It includes eight other "toxic heavy metals" - vanadium, chromium,
manganese, iron, cobalt, copper, molybdenum, and tin - which were listed by Frieden in
1972 (cf. Table 3.1.2B).
3.1.3 Application of the Classification Scheme to Categorize Wastes from
the Pharmaceutical Industry as Priority I or Priority II
Potentially Hazardous Wastes
As was discussed in Section 3.1.2, the toxicity or degree of hazard presented by a given
waste depends on many factors. In this preliminary survey of hazardous wastes from the
pharmaceutical industry potentially destined for land disposal, we were unable to make
final judgments on the degree of "hazard" for wastes from the industry. We recognize that
more information will be required on a plant by plant basis before the hazards at an
individual plant can be evaluated. In this report, we have focused on the "potential hazard"
in a given waste, choosing to label the potentially highly hazardous materials as Priority I
Hazardous Wastes, and the potentially moderately hazardous materials as Priority II Hazard-
ous Wastes.
Priority I hazardous wastes include all "elementary" toxic materials, viz., materials
which are potentially harmful, regardless of their state of chemical combination. Priority I
hazardous wastes also include materials which owe their hazardous properties to their mole-
cular arrangement and which fall in hazard grades 3 or 4 in Table 3.1.2A.
Priority II hazardous wastes owe their hazardous properties to their molecular arrange-
ment and fall in hazard grades 1 or 2 in Table 3.1.2A.
All other process wastes are considered essentially nonhazardous in this study if they
fall in the essentially nonhazardous section of Table 3.1.2A.
A list of Priority I inorganic chemicals was made up and used during interviews as a
checklist to see whether the plant had any of these materials in its waste (see Table 3.1.3A).
As the study proceeded, we found that we had to make some judgments as to whether cer-
tain wastes had significant concentrations of "hazardous" metals, as trace quantities of
metals can be found in almost any waste. Because of the approximately 15,000 active ingre-
dients used in the pharmaceutical industry, a similar list for organic compounds was im-
practical. The industry also uses some quantity of practically every organic solvent com-
mercially available, either in its R&D groups or production plants. As will be described later,
wastes from these solvents are incinerated. In this preliminary study we were not attempting
to catalog all possible components of waste streams, but were merely trying to identify
major hazardous wastes. In general, we were looking for information on waste solvents, still
bottoms, and solid wastes such as process "muds" or presscakes that were discharged from
the plants manufacturing active medicinal ingredients. Representative solvents and still
bottoms containing these solvents are characterized in Table 3.1.3B.
36
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TABLE 3.1.3A
PRIORITY I HAZARDOUS WASTES
Inorganic Elements and Compounds
Mercury 1 Molybdenum (molybdates)
Cadmium? on first proposed toxic pollutant list* Nickel
Cyanide ) Nitrites
Antimony Osmium
Arsenic Selenium
Azides Silver
Barium Thallium
Beryllium Tin
Chromium (chromates) Uranium
Cobalt Vanadium
Copper Zinc
Fluorides Radioactive elements
Lead
*Published in the Federal Register, 38FR 35388, December 27,1973.
TABLE 3.1.3B
CHARACTERIZATION OF TYPICAL WASTE SOLVENTS
OR STILL BOTTOMS CONTAINING THE LISTED CHEMICALS
Priority I Priority II
(Highly Hazardous) (Moderately Hazardous)
Acetone Ethylene Glycol
Acetonitrile Monomethyl Ether
Amyl Acetate Heptane
Benzene Methylene Chloride
Butanol Naphtha
Butyl Acetate
Chloroform*
Ethanol
Ethylene Dichloride
Isopropyl Alcohol
Methanol
Methyl Isobutyl Ketone
Toluene
Xylene
'Chloroform would normally be in the Priority II classification, but possible carcinogenic action
its shift to Priority I.
37
causes
-------
Anyone considering landfilling of returned Pharmaceuticals or disposal of active
ingredients is concerned with the possible hazardous properties of the ingredients. Formu-
lated Pharmaceuticals and most active medicinal ingredients are not hazardous because of
flammability, reactivity with water, self-reactivity, or corrosiveness to skin or eyes. Likewise
these products do not usually produce vapors that are toxic on inhalation. The principal
hazard categories that would place these Pharmaceuticals or ingredients in the hazardous
classification are aquatic toxicity (TLm), oral toxicity (LDSO), bio-concentration or car-
cinogenicity. It is unlikely that the Food and Drug Administration would leave a pharma-
ceutical on the market for general use that is a known carcinogen. There are essentially no
data on the TL values of these compounds and on their bio-concentration in natural
flora and fauna. However, there are extensive data on the oral toxicity of these compounds
in test animals.
We therefore decided to evaluate the toxicity of the most common products in five of
the largest selling pharmaceutical categories: analgesics, antibiotics, ataractics, cardio-
vasculars, and hormones. The oral LD5 0 values of typical compounds under each pharma-
ceutical category are listed in Table 3.1.3C. As indicated in the summary at the end of
Table 3.1.3C, 48 out of 66 compounds were in toxicity grade 1 (LD50 of 500 to 5000
mg/kg — essentially nonhazardous), 17 of the 66 were in grade 2 (50-500 mg/kg — moder-
ately hazardous) and only one compound was in grade 3 (5 to 50 mg/kg — highly
hazardous). While the pharmaceutical ingredients sometimes may have a high activity for
man when they are injected or ingested, the most active ones are usually dispensed in highly
diluted forms so that only a small percentage of active ingredient is present in the dosage
form. Although some of the active ingredients can qualify as moderately hazardous, we do
not consider the typical mix of returned goods that would actually 'be disposed of on land
to be hazardous. It is highly unlikely that the diluted ingredients would be ingested. Never-
theless, some companies have a few products (such as mercurial ointments) that they screen
out of their returned goods to ensure that the discarded material is environmentally accept-
able. If a company takes the conservative position that all returned goods and discarded
products are considered as moderately hazardous until they are examined, the handling and
disposal of these compounds can be done without hazard to personnel or the environment.
3.2 WASTE GENERATION DATA DEVELOPMENT
3.2.1 Approach to the Problem of Obtaining Valid Industry Hazardous Waste Data
No Federal law has yet been passed requiring industry to obtain and report data on
hazardous materials produced as wastes destined for land disposal. To conduct this study it
was therefore imperative to obtain the voluntary cooperation of companies that represented
a significant portion of the U.S. production of pharmaceutical products. Fortunately, the
Pharmaceutical Manufacturers Association (PMA) supported the planned attempt to obtain
useful information on which EPA's Office of Solid Wastes Programs could base its future
planning and programs. The PMA Environmental Control Committee lent us its support and
assisted in obtaining the cooperation of several major pharmaceutical producers.
38
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TABLE 3.1.3C
TYPICAL TOXICITIES OF PHARMACEUTICAL ACTIVE INGREDIENTS
AS MEASURED BY ORAL LD50 ON MICE AND RATS*
Oral LD50 (mg/kg)
Drug Class
Analgesics
Compound Mouse
A
B 815
C
D
E
F 18
G
H
I
J 693
K
L 84
M
N
Rat
2404
1500
4025
748
542
170
95
887
1650
1890
1600
Reference
1
2,3
4
4
5
1
6
7
8
9
10
5
1
11
Antibiotics
A
B
C
D
E
F
G
H
I
J
K
L
M
N
0
P
Q
R
>3750
2618
4600
>2880
808
1188
2500
3400
3000
2372
2000
1447
>4000
4800
300
807
3579
3550
702
12
1
13
1
12
14
1
15
16
1
17
12
18
1
1
1
1
1
*Table references follows table.
39
-------
TABLE 3.1.3C (Continued)
Oral LD50 (mg/kg)
Drug Class
Ataractics
Cardiovasculars
Hormones
Compound
A
B
C
D
E
F
G
H
I
J
K
L
M
N
A
B
C
D
E
F
G
H
I
J
K
L
M
N
0
A
B
C
D
Mouse
126
148-176
>515
980
150
1250
1350
330
213
292
300
680
890
>2500
1737
950
Rat Reference
433 19
548 20,1
710 1
346-460 21
840 , 1
22
710 23
1552 24,1
318 19
25
1800 4,26
995 1
740 27,26
28
56 1
2600 1
1 000 29
30
2221 1
1100 4
1750 1
31
>80 32
440 33,34
300 35
2500 26
36
1000 26
3200 4
>300 4
37
2952 1
1
Oral LDSO Summary of Typical Classes of Pharmaceuticals
(Classified
Toxicity Grade 4 (0-5)
Analgesics 0
Antibiotics 0
Ataractics 0
Cardiovasculars 0
Hormones 0
Total 0
by lower of
3 (5-50)
1
0
0
0
_0_
1
rat or mouse toxicity values)
2 (50-500)
3
1
6
6
J_
17
1 (500-5000)
10
18
8
9
_3_
48
0 (> 5000)
0
0
0
0
_p_
0
40
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REFERENCES TO TABLE 3.1.3C
1. Toxicol. Appl. Pharmacol., 18, 185, 1971. (TXAPA9 - Toxic Substance List, 1973)
2. Toxicol. Appl. Pharmacol., 23, 537, 1972. (TXAPA9 - Toxic Substance List, 1973)
3. J. Pharmacol. Exp. Ther., 99, 450, 1950. (JPETAB - Toxic Substance List, 1973)
4. Merck Index. (12VXA4 - Toxic Substance List, 1973)
5. J. Pharmacol. Exp. Ther., 134, 332, 1961. (JPETAB - Toxic Substance List, 1973)
6. J. Pharmacol. Exp. Ther., 103, 147, 1951. (JPETAB - Toxic Substance List, 1973)
7. J. Pharmacol. Exp. Ther., 92, 269, 1948. (JPETAB - Toxic Substance List, 1973)
8. Food Cosmet. Toxicol., 2, 327, 1964. (FCTXAV - Toxic Substance List, 1973)
9. Arch. Int. Pharmacodyn. Ther., 190, 124, 1971. (AIPTAK- Toxic Substance List, 1973)
10. Toxicol. Appl. Pharmacol., 7, 240, 1959. (TXAPA9 - Toxic Substance List, 1973)
11. J. Pharmacol. Exp. Ther., 89, 205, 1947. (JPETAB- Toxic Substance List, 1973)
12. Spector, W.S., ed. Handbook of Toxicology, Volume I: Acute Toxicities. W.B. Saunders Co.
(Philadelphia), 1956.
13. Toxicol. Appl. Pharmacol., 8, 398, 1966. (TXAPA9 - Toxic Substance List, 1973)
14. Toxicol. Appl. Pharmacol., 21, 516, 1972. (TXAPA9 - Toxic Substance List, 1973)
15. Toxicol. Appl. Pharmacol., 10, 402, 1967. (TXAPA9 - Toxic Substance List, 1973)
16. J. Antibiot, 19, 30, 1966. (JANTAJ - Toxic Substance List, 1973)
17. Toxicol. Appl. Pharmacol., 6, 746, 1964. (TAP- Journal)
18. Acta Pol. Pharm., 24, 451, 1967. (APPHAX - Toxic Substance List, 1973)
19. Toxicol. Appl. Pharmacol., 21, 315, 1972. (TXAPA9 - Toxic Substance List, 1973)
20. Mouse - Physicians Desk Reference (PDR), 1974 and Proc. Eur. Soc. Study Drug Toxicity, 8,
177, 1967. Rat-Toxicol. Appl. Pharmacol., 181, 185, 1971 (PSDTAP and TXAPA9 - Toxic
Substance List, 1973)
21. Physicians Desk Reference (PDR), 1974
22. J. Pharmacol. Exp. Ther., 727, 318, 1959. (JPETAB - Toxic Substance List, 1973)
23. Am. Ind. Hyg. Assoc. J., 30, 470, 1969. (AIHAAP - Toxic Substance List, 1973)
24. Mouse - J. Pharmacol. Exp. Ther., 723, 75, 1960. Rat- Toxicol. Appl. Pharmacol., 18, 185,
1971. (JPETAB and TXAPA9 - Toxic Substance List, 1973)
25. Toxicol. Appl. Pharmacol., 27, 302, 1972. (TXAPA9 - Toxic Substance List, 1973)
26. Barnes, C.C., Eltherington, L.G., Drug Dosage in Laboratory Animals — A Handbook, Univ. of
California Press, Berkeley, 1965. (DDLA- Toxic Substance List, 1973)
27. Smith, Kline and French Laboratories (Philadelphia ) — Mouse. Barnes, C.C., Eltherington,
L.G., Drug Dosage in Laboratory Animals — A Handbook. Univ. of California Press, Berkeley,
1965) (SKFL and DDLA - Toxic Substance List, 1973)
28. J. Pharmacol. Exp. Ther., 727, 318, 1959. (JPETAB - Toxic Substance List, 1973)
29. J. Pharmacol. Exp. Ther., 128, 22, 1960. (JPETAB - Toxic Substance List, 1973)
30. Toxicol. Appl. Pharmacol., 7, 598, 1965. (TXAPA9 - Toxic Substance List, 1973)
31. J. Pharmacol. Exp. Ther., 779, 580, 1971. (JPETAB - Toxic Substance List, 1973)
32. Arch. Ital. Sci. Farmacol., 6, 153, 1937. (AISFAR - Toxic Substance List, 1973)
33. J. Pharm. Pharmacol., 727, 179, 1960. (JPPMAB - Toxic Substance List, 1973)
34. Arch. Int. Pharmacodyn. Ther., 180, 155, 1969. (AIPTAK - Toxic Substance List, 1973)
35. Ann. N.Y. Acad. Sci., 707, 1,068, 1963. (ANYAA9 - Toxic Substance List, 1973)
36. Toxicol. App. Pharmacol., 27, 253, 1972. (TXAPA9 - Toxic Substance List, 1973)
37. Klin. Wochenschr., 18, 156, 1939. (KLWOAZ - Toxic Substance List, 1973)
41
-------
Because the industry had never had to report detailed composition of waste streams,
we realized that mailing of questionnaires would not produce usable information. We
therefore chose to conduct in-depth interviews and plant inspections at the plants of the
cooperating companies. We visited the principal production plants of companies repre-
senting 27 percent of total U.S. sales of ethical Pharmaceuticals. These plants represented an
even higher percentage of the active ingredient production of the industry. All facilities
visited had multiple operations so that good representative information was available on
R&D, fermentation, biological products, organic synthesis, extraction of animal glands and
formulation and packaging operations in the United States, including Puerto Rico. Infor-
mation given to us in the interviews and by letter was checked and confirmed with the
companies. From the collected data we extrapolated to obtain information applicable to the
entire industry.
During the course of the study we also visited eight landfills and four contractors that
were treating wastes, principally by incineration. We also interviewed 11 contractors by
telephone to confirm information obtained from plant visits.
As explained in Section 2.0 of this report, the SIC codes of the U.S. Department of
Commerce do not exactly follow functional divisions of the pharmaceutical industry. For
example, we were interested in obtaining information on R&D wastes and the R&D
category does not have a SIC code. Another complication in data collection from the plants
was that many of the pharmaceutical plants producing active ingredients were diversified,
i.e., some parts of the manufacturing complex produced materials for animal feeds, cos-
metics, pesticides, fine organic chemicals, etc., as well as medicinal ingredients. For this
study we have attempted to isolate those wastes that are associated only with the phar-
maceutical production.
The information that we collected on plant visits was categorized under three of the
four functional divisions of the pharmaceutical industry: (1) Research and Development,
(2) Production of Active Ingredients, and (3) Formulation and Packaging. The fourth
functional division, Marketing and Distribution, did not dispose of significant quantities of
process wastes or hazardous wastes, as damaged or outdated goods were normally returned
to the formulation plants for disposition.
As indicated in Section 2, we considered plants listed as 2831 and 2833 under the
production of active ingredients category and plants listed as 2834 under the formulation
and packaging category.
3.2.1.1 Wastes from Research and Development Installations
Based on surveys conducted by the Pharmaceutical Manufacturers Association that
show a total of approximately 23,000 personnel employed in research and development
(R&D) activities in its member firms, we estimate that total pharmaceutical R&D personnel
42
-------
amount to about 25,000. About one-half of the R&D staff is made up of scientific and
professional people and the other half is about equally divided between technical and
supporting staff.
R&D activities are often concentrated in research centers run by the industry that
employ from 200 to over 2000 R&D personnel so that sizable quantities of wastes may be
generated in these centers. On the other hand, some R&D activities are dispersed throughout
the individual companies so only a few R&D personnel may be in a given plant, and the
R&D wastes may not be segregated.
Depending on the type of research being done the wastes from these activities may
involve a heavy use of solvents in one installation while at another installation most of the
work may involve tests on animals. Thus in one case there will be waste solvents to be
disposed of and in the other there will be test animals to be incinerated. We found that the
average mixed solvent waste at the installations we visited was about 66 liters per
man-year or a yearly total of approximately 1500 metric tons in the United States.
Other hazardous wastes occurred in much smaller amounts than the solvents and were
usually handled as specified by the "Laboratory Waste Disposal Manual" issued by the
Manufacturing Chemists' Association. Heavy metal wastes, such as mercury or mercury salts,
were often stored until a sufficient quantity was on hand to sell to a reprocessor.
3.2.1.2 Wastes from the Production of Active Ingredients
In addition to the active ingredients that it produces itself, the pharmaceutical industry
purchases many of its active ingredients from chemical companies that are not really in the
pharmaceutical industry. Most of the plants listed under SIC 2831 (Biological Products) are
a part of the pharmaceutical industry and manufacture active ingredients consumed by the
industry. On the other hand, many of the products listed under "Medicinal Chemicals" by
the U.S. Tariff Commission are manufactured by chemical companies that are not in the
pharmaceutical business. A good example of the latter is choline chloride in the "Medicinal
Chemicals" category, which is made almost entirely by chemical companies, but which is
used almost entirely in animal feed production. We have subtracted substances such as
choline and other materials that are made mostly by the chemical companies to arrive at
the active ingredient production that could be assigned to SIC code 2833. We estimate that
the pharmaceutical industry's 1973 production of organic medicinal ingredients, excluding
antibiotic production, was no more than 34,000 metric tons (75 million pounds).
In the subsections that follow, we discuss methods of active ingredient production and
the generation of process and hazardous wastes. We have selected the processes shown from
the open literature, and they are typical of industry practice, but do not refer to a specific
company's installation.
43
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3.2.1.2.1 Synthetic Organic Medicinal Chemicals
The production of organic medicinal chemicals may involve the chemical (or biologi-
cal) modification of an antibiotic, botanical, or drug from animal sources, or it might be the
complete chemical synthesis of a complex chemical, such as vitamin A, whose synthesis
starts with acetone, acetic acid, acetylene, and methyl vinyl ketone. Unlike the "heavy
chemicals," those chemicals which are. produced by the chemical industry in thousands of
tons annually, the total annual production of any given organic chemical medicinal might
only be 1 or 2 tons. Heavy chemicals are produced in continuous processes and generate a
uniform waste stream, but many different medicinals are produced in single batches which
causes a wide variation in their waste streams.
The amount of process waste generated per ton of product will vary greatly, depending
on the number of synthesis steps, the yield in each step, and the solvents used. The chemical
synthesis may only require a two-step synthesis with recovery of unreacted raw materials,
such as in aspirin production, or as many as 13 steps as in the production of vitamin A.
With an overall yield of over 80%, less than 0.2 kg of organic residue waste would be
generated per kg of aspirin, whereas the overall yield in the production of vitamin A might
be as low as 15-20%, thus generating as much as 7 kg of organic waste per kg of product.
The by-product organic residue waste material is separated from the main product by any of
a number of methods such as extraction, distillation, precipitation, crystallization, or
filtration, and may be recovered as hard still bottoms, chemical muds, or in a solvent
solution. This residue may still contain residual hazardous organics such as hydroquinone,
pyridine, or oxalic acid.
Wastewater from the production of organic medicinal chemicals (containing up to
several thousand ppm of biodegradable organics such as isopropanol, acetone, ethanol, or
acetic acid) must be treated to meet effluent requirements.* This wastewater is usually
treated biologically, such as an activated sludge treatment, either on-site or in local
municipal treatment systems. This biological treatment, in turn, generates from 0.3 to 0.7
kg of biological sludge solids per kg of organic solids removed, the remainder being
converted to carbon dioxide and water by the biological sludge organisms.
The volume of solvent waste generated depends on the degree to which the solvent is
contaminated, to what extent solvent recovery is practiced, and the type of reaction and
solvent required. Some reactions, such as hydrogenation, may require no solvent at all; some
may use ethanol or acetic acid which is diluted and discharged to biological treatment, while
still others may use toluene or benzene which must be recovered or incinerated. A "typical"
synthetic organic medicinal chemical production process might be summarized as shown in
Figure 3.2.1.2.1.
*State or Federal.
44
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Raw Materials
(5,000,000 kg)
Finished Medicinal Products
(500,000 kg)
Recycle
I vents Aqeous Wastes
000,000kg) (1,400,000kg)
(solids)
Waste Solvents
(400,000 kg)
Biological Wastewater
Treatment
Solid Wastes (dry)
(300,000 kg)
Biological
Slud9e ** /
(700,000 kg) (solids) /
V
Incineration
Landfill
FIGURE 3.2.1.2.1 TYPICAL SYNTHETIC ORGANIC MEDICINAL CHEMICAL PROCESS
45
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Based on interviews and waste figures provided us by the industry, we have estimated
the average quantities of waste generated per ton of product as shown in Table 3.2.1.2.1.
The production of aspirin will generate less waste than the averages given in this table while
the production of certain tranquilizers and vitamins will generate more waste per ton of
product. We believe that the averages we present in Table 3.2.1.2.1 represent the waste
generated for a typical or "average" mixture of synthetic organic medicinal products.
The wastes as shown in this table are segregated into solvents, organic residues,
biological sludge, solid inorganic wastes containing materials such as filter aid and carbon
and heavy metal wastes.
Most of the hazardous waste generated in the synthesis of organic medicinal chemicals
is organic in nature (composed of hydrogen, oxygen, carbon, and nitrogen) and is generally
disposed of. by incineration. A limited amount of heavy-metal wastes, such as those
containing mercury, chromium, copper, arsenic, and zinc, is also generated, however.
Zinc waste generally occurs in pharmaceutical chemical production as metallic zinc,
zinc oxide, or zinc chloride. Metallic zinc is used as a reducing agent and its salts as a
catalyst. It is usually recovered (for disposal or recycle) from the reaction mixture by
filtration. The waste zinc salts are recovered by precipitation or solvent evaporation.
TABLE 3.2.1.2.1
ESTIMATED AVERAGE OF CHEMICAL WASTES GENERATED IN
ORGANIC MEDICINAL CHEMICAL PRODUCTION*
Kilogram of Waste per
Non-Hazardous Waste Metric Ton Product (dry basis)
- Biological Sludge 1400* (14,000 wet)
(from Organic Chemical Wastewater Treatment)
— High Inert Content Wastes (Filter and, Activated Carbon) 100
Kilogram of Waste per Heavy Metal Content
Metric Ton Product (kg Per Metric Ton Product
Hazardous Wastes** (dry basis) of Waste)
— Halogenated Solvent 100
— Non Halogenated Solvent 700
— Organic Chemical Residues
(Tars, Muds, Still Bottoms) 400
— Contaminated High Inert Content Wastes
(Filter and, Activated Carbon) 50
- Solid Heavy-Metal Wastes
Zinc 70 30
Arsenic 15 0.3
Chromium 0.7 0.3
Copper 0.1 0.04
Mercury 0.02 0.01
*From 2800 kg of solids in organic chemical wastewater.
"Contains some heavy metal, corrosive chemical, or flammable solvent
Source: Interviews and A.D. Little, Inc., estimates.
46
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To put the 2,200 metric tons/yr of zinc waste landfilled by the pharmaceutical in-
dustry in perspective, an estimated 36,000 metric tons of zinc oxide annually finds its way
into landfills throughout the United States as photocopy paper.
Arsenic wastes are generated in the pharmaceutical industry as a by-product of
arsenical production and where arsenic compounds are used as catalysts or oxidizing agents.
We do not believe there is widespread use of chromium or chromium salts in the
pharmaceutical industry. The oxide is used in the heavy chemical industry as one of many
catalysts for hydrogenation and oxidation, and as an oxidizing agent in some organic
chemical syntheses. However, many of these oxidation (dehydration) reactions can be
conducted, using other oxidizing agents, such as chlorates, peroxides or permanganates. In
the one case where we know that chromium is being used in the pharmaceutical industry,
the chromium waste is recovered by precipitation and filtration and then sold.
We know of only one pharmaceutical company which produces a copper waste, and it
is presently disposed of by deep-well injection.
We estimate that organic mercury wastes containing about 270 kg of elemental
mercury are produced by the pharmaceutical industry annually. A limited number of
pharmaceutical companies produce the mercurial products which include nitromersol and
thimerosal. These companies take considerable care to ensure that mercury is removed from
the plant wastewater effluents.
There are a number of processes available for the removal of mercury from wastewater.
Ion exchange, solvent extraction, carbon adsorption, sulfide precipitation, cementation, and
reduction/precipitation have all been used with varying degrees of success. The type of
mercury-removal process that should be used for a specific application depends on the
following:
• Concentration of mercury in the wastewater;
• Maximum allowable concentration of mercury in effluent;
• Chemical form of the mercury to be removed;
• Type and quantity of other chemical constituents in the wastewater; and
• Desirability of recovering metallic mercury.
According to our investigations, reduction/precipitation processes are being used in-
creasingly where the wastewater flow rate is relatively small and intermittent. Mercury is
recovered either as pure metallic mercury or as an amalgam.
47
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In the most common reduction/precipitation process, which is currently being com-
mercialized, a caustic solution of sodium borohydride (NaBH4) is mixed with the mercury-
containing wastewater where the ionic mercury is directly reduced to metallic mercury
which rapidly precipitates out of solution. The following reaction occurs:
4 Hg2+ + BH^ + 8 OH~ = 4 Hg + B(OH)^ + 4 H2O
If the mercury solution is in the form of an organic complex, the driving force of the
reduction reaction may not be sufficient to break the complex. In that case, the wastewater
must be chlorinated prior to the reduction step to break down the metal-organic bond.
When elemental mercury recovery is not desired, the reduction process can be used to
form mercury amalgams to produce a less hazardous solid waste for ultimate disposal by
encapsulation and landfill.
3.2.1.2.2 Inorganic Medicinal Chemicals
Antacids make up a major share of inorganic medicinal chemical production. Generally
antacids have magnesium hydroxide or aluminum hydroxide as their primary active ingredi-
ent. These antacids are produced by precipitating a water-insoluble compound from a
solution of a soluble aluminum or magnesium salt by a sodium salt. Some formulations also
include magnesium trisilicate, calcium carbonate, sodium bicarbonate, alumina gel, and
bismuth aluminate. The waste stream generated contains no toxic metals or salts and is
usually a solution of sodium chloride or sodium sulfate. Bad batches of antacid active
ingredient may occasionally be produced, and these are either reprocessed or disposed of by
landfilling, but they would also be considered nonhazardous.
We did find one toxic metal-containing waste generated in the production of inorganic
medicinal chemicals. This waste contains about 0.2% selenium and amounts to about
160,000 kg annually.
The pharmaceutical industry produces several laxatives of botanical origin such as
senna, cascara, and a synthetic organic medicinal, phenolphthalein. However, milk of
magnesia (magnesium hydroxide suspension) is the principal inorganic laxative. The produc-
tion of magnesium hydroxide for this use would also generate aqueous sodium sulfate or
sodium chloride.
Active ingredients for many other inorganic medicinals are purchased for products such
as mouthwashes, throat lozenges, and topical medicinals, such as the mercurials, zinc oxide
ointments, and foot powders. Since these purchased active ingredients are produced by the
chemical industry (rather than the pharmaceutical industry), the only waste containing
these purchased ingredients is that generated in the compounding and packaging of pharma-
ceutical preparations.
48
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3.2.1.2.3 Fermentation Products (Antibiotics)
Most commercial antibiotics are the products of living microorganisms, such as fungi
(molds) or bacteria. The crude antibiotic produced by the microorganism is recovered from
the fermentor broth (a water solution containing nutrients) by extraction, precipitation, or
adsorption, depending on the type of antibiotic. Bacitracin, the penicillins, cephalosporins,
and erythromycins are usually recovered from the filtered broth by solvent extraction.
Chlortetracycline is recovered by solvent extraction of the whole broth (containing
mycelium) or filtered broth. Streptomycin is recovered from the filtered broth by ion ex-
change. Oxytetracycline is recovered from the filtered broth by precipitation with a
quaternary ammonium compound.
Following recovery from the fermentor broth, the antibiotic is purified, in most cases,
by several stages of re crystallization. Other antibiotics, such as the semi-synthetic penicillins
and cephalosporin derivatives, are produced by chemically modifying antibiotics produced
by fermentation.
The production of antibiotics results in the generation of several large waste streams:
the filtered micro-organism (mycelium*); the filtered, extracted, fermentor broth; and
contaminated solvent generated in the solvent recovery operation.
The fermentor broth is sometimes concentrated and sold as an animal feed supplement, but
in most cases the fermentor broth and other wastewater streams are treated biologically to
meet effluent requirements. The 0.3 to 0.7 kg of biological sludge generated per kg of dis-
solved organics removed in wastewater treatment is either landfilled or incinerated.
A good example of antibiotic production (and a large volume product) is penicillin as
shown in Table 3.2.1.2.3 and Figure 3.2.1.2.3.
Commercial penicillin is produced by the submerged-culture fermentation process in
which a strain of Penicillium mold is grown in an aerated, stirred tank, the fermentor, in a
water medium. This medium contains carbohydrates (starches, sugars) as an energy source,
nitrogen in the form of ammonium salts or corn-steep liquor solids for mycelium cell wall
protein, and trace minerals, such as magnesium, which are necessary for growth. Rapid
growth of the mycelium takes place during the first 24 to 48 hours and the production of
penicillin takes place from 24 to 120 hours.
*The term mycelium should be reserved for describing the thread-like growth of molds, such as Penicillium,
or the analagous growth in Actinomyces. However, the term is commonly used in the industry to designate
the mixture of cells, filter aid, undigested grain solids, etc., that is filtered off and discarded from all types
of fermentations, including bacterial fermentations that do not produce true mycelia.
49
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TABLE 3.2.1.2.3
TYPICAL ANTIBIOTIC PRODUCTION PLANT (PROCAINE PENICILLIN G)
A. Annual Production 950,000 kg
B. Waste Characterization
Weight per 1000 kg Product
Non-Hazardous Waste Stream No. Dry Wet
Mycelium © 2,300kg 10,000kg
Biological sludge ® 3,500kg 35,000kg
Non-Hazardous Waste to Biological Treatment
Liters per 1000 kg Product
Waste fermentation broth @ 56,000
Crystallization water @ 100
Phosphate buffer solution © 3,000
Crystallization water © 100
Potassium chloride solution (§) 4,000
Hazardous Waste
Liters per 1000 kg Product
Solvent Waste Concentrate (2) 1,200
Solvent (butyl acetate) 600
Dissolved organics (fats, protein) 600
Source: Arthur D. Little, Inc., estimates.
Carbohydrate is fed to the fermentor over the course of the fermentation as an energy
source for the mycelium. After the initial mycelium growth phase, a precursor, such as
phenylacetic acid or its salts, is added to increase production of a specific type of penicillin.
The mold uses this precursor directly in producing the penicillin. With phenylacetic acid, the
yield of penicillin G is greatly increased.
The strain of penicillium, the exact composition of the growth medium, the yield of
penicillin, and some details of the purification of the penicillin are trade secrets of the
manufacturers. The penicillin produced and recovered from the fermentation may also be
chemically modified to produce one of many commercial penicillins, but the fermentation
process for initially producing the basic penicillin is generally the same.
A typical penicillin production process (Figure 3.2.1.2.3) consists of the initial fermen-
tation in which the antibiotic is produced by the micro-organism, the recovery of the crude
antibiotic from the fermentation broth by several stages of solvent and aqueous buffer
extraction, crystallization of the crude antibiotic, and finally the sterilization of the
antibiotic. The same process steps are used by many producers, but the exact conditions of
pH and temperature and extraction procedures (type of extractor, type of solvent, etc.) will
vary- from producer to producer. Likewise there was some variation in quantity of mycelium
waste reported by our industrial contacts. Nonetheless we believe that the system for
penicillin production, as shown in Figure 3.2.1.2.3, is representative of industry practice and
is representative of the types and quantities of waste generated in penicillin production and
antibiotic production in general.
-------
Sodium Phenylacetate
(300 kg)
Clarifier Broth
pH 7.0 and 25° C
Corn Steep Liquor Solids
Hydrolyzed Starch
Glucose
Ammonium Nitrate
Magnesium Sulfate
(10,000 kg]Y Wet
Mycelium Waste
(2,300 kg dry solids
Makeup Butyl Acetate
(700 liters
Butyl Acetate
Solvent Waste
(1200 liters
Butyl Acetate
3900 liters 7000 liters
Broth at pH 7.0
and 4°C
600 kg Butyl Acetate
600 kg Solids
5% Phosphate Buffer
Solution at pH 7.5 or
Potassium Acetate Solution
(3000 liters)
Water Solution of
Penicillin at pH 6.5-6.8
Waste Fermentation Broth
(56,000 liters)
(6700 kg solids
Phase to Disposa
(100 liters)
Water Phase to
Solvent Strip
and Disposal
(3002 liters
5
Procaine Penicillin Product
(1000kg)
Butyl Acetate
Solution of
Penicillin
Potassium Acetate
(200 kg)
Potassium Chloride
Water Waste j g
(4000 liters)
(leOkgKCI)
Solvent Waste to
utyl Acetate
Recovery
(120 liters)
Water Phase to C 1J
Solvent Stripping
and Disposal
(100 liters
Crude Potassium Penicillin
(700 kg)
©
Sources:
Brunner, Elder, Prescott, Rehm, Standen, Underkofler, Webb and Arthur D. Little, Inc., estimates
(see Bibliography at end of Section).
FIGURE 3.2.1.2.3 REPRESENTATIVE PROCESS FOR ANTIBIOTIC PRODUCTION
(PROCAINE PENICILLIN G)
51
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Nutrients necessary for mycelia growth and penicillin production are dissolved in water
to form the fermentation medium which is then sterilized by heat, either before or after
being added to the fermentor. Then the medium is cooled to near room temperature
(20-24°C) and inoculated with a concentrated culture of the Penicillium organism, about 5%
by volume. The inoculated medium is agitated by a turbine-type impeller and compressed,
sterile air necessary for the growth of the mycelium is sparged into the fermentor. After
24 hours the mycelium has grown to near its maximum concentration in the fermentor and
penicillin production by the mycelium increases rapidly. Penicillin production continues
with supplemental additions of carbohydrates and a precursor to the end of the fermenta-
tion cycle, about 5 days, when the penicillin reaches near maximum concentration. At this
point the fermentor is harvested and the mycelium is filtered from the spent growth
medium (broth). The filtered broth is chilled to prevent penicillin deterioration and
acidified to liberate penicillic acid which is extracted by a water-immiscible solvent such as
butyl or amyl acetate. The waste broth from this extraction may be neutralized and
discharged to a biological treatment system or concentrated for sale as an animal feed
supplement. The solvent containing the penicillin is extracted with an alkaline buffer to
form the sodium or potassium salt and remove it from the solvent into a water solution. At
this point the crude sodium or potassium salt may be precipitated out directly with a
solvent, or acidified and re-extracted by a water-immiscible solvent followed by neutraliza-
tion and crystallization. Finally, the crude salt is redissolved in water passed through a
sterile filter to a mix tank where it is combined with a sterile precipitating agent, and the
insoluble sterile salt is recovered by centrifuging and then dried in a vacuum drier. As an
alternative to recovery as the potassium or procaine salt, the penicillin may be chemically
modified to other penicillin derivatives before sterilization. In this report, the chemical
modification of antibiotics is considered to be part of the organic medicinal chemical
segment of the industry.
Since the medium in which this living organism, the mycelium, is grown is not toxic
to the organism, the spent medium would also be expected to have low toxicity. This is
generally true. The mycelium from the spent medium (fermentor broth) is incinerated,
landfilled, or used as a soil builder. Some states require that mycelium have a solid content
of 30% or more before it is landfilled, since higher concentrations of water might cause
leaching of hazardous materials from other substances in the landfill. To increase the solids
content of the mycelium from penicillin production, a filler such as sawdust may be added.
Mycelia from other antibiotic fermentations contains filter aid which is necessary for the
filtration of the more gelatinous mycelia produced in these fermentations, and this increases
the solids concentration to an acceptable level.
The extracted, acidified fermentation broth must be neutralized before it can be
disposed of by one of several methods such as incineration, biological treatment, or
concentration and sale as an animal feed supplement. In the case of biological treatment, the
resulting sludge must also be disposed of by incineration or landfill. In figure 3.2.1.2.3 we
have assumed biological treatment of the spent broth and other wastewater streams.
52
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The only hazardous wastes resulting from antibiotic production are the waste solvents
which contain organic material from the extracted broth and which are generated in the
recovery of the major portion of the solvent used in the process. In this report, any chemical
wastes from antibiotic modification are considered to be part of synthetic organic medicinal
chemical production.
3.2.1.2A Botanicals
The Pharmaceuticals produced from plant material — leaves, bark, and roots — include
the alkaloids such as quinine and reserpine, plant steroids for chemical synthesis of
cortisones and oral contraceptives, and laxatives such as emodin from cascara bark.
3.2.1.2.4.1 Alkaloid Production from Botanicals Alkaloids are usually defined as basic
(alkaline), nitrogenous botanical products which produce a marked physiological action
when administered to animals. Commercial alkaloids include quinine, emodin (a cascara
alkaloid), reserpine, and vincristine (a new anticancer drug). The alkaloid content of the
plant material can vary greatly. For example, quinine is present in amounts of up to 10% in
cinchona bark, while vinscristine is present in Vinca rosea (periwinkle) leaf in a concentration
of only about 0.02%.
A process flow sheet for the production of a (alkaloid) botanical medicinal from plant
material is presented as Figure 3.2.1.2.4.1, and Table 3.2.1.2.4.1 summarizes the waste-
streams. The dried, ground plant material (roots, bark, seeds, or leaf) is generally extracted
with an acidified water-miscible solvent such as alcohol and this leachate, in turn, is ex-
tracted with a water-immiscible solvent such as ethylene dichloride. Variations in this pro-
cedure include: (1) using an aqueous solvent mixture of water and alcohol for the initial
extractions, and (2) concentration of the initial alcohol extract before the second (liquid-
liquid) extraction, transferring the alkaloid into the water-immiscible solvent.
The equipment used for the initial extraction may be a series of stirred tanks, each
followed by a filter to remove the plant material, or a series of vessels with wire screen
supports to hold the plant material while the leaching solvent is changed after each
extraction.
The crude alkaloid is recovered from the second (water-immiscible) solvent by vacuum
evaporation and further purified by crystallization, precipitation, ion exchange, or chrom-
atography.
Waste solvent containing plant extract is the hazardous waste generated in the extrac-
tion of the crude alkaloids from plant materials. (The subsequent conversion of these
alkaloids to other derivatives may create additional hazardous wastes, but these wastes
would be included in organic medicinal chemical production.) The extracted plant material
waste must be steamed, however, to remove residual solvent that would otherwise pose a
fire hazard.
53
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Dried Leaves, Root, Seeds or Bark
(330 kg)
0
Wet Plant
Material
(660 kg)
To Landfill
60% wt Methanol
40% wt Water
(3500 liters)
Recovered Methanol/Water
(130 liters)
Filter
and
Concentrate
Steam (200 kg)
Chlorinated Solvent
(700 liters)
Makeup
Chlorinated
Solvent
(7 liters)
Sodium Hydroxide
(10kg)
Methanol/Water
(2100 liters)
Concentrated Methanol/Water
Extract
(11 00 liters)
Immiscible
Solvent
Exchange
Chlorinated
Solvent
Recovery
Methanol/Water
(1100 liters)
Alkaloid in
Chlorinated
. Solvent
Methanol/
Water
(3200 liters)
Crude Alkaloid
Recovery
(vacuum evaporation)
Crude Alkaloid
(2) Waste
Chlorinated
Solvent
(7 liters)
Organic Acid
(40 kg)
Makeup
Methanol/Water
(300 liters)
Methanol/Water
Recovery
©
i
Precipitation
Chromatography
or Ion Exchange
1
Solvent
Waste
(30 liters)
Solvent Waste (130 liters)
40 kg Methanol
20 kg Water
. 70 kg Plant Extract and
Organic Acid Salt
Active Alkaloid
(1 kg)
Source: Forbath, Manske, Nobler and Arthur D. Little, Inc., estimates. (See Bibliography)
FIGURE 3.2.1.2.4.1 REPRESENTATIVE PROCESS FOR BOTANICAL MEDICINALS
(PLANT ALKALOIDS)
54
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TABLE 3.2.1.2.4.1
TYPICAL PLANT FOR PRODUCING BOTANICAL MEDICINALS (PLANT ALKALOIDS)
A. Annual Production
B. Waste Characterization
Non-Hazardous Waste
Wet botanical material
680kg
Stream No.
Weight per kg Product
Dry
330kg
Wet
660kg
kg per kg
Botanical Material Quantity per kg Product
Hazardous Waste
Halogenated solvent
Methanol — water concentrate
Non-halogenated solvent
Source: Arthur D. Little, Inc., estimates.
®
0.03
0.36
0.06
Liters
7
130
30
kg
9
120
20
55
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The solvent waste generated in the initial extraction will contain alcohol, water, and
dissolved plant extract (resins, fats, etc.). In the second step of alkaloid isolation, extraction
of the alkaloid from the aqueous leaching solvent into a water-immiscible solvent, much of
the water-soluble organic material is left behind in the aqueous solvent. Consequently, not
as much of this second solvent (e.g., chlorinated solvent) becomes waste in this process.
In the final purification steps (e.g., crystallization, precipitation) of the alkaloid,
additional waste solvent is generated.
3.2.1.2.4.2 Steroid Production from Botanicals Most of the steroid products now
produced commercially were originally extracted from animal organs, requiring tons of
animal organs to produce a few grams of hormone. When the structures of the various hor-
mones and other steroids were determined and synthesis routes were developed, it became
possible to produce many of these hormones commercially on a large scale from steroids
present in plant materials. Soybeans and Mexican yams now supply the steroids stigmas-
terol and diosgenin, respectively, used in the commercial production of cortisone derivatives
and oral contraceptives.
In 1964, over 70% of the cortical hormones were produced from diosgenin from
Mexican yams. Since a high export tax must be paid in Mexico on shipments of crude
product, the diosgenin is extracted from the yams and purified or converted to other steroid
derivatives before export to the United States. Stigmasterol is produced in the United States
by the solvent extraction of soybean oil distillation residue. Table 3.2.1.2.4.2 summarizes the
wastestreams and Figure 3.2.1.2.4.2 shows a representative flow diagram for the latter
process.
TABLE 3.2.1.2.4.2
TYPICAL PLANT FOR PRODUCING BOTANICAL MEDICINALS
(STIGMASTEROL FOR HORMONE SYNTHESIS)
A. Annual Production of Stigmasterol 130 Metric Tons
B. Waste Characterization Weight per MT Product
Non-Hazardous Waste
Fused Soybean Steroid Ingots 5000 kg
Still bottoms from soybean oil refining, which contain around 20% Stigmasterol and
about 45% )3-sitosterol, are dissolved in a hot solvent mixture of hexane and ethylene
dichloride. About 1000 kg of 97% Stigmasterol product and 5000 kg of residue are
generated from 6000 kg of feed steriods through a series of crystallizations from a solvent
mixture of 63% ethylene dichloride and 37% hexane by volume. In each crystallization step,
56
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10,000 kg Heptane
35,000 kg Ethylene Bichloride
j-
Solvent
Drying
Recycled Solvent
Recycled Solvent
Ingot Casting of
Molten Steroids
Fused Soybean Waste
Steroid Ingots
(5000 kg)
Solvent Recovery
Steroid Melting
Steroid
Solution
Crystallization
Filtration
Steroid
Solution
1
Filter Cake
Feed Dissolving
and Filtering
Residue from Soybean
Oil Refining
(6000 kg)
Steroid
Solution
Filter Cake
Dissolving
Crystallization
Filtration
1000 kg Stigmasterol
Raw Material for Hormone Production
Sources: Poulos et al and Arthur D. Little, Inc., estimates. (See Bibliography)
FIGURE 3.2.1.2.4.2 REPRESENTATIVE PROCESS FOR BOTANICAL MEDICINALS
(STIGMASTEROL FOR HORMONE SYNTHESIS)
57
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successively purer stigmasterol is crystallized out by cooling the hot (60° C) solvent solution
to 30°C. The crystals of stigmasterol are recovered by filtration and then redissolved in the
solvent mixture for the next crystallization. At the end of the process, the 97% pure
stigmasterol containing 45-50% solvent is dried in a vacuum oven to less than 0.06% solvent.
Unlike many other of the extraction processes, the production of the steroid raw
material, stigmasterol, does not generate a hazardous waste stream, but instead generates a
solid waste of fused plant material steroids. The waste residue of soybean steroids from this
extraction process is fused at 160°C which, after cooling to a solid mass, is stored or
landfilled. As an alternative, this mixture of steroid residues (containing about 50%
/3-sitosterol) can be processed for recovery of the /3-sitosterol which also can be used as a
steroid raw material. The other major steroid raw material source, diosgenin from Mexican
yams, is imported from Mexico.
In January 1975, G.D. Searle & Company announced plans to produce raw material for
steroid synthesis by fermentation of the steroid, (3-sitosterol. Some of the 0-sitosterol which
was formerly a waste product may thus be recycled to produce other products.
The conversion of these steroids to cortisone and oral contraceptives is done by a
combination of fermentation and chemical synthesis steps. The wastes generated in these
conversion steps is included as part of the production of synthetic organic medicinal
chemicals (Section 3.2.1.2.1).
3.2.1.2.5 Medicinals from Animal Glands
The major medicinal products obtained from animal glands are insulin from beef and
hog pancreas and heparin from lung tissues. Since the extraction processes are similar, we
will use insulin production as an example. On a small scale in the laboratory, insulin can be
extracted from the pancreas by acidic water alone, but on a commercial scale this is
impractical, so acidic 90% denatured alcohol is used. A process for commercial production
of medicinals from animal glands (insulin) is presented in Figure 3.2.1.2.5, and Table
3.2.1.2.5 summarizes the wastestreams. The ground glands are extracted with acidic ethanol
or methanol and the extract recovered from the ground glands by centrifugation or
filtration. Neutralization of the extract with concentrated ammonium hydroxide to pH 8.0
precipitates extraneous protein. A stronger alkali, such as sodium hydroxide, or too high a
pH will decompose the insulin. The precipitated extraneous protein is filtered, and the
extract is acidified and then concentrated to about a seventh of its original volume by
vacuum evaporation at 20°C. The concentrated extract is raised quickly to 50°C to release
solubilized fats, then cooled to 20°C. The fats are skimmed and recovered for soap
manufacture and the extract filtered to remove additional precipitated protein. Crude insulin
is precipitated by dissolving sodium chloride in the concentrated clarified extract.
The crude insulin is further purified by redissolving the insulin in acidic water and
iso-electric precipitation at pH 5.2 and 4°C. In a final step, zinc insulin is prepared by
58
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Ground Glandular Material
(3200 kg)
36% Hydrochloric Arid
(80 kg)
Alrnhnl Makpnp
(200 liters)
1
Recovered Solvent
(700 liters)
( Ethanol
•j Methanol
/Water
J) Waste Solvent
(350 liters) ^
( Water
•j Alcohol
/ Fats, Oils
(7000 liters) ^
Ethanol
Methanol
Water
Hydrochloric
Acid
Recycled
Ethanol
Methanol
Water
(5500 liters)
Solvent
Recovery
^
Sol
St
i
Sodium Chloride^
(240 kg) *
sent
1
Extraction
pH 2.5
\
r
Centrifugation
(clarification)
1
!
Neutralization
pHS.O
\
i
Filter
\
!
Acidification
PH3.0
1
Evaporation
at 20°C
Heat to 50°C
1
1000 liters
,pH 2-2.5
Skim Tank
Cool to 20°C
i
r
Filter
!
i
Crude
Insulin
Precipitation
'
Extracted
Rendered
Pancreas (3000 kg)
for Fat Recovery CO
Sold as Feed Protein
Cone. (30?
Ammomur
(110
Precipitate
Aid to Lar
(160 kg w
(80 kg sol
Sulfuric
(65 kg)
Disso
ar
Precip
@ 50°C t
(D
Fats to
( 140 kg)
Precipitated
Protein and
Filteraid tow
*• (4)
Landfill W
(40 kg wet)
(20 kg solids)
4)
n Hydroxide
kg)
d Protein andFilter
dfill (2)
n)
ds)
kg Purified Bulk Zinc Insulin
Water
Iving
itation <0.2 kg)
t
i i
Water Waste
(80 liters) (5)
(60 liters)
0.04 kg Sulfuric Acid
! r
Dissolving and
Isoelectric Sodium Hydroxide
* Precipitation (0.04 kg)
Crude at pH 5.2, 4°C
(1.2kg)
i
70
Water
r
iters (V)
Waste
Ammonium Sulfate
Sodium Chloride Waste
(400 kg) (?)
Sources: Standen. Webb, and Arthur D. Little, Inc., estimates. (See Bibliography)
FIGURE 3.2.1.2.5 REPRESENTATIVE PROCESS FOR MEDICINALS FROM ANIMAL GLANDS
(INSULIN - 1 KG OF PRODUCT)
59
-------
TABLE 3.2.1.2.5
TYPICAL PLANT FOR PRODUCING MEDICINALS FROM ANIMAL GLANDS (INSULIN)
A. Annual Production
284kg
B. Waste Characterization
Non-Hazardous Waste
Rendered pancreas
Protein and filter aid
Recovered fats
Protein and filter aid
Ammonium sulfate/sodium
chloride
Insulin precipitation wastewater
Stream
No.
kg per
kg Animal
Glands
(Dry Wt.)
0.94
0.025
0.04
0.006
0.125
0.022
kg per kg Product
Dry
3000
80
140
20
400
Wet
160
40
70
Quantity per kg Product
Liters kg
Hazardous Waste
Waste solvent concentrate (
(Ethanol, methanol, water,
fats, oils)
Precipitation wastewater (
(May contain traces of zinc)
Source: Arthur D. Little, Inc., estimates.
0.10
0.025
350
320
80 80
(1-5 gm Zn per kg product)
redissolving the insulin in acidified water and then adding zinc acetate to precipitate zinc
insulin, or plain insulin may be precipitated by using acetone. The solution of sodium
chloride in water and alcohol is solvent-stripped to recover solvent and is then discarded.
The extracted glands are rendered to recover fat (and remove alcohol) and then are
sold as animal feed protein. The precipitated protein containing filter aid is landfilled.
The hazardous wastes generated in this process are the solvent concentrate (containing
fats and oils) left behind when the aqueous alcohol is recovered in the solvent recovery
system and the wastewater from insulin precipitation which may contain traces of zinc salts.
(Treatment of this wastewater with alkali would precipitate any zinc as the hydroxide which
can then be removed by filtration.)
3.2.1.2.6 Biologjcals
The biological products listed in SIC code 2831 include vaccines, toxoids, serum, and
human blood fractions. The vaccines (such as influenza vaccine) are produced by growing
virus mutants in chicken egg embryos, extracting the egg with a salt solution, and precipitat-
ing the active antigen with ammonium sulfate for use in vaccine production. Most toxoid
production today is effected by tissue cell culture of the virus, followed by formaldehyde
treatment of the culture medium to give the toxoid. Salk-type poliomyelitis toxoid is
produced by this method. 50
-------
Tetanus antiserum is produced from the blood of a horse that has been infected with
the tetanus organism. While the horse itself remains healthy and active, tetanus antibodies
are produced in its bloodstream.
Human blood plasma contains a series of protein fractions that have commercial
medicinal use. Included in these protein fractions are antihemophilic globulin (to arrest
severe hemorrhaging), gamma-globulins (for prevention of hepatitis, measles, chicken pox,
and tetanus), thrombin (for blood coagulation), and albumin (for treating shock).
The two major classes of biologicals produced in the United States today are virus
vaccines from chicken egg embryos and human blood fractions. A typical process for human
blood fraction production is described below. Whole blood is received from donors (or
obtained from placentas following childbirth) and the cells are removed (by centrifugation)
to yield plasma. The sterile plasma may be used as is, or processed further to produce blood
protein fractions. These protein fractions are precipitated from the plasma at -5°C by adding
ethanol containing sodium acetate-acetic acid buffer in steps to increase the ethanol
concentration and lower the pH. The number of steps and pH at each stage are dependent
on the "method" of fractionation used and the protein fractions desired. The final step of
Method 6 (outlined in Figure 3.2.1.2.6) is precipitation of albumin at pH 5.2 and 40%
ethanol. Following this final precipitation, there is generally less than 2% of the original
plasma protein left in solution.
The cells from the whole blood can be removed and discarded; they are removed for
recovery of erythrocytes (red cells) for therapeutic treatment or, as in more recent practice,
returned to the donor.
The production of commercial quantities of plasma protein fractions does not require
very large equipment. A typical fractionation facility may handle a batch size of 500 liters
of plasma (from over 1500 donors) with a maximum in-process volume of 2000 liters. From
1943-1963, an average of 50,000 liters per year of plasma were fractionated.
After the final precipitation, the diluted plasma contains about 40% ethanol by
volume, less than 1% salts (sodium acetate, chloride, phosphate, carbonate) and about
0.03% protein. This would generate a total waste stream of about 240,000 liters (60,000
gal.) per year of watery waste containing 40% ethanol.
This waste can be (1) diluted and treated biologically, (2) the ethanol can be recovered
and the residual liquor treated biologically, or (3) concentrated and incinerated. About 12
kg of diatomaceous earth per 500 liters of plasma are also used in this process as .filter aid.
If placentas are used, when discarded, they are incinerated. The other unwanted solids or
solutions are usually discharged to the sanitary sewer and are handled by the liquid waste
treatment system.
61
-------
ethanol 8% pLASMA
temp. -3°C
etha
temf
protein 5.1%
pH 7.2
Supernatant I
nol 25% 1
>. -5°C
,
Precipitate 1
Fibrinogen
(for treatment of hemophili
protein 3.0%
pH
6.9
1
Supernatant ll+lll
Precipitate ll+lll
ethanol
temp.
protein
pH
-5°C
1.6%
5.1
Immune Globulins
(for prevention of hepatitis, measles)
Supernatant IV-1
Precipitate IV-1
ethanol
temp.
protein
pH
40%
-5°C
1.0%
5.8
a-Globulin
Supernatant IV— 4
Precipitate IV-4
ethanol 40%
temp. —5°C
protein 0.8%
pH 4.8
a- and jS-Globulins
Supernatant V
1
Precipitate V
Aqueous Ethanol Waste
\
ethanol 10% | Albumin
temp. —3°C (for treatment of
protein 3% traumatic shock)
pH 4.5
Supernatant
Impurities
ethanol 40%
temp. —5°C
protein 2.5%
pH 5.2
\
Supernatant
Albumin
Aqueous Ethanol Waste
Source: A. Standen, Kirk-Othmer Encyclopedia of Chemical Technology. (See Bibliography)
FIGURE 3.2.1.2.6 DIAGRAMMATIC REPRESENTATION OF METHOD 6 BLOOD FRACTIONATION
62
-------
3.2.1.3 Pharmaceutical Preparations (SIC 2834)
Pharmaceuticals are prepared in dosage forms such as tablets, capsules, liquids, or
ointments from the bulk Pharmaceuticals and biologicals of SIC codes 2833 and 2831 and
from other purchased raw materials. The methods used to manufacture these dose forms of
Pharmaceuticals are described below:
• Tablets — The flowsheet for production of coated and uncoated tablets is
shown in Figure 3.2.1.3A. The active ingredient, filler, and binder are
weighed, blended, and granulated. Additional binder, of filler, is added, if
required, and the tablets are produced in a tablet press machine. Some
tablets are coated by tumbling with a coating material and drying. The filler,
(usually starch, sugar, etc.) is required to dilute the active medicinal to the
proper concentration, and binder (such as corn syrup or starch) is necessary
to bind the tablet particles together. A lubricant, such as magnesium
stearate, may be added for proper tablet machine operation. The dust
generated during the mixing and tabletting operation is collected and is
usually recycled directly in the same batch. Broken tablets are generally
collected and recycled to the granulation operation in a subsequent lot.
After the tablets have been coated and dried, they are bottled and packaged.
A small amount of breakage does occur during this operation, and this
does generate some nonhazardous solid waste.
• Capsules — Empty hard gelatine capsules are produced by machines that dip
rows of rounded metal dowels into a molten gelatine solution and then strip
the capsules from the dowels after the capsules have cooled and solidified.
Imperfect empty capsules are remelted and reused, if possible, or sold for
glue manufacture. Most pharmaceutical companies purchase empty capsules
from a few specialist producers.
Capsule filling and packaging operations are shown in Figure 3.2.1.3B. The
active ingredient and any filler are mixed and sometimes granulated before
being poured into the empty gelatine capsules by machine. The filled capsules
are then bottled and packaged. As in the case of tablet production, some dust is
generated. This is recycled and small amounts disposed of. Some glass and
packaging waste from broken bottles and cartons results from this operation.
• Liquid Preparations - The first step in liquid preparation is weighing the
ingredients and then dissolving' them in water. Injectable solutions are
packaged in bottles and heat- or bulk-sterilized by sterile filtration and then
poured into sterile bottles. Oral liquid preparations are bottled directly
without subsequent sterilization. There are small amounts of liquid wastes
generated in this process that go to the sewer. Solid wastes are non-
hazardous and consist of broken bottles and some packaging waste.
63
-------
Dust to
Recycle or
Waste
Raw Materials
Receiving
Raw Materials
Storage
A.
Blending,
Granulating,
and Drying
Blending
Slugging
Broken Tablets
to Recycle
or Waste
Tablet
Compression
Foiling
Granulating
ON
Pan Coating
and Polistiing
Tablet
Counter
Bottle
Labeling
f
Packing
Finished
Goods
Storage
Shipping
Broken Glass
to Waste
• Indicates Start of Alternate Process.
Source: Arthur D. Little, Inc.
FIGURE 3.2.1.3-A PHARMACEUTICAL TABLET PRODUCTION
-------
Dust to
Recycle or
Waste
Raw Materials
Receiving
Raw Materials
Storage
Blending
Capsule Filling
Capsule Printing
F-'oiling
Granulating
and
Drying
Capsule
Counter
Bottle
Labeling
Packing
Finished
Goods
Storage
Shipping
Broken Glass
to Waste
• Indicates Start of Alternate Process.
Source: Arthur D. Little, Inc.
FIGURE 3.2.1.2-B PHARMACEUTICAL CAPSULE PRODUCTION
-------
• Ointments and Salves — Ointment production is outlined in Figure 3.2.1.3C.
The active ingredients (zinc oxide, antibiotic, cortisone, or other) are mixed
and then blended with thickening agents such as petroleum jelly or lanolin.
The ointment or salve is then injected into tubes or jars and packaged.
FDA regulations require that all formulations be tested to assure that they contain the
proper concentration of active ingredient, and that all active ingredient have been accounted
for. For this reason, and because of the value of the product, a concerted effort is made by
the pharmaceutical companies to convert as much active ingredient into final product as
possible. This requires as much reprocessing of product as possible and the complete
"running out" of active ingredient during production of the pharmaceutical preparations.
Some formulated material is sent to the sewer in cleanup operations, but typically only a
few kilograms per day of material may be disposed of as solid waste from a large
formulation and packaging operation.
The largest source of waste material that has to be handled at any given time is from
recalled lots of Pharmaceuticals. The recall may be due to company action in discontinuing
a product, or due to some product deficiency, such as a loss of potency. In the latter case,
the FDA may enter the picture and require a recall of the questionable lot. Products may
also be recalled due to mislabeling or product mixups. Some of the" recalls are readily
correctable and the product can then be reshipped. In other cases it is necessary to destroy
the entire lot. The waste generated in these operations is about 85% broken glass and waste
packaging materials and only about 15% product waste. The product waste, in turn, is
estimated to contain only about 20% active ingredient on the average.
We estimate that the U.S. pharmaceutical industry disposes of approximately 10,000
metric tons of returned goods annually, primarily consisting of packaging materials and
dilute active ingredient. There are also occasional batches of material that must be rejected
due to cross-contamination, decomposition, and so forth, that must be disposed of. Certain of
the active ingredients and some formulations in bulk form may be hazardous enough to
warrant special disposal. We estimate that approximately 500 metric tons per year fall into this
hazardous category for disposal from plants in SIC 2834.
In addition, we estimated that 75,000 metric tons of general rubbish are produced by the
packaging and shipping sections of the industry. These rubbish wastes consist mostly of glass,
paper, wood, rubber, aluminum and the like. We estimate that only a small fraction of 1 per-
cent of this material consists of active ingredient. The material is disposed of in regular
municipal landfills, together with cafeteria wastes, office wastes, and so forth. For purposes of
this study we do not consider that this waste should be categorized as a "process waste."
3.2.1.4 U.S. Pharmaceutical Industry Process Wastes and Projections to 1977 and 1983
3.2.1.4.1 Annual Waste of Pharmaceutical Industry
Tables 3.2.1.4.1 A and B present our estimates of hazardous and non-hazardous
wastes generated by the pharmaceutical industry in 1973 and their distribution in
the EPA regions. The quantities of each type of waste for the various products were
66
-------
Raw Materials
Receiving
Raw Materials
Storage
Blending or
Homogenizing
0\
-J
Tube or Jar
Filler
Labeling
Packing
Finished
Goods
Storage
^^
(
Shipping
Damaged Tubes
or Jars
to Waste
-n ... , , , .
Indicates Start of Alternate Process.
Source: Arthur D. Little, Inc.
FIGURE 3.2.1.3-C PHARMACEUTICAL OINTMENT PRODUCTION
-------
TABLE 3.2.1.4.1.A
PHARMACEUTICAL INDUSTRY WASTE GENERATION ESTIMATE FOR
1973'
Metric Tons Waste (1973)
Industry Segment
a\
co
Solvent
Animals (Incinerated)
Heavy Metals (Coniract Disposal)
SIC Code 2833: Production of Active ingredients
Organic Medicinal Chemicals (34,000 Metric Tons/Yr)
Biological Sludge (from Wastewater Treatment)
High Inert Content Waste — Non-Hazardous {Filter aid, activated carbon)
High Inert Content Waste - Hazardous [Contaminated filter aid, activated carbon)
Organic Chemical Residue {Tars, muds, still bottoms)
Halogenated Solvent
Non-Halogenated Solvent
Heavy Metal Wastes
Zinc
Arsenic
Chromium
Copper
Mercury
Inorganic Medicinal Chemicals
Heavy Metals (i.e., selenium)
Antibiotics (by Fermentation, 10,000 Metric Tons/Yr)
Mycelium (plus filter aid and sawdust)
Biological Sludge (from wastewater treatment)
Waste Solvent Concentrate
Botanicals (Plant Alkaloids, 2,000 Metric Tons/Yr Plant Material)
Wet Plant Material
Aqueous Solvent Concentrate
Halogenated Solvent
Non-Halogenated Solvent
66 liters/researcher
Total for R&D
Tons/Ton Product
1.4
0.1
0.05
0.4
0.1
0.7
0.070
0.015
0.001
< 0.001
<0.001
Total for Organic Medicinal Chemicals
Rounded to
Total for Inorganic Medicinal Chemicals
7.5 tons (dry wt)/ton antibiotic
3.5 tons/ton antibiotic
1.2 tons/ton antibiotic
Total for Fermentation (Antibiotics)
1 ton (dry basis) per ton plant material
0.36 ton/ton plant material
0.03 ton/ton plant material
0.06 ton/ton plant material
Total for Plant Alkaloids (Botanical)
Non-Hazardous
Dry Basis Wet Basis
-
47,600 476,000
3,400 6,800
51,000 482^00
51,000 480,000
75,000 300,000
35,000 350,000
-
110,000 650,000
2,000 4,000
- -
-
-
Hazardous
Dry Basis
1,600
1,500
1,700
13,600
3,400
23300
2,200
450
20
4
1
45,175
45,000
200
200
_
_
12,000
12,000
720
60
120
Wet Basis "
1,500
1,500
3,400
13,600
3,400
23,800
2,200
460
20
4
1
46,875
47,000
200
200
_
-
12,000
12,000
850
60
120
2,000
4,000
900
1,030
-------
TABLE 3.2.1.4.1.A (Continued)
Metric Tons Waste (1973)
Industry Segment
Botanicals (Plant Steroids, 150 Metric Tons/Yr Stigmasterol)
Fused Plant Steroid Ingots
Medicinals from Animal Glands (8000 Metric Tons Glands/Yr)
Extracted Animal Tissue
Fats or Oils
Filter Cake (contains precipitated protein)
Aqueous Solvent Concentrate
SIC Code 2831: Biological Products
Aqueous Ethanol Waste from Blood Fractionation
Antiviral Vaccine
Other Biologicals (Toxoids, serum)
SIC Code 2834: Pharmaceutical Preparations (Formulation, Packaging and Returns)
Total Returned Goods (Primarily packaging material and dilute active ingredient)
Contaminated or Decomposed Active Ingredient
5 tons/ton Stigmasterol
Total for Plant Steroids
Tons/Ton Animal Glands
0.940
0.044
0.031
0.100
Total for Medicinals from Animal Glands
Total for Production of Active Ingredients (SIC Code 2833)
5 liters/liter plasma
Total for Biological Products SIC Code 2831
Total for Pharmaceutical Preparations
Totals for all Industry Segments
Rounded to:
Non-Hazardous
Dry Basis
750
750
7,500
350
250
8,100
172,000
-
-
10,000
10,000
181.850
1 82,000
Wet Basis
750
750
7,600
350
500
8,350
1,143,000
-
-
10,000
10,000
1,153,000
1 ,1 53,000
Hazardous
Dry Basis
-
800
800
59,000
250
300
200
750
500
500
61,650
62,000
Wet Basis*
-
1,600
1,600
62,000
600
300
200
1,100
500
500
65,100
65,000
*Wet weight estimates are given for all wastes. The two wastes that typically have the highest moisture content are biological sludge and mycelium from fermentations. Where the wet waste estimates are the same as
on the dry basis, the waste is usually disposed of with only a minor amount of moisture. However, disposal practices vary from plant to plant, depending on the form in which the waste is produced.
Source: Arthur D. Little, Inc., estimates.
-------
TABLE 3.2.1.4.1B
DISTRIBUTION OF PHARMACEUTICAL INDUSTRY WASTE GENERATION (1973)1
Metric Tons Waste
Regions 1 & II
Industry Segment
R&D
Synthetic Organic
Medicinals
Fermentation
(Antibiotics)
Botanicals
Animal Source
Biologicals
Formulation, Packaging,
Returned Goods
Heavy Metal Wastes from
Organic and Inorganic
Waste Type
Solvent
Biological Sludge
Inert Wastes
Contam. Inerts
Halogenated Solvents
Non-Halogenated Sovent
Organic Residues
Mycelia (Dry Basis)
Biological Sludge
Waste Solvent Concen.
Plant Material
Aqueous Solvent
Halogenated Solvent
Non-Halogenated Solvent
Animal Tissue
Fats or Oils
Filter Cake
Aqueous Solvent
Waste Solvent
Other
Returned Goods
Active Ingredient
Non-Haz.
_
28.600
2,000
-
-
-
-
34.000
15,000
-
1,200
-
-
"
4.400
200
140
-
-
-
4,400
-
Haz.
780
_
-
1,000
2.000
14.300
8,200
-
-
5,000
-
420
30
60
_
-
-
500
25
50
_
220
Region III
Non-Haz.
_
4.800
300
-
-
-
-
7,500
3.600
-
200
-
-
"
740
35
30
-
-
-
1,100
-
Haz.
_
-
-
150
300
2.400
1.400
-
-
1.200
-
100
10
20
Region IV Region
Non-Haz. Haz. Non-Haz.
_ _ _
4.800 - 7.100
300 - 500
150 -
300 -
2,400
1,400
30,000
14.000
- - -
200 - 300
50
5 -
u Region VI
-HjJ Non-Haz. Haz.
420 - 60
400
50
200 - -
500-50
3.600 _ 150
2.100 - 50
_ _
-
4.800
— _ _
100 __
10 __
Region VII
Non-Haz.
_
700
100
-
-
-
-
1,000
700
-
_
-
-
Haz.
60
_
-
100
100
350
160
^
_
200
_
_
_
10- 20__ __
740 - 1.200 -
-
-
80
25
50
60
35 - 50
30 - 40
80 -
25 -
50 -
1.000 - 1.800
50 -
- -
- -
120
60
120
300
90-15
200
15
5
-
_
-
500
-
-
_
50
50
100
_
25
Region VIII Region IX
Non-Haz. Haz. Non-Haz. Haz.
- - - 180
1.200
150
- - 100
- - 150
- 600
- - - 300
2,500
1.700
- - 800
100
50
- - - 5
10
- 220 -
- 15
e
70
65
- - - 130
900
40
Region X Total
Non-Haz. Haz. Non-Haz. Haz.
- - - 1.500
47.600
3,400
- 1,700
- - - 3,400
- - - 23,800
- - - 13.600
75,000
35,000
- - - 12,000
2,000
- - - 720
- - 60
- - - 120
7.500
- - 350
- - 250
- - 800
- - 260
- - - 500
10,000
- - 500
lapnd: Non-Haz. - = Non Hazardous
Haz. - Hazardous
Total
Is for All Industry Segments
Rounded to:
2,900
181,850 61.850
182.000 62.000
Arthur D. Little. Inc., estimates.
-------
extrapolated to an annual (1973) basis from data gathered at the plants visited using
the following three methods:
1. Production of a given pharmaceutical product at the plants visited compared
to total industry production in the United States;
2. Value of production of a pharmaceutical product at the plants visited as a
percentage of annual total value of that product in the United States; and
3. Generation of a given waste as related to total value of production or
number of production employees.
We estimated the total annual quantity of solvent waste originating from R&D
operations on the basis of quantities generated per researcher at the facilities we visited.
Since test animals are routinely incinerated on-site and the amount of heavy metal waste is
very small and disposed of by waste disposal contractors, we did not include figures for
these wastes in this table.
The production of organic medicinal chemicals creates waste solvents, chemical tars
and residues, wet filter aid or carbon, some heavy metal waste, and biological sludge from
on-site or off-site biological treatment of water-soluble organic compounds, such as acetic
acid or alcohol. The wet filter aid or carbon may be non-hazardous or may contain
contaminating materials such as solvent, corrosives or heavy metals that render it hazardous.
(The heavy metal contents of the heavy metal wastes listed in Table 3.2.1.4.1 A were
presented earlier in Table 3.2.1.2.1.)Many pharmaceutical companies also produce crude
antibiotics and growth stimulants such as arsanilic acid for the animal feed industry, but
these products are not listed as part of SIC code 2833. Several companies are also producers
of some heavy chemical fermentation products, such as citric and itaconic acid, but these
again are not part of SIC code 2833.
Inorganic, medicinal, chemical, active-ingredient production usually generates non-
hazardous aqueous waste salt solution and little or no solid hazardous waste. In addition, a
large portion of the active ingredients for manufacture of inorganic medicinals is purchased
from the heavy chemicals industry.
Fermentation is used for the production of most crude antibiotics, for chemical
conversion of some steroids, and for the production of some industrial heavy chemicals. The
fermentation, product recovery, and purification processes result in considerable quantities
of non-hazardous wastes, such as mycelia and spent nutrient broth. The main hazardous
waste generated is a solvent concentrate. This waste contains organics from recovery of
solvent used in the product recovery and purification sections of the process. The weight of
dry mycelia waste per ton of product is considerably higher for other antibiotics than it is
for penicillin, since it is necessary to use a significant amount of filter aid to remove the
mycelia from the broth and the yields of some of the other antibiotics per ton of mycelia is
71
-------
lower. Some State regulations also require a minimum solids content of the mycelia waste
for landfill disposal, so an additional filter such as sawdust must be added to increase the
solids content.
The extraction of botanicals, such as roots and leaves, and animal organs, such as
pancreas glands or lung tissue for alkaloid, steroid, and hormone products, respectively, is
usually accomplished using acidic aqueous alcohol and often requires a second halogenated
solvent in the purification process. These solvents are recovered for reuse, thus generating a
waste solvent concentrate. The wet botanicals are disposed of by landfill, but the animal
organ by-products (extracted glands and fats) are sold when possible.
The quantities of returned goods and active ingredients disposed of were projected as
being proportional to the total value of production.
The major wastes generated in the production of biologicals include aqueous alcohol
and dissolved salts from human blood plasma fractions and formaldehyde-egg waste from
antiviral production. There is a limited amount of production of other biologicals, such as
horse serum products and toxoids, but the total production of biologicals is quite small
compared to the production of other Pharmaceuticals.
Heavy metal wastes occur mostly in the production of organic medicinal chemicals. In
some cases, such as the selenium waste, the waste stream is unique to one process and one
manufacturer. In other cases, there are several producers that have a similar waste heavy
metal (mercurials), and yet other heavy metal wastes, such as zinc compounds, are found
throughout the industry. This factor was taken into consideration in estimating the annual
generation of each of these heavy metal wastes.
In Table 3.2.1.4.IB we have apportioned the waste generation figures for the whole
United States, as listed in Table 3.2.1.4.1 A, among the various EPA regions. Our estimates
of waste generation distribution are based on production figures for antibiotics, synthetic
organic medicinals, and biologicals of the pharmaceutical companies in these regions. Waste
generation from R&D facilities was estimated from PMA data showing locations of R&D
personnel. Location of major formulation and packaging facilities was used to estimate
distribution of returned goods. Regions I and II were combined in Table 3.2.1.4.IB to avoid
disclosure of confidential information on production or waste stream data on plants in
Region I which has only one large plant in SIC 2833.
Waste generation on a state-by-state basis is presented in Table 3.2.1.4.1C. Regional
and national totals are also given. State totals for heavy metals are not estimated because of
the difficulty in estimating the specialized use of these materials in individual plants. State
estimates for mycelium waste generation have also been omitted, because only 16 major
fermentation installations produce antibiotics in the continental United States. Seven states
have only one. plant each, one state has two, one state has. three, and only one state has four
major plants. Again, state-by-state figures on mycelium production would divulge, confiden-
tial information on several companies. Many states have so few people employed in the
pharmaceutical industry that the waste is considered insignificant, and blanks therefore
appear in the table. The reason for the spotty distribution is apparent when one considers
that SIC code 2833 (which contributes almost all the hazardous and nonhazardous waste
from the industry) contains only 54 installations that have more than 20 employees each.
72
-------
TABLE 3.2.1.4.1C
ESTIMATED DISTRIBUTION OF WASTE GENERATED BY THE PHARMACEUTICAL INDUSTRY IN 1973
(annual metric tons — dry basis)
State
IV Alabama
X Alaska
IX Arizona
VI Arkansas
IX California
VIII Colorado
Connecticut
II Delaware
V Florida
V Georgia
X Hawaii
X Idaho
V Illinois
V Indiana
VII Iowa
VII Kansas
V Kentucky
VI Louisiana
1 Maine
II Maryland
Massachusetts
V Michigan
V Minnesota
V Mississippi
VII Missouri
VIII Montana
VII Nebraska
IX Nevada
1 New Hampshire
1 New Jersey
VI New Mexico
1 New York
V North Carolina
VIII North Dakota
V Ohio
VI Oklahoma
X Oregon
III Pennsylvania
II Puerto Rico
1 Rhode Island
IV South Carolina
VIII South Dakota
IV Tennessee
VI Texas
VIII Utah
1 Vermont
III Virginia
X Washington
III West Virginia
V Wisconsin
VIII Wyoming
National Totals
Region Totals
1
II
III
IV
V
VI
VII
VIII
IX
X
Notes: 1. Includes R&D so
2. Includes biologic
3. Dry wt x 2 = we
Halogenated*
Solvent Waste
-
-
330
_
200
-
40
60
_
_
300
330
30
—
-
10
_
-
_
200
-
110
—
20
-
-
1,600
800
100
70
-
-
270
200
—
-
_
100
100
—
_
40
-
-
30
-
4,940
200
2,600
310
300
930
110
160
330
_
vent wastes
a! product organic w
weight
Non-Haloganata
Solvent Waste
:
-
1,600
_
1,400
-
400
500
_
_
2.900
3,100
130
—
_
10
_
-
_
1,900
-
440
—
80
-
-
11,000
6,000
900
600
-
-
3,300
2,000
—
-
_
800
140
-T-
_
550
-
-
200
-
37,950
1.4IXJ
19,000
3,850
2,600
8,700
150
650
1.600
_
4. Dryw
astes. 5 Dry w
6. Includ
7. Dryw
Hazardous
Organic
d (Chemicals)
Residues
-
-
430
—
500
-
250
200
—
_
760
810
50
—
-
5
—
-
_
450
-
170
—
30
-
-
4,700
2,300
550
150
-
-
1,250
750
—
-
—
450
45
-
_
200
-
-
50
-
14,100
500
7,750
1,450
1,450
2,220
50
250
430
_
x 10 = wet weight
t x 1.2 = wet weight
es filter cake tor animal
t x 4.35 = wet weight
Contaminated3
High Inerts
Waste
-
-
100
_
100
-
25
25
_
_
70
70
20
—
-
-
—
-
_
40
-
70
—
10
-
-
500
300
50
10
-
-
130
100
—
-
—
50
-
—
_
20
-
-
10
-
1,700
100
900
150
150
200
_
100
100
_
source pharmace
Active
:
-
40
—
20
-
5
5
—
-
30
30
5
—
-
-
—
-
_
20
-
20
—
-
-
-
120
60
20
10
-
-
50
20
-
-
—
20
15
—
—
10
-
-
-
-
500
'Al
200
60
50
90
15
25
40
_
uticals.
Heavy
Motals
-
„
-
_
_
„
_
-
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
__
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
2,900
—
-
_
_
_
_
-
_
_
Total
Hazardous *
-
—
2,500
_
2,220
_
720
790
_
_
4,060
4,340
235
_
_
25
_
_
_
2,610
_
810
_
140
_
_
17.920
9,460
1,620
840
_
_
5,000
3,070
_
_
_
1,420
300
_
_
820
_
_
290
_
59,190
2,220
30,450
5,820
4,550
12,140
325
1,185
2,500
_
•(excludes
metals)
Biological4
Sludge
-
90
2,900
—
3,000
-
500
500
—
-
7,000
7,600
700
—
-
40
—
600
600
4,600
800
700
—
-
-
-
24,200
12,000
1,500
1,500
-
-
6,500
3,800
—
500
_
1,000
270
—
—
1.100
-
200
400
-
82,600
J.600
40,000
8,400
4,800
21,100
400
1,400
2,900
_
Non-Haz
Plant Material5
Animal Tissue
Fats, Oil
-
330
—
400
-
100
100
—
-
500
560
110
—
-
-
—
70
100
340
200
70
—
35
-
-
3,200
1,600
300
110
„
-
800
500
—
100
—
200
-
—
_
100
-
30
50
-
9,905
500
5,300
1,000
1,000
1,560
_
215
330
_
ardous
High Inerts3-
Waste
(Non-Haz.)
10
150
—
100
-
30
30
—
-
180
190
50
—
-
10
—
20
100
120
50
35
—
20
-
-
1,140
600
120
40
-
-
250
200
—
20
—
80
30
—
_
50
-
10
10
-
3,645
200
1,940
330
330
540
50
105
150
_
6
Returned
Goods
-
70
900
_
300
-
100
100
—
_
600
650
100
—
-
30
—
80
100
400
200
300
—
100
-
-
2,400
1,200
300
120
-
-
850
400
—
100
—
200
200
—
_
140
-
30
30
-
10,000
400
4,000
1,100
1,000
1,800
300
500
900
_
Mycolium
-
-
-
_
-
-
-
-
_
_
_
_
-
_
_
_
_
_
_
_
_
-
_
_
_
-
-
-
-
-
-
-
-
-
—
-
—
-
-
—
_
-
-
-
-
_ -
75,000
—
-
_
_
_
_
_
_
_
Nonhazardous*
170
4,280
730
730
8,280
9,000
770
900
5,460
1,250
1,105
15,400
2,220
8,400
4,900
1,480
500
270
490
106,150
4,700
51,240
10,830
7,130
25,000
750
2,220
4,280
excludes
mycelium)
-------
3.2.1.4.2 Typical Types of Pharmaceutical Hazardous Wastes and Their Properties
Table 3.2.1.4.2 lists the typical types of hazardous waste materials discharged from
pharmaceutical operations. The physical, chemical, and biological properties of the hazard-
ous constituents of these wastes are listed in Appendix B.
3.2.1.4.3 Projections of Pharmaceutical Process Wastes to 1977 and 1983.
Medicinal ingredient production in the United States has increased at an annual
compounded rate of 6.3% for the past 20 years. Also, prescription numbers have been
increasing at approximately the same rate. However, we note that production has sometimes
slackened during recessions, and thus we anticipate that the present energy shortages and
disruptions of the economy may have an adverse effect on medicinal ingredient production
in the immediate future. We are therefore projecting waste increases on the basis of a 3
percent compounded rate until 1977. We expect passage of a National Health Care Act in
1976 and believe that growth will then be slightly above historical trends. We have therefore
projected waste growth from 1977 to 1983 on the basis of a 7 percent compounded rate.
Final effluent guidelines have not been set for the pharmaceutical industry. We examined
the preliminary recommendations for the industry and concluded that the guidelines will
not add to the tonnage of wastes to be landfilled from air and wastewater treatment pro-
cesses. Projections of hazardous and non-hazardous wastes by industry segments for 1977
and 1983 are shown in Table 3.2.1.4.3A. The totals of hazardous and non-hazardous waste
generated in 1973 and the waste generation factors for each waste (metric tons of waste per
metric ton of product or raw material) were developed earlier in Table 3.2.1.4.1 A and
Section 3.2.1.2.1. The projected distribution of wastes by state was calculated from Ta-
ble 3.2.1.4.1C by using the same 3 percent and 7 percent compounded rate referred to above.
Estimates of state data for 1977 are presented in Table 3.2.1.4.3B and for 1983 in
Table 3.2.1.4.3C. Due to rounding, totals of the various tables may not agree exactly.
74
-------
TABLE 3.2.1.4.2
SUMMARY OF TYPICAL TYPES OF
PHARMACEUTICAL HAZARDOUS WASTE MATERIALS*
Antibiotics (Penicillin, Tetracyclines, Cephalosporins)
Recovery Solvents
Amyl acetate
Butanol
Butyl acetate
Methylisobutyl ketone
Alkaloids (Quinine, Reserpine, Vincristine) from Plant Material
Purification Solvents
Butanol
Acetone
Ethylene Glycol Monomethyl Ether
Extraction Solvents
Methanol
Acetone
Ethanol
Chloroform
Heptane
Ethylene Dichloride
Crude Steroids from Plant Material
Still bottoms (Soybean Oil Residue)
Medicinals from Animal Organs (Insulin, Heparin)
Ethanol
Methanol
Acetone
Synthetic Organic Medicinals
Typical Solvents
• Acetone
Toluene
Xylene
Benzene
Isopropyl alcohol
Methanol
Ethylene Dichloride
Acetonitrile
Organic Residues (Still Bottoms, Sludges,
Polymers, Tars)
Terpenes
Steroids
Vitamins
Tranquilizers
Blood Plasma Fractions
Solvent
Ethanol
Source: Arthur D. Little, Inc., estimates.
Purification Solvents
Ethylene Dichloride
Naphtha
Methylene Chloride
Benzene
Inert Solids (Generally Non-Hazardous)
Activated Carbon
Filter Aid
Filter Cloths
Heavy Metals
Copper
Mercury
Arsenic
Selenium
Zinc
Chromium
Salts
Sodium Acetate
Sodium Chloride
Sodium Phosphate
75
-------
TABLE 3.2.1.4.3A
ESTIMATES OF PHARMACEUTICAL INDUSTRY GENERATED WASTES FOR 1973, 1977 AND 1983*
(All Figures in Metric Tons Per Year)
1973
1977
1983
Industry Segment
R&D
Solvent
Total R&D
SIC Code 2833: Production of Active Ingredients
Organic Medicinal Chemicals (34,000 Metric Tons/Yr)
Biological Sludge (from wastewater treatment)
High Inert Content (filter aid, carbon)
Contaminated High Inert Content (i.e., filter aid and solvent)
Organic Chemical Residues {tars, mud, still bottoms)
Halogenated Solvent
Non-Halogenated Solvent
Heavy Metal Wastes
Zinc Compounds
Arsenic Compounds
"~-J Chromium Compounds
Copper Compounds
Mercury Compounds
Total for Organic Medicinal Chemicals
Rounded to:
Inorganic Medicinal
Heavy Metals (i.e., selenium waste)
Antibiotics (by Fermentation, 10,000 Metric Tons/Yr)
Mycelium (plus filter aid and sawdust)
Biological Sludge
Waste Solvent Concentrate
Total for Antibiotics
Rounded to:
Botanicals (Plant Alkaloids, 2,000 Metric Tons/Yr Plant Material)
Wet Plant Material
Aqueous Solvent Concentrate
Halogenated Solvent
Non-Halogenated Solvent
Total for Plant Alkaloids
Botanicals (Plant Steroids, 150 Metric Tons/Yr Stigmasterol)
Fused Plant Steroid Ingots
Non-Hazardous
Dry Basis Wet Basis
-
-
47,600 476,000
3,400 6,800
- —
51,000 482,800
51,000 480,000
-
75,000 300,000
35,000 350,000
1 1 0,000 650,000
110,000 650,000
2,000 4,000
Hazardous
Dry Basis
1,500
1,500
1,700
13,600
3,400
23,800
2,200
450
20
4
1
45,175
45,000
200
12,000
12,000
12,000
720
60
120
Wet Basis f
1,500
1,500
3,400
13,600
3,400
23,800
2,200
450
20
4
1
46,875
47,000
200
1 2,000
12,000
12,000
850
60
120
2,000
4,000
900
1,030
Non-Hazardous
Dry Basis Wet Basis
-
53,600 536,000
3,800 7,600
- _
a7,400 543,600
57,000 540,000
-
84,400 338,000
39,400 394,000
123,800 732,000
1 24,000 730,000
2,250 4,500
Hazardous
Dry Basis
1,900
1,900
1,900
15,300
3,800
26,800
2,500
500
22
4
1
50,827
51,000
225
13,500
13,500
14,000
810
70
140
Wet Basis*
1,900
1,900
3,800
15,300
3,800
26,800
2,500
500
22
4
1
52,727
53,000
225
1 3,500
13,500
14,000
960
70
140
2,250
4,500
840
1,020
Non-Hazardous
Dry Basis Wet Basis
-
80,400 804,000
5,700 11,400
- -
- -
- -
- —
_ _
- -
- —
- -
- -
86,100 815,400
86,000 815,000
-
127,000 508,000
60,000 , 600,000
— -
187,000 1,108,000
190,000 1,100,000
3,400 6,800
- —
- —
-
Hazardous
Dry Basis
2,700
2,700
-
2,900
23,000
5,700
40,000
3,700
750
35
6
1
76,092
76,000
350
_
-
20,000
20,000
20,000
_
1,200
100
200
Wet Basis*
2,700
2,700
—
5,800
23,000
5,700
40,000
3,700
750
35
6
1
78,992
79,000
350
_
-
20,000
20,000
20,000
_
1,400
100
200
3,400
1,000
6,800
1.0OO
1,400
1,700
-------
TABLE 3.2.1.4.3A (Continued)
Industry Segment
Medicinals from Animal Glands (8,000 Metric Tons Glands/Yr)
Extracted Animal Tissue
Fats or Oils
Filter Cake (Containing protein)
Aqueous Solvent Concentrate
Total Medicinals from Animal Glands
Total for Production of Active Ingredients (SIC Code 2833)
SIC Code 2831: Biological Products
Aqueous Ethanol Waste from Blood Fractionation
Antiviral Vaccine
Other Biologicals
Total for Biological Products
SIC Code 2834: Pharmaceutical Preparations
Returned Goods
Contaminated or Decomposed Active Ingredient
Totals for All Industry Segments
Rounded to:
Non-Hazardous
Dry Basis
7,500
350
250
8,100
172,000
-
Wet Basis1
7,500
350
500
8,360
1,143,000
-
Hazardous
Dry Basis
800
800
59,000
250
300
200
Wet Basis1
1,600
1,600
62,000
600
300
200
Non- Hazardous
Dry Basis
8,400
400
280
9,080
193,000
-
Wet Basis1
8,400
• 400
560
9,360
1 ,285,000
-
Hazardous
Dry Basis
900
900
67,000
280
350
225
Wet Basis1
1,800
1,800
70,000
680
350
225
Non-Hazardous
Dry Basis
12,500
600
420
13,520
294,000
-
Wet Basis1
12,500
600
840
13,940
1,937,000
-
Haza
Dry Basis
1,350
1,350
99.000
400
500
350
rdous
Wet Basis1
2,700
2,700
103,000
1.000
500
350
10,000
10,000
181,850 1,153,000
182,000 1,153,000
1 1 ,300
1 1 ,300
11,300
11,300
61,650
62,000
65,100
65,000
204,300 1,836,300
204,000 1,836,000
70,445
70,000
73,755
74,000
17,000
17,000
311,000
310,000
17,000
17,000
1,954,000
1,954,000
1,250
900
103,850
1 04.000
1,850
900
108,450
108,000
'Source: Arthur D. Little, Inc., estimates.
Wet weight estimates are given for all wastes. The two wastes that typically have the highest moisture content are biological sludge and
mycelium from fermentations. Where the wet waste estimates are the same as pn the dry basis, the waste is usually disposed of with only
a minor amount of moisture. However, disposal practices vary from plant to plant, depending on the form in which the waste is produced.
-------
TABLE 3.2.1.4.3B
PROJECTED DISTRIBUTION BY STATE OF WASTES GENERATED BY THE PHARMACEUTICAL INDUSTRY IN 1977
(annual metric tons — dry basis)
Halogenated"
Slate S
V Aldbama
X Alask;.
IX Arizona
VI Arkansas
X Cahlorm,]
VIII Colorado
Connecncui
II Delaware
V Florida
V Georgia
X Hawaii
X Idaho
V Illinois
V Indiana
VII Iowa
VII Kansas
IV Kentucky
VI Louisiana
1 Maine
III Maryland
1 Massachusetts
V Michigan
V Minnesota
IV Mississippi
VII Missouri
VIII Montana
VII Nebraska
IX Nevada
1 New Hampshire
II New Jersey
VI New Mexico
H New York
V North Carolina
VIM North Dakota
V Ohio
VI Oklahoma
X Oregon
1 I Pennsylvania
II Puerto Rico
1 Rhode Island
IV South Carolina
VIM South Dakota
IV Tennessee
VI Texas
VIII Utah
1 Vermont
HI Virginia
X Washington
III West Virginia
V Wisconsin
VIII Wyoming
National Totals
Region Totals
1
II
Ml
IV
V
VI
VII
VIM
IX
X
tes: 1. Includes R&D solver
2. Includes biological p
1 UUat iiuciinht ~ Hrv we
370
220
45
70
340
370
35
_
10
_
_
__
220
_
_
120
_
20
_
_
1,800
_
900
110
80
-
_
300
220
-
-
_
110
110
_.
_
45
-
_
35
-
5,530
220
2,920
345
335
1,045
120
175
-
370
_
t waste
rortuct organic
iaht x 2.
Nan Halogens
_
1.800
_
1.600
_
450
560
_
3,300
3,500
150
-
10
__
_
2,100
_
_
490
_
90
_
_
12,400
_
6,760
1,000
—
680
-
-
3.700
2,200
-
-
_
900
160
-
—
620
-
-
220
-
42,690
1,600
21,360
4.320
2,910
9,800
170
730
-
1,800
5.
wastes 6.
7.
Organic" Co
n laminated
ed (Chemical) High Inert* A
_
480
560
_
280
220
_
_
860
910
55
-
_
6
__
_
_
510
_
_
190
_
35
_
_
5,300
_
2.600
620
_
170
-
-
1,400
840
—
-
510
50
-
_
220
-
-
55
-
15.871
560
8,740
1,620
1,630
2,505
56
280
480
Wet weight = dry weight
Includes filter cake from
Wet weight = dry weight
Plant Material5
ctiwe Heavy
Waste Ingredient Metals
110
110
_
30
30
_
_
80
80
20
-
-
_
_
_
45
_
_
80
_
10
_
_
560
_
340
55
_
10
__
-
150
110
-
-
_
55
-
_
20
-
_
10
-
1,905
110
1.010
170
170
225
_
110
-
110
x-1.2.
animal source pha
x 4.35.
.45
_
20
_
6
6
_
_
35
35
6
-
_ —
-
_
_ _
_
20
_ —
_
20
_ _
_
_ -
_ _
130
_ __
70
20
_ __
10
- _
—
55
20
_
-
- _
20
15
- __
_
10
-
_ _
-
-
543 3,260
20
220
65
52
100
15
26
- -
45
—
rmaceuticals.
Total
Hazardous'
_
_
2,805
_
2,510
_
811
886
_
_
4.615
4,895
266
-
_
26
_
_
_
2,895
_
_
900
_
155
_
_
20.190
_
10,670
1,805
_
950
_
_
5,605
3,390
_
_
_
1.595
335
_
_
915
_
_
320
-
66,539
2.510
34,250
6,520
5,097
13,675
361
1,321
-
2.805
—
' (excludes
metals)
Biological4
Sludge
_
100
3,300
_
3,400
_
560
560
_
_
7.900
8,600
790
-
_
45
_
680
680
5,200
_
900
790
_
_
_
_
27.200
_
13,500
1,700
_
1.700
-
_
7,300
4,300
-
560
_
1,100
300
-
_
1,200
-
220
450
-
93,035
4,080
45.000
9.400
5,380
23,850
445
1,580
-
3,300
—
Animal Tissue,
Fats, Oil
_
_
„
370
_
450
_
110
110
_
_
560
630
120
-
_
_
_
80
110
380
_
220
80
_
40
_
_
3,600
_
1.800
340
_
120
-
_
900
560
-
110
-
220
-
-
_
110
—
35
55
-
11.110
560
5,960
1,125
1,110
1,745
—
240
—
370
—
High Insets"
Waste
(Non-Hal.)'
_
10
170
_
110
_
35
35
_
_
200
210
55
-
_
10
_
20
110
130
_
55
40
_
20
—
-
1,300
—
680
130
_
46
-
—
280
220
-
20
-
90
35
—
_
55
-
10
10
-
4,085
220
2,200
365
365
595
55
115
—
170
—
Returned
Goods Mynllum
_
_ —
_ —
80
1,010
- —
340
— —
110 -
110
- —
- —
680
730
110
~ -
— —
35
__ —
90
no -
450
— —
220
340
— —
110
— —
— —
2.700
— —
1.350
340
_ —
130
— —
— —
960
450
— —
110
— —
220
220
— —
— —
160
— —
35
35
-
1 1 .235 84.000
450
4,500
1.245 -
1,110
2,025
335
560
— —
1,010 -
— —
Total
Non-Hazsrdouj-
_
~
—
190
4,850
—
4,300
—
815
815
—
—
9.340
10.T70
1.075
~
—
90
—
870
1,010
6,160
—
1,395
1.250
—
170
—
—
34,800
—
17,330
2.610
—
1,996
—
—
9,440
5,530
—
800
—
1,630
555
—
—
1,525
—
300
550
~
119,465
5,310
57.660
12.135
7.965
28.215
835
2,495
—
4.860
"(excludes
mycelium)
-------
TABLE 3.2.1.4.3C
PROJECTED DISTRIBUTION BY STATE OF WASTES GENERATED BY THE PHARMACEUTICAL INDUSTRY IN 1983
(annual metric tons — dry basis)
State
Alabama
Alaska
Arizona
Arkansas
California
Colorado
Connecticut
Delaware
Florida
Georgia
Idaho
Illinois
Indiana
Iowa
Kansas
Kentucky
Louisiana
Maine
Maryland
Massachusetts
Michigan
Minnesota
Mississippi
Missouri
Montana
Nebraska
Nevada
New Hampshire
New Jersey
New Mexico
New York
North Carolina
North Dakota
Ohio
Oklahoma
Oregon
Pennsylvania
Puerto Rico
Rhode Island
South Carolina
South Dakota
Tennessee
Texas
Utah
Vermont
Virginia
Washington
West Virginia
Wisconsin
Wyoming
nal Totals
Regional Totals
1
II
111
IV
V
VI
VII
VIII
IX
X
Notes: 1. Inc
2. Inc
3. Wei
4. Wei
Halogenated*
Solvent Waste
_
_
_
_
560
_
340
_
70
100
_
510
560
50
-
_
15
_
_
-
340
_
_
190
-
30
_
_
2,700
_
1,300
170
_
120
_
-
460
340
_
_
_
170
170
_
-
70
-
_
SO
-
8,315
340
4,340
530
510
1,580
185
270
—
560
-
ludesR&D solvent wast
ludes biological product
[ weight = dry weight x
[ weight = dry weight x
Non-Halogenated
Solvent Waste
_
_
-
_
2,700
-
2,400
_
680
840
„
4,900
5,200
220
-
_
15
_
~
-
3,200
_
_
740
-
130
_
_
18,600
_
10,100
1,500
_
1,000
-
-
5,600
3,400
_
_
-
1,300
240
-
-
930
-
-
340
_
64,035
2,400
32,100
6,530
4,320
14,640
255
1,090
—
2,700
-
es.
r organic wastes.
2.
10.
Hazardous
Organic3
(Chemical)
Residues
_
_
_
_
730
_
840
_
420
340
_
1,300
1,400
85
-
_
10
—
_
_
760
_
_
290
_
50
_
_
7,900
_
3,900
930
_
250
_
-
2,100
1,300
_
_
_
760
80
_
-
340
-
_
85
_
23,870
840
13,100
2,440
2,450
3,795
90
425
_
730
-
5. Wet weight
6. Includes fil-
7. Wet weight
Cant am! naiad3
High Inerts
Waste
_
_
_
_
170
_
170
_
40
40
_
120
120
30
-
_
_
_
_
-
70
_
-
120
-
15
_
_
840
_
510
85
_
15
_
-
220
170
_
_
-
85
—
-
-
30
-
-
15
_
2,865
170
1,520
250
250
340
-
165
—
170
-
= dry weight x 1.2.
ter cake from animal s(
= dry weight x 4.35.
Active
Ingredient
_
_
_
_
70
_
30
_.
10
10
_
50
50
10
-
_
_
_
_
-
30
_
_
30
_
-
_
_
200
_
100
30
_
15
_
_
80
30
_
_
_
30
25
_
-
16
-
_
-
_
815
30
330
95
80
145
25
40
—
70
-
Jurce pharmai
Heavy Total
Metals Hazardous*
_ _
_ „
-_ _
4,230
_ _
3,780
_ _
1 ,220
1 ,330
I I
6,880
7,330
395
_ _
_ _
40
_ _
_ _
__ „
4,400
_ _
__ _
- 1 ,370
_ _
225
_ _
_ _
30,240
_ _
- 15,910
2,715
_ _
1 ,400
_ _
_ _
8,460
5,240
_ _
_ _
_ _
2,345
- 515
_ _
_ „
1,385
_ _
_ _
490
_ _
4,900 99,900
3,780
51,390
9,845
7,610
20,500
555
1,990
— _
4,230
- -
* (excludes r
ceuticals. "(excludes r
Biological*
Sludge
_
_
-
150
4,900
-
5,100
_
840
840
_
11,800
12,800
1,200
-
_
70
-
1,000
1,000
7300
—
1,300
1.200
-
-
-
-
40,900
_
20,300
2,500
_
2,500
-
-
1 1 ,000
6,400
_
840
-
1,700
460
-
-
1,900
-
340
680
-
139,520
6,100
67,600
14,240
8,020
35,580
680
2,400
_
4,900
-
netals)
nycelium)
Non-Haz
Plant Material5
Animal Tissue,
Fats, Oil
_
_
-
-
560
-
680
_
170
170
_
840
950
190
-
_
-
-
120
170
570
_
340
120
-
60
-
-
5,400
—
2,700
510
—
190
-
—
1,300
840
_
170
—
340
-
-
-
170
-
50
85
_
16,695
850
8,940
1,640
1,700
2,635
—
370
_
560
-
ardous
High Inerts3-6
Waste
(Non-Haz.)
_
-
-
15
250
-
170
—
50
50
_
300
320
85
-
-
15
-
30
170
200
—
85
60
-
30
-
-
1,900
—
1,000
200
—
70
-
-
420
340
—
30
-
130
50
-
-
85
-
15
15
-
6,085
340
3,240
550
545
905
80
175
_
250
-
Returned
Goods
_
-
-
120
1,500
-
510
—
170
170
_
1,000
1,100
170
-
-
50
-
130
170
680
—
340
510
—
170
—
-
4,000
—
2,000
510
—
200
-
-
1,400
680
—
170
-
340
340
-
-
240
-
50
50
-
16,770
680
6,680
1,820
1,700
3,030
510
350
_
1,500
-
Total
Non-Hazardous,
285
7,210
1,230
1,230
13,940
15,170
1,645
1,280
1,510
9,250
2,065
1,890
260
52,200
26,000
3,720
14,120
8,260
2,510
850
455
830
179,070
7,970
86,460
18,250
11,965
42,150
1,270
3,795
7,210
-------
DATA SOURCES FOR SECTION 3.1
A. GENERAL SOURCES
Manufacturers' Technical Bulletins - This is usually the best single source of
general information about the compound.
Material Safety Data Sheets - Provided by the manufacturer using the U.S.
Department of Labor Form OSHA-20 or an approved modification.
Code of Federal Regulations - Office of the Federal Register, Archives and
Record Service, Washington, D.C., 1972. Titles 46 (Shipping) and 49 (Transportation) in the
most recent revision available.
Chemical Safety Data Sheets — Manufacturing Chemists Association, Washington,
D.C.
Industrial Safety Data Sheets — National Safety Council, Chicago, Illinois.
International Maritime Dangerous Goods Code — Inter-Governmental Maritime
Consultative Organization (IMCO), London, 1972.
Petroleum Products Handbook - V.B. Guthrie (ed.), McGraw-Hill, New York,
1960.
Glossary of Terms Used in Petroleum Refining — 2nd edition, American Petroleum
Institute, New York, 1962.
The Handling and Storage of Liquid Propellants - Office of Defense Research and
Engineering, U.S. Government Printing Office, Washington, D.C., 1963.
Industrial Chemicals - W.L. Faith, D.B. Keyes, and R.L. Clark, 3rd edition, Wiley,
New York, 1965.
Chemical Technology of Petroleum - W.A. Gruse and D.R. Stevens, 3rd edition,
McGraw-Hill, New York, 1960.
Chemical Rocket/Propellant Hazards - CPIA Publication No. 194, Vol. Ill, 1970.
Organic Solvents - J.A. Riddick and W.B. Bunger, 3rd edition, Wiley-Interscience,
New York, 1970.
Transport of Dangerous Goods - (4 vols) United Nations, New York, 1970.
80
-------
Kirk-Othmer Encyclopedia of Chemical Technology- 1st edition (1947-1960)
and 2nd edition (1963-1970), Interscience-Wiley, New York.
Evaluation of the Hazard of Bulk Water Transportation of Industrial Chemicals, A
Tentative Guide - National Academy of Sciences, Washington, D.C., 1970; includes supple-
ment with additions to September 1972.
System for Evaluation of the Hazards of Bulk Water Transportation of Industrial
Chemicals — National Academy of Sciences, Washington, D.C., 1974.
B. HEALTH HAZARDS
Industrial Hygiene and Toxicology — F.A. Patty, 2nd edition, Vol. II, Inter-
science, New York, 1963.
Toxicity and Metabolism of Industrial Solvents — E. Browning, Elsevier, New
York, 1965.
Practical Toxicology of Plastics — R. Lefaux, CRC Press, Cleveland, Ohio, 1968.
Industrial Toxicology — L.T. Fairhill, Williams and Wilkins, 2nd edition, Balti-
more, Maryland, 1957.
Toxicology of Drugs and Chemicals — W.B. Deichmann and H.W. Girarde,
Academic Press, New York, 1969.
Clinical Toxicology of Commercial Products — M.N. Gleason, et al., 3rd edition,
Williams and Wilkins, Baltimore, Maryland, 1969.
Handbook of Toxicology: Acute Toxicities of Solids, Liquids and Gases to
Laboratory Animals — W.S. Spector, Saunders, Philadelphia, Pa., 1956.
Occupational Diseases: A Guide to Their Recognition — U.S. Department of
Health, Education, and Welfare, Public Health Service Publication No. 1097. Superintendent
of Documents, Washington, D.C., 1964.
First Aid Textbook - American National Red Cross, Washington, D.C., 1972.
Electrical Safety Practice: Odor Warning for Safety - Monograph 113 Instrument
Society of America (ISA), Pittsburgh, Pa., 1972.
Toxic Substances- Annual List 1973- H.E. Christensen, U.S. Department of
Health, Education, and Welfare, Superintendent of Documents, Washington, D.C., 1973.
81
-------
Encyclopedia of Occupational Health and Safety, Two Volumes, International
Labour Organization, Geneva, 1972.
Fawcett, H.H., Toxicity vs. Hazard, pages 279-289, and Foulger, J.H., Effect of
Toxic Agents, pages 250-278, in Fawcett and Wood, Safety and Accident Prevention in
Chemical Operations, Interscience, Wiley, New York, 1965.
Murphy, Sheldon C., The Toxicity of Pesticides and Their Metabolites, pages
313-335, in Degradation of Synthetic Organic Molecules in the Biosphere— Natural,
Pesticidal, and Various Other Man-Made Compounds, Proceedings of a Conference, San
Francisco, California, June 12-13, 1971, Committee on Agriculture and the Environment,
ISBN 0-309-02046-8, National Academy of Sciences, 2101 Constitution Avenue, N.W.,
Washington, D.C. 20418, 1972.
C. FIRE HAZARDS
The Fire and Explosion Hazards of Commercial Oils — W. Vlachos and C.A.
Vlachos, Vlachos and Co., Philadelphia, Pa., 1921.
1972 Annual Book of ASTM Standards — American Society for Testing and
Materials, Philadelphia, Pa., 1972.
Fire Protection Guide on Hazardous Materials — 5th edition, Nos. 325A, 325M, 49,
491M, and 704M, National Fire Protection Association (NFPA), Boston, Mass., 1972.
Fire Protection Handbook — G.H. Tryon (ed.), 13th edition, National Fire Protec-
tion Association (NFPA), Boston, Mass., 1969.
Handbook of Industrial Loss Prevention — 2nd edition, Factory Mutual Engineering
Corp., McGraw-Hill, New York, 1967.
D. WATER POLLUTION
Water Quality Criteria Data Book - Vol. 1 - Organic Chemicals (1970) and Vol.
2- Inorganic Chemicals (1971), Vol. 5- Effect of Chemicals on Aquatic Life (1974),
United States Environmental Protection Agency, Superintendent of Documents, Washing-
ton, D.C.
Engineering Management of Water Quality - P.H. McGauhey, McGraw-Hill, New
York, 1968.
The BOD of Textile Chemicals - Proceedings of the American Association of
Textile Chemists and Colorisis, American Dyestuff Reporter, August 29, 1966, p. 39.
Biodegradable Surfactants for the Textile Industry - American Dyestuff Reporter,
January 30, 1967.
82
-------
Water Quality Criteria - J.E. McKee and M.W. Wolf, 2nd edition, California State
Water Quality Control Board, Sacramento, California, 1963.
Water Quality Criteria — National Technical Advisory Committee, Federal Water
Pollution Control Administration, Washington, D.C., 1968.
OHM-TADS (EPA) - The Oil and Hazardous Materials Technical Assistance Data
System (OHM-TADS) has been developed by the Environmental Protection Agency (EPA)
to provide information on physical and chemical properties, hazards, pollution character-
istics, and shipping information for over 800 hazardous materials. OHM-TADS consists of a
computerized data base which can be accessed from terminals at the 10 EPA Regional
Offices and from EPA Headquarters in Washington, D.C. The system can provide either
information on specifically requested properties for a material, or it can print all the
information in its files for that material.
Water Quality Characteristics of Hazardous Materials, 4 Volumes, — R.W. Hann,
Jr. and Paul A. Jensen, Environmental Engineering Division, Civil Engineering Department,
Texas A&M University, College Station, Texas, 1974.
83
-------
BIBLIOGRAPHY FOR ANIMAL ORGAN EXTRACTS AND BIOLOGICALS
ANIMAL ORGAN EXTRACTS
Standen, A. (editor), Kirk-Othmer Encyclopedia of Chemical Technology, 2nd Edit.,
Vol. 11 (1966) pp. 838-845.
Webb, F.C., Biochemical Engineering, D. Van Nostrand Co., London (1964), pp.
539-540.
BIOLOGICALS
Standen, A. (editor), Kirk-Othmer Encyclopedia of Chemical Technology, 2nd Edit.,
Vol. Ill (1966)pp. 576-601.
Webb, F.C., Biochemical Engineering, D. Van Nostrand Co., London (1964) pp.
449-450.
84
-------
DATA SOURCES FOR SECTION 3.2
BIBLIOGRAPHY FOR ANTIBIOTIC MANUFACTURE
PENICILLIN
Brunner, R., G. Machek, E. Brandl and A. Schmid, Die Antibiotica Band I Die
Grossen Antibiotica Verlag Hans Carl, Nurnberg (1962) pp. 285-376.
Elder, Albert L. (editor), "Centrifugal Solvent Extraction" in The History of Penicillin
Production, Chemical Engineering Progress Symposium Series, No. 100, Vol. 66 (1970),
American Institute of Chemical Engineers, Chap. VI.
Prescott, S.C., and C.G. Dunn, Industrial Microbiology, 3rd Edit., McGraw-Hill
(1959), pp. 77-784.
Rehm, Hans-Jurgen, Industrielle Mikrobiologie, Verlag Springer, Berlin (1967) pp.
159-180.
Standen, A. (editor), Kirk-Othmer Encyclopedia of Chemical Technology, 2nd Edit.,
Vol. 14 (1967) pp. 688-707.
Underkofler, L.A., and Richard Hickey, Industrial Fermentations, Vol. II, Chemical
Publishing Co., New York (1954) pp. 226-384.
Webb, F.C., Biochemical Engineering, D. Van Nostrand Co., London (1964) pp.
549-550,645-661.
TETRACYCLINE
Rehm, Hans-Jurgen, Industrielle Mikrobiologie, Verlag Springer, Berlin (1967) pp
215-219.
Forbath, T.P., "Tetracycline: Engineered to Market," Chemical Engineering, (March,
1957) pp. 228-231.
BACITRACIN AND ERYTHROMYCIN
Underkofler, L.A. and Richard Hickey, Industrial Fermentations, Vol. II, Chemical
Publishing Co., New York (1954) pp. 304-308,316-318.
85
-------
BIBLIOGRAPHY FOR BOTANICAL MEDICINALS
ALKALOIDS
Forbath, T.O., "Liquid Extraction Commerciallizes Reserpine" Chemical Engineering
(April, 1957) pp. 230-233.
Manske, R.H.F., The Alkaloids, Vol. I, Chap. I "Sources of Alkaloids and their
Isolation."
Nobler, Carl L., Chemistry of Organic Compounds, 2nd Edit., W.B. Saunders, Co.
(1957) pp. 648-655.
STEROIDS
Nobler, Carl L., Chemistry of Organic Compounds, 2nd Edit., W.B. Saunders, Co.
(1957) pp. 868-872.
Krieg, Margaret B., Green Medicine, Rand McNally (1964) pp. 269-291.
Poulos, Arthur; J.W. Greiner and G.A. Fevig. "Separation of Sterols by Countercurrent
Crystallization," Industrial and Engineering Chemistry, Vol. 53, No. 12 (December 1961)
pp. 949-962.
Underkofler, L.A., and Richard Hickey, Industrial Fermentations, Vol. II, Chemical
Publishing Co., New York (1954) pp. 398-410.
86
-------
4.0 TREATMENT AND DISPOSAL TECHNOLOGIES
4.1 BACKGROUND
Approximately 244,000 metric tons of land-destined process wastes (dry weight basis)
are generated annually by the pharmaceutical industry.* The amount of hazardous wastes
generated is about 25 percent of the total waste, or 61,000 metric tons per year. The waste
generation rate is expected to grow to nearly 400,000 metric tons of total wastes per year
and to 100,000 metric tons of hazardous wastes per year by 1983.
4.2 DESCRIPTION OF PRESENT TREATMENT AND DISPOSAL TECHNOLOGIES
Approximately 85 percent of current total wastes generated and 60 percent of current
hazardous wastes generated are estimated to be both treated and then disposed of by
contractors. Of the current total wastes generated, ADL estimates that 60 percent, or
150,000 metric tons, are disposed of on land. About 9 percent, or 5600 metric tons, of
current hazardous wastes generated are disposed of on land. These percentages reflect the
extensive use of incineration by the pharmaceutical industry both on-site and by contractors
off-site. Where possible, materials are recovered for reuse. Secure chemical landfills and
encapsulation techniques are now being used — and will most probably be in the future —
for the disposal of heavy metal wastes which are too dilute or contaminated for recovery,
and general process wastes of a non-hazardous nature.
The current process waste treatment and disposal methods are briefly described in
Section 4.2.1; for each hazardous waste identified in Chapters, current treatment and
disposal practices are discussed in Sections 4.2.2 to 4.2.6. Section 4.2.7 describes the
treatment and disposal methods discussed in the sections on hazardous waste treatment and
disposal.
4.2.1 Present Treatment/Disposal Technologies for General Process Wastes
(Hazardous and Non-hazardous)
4.2.1.1 Research and Development
Numerous large pharmaceutical companies have research and development operations.
In fact, there are currently 25,000 researchers within the industry.
The wastes from this industry section include:
• waste solvents and still bottoms, and
• test animals.
*See Table 3.2.1.4 for summary of total process wastes and potentially hazardous wastes for the
pharmaceutical industry in 1973.
87
-------
Waste solvents and still bottoms (1500 metric tons annually) are either disposed of by
contract incineration, or are company-incinerated, if the research facility is located near
pharmaceutical manufacturing operations with liquid incineration capability.
Test animals are either rendered or incinerated. Large animals are rendered with the
bones converted to bonemeal. Small animals are usually incinerated and the inert ash is sent
to a landfill. Often these small animals are either autoclaved or frozen, if the animals are not
to be incinerated immediately.
4.2.1.2 Production of Active Ingredients (SIC 2831 and 2833)
4.2.1.2.1 Organic Medicinal Chemicals
Pharmaceutical companies manufactured about 75 million pounds of organic medicinal
chemicals in 1973.* The wastes from these operations include:
• waste solvents, halogenated and non-halogenated;
• organic chemical residues;
• biological sludge (from organic chemical wastewater treatment);
• heavy metals, and
• high inert content wastes such as filter cakes.
With the exception of the biological sludge and part of the high inert content wastes,
they are all hazardous wastes. The present methods of hazardous waste treatment and
disposal are discussed in more detail in Sections 4.2.2 through 4.2.6.
The pharmaceutical industry recovers a large amount (95 percent or more) of its
process solvents for reuse. Those solvents that are considered wastes come from solvent-
recovery operations. Essentially all of these waste solvents are incinerated, either on-site or
by contractors off-site. Organic chemical residues are usually incinerated, although some
operations are sending them to landfills off-site.
ADL surveyed about 25 to 30 percent of the pharmaceutical companies' production
capacity of organic chemicals for this study. Of those visited, half had on-site biological
treatment of waste water; 90 percent disposed of the resulting sludge in off-site landfills.
Heavy metals are used as catalysts, oxidants, and product ingredients in the production
of organic medicinal chemicals. A limited amount is used within the pharmaceutical
industry (see Section 3.2.1.2.1). The locations using heavy metals are also limited. The heavy
metal wastes are handled in various ways, including recovery off-site and encapsulation and
*See Section 3.2.1.2.
88
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landfill in a separate section of a landfill. These methods are discussed further in Section
4.2.5.
The properties of the high inert content wastes vary greatly. ADL estimates that as
much as 30 percent of those materials are potentially hazardous because of flammability,
corrosiveness, or toxicity. The remaining 70 percent are innocuous materials, such as filter
aid and water or charcoal and water, which are usually landfilled. Of the 30 percent that are
potentially hazardous some are considered potentially hazardous from the standpoint of
flammability because of the presence of solvent. These can be rendered non-hazardous by
incineration. About 25 companies incinerate this material. The remainder of the potentially
hazardous waste must be landfilled with special precautions because they contain material
such as heavy metals. These cannot be incinerated.
4.2.1.2.2 Inorganic Medicinal Chemicals
Since most inorganic medicinal-chemical active ingredients are purchased from
sources outside the pharmaceutical industry, there is little waste produced in this industry
section. Preparations such as stomach antacids are, however, generally produced within the
pharmaceutical industry. While the majority of the process waste leaves with the water
effluent, there may infrequently be reject materials, such as aluminum hydroxide or
magnesium hydroxide. These wastes may be landfilled.
The only hazardous waste stream we found in this industry segment was a waste which
contained about 0.2 percent selenium. The waste, about 160,000 kg per year, is in its most
insoluble form, the sulfide, when it is disposed of by a contractor in a state-approved secure
chemical landfill.
4.2.1.2.3 Fermentation Products
When active ingredients such as antibiotics are produced by fermentation, three types
of wastes that are destined for land disposal are also produced.* They are:
• Mycelia;
• Biological sludge from spent broth treatment;
• Solvent concentrate (hazardous waste, see section 3.2.1.2.3).
Because there are few companies involved in fermentation and most of the operations
are large scale, ADL was able to study about 65 percent of the U.S. fermentation
production capacity. The volumes of waste from such operations represent a significant
problem to the industry.
h Figure 3.2.1.2.3 shows the waste generation from a typical fermentation product - penicillin.
89
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Of the estimated 75,000 metric tons of mycelia (on a dry basis) produced by
fermentation operations each year, ADL estimates that 85 to 90 percent of the waste is
land-disposed at some off-site location. Of the remainder, some portions are incinerated or
used as soil builders. In the past, ocean dumping was used for mycelia disposal, until 1972
EPA regulations on ocean dumping halted this practice temporarily by invoking stricter
requirements on analysis of wastes prior to permit renewals. A typical large operation has on
the order of 25,000 to 45,000 metric tons of mycelia to dispose of each year. Since this
material is wet (generally 25 to 35 percent solids after dewatering), it must be disposed of
immediately to eliminate odor problems.
Many disposal methods have been investigated. When mixed with 1 percent lime, for
example, mycelia can be used as a soil builder. It can also be incinerated, but the water
content is too high for the operation to be cost-effective. Although this waste is not
considered hazardous, it is indeed a problem for the industry.
Waste broth solids are high-volume materials which can either be disposed of as a waste
or can be changed to a useful by-product. About 72,000 metric tons are produced annually
by fermentation operations. Until stricter effluent restrictions were placed on fermentation
operations, the spent broth was usually treated biologically, producing a sludge that was
landfilled. Approximately 0.5 kg of biological sludge is produced for each kg of waste broth
solids. Since the spent broth contains a significant amount of food value, it can be
concentrated by evaporation and sold as a molasses substitute in animal feeds. Still some
operations handle the broth as a waste either because the capital investment for the
equipment is too great, or because there is no market for the concentrate. None of those
operations producing the broth concentrate are making a profit, just breaking even at best.
On the other hand, they do not have the significant cost of biologically treating the high
BOD waste. Occasionally the waste broth is incinerated, even though incineration is
expensive because of the relatively low-Btu content of the waste broth.
The third type of waste, the solvent concentrate, which is a waste product of solvent
recovery operations, contains as much as 50 percent by weight of organic solids. About 50
million pounds of the concentrate is produced annually by fermentation operations within
the United States. Sixty-five percent of the pharmaceutical industry fermentation produc-
tion capacity was surveyed. The waste solvent concentrate at all these locations was
incinerated either on-site or by contractors off-site. Because of the similar nature of the other
plants in this industry, we estimate that all of this waste is currently being incinerated,
either on-site or by contractors off-site. Because this waste is flammable, it is considered
hazardous. Disposal is discussed further in Section 4.2.2.2.3.
4.2.1.2.4 Botanicals
Medicinal active ingredients, such as alkaloids and steroids, are obtained from plant
material. The wastes potentially destined for land disposal are listed below, the last two
being hazardous:
90
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• Moisture-laden plant material,
• Waste solvent (50 percent solids and 30 percent water), and
• Waste chlorinated hydrocarbons.
A typical alkaloid operation* produces 1820 kg per day of wet waste plant material
and operates 250 days per year. This totals to 454 metric tons per year of waste plant
material. The waste is steamed to remove residual solvent and is then sent to sanitary landfill
off-site.
Three types of solvents are used in the extraction process to produce alkaloids. The one
used in the initial extract ends up with water, plant extract, and organic acid salts
after solvent-recovery operations. This waste solvent is either incinerated on-site or by
contractors off-site. A second water-immiscible, chlorinated solvent, is used to extract the
alkaloid from the first solvent. More of the chlorinated solvent can be recovered than the
first solvent which contains most of the water-soluble organic material after extraction. But,
since this second solvent is chlorinated, problems can develop if it is incinerated without the
proper precautions. The amount of chlorinated solvent is only 5 cubic meters (1,250
gallons) per year for the typical plant, five percent of the total solvent. This amount is small
enough to drum for contractor incineration. We estimate that 60 percent of each of the two
waste solvents are incinerated on-site and the remainder off-site by contractors. A third waste
solvent is non-halogenated.
4.2.1.2.5 Drugs from Animal Sources
Medicinal products such as insulin or heparin are obtained from animal sources. The
wastes from these operations that are destined for land disposal include:
• rendered organs or animal tissue;
• fats and oils;
• filter cake, containing precipitated protein; and
• aqueous solvent (hazardous waste, see Section 3.2.1.2.5).
The typical extraction operation** will dispose of 839 metric tons of organs or animal tissue
annually in the production of 284 kg of active ingredient. Two methods of disposal are used
interchangeably in most operations. When a market exists, the waste product is sold as a
protein-source feed for animals; otherwise it is disposed of in a sanitary landfill. The fats (40
metric tons per year) are recovered for sale to soap manufacturers. The filter cake (25.5
metric tons per year), which contains precipitated protein, is landfilled or incinerated if the
operation is near other pharmaceutical operations with incineration capability.
'Figure 3.2.1.2.4.1 presents the flow scheme of waste generation for a typical alkaloid operation.
* Figure 3.2.1.2.5 describes the waste generation in a typical operation extracting glandular materials.
91
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The hazardous waste from the operation in which medicinals are obtained from animal
glands is a waste solvent emanating from the solvent-recovery system. A typical operation
produces 91 metric tons (25,000 gallons) of waste solvent annually, a generation rate of 350
liters per kilogram of product. These solvents, which contain 50 percent water and 25
percent organic solids, are incinerated either on-site or by a contractor off-site.
4.2.1.2.6 Biological Products
Some pharmaceutical companies manufacture biological products such as blood prod-
ucts, vaccines, serums and toxoids. The wastes from these operations include:
• Aqueous solvent waste;
• Miscellaneous incineratable wastes; and
• Filter material.
ADL estimates that SIC 2831 has 500 metric tons of hazardous waste. Most of this amount
is considered hazardous because of its flammability. All hazardous wastes are incinerated
either on-site or by contractor off-site. The filter material contains only traces of protein
and can be landfilled.
4.2.1.3 Formulation and Packaging (SIC 2834)
The wastes from the formulation and packaging segment of the pharmaceutical
industry are returned goods and reject material.* The total returned goods and reject
material from this segment annually are indicated below:
• Glass, paper, water, etc. 10,000 metric tons
• Active ingredient 500 metric tons
Normal trash waste from the formulation and packaging segment of the industry is handled
in much the same way as in other industries. Paper, cartons, and the like, not identifiable as
the company's own can be recycled through salvage dealers, while materials bearing the
company's name are either shredded or incinerated on-site.
Returned goods are handled specifically by the formulating and packaging operations
of a company. "Controlled drugs," such as narcotics, must be destroyed in the presence of
Drug Enforcement Agency (DEA) personnel, according to the regulation which is presented
on the next page. Other Pharmaceuticals are handled in a method detailed by the specific
company and Pharmaceuticals recalled by the FDA may be required to be destroyed under
FDA observation. Generally, non-salvageable goods are crushed on-site and then sent to
landfill. Smaller percentages are either incinerated or are slurried with water which is sent to
an activated sludge treatment facility.
*Section 3.2.1.3 discusses waste generation in this industry segment.
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federal Regulations; . Disposal of Controlled Pharmaceuticals'
§ 1307.15 Incidental manufacture of
controlled substances.
Any registered manufacturer who, In-
cidentally but necessarily, manufactures
a controlled substance as a result of the
manufacture of a controlled substance
or basic class of controlled substance for
which he is registered and has been is-
sued an individual manufacturing quota
pursuant to Part 1303 of this chapter (if
such substance or class is listed in sched-
ule I or II) shall be exempt from the
requirement of registration pursuant to
Part 1301 of this chapter and, if such
incidentally manufactured substance is
listed in schedule I or II, shall be exempt
from the requirement of an individual
manufacturing quota pursuant to Part
1303 of this chapter, if such substances
are disposed of in accordance with
§ 1307.21.
DISPOSAL OF CONTROLLED SUBSTANCES
§ 1307.21 Procedure for disposing of
controlled substances.
(a) Any person in possession of any
controlled substance and desiring or re-
quired to dispose of such substance may
request the Regional Administrator of
the Administration in the region in
which the person is located for author-
ity and instructions to dispose of such
substance. The request should be made
as follows:
(1) If the person is a registrant re-
quired to make reports pursuant to Part
1304 of this chapter, he shall list the con-
trolled substance or substances which
he desires to dispose of on the "b" subpart
Oi the report normally filed by him, and
submit three copies of that subpart to
the Regional Administrator of the Ad-
ministration in his region;
(2) If the person is a registrant not
required to make reports pursuant to
Part 1304 of this chapter, he shall list the
controlled substance or substances which
he desires to dispose of on DEA Form
41. and submit three copies of that form
to the Regional Administrator in his reg-
ion; and
(3) If the person is not a registrant,
he shall submit to the Regional Admin-
istrator a letter stating:
(1) The name and address of the
person;
(il) The name and quantity of each
controlled substance to be disposed of;
till) How the applicant obtained the
substance, If known; and
(iv) The name, address, and registra-
tion number, if known, of the person
who possessed the controlled substances
prior to the applicant, if known.
(b) The Regional Administrator shall
authorize and instruct the applicant to
dispose of the controlled substance in
one of the following manners:
(1) By transfer to person registered
under the Act and authorized to possess
the substance;
(2) By delivery to an agent of the
Administration or to the nearest office
of the Administration;
(3) By destruction in the presence of
an agent of the Administration or other
authorized person; or
(4) By such other means as the Re-
gional Administrator may determine to
assure that the substance does not be-
come available to unauthorized persons.
(c) In the event that a registrant
is required regularly to dispose of con-
trolled substances, the Regional Admin-
istrator may authorize the registrant to
dispose of such substances, in accord-
ance with paragraph (b) of this section,
without prior approval of the Adminis-
tration in each instance, on the condi-
tion that the registrant keep records of
such disposals and file periodic reports
with the Regional Administrator sum-
marizing the disposals made by the regis-
trant. In granting such authority, the
Regional Administrator may place such
conditions as he deems proper on the
disposal of controlled substances, includ-
ing the method of disposal and the fre-
quency and detail of reports.
(d) This section shall not be construed
as affecting or altering in any way the
disposal of controlled substances through
procedures provided in laws and regula-
tions adopted by any State.
[36 F.B. 7801, Apr. 24. 1971, as amended at
37 FJt. 16922, Aug. 8, 1972]
§ 1307.22 Disposal of controlled sub-
stances by the Administration.
Any controlled substance delivered to
the Administration under § 1307.21 or
forfeited pursuant to section 511 of the
Act (21 U.S.C. 881) may be delivered to
any department, bureau, or other agency
of the United States or of any State upon
proper application addressed to the Ad-
ministrator, Drug Enforcement Adminis-
tration, Department of Justice, Washing-
ton, D.C. 28083. The application shall
show the name, address, and official title
of the person or agency to whom the con-
trolled drugs are to be delivered, includ-
ing the name and quantity of the sub-
stances desired and the purpose for
which intended. The delivery of such
controlled drugs shall be ordered by the
Administrator, if, in his opinion, there
exists a medical or scientific need there-
for.
'''Source: Code of Federal Regulations, No. 21, Food and Drugs, Part 1300 to end.
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Reject material from formulation is very limited. Because of the value of the raw
materials involved, potentially faulty batches of Pharmaceuticals are reformulated to meet
specifications. When a material cannot be upgraded, the "bad batches" are either in-
activated, by neutralization, for example, and sent through biological treatment, or are
landfilled or incinerated, depending upon the nature of the material.
(For the purpose of this study, a portion of the returned goods and reject material have
been segregated as potentially hazardous wastes.) Section 4.2.4 provides a more detailed
discussion on present treatment and disposal technologies of the potentially hazardous
wastes resulting from the returned goods and reject material, Section 4.5.5 describes Level I,
II, and III technologies for treating and disposing of returned goods and reject material from
formulation.
4.2.1.4 Marketing and Distribution
Wastes from marketing and distribution merely represent large volumes of paper, wood,
and cardboard. Since there are no process wastes from this segment of the industry and
returned goods are normally sent back to the formulation and packaging facilities, this
segment of the industry has not been studied further,
4.2.1.5 Pharmaceutical Operations in Puerto Rico,
An organization called Fomento was set up by the Puerto Rican government to
encourage industry to settle in Puerto Rico and to provide assistance to those companies in
the areas of siting, employment, and services, such as electricity, water, and regional
wastewater treatment. Industries investigating the attractive tax-break offers in the mid-'60's
were also told that, should they settle in an area like Barceloneta (about 40 miles west of
San Juan) adequate regional wastewater treatment facilities would be provided. The planned
completion date has slipped a little. It was planned to be on stream in 1974, but it will
probably not be in operation until mid-1975. Therefore, pharmaceutical companies involved
have had to ocean-dump their process wastewater, because they are not permitted to send it
to the nearby Manati River.
Numerous U.S. and European pharmaceutical firms were encouraged to construct
operations in Puerto Rico. Since the early '60's, the number of these installations has been
growing rapidly. At present, we estimate that as many as 42 plants have been constructed
and are now in operation. These operations have severe impacts on the pollution control
problems of the area.
Solid waste disposal sites are provided by the local municipal governments in Puerto
Rico (see Figure 4.2.1.5 for outline of current facilities). In the past these disposal sites have
simply been dumps with open burning of trash. The Puerto Rican Environmental Quality
Board (EQB) is pressuring the municipalities to upgrade the disposal sites and to provide
sanitary landfills. The EQB does not consider two of the sites - the Manati dump and the
94
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o Sanitary Landfill
o Dumps Converted to
+ Sanitary Landfill
Source: Environmental Quality Board of Puerto Rico.
o Approved Lands
n Open Dump with Burning
• Lands Under Study
FIGURE 4.2.1.5 SOLID WASTE DISPOSAL FACILITIES IN PUERTO RICOt
-------
Barceloneta landfill — to be satisfactory for disposal of chemical wastes. But the EQB
considers a third site — the landfill at Mayagiiez — suitable for chemical wastes. In addition
a new site has been recommended between Barceloneta and Arecibo in the Cana Tiburones
area which the EQB feels will be satisfactory for chemical waste disposal. We visited the
Manati, Barceloneta, and Mayagiiez disposal sites. The Manati dump clearly is not satis-
factory for chemical disposal and is currently no longer being so used. The Barceloneta
landfill is currently being used for chemical waste disposal and, on casual examination, it
appears that the site could be upgraded to serve as .a satisfactory site for chemical waste
disposal. However, studies by the EQB indicate that subsurface drainage to the nearby
Manati River would be excessive, and hence the EQB is attempting to stop the municipality
from accepting chemical wastes. There may be a problem for several months as the
pharmaceutical companies were assured of municipally operated solid waste and liquid
waste facilities. The Mayagiiez landfill appears to be well located, well run, and should be
satisfactory for chemical waste disposal. There is at least one company available to recover
and incinerate solvents on a contract basis in the Barceloneta area.
The Commonwealth of Puerto Rico appears presently to be making good progress in
improving the handling of solid wastes, but regulations and facilities have lagged behind U.S.
mainland practices. An excerpt from a development plan for a proposed Solid Waste
Management Authority is presented on the following page.
4.2.2 Present Treatment/Disposal Technologies for Waste Solvents
Small companies and R&D installations in isolated areas are currently disposing of
some solvents by landfill, but the trend is to incinerate waste solvents. Depending upon local
conditions, outside contractors may be used for waste incineration by both large and small
companies, or large companies may choose to install their own incinerators. Table 4.2.2
summarizes the disposal methods used for waste solvents in the pharmaceutical industry.
Incineration is an environmentally adequate means of waste solvent disposal.* Where
quantities of halogenated solvent are incinerated the use of scrubbing to minimize the air
pollution risk should be investigated.
4.2.2.1 Research and Development
Since there is no measurable unit of production for the research and development
operations, the amount of wastes has been estimated on the basis of the number of
researchers. Although the degree of recovery is not well known for this segment of the
industry, solvents are commonly distilled for reuse. The 25,000 members of the R&D
section of the industry produce approximately 1500 metric tons of mixed waste solvents
each year. This number is based upon an extrapolation using data supplied to ADL by a
number of comoanies.
*Tables 4.5.1-A and 4.5.1-B describe the various levels of treatment and disposal technologies used for
waste-solvent disposal in the pharmaceutical industry.
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A Plan for Hazardous Waste Disposal in Puerto Rico1"
The proposed Authority should have the sole responsi-
bility in Puerto Rico for processing, recovery, disposing,
and storing of hazardous and toxic wastes, in order to pro-
vide uniform and reliable control. The proposed Authority
should serve as a servicing agent for all producers of
hazardous and toxic wastes. Sites and handling techniques
conforming to Puerto Rico Environmental Quality Board
and Federal standards should be established. Special user
fees should be charged producers of these wastes, based
upon difficulty and expense of providing this service. The
service should not only be self-liquidating financially, but
produce a replacement fund for facilities and equipment.
Program Recommendations
Currently, Federal standards governing hazardous and
toxic wastes are still pending, and patterning a program for
Puerto Rico according to these standards appears specu-
lative. Nevertheless, enough is now known about types
and classes of these wastes to begin forming directions for
Puerto Rico. Therefore, the following steps should be
taken to initiate an operating capability for handling
hazardous and toxic wastes by the proposed Authority.
1. Conduct an island-wide survey to determine the
types, amounts, and locations of hazardous and toxic
waste production. Identification of present storage
sites should be made as well.
2. Investigate and evaluate existing Commonwealth
of Puerto Rico and Federal regulations applicable to
hazardous and toxic wastes.
3. Develop a plan which can bo implemented by the
Authority for handling hazardous and toxic wastes in
Puerto Rico. The plan should consider such aspects as:
(a) Land disposal methods
(b) Disposal facility locations
(c) Topographical and geological conditions
(d) Drainage control
(e) Protection of water supplies
(f) Handling hazards and protection
(g) Transportation and unloading
(h) Security
(i) Personnel training and safety
(j) Records and monitoring
(k) Technologies of processing and storing
(I) Prevention of accidental catalytic reactions
(m) Abandonment of sites
4. An adjunct to this plan should be a locational
plan showing desirable locations for new industries
which may have hazardous and toxic substances as a
manufacturing by-product. These locations should be
amenable to the environment. Industries producing
hazardous and toxic wastes should be prohibited from
any location not specified for this purpose. The indus-
trial location plan should be developed and implement-
ed in conjunction with the Environmental Quality
Board, Fomento, Department of Natural Resources,
the Planning Board, and the Department of Health.
5. All plans developed for hazardous and toxic
wastes must comply with regulations of the Environ-
mental Quality Board, the Environmental Protection
Agency and other applicable Commonwealth of Puerto
Rico standards.
'''Source: Proposed Solid Waste Management,Environmental Quality Board, Puerto Rico.
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TABLE 4.2.2
WASTE SOLVENT DISPOSAL METHODS1
Industry Segment
Total
Hazardous
Waste
(metric tons
per year)
Current Disposal Methods
On-Site
Off-Site
Incineration
Incineration
At Nearby
Company-
Owned
Facility
Other*
Incineration by
Contractor
R&D 1,500 - 450
Active Ingredient Production
Organic Medicinal Chemicals
Halogenated solvent 3,400 800 -
Non-halogenated solvent 23,800 9,300
Inorganic Medicinal Chemicals 0 — -
Fermentation products 12,000 5,000 —
Botanicals
Aqueous solvent 1,000 400 -
Halogenated solvent 50 5 —
Non-halogenated solvent 120 50 —
Drugs from Animal Sources 800 260 —
Biologicals 250 100 -
Formulation & Packaging 0 — —
Total 42,920 15,915 450
1,050
40
40
2,600
14,500
7,000
600
45
70
500
150
26,515
"Treatment in on-site biological wastewater treatment facility or in municipal system.
Source: Interviews and Arthur D. Little, Inc., estimates.
R&D installations surveyed were either sending waste solvents to contractors for
incineration off-site (about 70 percent is estimated to be disposed of in this manner), or were
incinerating them in nearby company-owned facilities. The Laboratory Waste Disposal
Manual published by the Manufacturing Chemists' Association, Inc., suggests incineration
for even very small amounts of solvents. Incineration of these waste solvents is an environ-
mentally adequate disposal technique.
4.2.2.2 Production of Active Ingredients (SIC 2831 and 2833)
When the pharmaceutical industry was much smaller, most pharmaceutical companies
discarded waste solvents and still bottoms in dumps or landfills. With the increased
production of active ingredients, greater difficulty in finding suitable landfills, and more
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stringent state and local government controls, incineration is being increasingly employed
for disposal of waste solvents.
4.2.2.2.1 Organic Medicinal Chemicals
We estimate that all waste solvents from solvent-recovery operations used in the
production of organic medicinal chemicals are disposed of by incineration. Approximately
half of the larger pharmaceutical companies have some on-site incineration capacity, even
though they may send more troublesome wastes, such as halogenated solvents, to off-site
contractors. Others continue to utilize outside contractors; however, some additional
pharmaceutical companies are currently planning on-site incineration. For this study, ADL
surveyed about 25 to 30 percent of the production capacity of organic medicinal chemicals
of the pharmaceutical companies. Since the production of active ingredients is centered in
the larger pharmaceutical companies, such disposal methods as found would also extend to
the part of the industry not interviewed.
There are about 10,100 metric tons per year of on-site incineration capacity. This
figure is predicated on the basis of 27,200 metric tons of solvent for the pharmaceutical
companies involved in organic medicinal chemical production. Not all of the in-place
incinerator capacity can adequately handle air and water pollution control for all waste
solvents. Often, because of stack emissions or potential equipment corrosion, halogenated
solvents are not handled in on-site incinerators. Since liquid incinerators are relatively new
to the pharmaceutical industry, potential problem wastes are often sent to outside contrac-
tors for incineration.
Off-site incineration techniques range from excellent to poor. There are numerous
contract disposal and recycling operations across the country that are well designed and
operated.
4.2.2.2.2 Inorganic Medicinal Chemicals
There are no known significant amounts of waste solvents or organics from this industry
section.*
4.2.2.2.3 Fermentation Products
The disposal of solvents used in fermentation operations is in the form of a solvent
concentrate from the solvent-recovery operations. This material, which may contain as
much as 50 percent of organic solids, is hazardous, mainly because of its flammability.
'Section 3.2.1.2.2 discusses wastes from this industry segment.
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Approximately 12,000 metric tons of waste solvent concentrate from fermentation
operations is disposed of annually. We estimate that all of the concentrate is incinerated
either on-site or by contractors off-site. The trend is toward on-site incineration. Some
plants which are currently sending these materials out to contractors for disposal have
incineration units being designed, on order, or under construction. This incineration is very
straightforward, as is evidenced by the number of on-site units.
The study encompassed approximately 65 percent of the U.S. fermentation capacity.
On the basis of the estimated 12,000 metric tons per year of waste solvent concentrate,
there is approximately 5000 metric tons per year of on-site incineration capacity. Most of
the in-place incinerators have adequate air and water pollution control equipment. This
essentially means particulate control only. However, since most fermentation operations are
also associated with other active ingredient manufacturing operations, there is generally
co-incineration of the wastes which may dictate additional pollution control requirements.
Approximately 7000 metric tons (1.5 million gallons) per year is sent to outside contractors
for incineration. A typical charge for this material would be $0.30 per gallon.
4.2.2.2.4 Botanicals
Nearly 1200 metric tons (310,000 gallons) of waste solvent are estimated to be
disposed of annually by operations producing botanicals. Three types of solvent wastes are
produced in extracting alkaloids from plant material. The first solvent waste is a non-
halogenated solvent concentrate containing water plant extract and organic acid salts. The
second solvent waste is a concentrate of the water-immiscible chlorinated solvent used to
extract the alkaloid from the first solvent. The third, a non-halogenatedlsolvent waste, is
generated in the purification of the crude alkaloid. The first ends up both with water, plant
extract, and organic acid salts and as a more concentrated non-halogenated solvent stream.
The second is used to extract the alkaloid from the first solvent. Water-immiscible chlori-
nated solvents are used for the second solvent. The chlorinated solvent is five percent of the
total. These waste solvents are either incinerated on-site or by contractors off-site. We
estimate that 60 percent are incinerated by contractors off-site.
4.2.2.2.5 Drugs from Animal Sources
The waste solvent from the operation of obtaining medicinals from animal glands is an
aqueous solvent containing as much as 50 percent water and 25 percent organic solids. The
800 metric tons (220,000 gallons) of waste solvent are generally incinerated or, when the
amount is small, treatment in a biological wastewater treatment facility provides environ-
mentally adequate disposal.
4.2.2.2.6 Biologicals
Much of the solvent from biological operations is recoverable. An industry total of 250
metric tons (60,000 gallons) must be disposed of from biological operations. It is in-
cinerated on-site or by contractors off-site. We estimate that 60 percent is handled by
contractors off-site.
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4.2.3 Present Treatment/Disposal Technologies for Organic Chemical Residues
In many instances, little is known about the constituents in organic chemical residues.
The recovery operations which produce many of them are used for many various solvents
and products. The residues may contain contaminants that have been removed from the
product, non-reclaimable product, and other materials. Since these residues are so varied,
the trend in the pharmaceutical industry has been to incinerate them. Extensive testing will
be needed if these materials are to continue to be landfilled. Table 4.2.3 shows the total
organic chemical residues and indicates the various methods by which they are disposed.
TABLE 4.2.3
ORGANIC CHEMICAL RESIDUE DISPOSAL METHODSt
Current Disposal Methods
Total Hazardous
On-Site Off-Site
Waste
(metric tons per Incineration by Landfill
Industry Segment year) Incineration Other* Contractor by Contractor
R&D Nil
Active Ingredient Production
Organic medicinal chemicals 13,600. 5,440 1,360 3400 min. 3400 max.
6800 max.
Inorganic medicinal chemicals Nil — — — —
Fermentation products Nil — — — —
Botanicals Nil - — - —
Drugs from animal sources Nil — — — —
Biologicals Nil - - - —
Formulation & Packaging 0 — — ~ ~
Total 13,600 5,440 1,360 3400-6800 < 3,400
*About 10 percent of the residues are disposed of on-site by other methods, such as mixing with plant waste-
water prior to its treatment
^Source: Interviews and Arthur D. Little, Inc. estimates.
4.2.3.1 Research and Development
Organic chemical residues from research and development are disposed of with the
waste solvents. This means that they are either sent for incineration by a contractor, or are
incinerated in company-owned facilities that are associated with the manufacturing opera-
tions.
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4.2.3.2 Production of Active Ingredients
4.2.3.2.1 Organic Medicinal Chemicals
Organic chemical residues from organic medicinal chemical production are generally
incinerated. Approximately 40 percent of the active ingredient producers have on-site
incineration for their residues. This is becoming increasingly true since these residues are
seen as potential problems. Consequently, plant personnel are removing less solvent than the
common previous practice to maintain pumpability for liquid type incineration. Another 25
to 50 percent utilize off-site incineration contractors. Tracing the ultimate disposal of these
materials is difficult. Some are incinerated by the contractor, while others are landfilled in
containers by the contractor. In addition, about another 10 percent utilize other methods of
disposal, such as mixing with plant wastewater prior to its treatment.
4.2.3.2.2 Inorganic Medicinal Chemicals
There are no organic chemical residues from these operations.
4.2.3.2.3 Fermentation Products
The solvent concentrate from fermentation operations is discussed as a waste solvent in
this report (see Section 4.2.2.2.3).
4.2.3.2.4 Botanicals
There are no significant amounts of organic chemical residues from this industry
segment. They are either handled with waste solvents or are sent to biological treatment or
landfill.
4.2.3.2.5 Drugs from Animal Sources
There are no significant amounts of organic chemical residues from this industry
segment. They are either handled with waste solvents or are sent to biological treatment or
landfill.
4.2.3.2.6 Biologjcals
There are no significant amounts of organic chemical residues from this industry
segment. They are either handled with waste solvents or are sent to biological treatment or
landfill.
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4.2.4 Present Treatment/Disposal Technologies for Potentially Hazardous High
Inert Content Wastes (Such as Filter Cakes)
While high inert content wastes may show up in small amounts in the R&D segment of
the industry, by far the bulk occurs in the production of organic medicinal active ingre-
dients. Generally, they are handled in the same manner no matter which type of active
ingredient is being produced. Most are landfilled, but a growing percent is being incinerated
to remove the organic portion. The ash is then landfilled. Table 4.2.4 shows the total high
inert content wastes and indicates the various methods by which they are disposed.
Approximately 75 percent of the solid materials, such as filter cake and filter paper
from organic medicinal chemical production, are disposed of in landfills. Most of these
landfills are either municipal or private commercial facilities located off-site, and they are
generally operated as sanitary landfills. The industry has been careful to avoid bad publicity
that might accompany poor disposal techniques. Another 25 percent of the solids of this
type are incinerated either on-site or off-site.
TABLE 4.2.4
HIGH INERT CONTENT WASTES DISPOSAL METHODS*
Industry Segment
Total
Hazardous
Waste
(metric tons
per year)
Current Disposal Methods
On-Site
Incineration*
Off-Site
Incineration'*
Landfill
R&D
Active Ingredient Production
Organic medicinal chemicals
- Waste containing flammables only
- Waste containing heavy metals or
corrosives
Total
Nil
850
850
1,700
225
225
200
200
425
850*
1,275
oene waste is neutralized, or the heavy meta, is precipitated,«, <,„ place,Mna
secure chemical landfill. Nearly 40 percent is placed untreated ,n a secure chem.cal landf.ll, often
capsulated in drums. The remainder goes to general landfill locations.
Source: Interviews and Arthur D. Little, Inc., estimates.
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4.2.5 Present Treatment/Disposal Technologies for Heavy Metal Wastes
ADL has surveyed pharmaceutical active ingredient manufacturers producing an esti-
mated 20 to 40 percent of the heavy metal wastes. Table 4.2.5 shows the total heavy metal
wastes and indicates the various methods by which they are disposed.
TABLE 4.2.5
HEAVY METAL WASTE DISPOSAL METHODS*
Total Hazardous Current Disposal Methods
WaStC On-Site Off-Site
(metric tons
Industry Segment per year) Recovery Landfill*
R&D Nil - x -
Active Ingredient Production
Organic medicinal chemicals 2,675 — 575 2,100
Inorganic medicinal chemicals 200 — — 200
Total 2,875 - 575 2,300
*Heavy metal is converted to its most insoluble form,and is generally drummed and placed in a secure
chemical landfill.
Source: Interviews and Arthur D. Little, Inc., estimates.
With the exception of recovered R&D wastes and some large amounts of zinc and
chromium wastes that are sent off-site for recovery, the heavy metal wastes are usually too
dilute or contaminated for recovery. The number of facilities using heavy metals within the
pharmaceutical industry is limited. Production appears to be exclusively with the larger
companies. Most non-recovered heavy metal wastes are landfilled. Zinc oxide is a relatively
stable and insoluble form of zinc, and much of the landfilled zinc takes this form.
Arsenic is landfilled in drums with the surrounding soil conditioned with lime to
inhibit its change to a soluble form in case a drum develops a leak. The landfilled selenium
wastes are dilute (an estimated 0.2 percent selenium sulfide). Mercurial wastes, generally as
amalgams, are landfilled. A number of heavy metal wastes are deep-well disposed in
Michigan where state approval can be obtained.
4.2.6 Present Treatment/Disposal Technologies for Returned Goods and Reject Material
from Formulation
Returned goods (as described in Section 3.2.1.3) are handled specifically by the
formulating and packaging operations of a company. Table 4.2.6 shows the total returned
goods and reject material and indicates the various methods by which they are disposed.
104
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TABLE 4.2.6
DISPOSAL METHODS FOR RETURNED GOODS AND REJECT MATERl AL*
Total Hazardous Current Disposal Methods
Waste On-Site Off-Site
(metric tons
Industry Segment per year) Incineration Other* Landfill**
Formulation and Packaging 500 50 100 350
* Material is crushed and slurried with water, and the resulting slurry is sent to a biological wastewater
treatment facility.
** The waste is crushed on-site to form a sludge or cake before it is sent to off-site landfill.
Source: Interviews and Arthur D. Little, Inc., estimates.
Handling the amounts of Pharmaceuticals that have been returned - for instance because
they have reached their expiration date - requires care. Some returned goods can be
salvaged, but of the returned goods that are non-salvageable, somewhere in the range of
60-80 percent are crushed in special equipment on-site to form a sludge or cake, which is
then sent to a landfill off-site. The remainder is either incinerated on site, or crushed and
slurried with water which is sent to an activated sludge treatment facility on-site, while the
glass, metal, rubber, and cardboard are sent to a landfill off-site. Numerous types of crushers
are used. Some of the names include Somat, Wascon, Rodeva, and Cumberland.
The disposal of Pharmaceuticals in landfills raises many questions. Dosage levels in
medicines are generally measured in milligrams; nevertheless, because many of the products
may have biological or physiological effects on the environment and on man, disposal of
these wastes must be carefully controlled. Because of the Drug Enforcement Agency's strict
regulation on the disposal of controlled substances, there is little chance that controlled
materials would be scavengable from any landfilled wastes.
Fearing the possibility of bad publicity from the scavenging of a returned good, each
pharmaceutical firm has extended the care in handling controlled substances (such as
narcotics) to the disposal of non-controlled substances as well. Representatives of the
company witness the destruction of returned goods, whether on-site or off-site, to ensure
that no tablet, vial, capsule, or the like is scavengable. To this extent, the disposal practices
of the industry are excellent. Yet, little is known of the effect of such items on the landfill
and the potential for hazardous quantities to leach into groundwater or streams. In this
study, in an attempt to provide some basis from which to work, we used the toxicity of the
active ingredients to assess the hazard.* However, additional work in this area is advisable.
'Section 3.1.3 discusses the properties of these materials.
105
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4.2.7 General Description of Treatment and Disposal Technologies
Treatment processes should reduce the volume, separate components, detoxify, and
recover as much as possible for reuse. In general, no single process can adequately perform
these functions. Table 4.2.7-A presents those treatment and disposal technologies found
within the pharmaceutical industry, and each is discussed in the subsections which follow.
In order to fully utilize the information obtained in the study,* those processes which
treat liquid effluent streams have been viewed as waste-producing steps rather than as
waste-treatment steps. Table 4.2.7-B presents the processes, their functions, and the types of
wastes treated.
4.2. 7.1 Segregation of Wastes
There is great need to segregate wastes to obtain optimum waste treatment and
disposal. Not only is segregation necessary for recovery, treatment, and disposal, it is also
necessary for safe handling, transport, and treatment. Use of a system of chemical compati-
bility which was developed by the National Academy of Sciences has been proposed for use
as a guide for the compatibility of waste materials.** Usually the same handling techniques
are required for wastes as for the raw materials.
4.2. 7.2 Incineration of HalogenatedandNon-halogenated Solvents
When high-energy content solvents with small amounts of water and solids persist
through normal process-recovery operations, they are often destroyed by thermal oxidation
at high temperatures in liquid injection incinerators. These units typically operate at or
above 1800°F and with sufficient turbulence and time to destroy solvents effectively. If
combustion is controlled, by means of excess air, for example, no air pollution control
devices are needed for solvents containing only carbon, hydrogen, and oxygen. However,
these liquid injection incinerators are being increasingly equipped with air pollution control
systems, because solvents often contain either suspended and dissolved solids or substances
which could react to form noxious gases, such as hydrogen chloride, sulfur oxides, and
nitrogen oxides.
*We had difficulty in tracing all disposal steps, and considerable overlap with the work on the water
effluent guidelines' study being prepared by Roy F. Weston, Inc., occurred.
'Witt, Philip A., Jr. "Disposal of Solid Wastes," Chemical Engineering, October 4, 1971, p. 61.
106
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TABLE 4.2.7-A
FUNCTIONS AND WASTE TYPES OF CURRENTLY USED
HAZARDOUS WASTE TREATMENT AND DISPOSAL PROCESSES
Process
Functions Performed
Types of Waste
Chemical Treatment:
— Oxidation of sludges
Detoxification
Thermal Treatment:
— Incineration of solvents
— Incineration of solids
Volume reduction,
detoxification,
disposal
• Biological Treatment:
— Activated sludge or
other biological
treatment
• Disposal/Storage:
— Land burial
Detoxification
Disposal
— Deep-well injection
Disposal
Inorganic chemical with/without
heavy metal
Organic chemical with/without
heavy metal
Organic chemical without heavy
metal
Biological
Flammable
Explosive
Organic chemical
without heavy metal
Inorganic chemical with/without
heavy metal
Organic chemical with/without
heavy metal
Biological
Flammable
Explosive
Only liquids can be disposed of in
this manner; all those listed for
land disposal, with the excep-
tion of explosives, are disposable
in this manner with proper pre-
cautions.
— Ocean dumping
Disposal
— Engineered storage
Source:
Storage
Inorganic chemical with/without
heavy metal
Organic chemical with/without
heavy metal
Flammable
Explosive
All as in land burial
Colonna, R.A., and McLaren, C., "Appendix D. Hazardous Wastes," Decision-Makers Guide
in Solid Waste Management, Environmental Protection Agency, 1974, p. 146.
107
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Process
TABLE 4.2.7-B
WASTE TREATMENT PROCESSES USED TO SEPARATE
A WASTE1" DESTINED FOR LAND DISPOSAL
Function Resource Recovery
Performed* Types of Waste** Capability
Physical Treatment:
Carbon Sorption
Dialysis
Electrodialysis
Evaporation
Filtration
FI occu I atio n/Settl i ng
Reverse Osmosis
Ammonia Stripping
Chemical Treatment:
Calcination
Ion Exchange
Neutralization
Oxidation
Precipitation
Reduction
Thermal Treatment:
Pyrolysis
Incineration
Biological Treatment:
Activated Sludge
Aerated Lagoon
Waste Stabilization Ponds
Trickling Filter
Disposal/Storage:
Deep-well Injectiont
Se
Se
Se
Se
Se
Se
Se
Se
Se, De
De
De
Se
De
VR.De
De, Di
1,3,4
1,2,3,4
1,2,3,4,6
1,2
1,2,3,4
1,2,3,4
1,2,4,6
1,2,3,4
1,2
1,2,3,4
1,2,3,4
1,2,3,4
1,2,3,4
1,2
3,4,6
3,6,7,8
De
De
De
De
Di
3
3
3
3
1,2,3,4,6,7
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
*Se — segregation
De — detoxification
VR — volume reduction
Di — disposal
** 1. Inorganic chemical without heavy metal
2. Inorganic chemical with heavy metal
3. Organic chemical without heavy metal
4. Organic chemical and heavy metal
5. Radiological1^
6. Biological
7. Flammable
8. Explosive
t A waste is formed either when solids must be filtered out, or when a substance must be precipitated
out because of chemical incompatibility with substances underground.
tt Use and disposal of radiological wastes within the pharmaceutical industry is not discussed in this
report.
Source: Colonna, R.A. and McLaren, C., "Appendix D. Hazardous Wastes," Decision-Makers Guide in
Solid Waste Management, Environmental Protection Agency, 1974, p. 146.
108
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The most common air pollution control device for removing acidic gases is a wet
scrubber like the venturi. A significant operating cost for these incinerators may be incurred
in providing the caustic scrubbing liquors for the venturi such as lime, sodium hydroxide, or
ammonia for removal of halogens from off-gases. Disposal of the scrubber liquors is usually
via introduction into wastewater treatment systems. This means that a significant load of
dissolved solids may be imposed. Although the effectiveness of liquid injection incinerators
may vary widely in the destruction of solvent-type wastes, the efficiency of destruction is
relatively high in a properly operated incinerator. In general, the liquid injection incinerators
need auxiliary fuel for solvents with low heating values. Consequently, the disposal costs are
inversely related to the heating values of the wastes: the higher the heating value of the
solvent, the lower the disposal cost. Some waste solvents can be recovered for their fuel
value. The wastes then have a net worth; thus increasing attention is being given to their
recovery, especially by some of the contract waste disposers that have sophisticated systems
for recovery and conversion. Instead of paying for the disposal of some waste solvents, they
can be sold. However, the industry often uses high heating value wastes (i.e., solvents) to
destruct low heating value waste (watery wastes) in company-owned facilities. As regula-
tions regarding disposal become stricter, an increasing number of companies are contracting
for waste disposal. This is true especially where a variety of liquids as well as solid wastes
must be destroyed.
4.2. 7.3 Incineration of Solid Wastes
The incinerator furnace provides the environment for controlled combustion of solid
wastes with air. The waste is processed by controlled oxidation with the liberation of heat,
producing flue or combustion gases and a residue or ash. Most incineration furnaces have
either a refractory hearth to support the burning waste, or a variety of grate-type hearths
which stroke the waste. Neither the stationary hearth nor the rotary kiln furnace systems
have grates. The typical stationary hearth furnace has a refractory floor which may have
openings to let slightly pressurized air in underneath the burning wastes. Stationary hearth
furnaces are used for commercial and small industrial incinerators. For hospital wastes, they
are equipped with auxiliary gas or oil burners to maintain the furnace temperature above
1200 to 1600°F. At these temperatures, the combustible solids and vapors will be
completely eliminated as long as high oxygen content air is well dispersed throughout the
gas. This may require auxiliary fuel burners in the secondary combustion chamber.
The rotary kiln incinerator has been used for several hundred years in the pyropro-
cessing industry. Unless special provisions are made for air or water cooling, the metal
cylinder is lined with refractory material to prevent overheating of the metal. The move-
ment of the solids being processed is controlled by the speed of rotation of the kiln which is
inclined toward the discharge end. The rotary kiln normally requires all the air for
combustion to enter with the waste at the feed end.
109
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Because of their versatility in handling solids, sludges, and containers, rotary kiln
incinerators are being used increasingly for the thermal destruction of wastes. The incinera-
tors are used by a number of contractors and individual plants. Since the feed rates of wastes
cannot be controlled closely, as is done in liquid injection incinerators, the rotary kiln
incinerator usually operates less thermally efficient than the liquid injection incinerators to
ensure effective destruction while meeting air pollution regulations. However, these incinera-
tors are especially sensitive to erratic conditions, such as the rupture of containers. Any
volatile substances which are released cause oxygen deficiencies in the reaction chamber and
consequently smoke forms. Thus, extensive afterburner chambers and control methods are
required to prevent smoke.
The most common off-gas cleaning systems for rotary kiln incinerators like those used
in liquid injection incinerators are wet scrubbers. Because of their versatility in handling
different forms of wastes, especially wastes with high heating values, use of the rotary kiln
incinerator is expected to increase. As in the case of the liquid injection incinerator, the
costs generally are inversely related to the heating value of the wastes; the higher the heating
value of the waste, the lower the disposal cost. Because tarry substances take longer to burn,
they will cost more to dispose of than the non-tarry substances.
Stationary grates have been used in incinerator furnaces for a long time. The original
stationary grates consisted of metal bars or rails supported in the masonry sides of the
furnace chamber. Subsequently, these bars were replaced with cast metal or fabricated metal
grates with provisions for rotating the grate sections to permit dumping of the ash residue.
Such stationary grates are still used in many of the older incinerators.
Mechanically operated grates installed in batch-type furnaces evolved from the station-
ary grates in batch-type furnaces. Many of the new, small-capacity incinerators still utilize
batch-fed furnaces either with stationary or mechanically operated grates. Although other
thermal destruction systems such as multiple hearths or fluidized beds might be used for
waste disposal, especially sludges from wastewater treatment plants, filter cakes or centri-
fuge solids, these are not used much in the pharmaceutical industry.
Conventional incinerator furnaces are made from refractories such as fire bricks,
metals, and refractory-covered metals, such as castable or fire brick refractory linings 1 to 9
inches thick.
A rotary kiln furnace may be lined either with castable refractories or with kiln blocks.
Alternatively, if the kiln is unlined, it must be cooled externally with air or water with an
optional water film on the inside of the cylinder. Since furnaces are subject to temperature
changes, refractory linings are susceptible to damage from spalling, fluxing, or slagging.
Corrosion must also be considered for any incinerator furnace material whether refractory
or metal.
110
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Many incinerator design specifications require a secondary combustion chamber. In the
primary combustion chamber wastes are ignited, vaporized, and burned above the incinera-
tor grates. The secondary combustion chamber may consist of a separate down stream
chamber wherein gases emitted from the primary chamber containing soot, hydrocarbons,
and other combustibles are burned. They will be completely eliminated as long as the gases
in the secondary combustion chamber are heated above 1500 to 1600°F. After complete
incineration of the waste, the ash residue drops into an ash chamber or chute from the end
of the grate or kiln, directly into a container, onto conveyors for disposal, or into water for
quenching and cooling.
Wastewater at incinerator installations comes from various sources such as chamber
sluicing, the quenching of ash, and parts of the ash conveyor system, the flue gas cooling
chamber, or the flue gas scrubbers. Because of the costs of water treatment facilities
required to prevent water pollution, this wastewater flow is minimized. For example, ash
can be quenched with air near the discharge end of the grate or in a separate ash cooler; gas
can be cooled with a gas-to-air heat exchanger or by total evaporation of fine water sprays;
and dry dust collection systems can be used instead of wet ones.
Acceptable ash residue can only be achieved by prudent operation. This requires
teamwork on the part of the entire staff. Materials must be mixed to provide a relatively
homogeneous feed stream. The furnace operator must constantly check and adjust the air
ratio, the degree of agitation, the temperature of the furnace, and the residence time of the
waste flowing through the furnace. Such an operation requires constant attention and, when
waste is difficult to burn, waste flow may be reduced. Knowing the composition of the
residue is important as a diagnostic aid to detect operational problems, determine complete-
ness of combustion, and identify potential water pollutants.
A well operated modern incinerator will burn out 97 percent of the combustible
materials. The water solubility of the residue is of interest primarily to evaluate potential
groundwater pollution, because this fraction will, to some extent, be leached from the ash
over long periods of time and may contaminate groundwater. Such leaching may or may not
be harmful, depending upon the materials which are dissolved and the rate of solution. In
general, the amount of water-soluble materials in the ash will be quite small and will reflect
the composition of the waste burned and the operating practices of the incinerator. The
extent to which groundwater contamination occurs depends primarily on the fill operation,
the local rainfall, drainage patterns, and geology all of which vary widely. Each fill site is
different.
The organic-soluble fraction of the residue will support undesirable forms of life such
as insects, rodents, and bacteria. If the level of these materials is found to be over 1 percent
of the residue ash, the incinerator is not being operated properly. All organic materials are
combustible. Increased residence time in the furnace, high temperatures, good agitation, and
proper air distribution will reduce these materials to less than 1 percent of the residue ash.
To determine if living organisms are in the ash, samples of the ash can be incubated. If
111
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organisms are present, they should be classified to establish which fraction is pathogenic.
Fungi or bacteria indicate that burn out of the ash is not complete.
The air pollutants associated with incinerators fall into three categories: particulates
(both mineral and combustible), combustible gases (which include carbon monoxide and
hydrocarbons), and non-combustible gases (including nitrogen oxides, sulfur oxides, and
hydrogen chloride).
4.2.7.4 Land Disposal
The disposal methods used by many industries are those used for residential and
commercial wastes: landfill and incineration. Landfills are either dumps, land burial opera-
tions, or sanitary landfills. Dumps and land burial operations are generally unsuitable
disposal methods, land burial being a dump that is covered. Sanitary landfilling is defined as
an engineering method of disposing of solid waste on land in a manner that minimizes
environmental hazards by spreading the waste in thin layers, compacting the wastes to the
smallest practical volume, and applying the compacting cover material at the end of each
operating day.
Where land is available, a sanitary landfill is usually more cost-effective than incinera-
tion for disposing of solid wastes. A number of pharmaceutical companies are located in
areas where land availability is not a problem. On the other hand, in areas such as New
Jersey, there is increased difficulty in locating landfill operations willing to accept industrial
wastes.
Current practice dictates that the potential sanitary landfill site be examined for soil
condition and proximity of groundwater. Because so little is known of the properties of
chemical wastes in landfills, an effective monitoring system for toxic waste disposal areas
may become a routine requirement.
A safety hazard exists with landfilling organic waste. Fires and explosions occur in
landfills which handle liquid organics. Further, the California Water Pollution Control Board
found that water that has gone through landfilled incinerator ash will leach alkalies and salts
from the fill. Gases such as methane, ammonia, and hydrogen sulfide are produced in land
disposal areas. Because landfilling of materials with high water content can produce adverse
effects within a landfill, States such as Indiana and New Jersey are considering, or have
instituted, strict requirements on landfill operations. As regulations on a State and local
level become effective, the number of landfills accepting organic liquids is expected to
decrease.
Increased consideration will be given to thermal destruction as regulatory agencies
establish more stringent rules and regulations for landfill disposal. There are economic
reasons for landfill disposal. Costs of landfilling range from $4 to $10/ton of solids because
of relatively low capital investment and energy requirements, while incineration costs fall in
112
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the range of $25 to $50/ton of solids. Incineration of solid wastes is capital- and energy-
intensive. Additional fuel is required when the wastes have low heating values. Therefore, in
spite of increasing pressure to minimize landfill, the rapidly escalating energy costs and
capital investment requirements for thermal destruction will mean that landfill costs will
continue to be more economically attractive than thermal destruction.
Secure chemical landfills (i.e., lined landfills, limited to chemical wastes, with adequate
local soil conditions and often using leachate control) will probably be an important aspect
of long-term disposal of selected pharmaceutical wastes. Inorganic salts and other sub-
stances, such as metallic compounds, which cannot be converted into innocuous substances
will present continuing disposal problems. The magnitude of these problems will be
determined by the volume and toxicity of the substances. Among these problem wastes are
mercury, arsenicals, chromium, copper, and zinc. Since some of these substances, such as
mercury, arsenic, and zinc would be vaporized in thermal destruction facilities, and perhaps
widely dispersed by atmospheric transport, careful consideration must be given to the
methods for their disposal. The "concentrate and contain" philosophy of land disposal will
have to be exercised for these wastes which cannot be altered in toxicity or hazardousness.
4.2.7.5 Recovery for Reuse
There are many processes for resource recovery. Important factors in deciding which
method to use include type, form, and volume of waste, as well as the economics of the
processes. Solvents are now recovered for economic reasons. Heavy metals, on the other
hand, may be removed to keep them out of the wastes to be disposed.
Within the pharmaceutical industry, most recovery operations, with the exception of
solvent recovery, are performed off-site by contractors. In our study, we found that firms
handling recovery were often reluctant to discuss the source and potential market for
recovered materials. The competition for recovery appears to be great in areas such as New
Jersey and Illinois.
4.2. 7.6 Wet Oxidation
Wet oxidation is oxidation of organic materials in a liquid state under high pressure at
moderate temperatures. Sulfur, nitrogen, and halogen breakdown products are retained in
the liquid effluent. Waste treatment techniques, such as wet oxidation, are found infre-
quently in the pharmaceutical industry. However, this particular technique is used when the
total energy content of the wastes is too low for cost-effective incineration. In wet
oxidation a complex mixture of organic materials may be degraded to a more simple series
of components which are amenable to further treatment by well-established processes such
as biochemical treatment. This method is usually employed for slurries and sludges with the
concomitant need to dispose of solids' which, of course, are much more stable and of less
potential environmental concern than the original waste. This process may be a candidate
for those wastes which have inhibitory effects on biochemical systems. Its utilization will
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require an assessment of the specific waste compositions. Treatment costs range from $1 to
$20 per thousand gallons.
4.2.7. 7 Deep-well Injection
Deep-well injection for disposal of industrial wastes became popular during the late
1950's. Of the approximately 300 wells drilled in the United States, close to 200 are still in
use, mostly in Texas and Michigan. To be effective the wells must have a complete and
permanent separation between the stratum being used for disposal and useful strata. The
rock must have the desired porosity and permeability at the level the waste is to be injected.
Approximately 30 new wells are being built each year. Deep-well injection is a method of
aqueous liquid waste disposal. It was investigated because a limited number of pharma-
ceutical plants manufacturing active ingredients use deep-well injection for their wastewater,
and often solid wastes are formed while preparing the liquid for injection. In addition, if
deep-well injection were to be banned, these companies would have to find some alternate
method of disposal. The pollutants typically sent to deep-wells are difficult to remove using
standard biological methods. Chemical methods such as precipitation or adsorption would
probably be used, forming a potentially hazardous solid waste for land disposal.
Since Michigan's Department of Natural Resources officials have indicated that deep-
well injection will continue, we investigated only those solid wastes produced prior to
injection to meet the limitations of deep-well disposal. That is, wastes must be compatible
with the brine naturally occurring in the selected porous rock stratum. If they are not
compatible, solids which can plug the pores of the rock will precipitate. For example, if the
stratum were a limestone, sulfates, phosphates, and aluminum salts would not be com-
patible.
4.3 ANALYSIS OF ON-SITE/OFF-SITE DISPOSAL METHODS
The pharmaceutical industry makes extensive use of waste disposal contractors. Eight-
five percent of the pharmaceutical industry's total process waste and 60 percent of the
hazardous wastes are disposed of off-site by contractors. Contractors either haul and dispose
of the wastes, or in areas such as northern New Jersey, trucking firms transport the waste
from the pharmaceutical plant to the disposer. Within the State of New Jersey independent
licenses are granted for transporting wastes and disposing of wastes. Occasionally, the
pharmaceutical company delivers the waste to the disposal site.
Waste disposal contractors contacted indicated that pharmaceutical companies segre-
gated their wastes and provided information, on the constituents' characteristics and recom-
mended handling techniques. Their work relationship appears to be open and functional.
The pharmaceutical companies take considerable care to ensure that reliable methods of
final disposal are used by their contract disposers. Hazardous wastes are usually landfilled in
areas of low soil permeability, and are often encapsulated and segregated from other wastes.
114
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Contract disposers are very visible and are rapidly coming under the strict regulations
of air, water, and hazardous waste authorities. Because contract disposal operations are
susceptible to shutdowns that can last hours or months, the larger pharmaceutical com-
panies are tending toward installation of their own liquid and solid incineration capacity.
A large amount of the general process wastes, such as mycelia from fermentation, is
landfilled. Most of the landfilling is handled by private commercial operations. In total,
about 80 percent of the pharmaceutical industry process wastes disposed of by contractors
are landfilled. Some of the remaining wastes are recovered, but most are incinerated.
Eighty-five percent of the hazardous waste handled by contractors are incinerated or
recovered. Most of this waste is solvent. While some contractors are set up to recover
valuable products from this waste, most is incinerated. Most of the remainder of the
hazardous wastes are landfilled. These wastes include potentially hazardous high inert
content wastes, such as filter cakes, and heavy metal wastes.
Of those hazardous process wastes disposed of on-site, all except 8 percent are
incinerated either in liquid injection incinerators or in solid-waste incinerators.
Table 4.3 summarizes current on-site/off-site disposal methods and indicates the
amount of wastes by specific category.
4.4 SAFEGUARDS USED IN DISPOSAL
Numerous safeguards were found to be used in waste disposal. Table 4.4 summarizes
the use of the various safeguards.
4.5 TREATMENT AND DISPOSAL TECHNOLOGY LEVELS AS APPLIED TO LAND-
DESTINED HAZARDOUS WASTE STREAMS FROM THE PHARMACEUTICAL
INDUSTRY
The various levels of technology within the pharmaceutical industry are described in
this subsection for those hazardous waste streams identified in Section 3. They are described
on the basis of EPA definitions for the industry studies:
Technology Level I-This level encompasses the broad average of technologies
which are currently used in typical facilities. There may be more than one Level I
technology used by the facilities in an industry section. Although the possible
variations within a technology are often numerous, Level I is defined broadly to
distinguish between technologies such as incineration and landfill or chemical
landfill and sanitary landfill.
115
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TABLE 4.3
ANALYSIS OF ON-SITE/OFF-SITE DISPOSAL METHODS™
Current Disposal Methods
Industry Segment
• R&D
Solvent
Animals
Heavy metals
• Active Ingredient Production
— Organic medicinal chemicals
Non-halogenated waste solvent
Halogenated waste solvent
High inert content wastes
— containing flammables only
— containing heavy metals or corrosives
Heavy metal wastes
Organic chemical residues
— Inorganic medicinal chemicals
Heavy metal wastes
— Fermentation Products
Waste solvent concentrate
— Botanicals
Aqueous solvent
Waste halogenated solvent
Non-halogenated solvent
— Drugs from animal sources
Aqueous alcohol
— Biologicals
Aqueous alcohol
Antiviral vaccines
Other biologicals (toxoids, serum)
• Pharmaceutical Preparations
Total
Total Hazardous Waste
(metric tons per year) Quantity
1,500
23,800
3,400
850
850
2,585
13,600
200
12,000
1,000
50
120
800
250
300
200
500
62,005
On^Site
Incineration Other
Quantity
450
X
—
9,300
800
225
—
-
5,440
-
5,000
400
5
50
260
100
100
—
50
22,180
% Quantity %
30
X**
—
40
24
26
_ _ _
_ _ _
40 1,360*** 10
_
42
40
10
40
33 40 5
40
33 100* 33
200 r 100
10 100 20
36 1 ,800 3
(incineration
Quantity
1,050
—
14,500
2,600
200
-
—
5,100
-
7,000
600
45
70
500
150
100
_
-
31,915
%
70
-
60
76
24
-
—
38
-
58
60
90
60
62
60
33
_
-
51
Off-Site (Contractors)
Landfill
Quantity %
— -
— -
425 50
850 100
2,010 78
1 ,700 1 2
200 1 00
-
— —
- -
-
_
_ _
350 70
5,535 9
Recovery*
Quantity %
- -
x —
- -
_ _
— —
575 22
- —
-
-
—
— -
- -
-
_
—
_ _
- -
575 1
*Solvent recovery is a very common practice on-site at pharmaceutical plants; it has been excluded from this study as a waste treatment process. The recovery discussed here is heavy metal
recovery from waste.
**Small animals are often autoclaved if they cannot be incinerated immediately.
***Dilute and sent to on-site biological wa'stewater trealjnent.
t Autocfaved.
tt Source: Interviews and Arthur D. Little, Inc., estimates.
-------
TABLE 4.4
USE OF SAFEGUARDS IN DISPOSAL OPERATIONS7
Type of Safeguard and Related Waste
• Segregation of wastes;
Hazardous
• Reduction of water content;
Mycelia (non-hazardous)
• Detailed handling instructions;
Hazardous
• Careful and informative labelling
of waste containers;
Hazardous
• Drummed disposal of hazardous
wastes in landfills;
High inert content wastes
Heavy metal wastes
Organic chemical residues
• Sealed landfills;
High inert content wastes
Heavy metal wastes
Organic chemical residues
• Soil conditioning to inhibit conver-
sion of a heavy metal waste to a
a water soluble form;
High inert content wastes
Heavy metal wastes
Amount of
Waste (Metric
Tons per Year)
62,000
300,000
62,000
62,000
1,275
2,010
1,700
1,275
2,010
1,700
425
2,010
Percent of Waste
Disposed Using
Safeguard
100
100
100
80
50
100
60
50
100
50
0
20
Estimated Number
of Locations
Where Used
54
19*
54
43
15
15
32
15
15
27
0
2
ExtensJveness
of Use
Very
Very
Very
Very
Moderate
Very
Moderate
Moderate
Very
Moderate
No examples found
Slight
*This number only includes principal fermentation installations.
^ Source: Interviews and Arthur D. Little, Inc., estimates.
-------
Technology Level II- This level includes the best technologies which are cur-
rently used in at least one pharmaceutical facility, that is, they are the soundest
treatment or disposal methods on a commercial scale from an environmental and
health standpoint. In some cases the technologies may be the same as in Level I.
Pilot and bench-scale installations are not considered.
Technology Level III - This level includes the technologies which are necessary to
provide adequate health and environmental protection. Existing pilot or bench-
scale processes that have high potential for meeting the needs of the industry if
scaled up are considered.
Tables 4.5.1-A through 4.5.5 describe the technology levels and provide relevant
information such as current usage of the identified levels of technology, present adequacy,
future adequacy based upon waste stream volume, composition, suitability for retrofit, non
land-related environmental impact such as energy and water requirements, residual wastes
finally disposed of on land, problems, limitations and reliability of the technology, imple-
mentation time, and environmental impact.
As a basis for calculating the number of facilities employing various treatment and
disposal technologies, we estimated that approximately 54 company operations large
enough to have significant wastes participate in the manufacture of pharmaceutical active
ingredients. Another 175 operations large enough to produce significant wastes formulate
and package these and other ingredients into final pharmaceutical preparations. The derived
estimates of facilities using the various treatments appear in the following sections.
4.5.1 Treatment and Disposal Levels for Halogenated and Non-Halogenated Waste Solvents
ADL estimates that 39,470 metric tons of non-halogenated waste solvents are gener-
ated annually by the pharmaceutical industry. This amount includes 1500 metric tons from
research and development, 23,800 metric tons from organic medicinal chemicals, 12,000
metric tons from the production of fermentation products, 1000 metric tons of aqueous
solvent concentrates (720 metric tons on a dry basis) from the production of botanicals and
an additional 120 metric tons of non-aqueous solvents from botanicals, 800 metric tons
from the production of drugs from animal sources, and 250 metric tons from the produc-
tion of biologicals.
In our survey of the industry, we found that approximately 50% of the industry
facilities had onsite incineration capability; the remainder used contractor incineration to
dispose of these solvent wastes. These two treatment technologies, therefore, are defined as
Level I in Table 4.5.1-A. Both of these disposal techniques are presently adequate. A
limitation of this kind of incineration is that liquid incinerators cannot handle a high
inorganic salt content waste.
Because there are a number of contractors who provide energy and resource recovery
at their own sites, we have included this technology in our Level II discussion. By energy
recovery we mean that the contractor has the capability to produce steam during
118
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TABLE 4.5.1-A
TREATMENT AND DISPOSAL TECHNOLOGY LEVELS
FOR NON-HALOGENATED WASTE SOLVENTS*
Amount of Waste:* 39,470 Metric Tons per Year
Hazardous, Physical, and Chemical Properties of Waste: Flammable organic liquid.
Technology
Current Usage
— Percent of Industry
Facilities
— Number of Facilities
Risk
— Risk from Fires or
Explosions
— Transport Risks
- Pollution Risk
Present Adequacy
Future Adequacy
Residual Waste**
Reliability of Technology
Limitations or Problems
Suitability for Retrofit
Non-Land Related Impact
Implementation Time
Level I
1) Incineration on-
site
2) Contractor in-
cineration
Level II
1) As Level I
2) Includes energy
and resource re-
covery at the
contractor's site.
1) 50
2) 50
1) 27
2) 27
1) 50
2) 12
1) 27
2) 6
Moderate
Minimized with
on-site incinera-
tion
Minor
1) Excellent
2) Excellent
1) Good
2) Good
0
1) Good
2) Many reliable
contract dis-
posal firms
1) Cannot handle
high inorganic
salt content
2) Same as 1) above
Excellent
None, excepting
salt plume
1) Two years
2) Minimal
Moderate
Minimized with on-
site incineration
Minor
1) (2) Excellent
1) Good
2) Excellent
0
As Level I
J
Level III
1) As Level I***
2) As Level 11***
0
As Level I
None
Technology not
yet proven for salt
removal by scrubbing
*Generated, i.e., prior to treatment or disposal (see Table 4.2.2).
**Finally land disposed.
***With scrubber for salts when they are present in concentrations that require scrubbing.
Source: Interviews and Arthur D. Little, Inc., estimates.
119
-------
incineration of the waste. Resource recovery is possible if the contractor produces a
low-grade, salable fuel from the various waste solvents that he collects. We estimate that
approximately 12% of the pharmaceutical facilities are currently using contractors which
are using energy and resource recovery techniques.
The Level III technology is the same as Levels I and II, except that a scrubber is added
to handle salts when they are present in concentrations that require scrubbing. Although
there have been numerous attempts to work out this technological problem, there is
currently no proven method for complete salt removal by scrubbing. In Table 4.5.1-B we
discuss the treatment and disposal technology levels for halogenated waste solvents. There
are approximately 3450 metric tons of halogenated waste solvents generated annually in the
pharmaceutical industry. These materials are usually flammable and the halogen is typically
chlorine.
In our survey of the industry, we found that those facilities which had incineration
capability onsite either diluted the halogenated solvents with their other solvents, or they
had them incinerated by a contractor. Those plants which had no incineration capability
onsite also had their waste solvents incinerated by contractor. In both cases, the contractor
had the capability for scrubbing forHCl. We have estimated that about 35% of the industry's
facilities with this kind of solvent waste were diluting and incinerating onsite. In so doing
they were meeting current air pollution control regulations. A specific limitation on this
kind of incineration, however, is that it tends to corrode the incinerator. Because we had
identified offsite facilities which used incineration and energy- and resource-recovery tech-
niques, we have included energy and resource recovery as a technology level within Level II.
About 10% of pharmaceutical industry facilities utilize offsite contractor incineration with
energy and resource recovery. As long as care is taken to maintain proper operating
conditions, Level I and Level II technology provides adequate waste disposal.
It takes approximately two years to design and install an onsite incinerator within a
pharmaceutical plant. However, there is an adequate supply of reliable contract disposal
firms in most areas of the country. Also, under Level I we believe that the incineration
onsite that is accomplished by dilution of the halogenated solvent with other solvents is
satisfactory, because the use of halogenated solvents within the pharmaceutical industry
does not constitute a major portion of the solvents.
4.5.2 Treatment and Disposal Levels for Organic Chemical Residues
Based on its 1973 production level, we estimate that the pharmaceutical industry
generates 13,600 metric tons of organic chemical residues annually. By far the majority of
these residues results from the production of the active ingredients used in organic medicinal
chemicals. We further estimate that about 10% of these residues are disposed of onsite by
methods other than incineration; for example, by mixing the residue with plant wastewater
prior to its treatment. We have not cited this method as a unique technology level because
we found it to be used for only a small amount of waste within a given plant, and only when
120
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TABLE 4.5.1-B
TREATMENT AND DISPOSAL TECHNOLOGY LEVELS
FOR HALOGENATED WASTE SOLVENTSt
Amount of Waste:* 3450 Metric Tons per Year
Hazardous, Physical, and Chemical Properties of Waste: Flammable, Chlorinated Organic
Liquid.
Level I
Level 11
Technology
• Current Usage
— Percent of Industry
Facilities
— Number of Facilities
• Risk
— Risk from Fires or
Explosions
— Transport Risks
- Pollution Risk
• Present Adequacy
• Future Adequacy
• Residual Waste**
• Reliability of Technology
• Limitations or Problems
• Suitability for Retrofit
• Non-Land Related Impact
• Implementation Time
1) Incineration on- 1) as Level I***
site (diluted with
other solvents)
2) Contractor incin- 2) With energy and
eration with resource recovery
scrubbing for HCI
Level III
1) as Level I
2) as Level 11
1) 35
2) 65
1) 19
2) 35
1) Moderate
2) Moderate
Minimized by on-
site incineration
1) Moderate
2) Slight
Good
Good
Nil
Good
1) Corrosion and
pollution may
occur at high
percentage
chlorine.
Good
1) Two years
2) Minimal
1) 35
2) 10
1) 19
2) 5
1) Moderate
2) Moderate
Minimized by on^site
incineration
1) Moderate
2) Slight
1) Good
2) Excellent
1) Good
2) Excellent
Nil
Good
Good
1) Two years
2) Minimal
*Prior to treatment or disposal.
**Finally land disposed.
***Assuming that the relatively small percentage of halogenated solvents will continue.
'''Source: Interviews and Arthur D. Little, Inc., estimates.
121
-------
the waste was compatible with the onsite treatment. The other methods currently used to
dispose of these residues are onsite and contractor incineration and landfill.
Only the smaller facilities are likely to place these materials in a landfill. We estimate
that 40% of the industry facilities use onsite incineration and another 40% use contractor
incineration. The present adequacy of the incineration method is excellent, while the
landfill can be defined as only fair. In many instances, little is known about the constituents
in organic chemical residues. For that reason we have described the future adequacy of
the landfill method as poor. There is little residual waste from the incineration of these
materials. Often the amount of solvent in the residue is maintained at a level that allows it
to remain pumpable, so that it can be incinerated in a liquid-feed incinerator. In the past,
the residue was allowed to flow into a steel drum while still hot. As the material cooled, it
turned into a hard, glassy substance which was then landfilled. A potential for groundwater
contamination is inherent in this method. With Level II, either onsite or contractor incinera-
tion is recommended, and Level III is the same as Level II.
Table 4.5.2 provides information on the contractor-recommended levels of treatment
and disposal of organic chemical residues.
4.5.3 Treatment and Disposal Levels for Potentially Hazardous High Inert-Content Wastes,
Such as Filter Cakes
To discuss these high inert-content wastes effectively, we divided such as filter cakes, in
two classes, one of which contains flammable solvent, and the other which contains
corrosives or trace amounts of heavy metals. Based on information obtained in our
interviews, we estimate that approximately half of the wastes contains solvents and the
other half heavy metals and corrosives. These materials are either semi-solid or solid. The
inert content may be filter aid or materials, such as charcoal.
In Table 4.5.3-A, we discuss the wastes which contain flammable solvent. Currently,
about one half of the plants generating this kind of waste send the material to contractor
landfill. The others have some means of incinerating, generally in rotary kilns or multiple
hearth furnaces. The content in these wastes ranges from under five to as much as 60
percent solvent.
The present adequacy of the landfill method is only fair and its future adequacy has
been determined to be poor because of the possibility of fires in the disposal area. On the
other hand, incineration provides an excellent means of making the waste inert as it burns
off all solvent and the only residual is the inert ash. A facility for the incineration of these
materials would take about two years to design and install.
For Level II technology, we are recommending incineration as the best method
currently used. Because it provides an environmentally acceptable method for disposing of
these materials, we have also stated that Level III should be incineration. In Table 4.5.3-B,
122
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TABLE 4.5.2
TREATMENT AND DISPOSAL TECHNOLOGY LEVELS
FOR ORGANIC CHEMICAL RESIDUES*
Amount of Waste:* 13,600 metric tons per year
• Technology
• Current Usage
— Percent of Industry
Facilities
— Number of Facilities
• Risk
— Risk from Fires' or
Explosions
— Transport Risks
- Pollution Risk
• Present Adequacy
• Future Adequacy
• Residual Waste**
• Reliability of Technology
• Limitations or Problems
• Suitability for Retrofit
• Non-Land Related Impact
• Implementation Time
Level I
1) On-site incinera-
tion
2) Contractor in-
cineration
3) Landfill1"
1) 40
2) 40
3) 20
1) 22
2) 22
3) 11
3) Yes
Level 11
Level III
1) On-site incinera- as Level
tion
2) Contractor in-
cineration
1) 40
2) 40
1) 22
2) 22
Moderate
2) Moderate
3) Moderate
3) Yes
1) (2) Excellent
2) Moderate
Nil
Excellent
3) Fair
1) (2) Excellent
3) Poor
1) (2) Minimal1'1'
1) (2) Good
3) Unknown
1) (2) None
3) Landfill ade-
quacy unknown
1) Good1"1'1'
3) Potential
groundwater
pollution
1) Two years
Excellent
Minimal
Good
None
Good
Nil
1) Two years
* Generated, i.e., prior to treatment or disposal.
**Finally land disposed.
tSince smaller facilities are more likely to use landfilling, it is included here.
ttlf enough solvent remains to keep waste pumpable, it can be incinerated in liquid-feed
incinerator with little residual waste.
tttHeated feed to existing liquid injection incinerator is possible.
* Source: Interviews and Arthur D. Little, Inc., estimates.
123
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TABLE 4.5.3-A
TREATMENT AND DISPOSAL TECHNOLOGY LEVELS
FOR POTENTIALLY HAZARDOUS HIGH INERT CONTENT WASTES*
(such as filter cakes, which contain flammable solvent)
Amount of Waste:* 850 Metric Tons per Year
Hazardous, Physical, and Chemical Properties of Waste: Flammable, Semi-Solid or Solid
with High Inerts Contents
• Technology
• Current Usage
- Percent of Industry
Facilities
— Number of Facilities
• Risk
— Risk from Fires or
Explosions
- Transport Risk
- Pollution Risk
* Present Adequacy
• Future Adequacy
• Residual Waste**
• Reliability of Technology
• Limitations or Problems
• Suitability for Retrofit
• Non-land Related Impact
• Implementation Time
Level I
Level II
Level III
1) Landfill
2) Incineration
1) 50
2) 50
1) 27
2) 27
1) Yes
Slight
1) Yes
1) Fair
2) Excellent
1) Poor
2) Excellent
1) All
2) Inert ash
1) Unknown
2) Excellent
Fire risk
1) Not recom*
mended
2) Good
Incineration as Level II
50
27
27
Minimal
Slight
Nil
Excellent
Excellent
Inert ash
Excellent
None
Good
2) Two years
Two years
*Prior to treatment or disposal
**Finally land disposed
Source: Interviews and Arthur D. Little, Inc., estimates.
124
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TABLE 4.5.3-B
TREATMENT AND DISPOSAL TECHNOLOGY LEVELS
FOR POTENTIALLY HAZARDOUS HIGH INERT CONTENT WASTES1"
(such as filter cakes, which contain heavy metals or corrosives)
Amount of Waste:* 850 Metric Tons per Year
Hazardous, Physical, and Chemical Properties of Waste: Toxic, Semi-Solid or Solids with
high inerts content (may contain solvent)
Level I
Level II
Level III
Technology
1) Secure chemical Neutralize or prer as Level II
landfill cipitate heavy
2) Sanitary land- metal, then place
fill
1) 40
2) 40
1) 22
2) 22
Slight
in secure chemical
landfill
20
11
Slight
Slight to moderate Slight
1) Slight Slight
2) Moderate***
1) Good
2) Fair
1) Fair
2) Poor
All
1) Good
2) Fair
1) (2) Soil con-
ditions
Good
Good
Current Usage
— Percent of Industry
Facilities
— Number of Facilities
• Risk
— Risk from Fires or
Explosions
— Transport Risks
— Pollution Risk
• Present Adequacy
• Future Adequacy
• Residual Waste**
• 1 Reliability of Technology
• Limitations or Problems
• Suitability for Retrofit
• Non-Land Related Impact
• Implementation Time
*Prior to treatment or disposal.
**Finally land disposed.
***Anaerobic conditions can occur in sanitary landfill which will dissolve heavy metals and
make them mobile.
More stable
Good
Soil conditions
Source: Interviews and Arthur D. Little, Inc., estimates.
125
-------
we outline our evaluation of treatment and disposal of those high inert-content wastes
which contain corrosives or trace amounts of heavy metals. We estimate that the pharma-
ceutical industry generates 850 metric tons of these wastes annually. Because they contain
corrosives, they are generally not incinerated.
Because these materials cannot be incinerated, they are currently landfilled. We
estimate that about 40% of the facilities dispose of these wastes in sanitary landfills, which
means that wastes other than chemical wastes are being disposed of. We estimate that a
second 40% disposes of these wastes in a secure chemical landfill that is both limited to
chemical wastes and has to be lined with some material to ensure that materials do not leach
into groundwater. The present adequacy of the sanitary landfill method is only fair and is
not recommended for future disposal. Anaerobic conditions can occur in sanitary landfills
which will dissolve heavy metals and make them mobile.
Secure chemical landfills provide better environmental conditions, but even these can
create problems because of local soil conditions. Level II technology, which is currently
used by about 20% of the facilities, involves the neutralization of the corrosive material or
precipitation of the trace amounts of heavy metal. Then, the material which is less soluble
and less toxic is placed in a secure chemical landfill. Because of the nature of these wastes
and the inability to recover the trace amounts of heavy metal, we have recommended this
Level II treatment as Level III also.
4.5.4 Treatment and Disposal Levels for Heavy Metal Wastes
ADL estimates that the pharmaceutical industry generates 2875 metric tons of heavy
metal wastes annually. Pharmaceutical facilities which produce these heavy metal wastes are
not common within the industry. In fact, we estimate that only 15 pharmaceutical plants
generate heavy metal wastes. About 80% of these facilities currently convert the heavy
metal wastes into their most insoluble form, place them in drums, and then bury them in a
secure chemical landfill. All the plants we visited that used landfill for disposal used a secure
chemical landfill for their heavy metal wastes. However, we believe that a small percentage
of the heavy metal wastes may be placed in normal sanitary landfills. As we mentioned
before, anaerobic conditions can occur in sanitary landfills which may dissolve the heavy
metals and make them mobile.
About 20% of the industry facilities currently subject their heavy metal wastes to a
recovery process at an offsite contractor location. From an environmental control view-
point, this technique is excellent, since only a small portion of the wastes is then disposed of
on land. The limitations of this kind of disposal include the economics of the recovery and
the market for the recovered metal. For Level III, we recommend both the recovery as
described in Level II and engineered storage. However, in our survey, we did not find any-
one utilizing engineered storage. We include engineered storage in this Level III technology
because there are some heavy metal wastes which do not lend themselves to recovery and
therefore must be subjected to some secure method of disposal.
126
-------
Table 4.5.4 provides information on our recommended levels of treatment and disposal
of heavy metal wastes.
4.5.5 Treatment and Disposal Levels for Returned Goods and Reject Materials
from Formulation
ADL estimates that the pharmaceutical industry annually generates 500 metric tons of
waste from returned goods and reject material from formulation operations. The technology
most commonly used within the industry for handling these wastes is to crush the material
and dispose of it in a sanitary landfill. We estimated that approximately 60% of the industry
facilities use this method. Because more information is needed on the effects of these
materials being landfilled, we have described their present adequacy as good, but have
recommended other treatment for Level II.
In Level II technology in our survey we have found that these wastes were both being
incinerated by either a contractor or at a company-owned facility and also treated in an
onsite biological wastewater treatment system. Approximately 10% of these facilities
currently use incineration and about 20% use the biological treatment. The residual from
the incineration is a non-hazardous ash.
The problems and limitations associated with these two methods involve the avail-
ability of either incineration or onsite biological treatment. We have described Level III to
be the same as Level II, because we believe these two methods provide environmentally
adequate methods of disposal.
Table 4.5.5 provides information on our recommended levels of treatment and disposal
of returned goods.
127
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TABLE 4.5.4
TREATMENT AND DISPOSAL TECHNOLOGY LEVELS
FOR HEAVY METAL WASTES1"1"
Amount of Waste:* 2875 Metric Tons per Year
Technology
• Current Usage
— Percent of Industry
Facilities
— Number of Facil-
ities^
• Risk
— Risk from Fires or
Explosions
— Transport Risks
- Pollution Risk
• Present Adequacy
• Future Adequacy
• Residual Waste**
• Reliability of Technology
• Limitations or Problems
• Suitability for Retrofit
• Non-land Related Impact
• Implementation Time
Level I
Convert heavy metal to
most insoluble form,
drum, and place in se-
cure chemical landfill***
80
12
Level II
1) Recovery off-site
2) As Level I
1) 20
2) 80
1) 3
2) 12
Level III
1) Recovery off-site
2) Engineered storage
1) 20
2) 0
1) 3
2) 0
Slightly
Moderate
Good
Good
All
Good
Soil conditions
D(2) Slight
1) Minimal
2) Moderate
1) Excellent
2) Good
1) Excellent
2) Good
1) Some
2) As Level 1
1) (2) Good
1) Market for heavy
1)(2) Slight
1) Minimal
2) Slight
1) (2) Excellent
1) (2) Excellent
1) Some
2) All
metal
2) Soil conditions
1) Minimal
1) Two years
* Prior to treatment of disposal
**Finally land disposed
***AII of the plants we visited that used landfill for disposal used a secure chemical landfill for their heavy
metal wastes. We believe, however, that a small percentage of the heavy metal wastes may be land-
filled in sanitary landfills.
15 pharmaceutical plants are estimated to have heavy metal wastes.
Source: Interviews and Arthur D. Little, Inc., estimates.
128
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TABLE 4.5.5
TREATMENT AND DISPOSAL TECHNOLOGY LEVELS
FOR POTENTIALLY HAZARDOUS RETURNED GOODS AND
REJECT MATERIAL FROM FORMULATION™
Amount of Waste:* 500 Metric Tons per Year
• Technology
Current Usage
— Percent of Industry
Facilities
— Number of Facilities
• Risk
— Risk from Fires or
Explosions
— Transport Risks
— Pollution Risk
• Present Adequacy
• Future Adequacy
• Residual Waste**
• Reliability of Technology
• Limitations or Problems
• Suitability for Retrofit
• Non-Land Related Impact
• Implementation Time
Level I
Crush on-site and
landfill in sanitary
landfill.
60
122
None
None
Slight
Good
***
All
Good
Level II
1) Incineration by
contractor or at
company-owned
facility.
2) Treatment in on-
site biological waste-
water treatment
system.
1) 10
2) 20
1} 15
2) 30
1) (2) None
1) (2) None
1) (2) None
1) (2) Excellent
1) (2) Excellent
1) 60 percent of waste
1) (2) Good
1) (2) Availability
Level III
as Level 11
*Prior to treatment or disposal.
**Finally land disposed.
***More information needed.
tNon-hazardous ash.
^Source: Interviews and Arthur D. Little, Inc., estimates.
129
-------
GENERAL BIBLIOGRAPHY
Section 4.0
Achinger, W. C. and L. E. Daniels. An Evaluation of Seven Incinerators, Proceedings of the
1970 National Incinerator Conference, p. 32.
Adinoff, J. "Waste Disposal" Industry and Power, July 1953, p. 80.
Black & Veatch and Rafael A. Domenech & Associates. "Industrial Waste Survey, Bar-
celoneta Region, Puerto Rico," Prepared for the Puerto Rico Aqueduct and Sewer
Authority, Commonwealth of Puerto Rico, July 1973.
Breaz, Emil. "Drug Firm Cuts Sludge Handling Costs," Water and Waste Management,
January 1972, p. A-22.
Bridge, D. P. and J. D. Hammel. "Incinerator Design Specifically to Burn Waste Liquids and
Sludges," Proceedings of 1972 National Incinerator Conference, p. 55.
Colonna, Robert A., and Cynthia McLaren. "Appendix D, Hazardous Wastes," Decision-
Makers Guide in Solid Waste Management, Environmental Protection Agency, 1974,
p. 146.
Danielson, C. N., W. G. Robrecht. "Deep-well Disposal of Chemical Wastes: Solid Backbone
of a Total Waste Control Program."
Davis, Ken E. and Rabey J. Funk. "Deep-Well Disposal of Industrial Wastes," Industrial
Wastes, Vol. 21, No. 1, January/February 1975, p. 28.
Eckenfelder, W. Wesley, Jr., and Edwin L. Barnhart. "Biological Treatment of Pharma-
ceutical Wastes," Biotechnology and Bio engineer ing, Vol. IV, 1962, p. 171.
Heaney, Frank L., and Charles V. Keane, Solid Waste Disposal (Camp, Dresser and McKee
Company).
Hescheles, C. A. "Ultimate Disposal of Industrial Wastes," Proceedings of 1970 National
Incinerator Conference, p. 235.
Kroneberger, G. F. "Porteous Conditioning of Sludges for Improved Dewatering," Solid
Waste Treatment, Vol. 68, No. 122, p. 176.
Kumar, J. and J. A. Jedlicka. "Selecting and Installing Synthetic Pond-Linings," Chemical
Engineering, February 5, 1973, p. 67.
130
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Laboratory Waste Disposal Manual, Manufacturing Chemists Association, Revised July
1974.
Lawson, J. Ronald, Michael L. Woldman, and Paul P. Eggermann. "Squibb Solves Its
Pharmaceutical Wastewater Problem In Puerto Rico," Chemical Engineering Progress
Symposium Series, 1970, p. 401.
McGill, Douglas L., and Elbridge M. Smith. "Fluidized Bed Disposal of Secondary Sludge
High in Inorganic Salts," Proceedings of 1970 National Incinerator Conference, p. 79.
Mead, Berton E., and William G. Wilkie. "Leachate Prevention and Control from Sanitary
Landfills," Presented at the 68th National Meeting of the American Institute of
Chemical Engineers, March 2, 1971, p. 1.
Melcher, R. R. "Experience with Pharmaceutical Waste Disposal by Soil Injection," Speech
presented at the American Chemical Society, September 7, 1961.
"Ocean Dumping," Federal Register, Environmental Protection Agency, Part II, Volume 38,
No. 94, May 16, 1973.
Proposed Solid Waste Management Authority Development Plan, Solid Waste and Noise
Control Program, Office of the Governor, Commonwealth of Puerto Rico, p. 69.
Quane, D. E. "Air Pollution Control Techniques: Reducing Air Pollution at Pharmaceutical
Plants," Chemical Engineering Progress, Vol. 70, No. 5, May 1974, p. 5.
Routson, R. C. and R. E. Wildung. "Ultimate Disposal of Wastes to Soil," Chemical
Engineering Progress Symposium Series, No. 97, Vol. 65, Winter, 1969, p. 19.
Rules of the Bureau of Solid Waste Management, New Jersey Department of Environmental
Protection, July 1, 1974.
Santoleri, Joseph J. "Chlorinated Hydrocarbon Waste Recovery and Pollution Abatement,"
Proceedings of 1972 National Incinerator Conference, p. 66.
Scurlock, Arch C., Alfred W. Lindsey, Timothy Fields, Jr., and David R. Huber. "Incinera-
tion in Hazardous Waste Management," Division of the Environmental Protection
Agency, April 1974.
"Solid Waste Management in the Drug Industry," Prepared for the Environmental Protec-
tion Agency, 1973.
Sorg, Thomas J. "Industrial Solid Waste Problems," AIChE Symposium Series, No. 122,
Vol. 68, 1972, p. 1.
131
-------
Stone, Ralph. "Sanitary Landfill Disposal of Chemical Petroleum Waste," Solid Waste
Treatment, AIChE Symposium Series, No. 122, Vol. 68, p. 35.
"Synthetic Organic Chemicals, United States Tariff Commission, United States Production
and Sales, 1971, p. 101.
"The Form of Hazardous Waste Materials," Rollins Environmental Services, September 7,
1972.
Walker, William H. "Monitoring Toxic Chemicals in Land Disposal Sites," Pollution Engi-
neering, September 1974, p. 50.
Witt, Philip A., Jr. "Disposal of Solid Wastes," Chemical Engineering, October 4, 1971,
p. 61.
132
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5.0 COST ANALYSIS
5.1 BACKGROUND
Total production of active ingredients within the pharmaceutical companies in 1973 is
estimated at 45,000 metric tons. Overall, production of these ingredients is expected to
grow at a rate of 3 percent per year through 1977 and at a 7 percent rate thereafter.* Waste
generated and destined for land disposal in 1973 for the pharmaceutical industry is
estimated at 244,000 metric tons per year. The hazardous waste represents about 25 percent
of the total waste or 61,000 metric tons per year in 1973. Wastes are expected to grow to
400,000 metric tons per year of total wastes and to 100,000 metric tons per year of
hazardous wastes by 1983. Approximately 85 percent of total wastes and 60 percent of
hazardous wastes are estimated to be treated and disposed of by contractors.
Approximately 54 company operations estimated to be large enough to have signifi-
cant wastes participate in the manufacture of pharmaceutical active ingredients. Another
175 operations large enough to produce significant wastes formulate and package these and
other ingredients into final pharmaceutical preparations. In order to calculate total industry
costs, we used the above estimates of company operations in conjunction with industry
production estimates and treatment and disposal costs per ton of product.
5.2 SUMMARY OF COSTS FOR CONTROLLED TREATMENT AND DISPOSAL OF
LAND-DESTINED HAZARDOUS WASTES
Tables 5.2-A,-B, and-C summarize the costs of end-of-pipe treatment and disposal
systems either currently in use or recommended for future use in pharmaceutical production
facilities. No costs are given for in-process changes made to minimize or change the
hazardous character of the wastes. Because typical plants were used to develop an estimate
of the total industry cost of treatment and disposal of hazardous wastes, the total industry
costs should be taken only as an indication of the order of magnitude of such costs rather
than as the outcome of a detailed industry survey of the costs. Issues such as site specific
costs, different products or product mixes, local disposal rates, and available disposal
methods were not included in this estimate. Where it is necessary to reflect different
economics of large versus small plants and separate hazardous waste streams, costs have been
developed typically for more than one plant in each industry section. These product-specific
analyses are presented in Tables 5.4.2.1 to 5.4.3.
5.3 RATIONALE AND REFERENCES USED IN COST ESTIMATING
Eighty-five percent of the total pharmaceutical industry process waste are disposed of
through contractors. The onsite disposal facilities are liquids incinerators and solids incinera-
tors. However, almost 70 percent of the incineration capability are located offsite with
contractors. There is, however, a trend toward onsite incineration. In our survey, we
contacted numerous pharmaceutical companies that had recently installed incineration
*The industry growth rate is discussed in Section 2.7.
133
-------
capacity or were planning installation. Because of the patterns of offsite disposal, costs in
this report have usually been determined for representative plants on the basis of contractor
disposal. In addition, there is information presented on the cost of onsite incinerators for
solids. The data are presented for various size ranges. Installation of these units is usually
determined by individual company location and policy. Where industry in an area is sparse,
there may be limited availability of contractor incineration. On the other hand, in some
areas, pharmaceutical companies may find an adequate supply of disposers, but find that
they are constantly on the brink of being shut down by local regulatory agencies for air or
water regulation violations. These pharmaceutical companies may decide in favor of onsite
incineration to ensure that they have a reliable disposal method.
TABLE 5.2-A
PERSPECTIVE ON THE PHARMACEUTICAL INDUSTRY:
COSTS PERUIV
($/metric ton)
TREATMENT AND DISPOSAL COSTS PER UNIT OF HAZARDOUS WASTE*
Product Category Level I Level II Level III
• Bulk Active Ingredient
— Organic Medicinal Chemicals
Non-halogenated waste solvent 68 68 68
Halogenated waste solvent 184 184 184
High inert content wastes 26 43 43
Heavy metal waste 50 50 60
Organic chemical residues 100 100 100
— Inorganic Medicinal Chemicals
Heavy metal waste 50 50 60
— Fermentation Products
Waste solvent concentrate 120 120 120
— Botanicals
Aqueous solvent 144 144 144
Waste halogenated solvent 180 180 180
Non-halogenated waste solvent 68 68 68
— Drugs from Animal Sources
Aqueous alcohol 142 142 142
- Biologicals
Aqueous alcohol 142 142 142
Antiviral vaccine 30 30 30
Other biologicals (toxoids, serum) 30 30 30
• Pharmaceutical Preparations 28 67 67
Source: Arthur D. Little, Inc., estimates.
134
-------
TABLE 5.2-B
PERSPECTIVES ON THE PHARMACEUTICAL INDUSTRY:
HAZARDOUS WASTE TREATMENT AND DISPOSAL COSTS»f
Estimated
Total Annual Costs ($000)**
Product Category 1973 1977 1983
• Bulk Active Ingredient
— Organic Medicinal Chemicals
Non-halogenated waste solvent 1,620 1,820 2,585
Halogenated waste solvent 630 705 1,000
High inert content wastes 45 80 110
Heavy metal wastes 145 160 275
Organic chemical residues 1,360 1,530 2,170
— Inorganic Medicinal Chemicals***
Only one hazardous waste identified - - -
— Fermentation Products
Waste solvent concentrate 1,440 1,620 2,300
— Botanicals
Aqueous solvent 145 160 230
Halogenated waste solvent 10 10 15
Non-halogenated waste solvent 10 10 15
— Drugs from Animal Sources
Aqueous alcohol 115 130 180
— Biologicals
Aqueous alcohol 35 40 60
Antiviral vaccines 10 10 15
Other biologicals (toxoids serum) 5 10 10
• Pharmaceutical Preparations 15 40 50
Partial Total"1" 5,585 6,325 9,015
*Based on average treatment costs and pharmaceutical industry waste esti-
mates.
**December 1973 dollars.
***lncluded in heavy metal wastes under organic medicinal chemicals
+Excludes R&D costs.
Source: Arthur D. Little, Inc., estimates.
135
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TABLE 5.2-C
PERSPECTIVES ON THE PHARMACEUTICAL INDUSTRY:
COST IMPACTOF HAZARDOUS WASTE TREATMENT AND DISPOSAL
Estimated Hazardous Waste
Control Cost as Percent of Price*
Product Category
• Bulk Active Ingredient
Organic Medicinal Chemicals
Inorganic Medicinal Chemicals'
Fermentation Products
Botanicals
Drugs from Animal Sources
Biologicals
1973
Selling Price
$/kg
22
44
*##
**#
#**
Level I
0.2%
0.34%
Level II
Level III
0.22% as Level 11
as Level I as Level I
as Level I as Level I
* Manufacturers selling price in the case of pharmaceutical preparations; value of sales, that
is, the net selling value FOB plant or warehouse, or delivered value, whichever represents
the normal practice for bulk active ingredient.
** Representative data not available because most inorganic medicinal ingredients that might
produce a hazardous waste are purchased from the chemical industry.
*** Data not available; the selling price of many of these products is stated in terms of
biological activity.
Source: Arthur D. Little, Inc., estimates.
In each of the representative operation cost analyses, typical plant situations are
identified in terms of production capacity, process waste load, hazardous waste load, and
product value. Annual capital costs have been assumed to be a constant percentage (10
percent of fixed investment). Depreciation costs have been calculated on the straight-line
method (10 percent per year) over 10 years, even though the physical life is longer. Taxes
and insurance are included as 1-1/2 percent of the capital investment. All estimates are
reported in December 1973 dollars. The Engineering News Record (ENR) Construction Cost
Index (1158) and the Chemical Engineering (CE) Plant Cost Index (148.2) have been used
to prepare these estimates. Land requirements for onsite treatment are not significant;
therefore, no cost allowance has been made. Offsite treatment and disposal land require-
ments are not considered directly. Land costs are included in the contractor's charges.
Cost-effectiveness relationships are implicit in the calculation of these costs, together with
the technology levels achieved. For example, when considering a small pharmaceutical plant,
the use of contractor disposal is more cost-effective because of the economies of scale and
the potential for energy and resource recovery. With larger pharmaceutical operations,
onsite and offsite incineration have approximately equal cost-effectiveness. The major issue
in these instances would be the availability of capital.
136
-------
Table 5.3-A presents costs for transporting wastes for offsite disposal:
TABLE 5.3-A
COST OF TRANSPORTING WASTES1"
Distance Liquids Solids
(miles) ($/m3) ($/1000gal) ($/metric ton)
5 0.92 3.50 1.85
10 1.02 3.85 2.10
20 1.48 5.60 2.70
40 1.94 7.35 3.40
50 2.03 7.70 3.70
Source: Arthur D. Little. Inc., estimates.
A number of contractors were contacted in this study, primarily in EPA Regions II and V
where concentrations of the pharmaceutical industry are found. Table 5.3-B summarizes the
information obtained, supplemented and checked by ADL estimates. No factors are in-
cluded for areas of the country, as no obvious differences were found in our analysis.
TABLE 5.3-B
CONTRACT DISPOSAL CHARGES FOR HAZARDOUS WASTES*
Method $/Metric Ton
General Landfill* 8
Secure Chemical Landfill** 17
Approved Secure Landfill*** 30
Incineration
Non-halogenated solvents (organic
content 85% and over) 90
Solids 30
Neutralization (or precipitation of
components) of Wastes 30
**.
***
Operated as sanitary landfill.
Lined landfill limited to chemical wastes.
Lined landfill limited to hazardous wastes with monitoring.
tSource: Interviews and Arthur D. Little, Inc., estimates.
137
-------
Also, the costs for offsite disposal vary, depending upon the amount of waste to be
disposed, the collection frequency, and the onsite storage facilities. Figure 5.3-A gives an
example of how these factors affect costs. Figure 5.3-B presents capacity ranges and
investment costs for industrial solid waste incinerators, and Table 5.3-C presents background
information. Figure 5.3-C gives operating costs in terms of dollars per metric ton.
5.4 COSTS FOR TREATMENT AND DISPOSAL OF HAZARDOUS WASTES
5.4.1 Research and Development
The hazardous wastes produced within the R&D section of the industry include both
waste solvents and test animals. Waste solvents can be incinerated either by contractors or in
company-owned facilities for about $0.30 per gallon. A research facility with 100 re-
searchers will produce about 2000 gallons of waste solvent annually. The cost of incinerat-
ing that waste will be approximately $600 annually.
Most pathological incineration capacity for test animals within the R&D section of the
industry is installed. It is not discussed here.
5.4.2 Production of Active Ingredients (SIC 2831 and 2833)
J. 4.2.1 Organic Medicinal Chemicals
Of the 27,200 metric tons of waste solvent produced by the pharmaceutical companies
in the manufacture of organic medicinal chemicals, about 10,100 metric tons per year can
be incinerated onsite by the industry. Onsite incineration capacity and its associated
pollution control equipment (both air and water) are expected to increase.
Offsite contractors dispose of the remainder of the waste solvent, about 17,100 metric
tons per year. After surveying the disposers, we found the typical charge for incineration of
pharmaceutical waste solvents to be $0.20 to $0.35 per gallon for a solvent of medium-range
Btu content, depending mainly on the Btu content. The purer solvents can potentially be
recovered and sold, reducing the disposal charge, or used as a fuel for the incineration of
wastes with a higher water content. Those lower Btu content wastes may vary from $0.35 to
$0.60 per gallon for those with high water content; perhaps up to $1.00 for those with high
chlorine content as well.
Since the actual quantities of medicinals which are produced in an operation are often
difficult to determine, we based the plant size on the number of production workers. A
typical operation producing organic medicinal chemicals has 300 production workers. In
other industries, the production is related to the number of production workers. That ratio
remains relatively constant from plant to plant within an industry. Within the pharma-
ceutical industry, where the number of intermediate production steps can range from 1 to
'138
-------
100
"o
Q
s 10
0.1
1 10
Metric Tons (dry solids)/day
100
Source: Arthur D. Little, Inc., estimates
FIGURE 5.3-A IN-PLANT STORAGE AND LANDFILL CHARGES1"
400,000
300,000
200,000
100,000
50,000
30,000
Semi-batch Incinerator
V
300
10,000
1000 2000
Incinerator Capacity (Ib/hr)
*ENR Construction Cost Index: 1158
Source: Arthur D. Little, Inc., estimates.
FIGURE 5.3-B GENERAL INDUSTRIAL SOLID WASTE INCINERATION
CAPACITY RANGES AND IN VESTMENT COSTS*1
o
U c
30
25
20
°£ 15
10
Single Shift Operation
Two-shift Operation
I I I I J_
I I l
500 1000 2000 4000
Solid Waste (metric tons/year)
"Includes capital-related charges.
Source: Arthur D. Little, Inc., estimates.
FIGURE 5.3-C GENERAL INDUSTRIAL SOLID WASTE
INCINERATION OPERATING COSTS**
139
-------
TABLE 5.3-C
CAPITAL INVESTMENT FOR INDUSTRIAL SOLID WASTE INCINERATION7
Capacity 600 Ib/hr
Annual Capacity (single-shift operation) 450 tons*
Type Batch
Capital Cost
Incinerator $25,000
Freight 2,000
Installation (includes foundations,
electrical, plumbing, oil storage) 5,000
Total Fixed Capital Investment (FCI)
Engineering @ 10% of FCI
Contractor's Fee @ 7% of FCI
Contingency @ 15% FCI
Total $42,000
1200 Ib/hr
900 tons**
Batch
$45,000
3,000
8,000
2500 Ib/hr
1875 tons***
Semi-Automatic
$100,000
5,000
15,000
32,000
3,000
2,000
5,000
56,000
5,000
3,000
8,000
120,000
12,000
8,000
18,000
$72,000
$158,000
*410 metric tons
**820 metric tons
***1700 metric tons
Installation costs for an incinerator within an operating plant are lower than those for
for an incinerator located in areas where these facilities are not already available.
Source: Arthur D. Little, Inc., estimates.
140
-------
15, we studied the various plants for which production figures were available and found that
for operations of approximately the same complexity the production per production worker
stays relatively constant also. Ratios varied from 8000 pounds per year per production
worker* to 30,000 to 40,000 pounds per year per production worker for large-scale
operations making relatively simple products such as aspirin.
The costs of treatment and disposal of hazardous wastes from organic medicinal
chemical active ingredient production for a typical plant of 300 production workers are
presented in Tables 5.4.2.1-A,-B,-C, and -D. There are smaller operations in the industry
ranging down to almost 100 production workers. Few facilities can operate with fewer than
this number. Some of the larger operations employ close to 1000 production workers. The
problems and the associated costs per amount of waste are generally of the same magnitude
as the typical plant.
5.4.2.2 Inorganic Medicinal Chemicals
No individual costs have been developed for the treatment and disposal of inorganic
medicinal chemical wastes. We found only one hazardous waste in our survey. We have
included its treatment and disposal cost in the overall number for the organic medicinal
chemical hazardous waste treatment and disposal cost. We have estimated that the treatment
and disposal cost for this waste is approximately $50 per metric ton.
5.4.2.3 Fermentation Products
As we have indicated in Tables 5.4.2.3-A and -B, although the plant size varies, both
the large and small plants incur the same average treatment and disposal cost of 14^/kg of
product and $120/metric ton of waste to dispose of a material which is a waste solvent
concentrate containing about 50% solids.
5.4.2.4 Botanicals
We have identified three hazardous wastes from the production of botanicals, specifi-
cally alkaloids. These materials are an aqueous solvent with 50% solids, a halogenated waste
solvent, and a non-halogenated waste solvent. Each of these waste streams was disposed of
by incineration. Although there are onsite facilities for incineration of these wastes, as our
example we have chosen a typical plant which is using incineration by contractor offsite.
The average treatment and disposal costs of these wastes range from $68/metric ton of
waste for the non-halogenated waste solvent to $144/metric ton of waste for the aqueous
solvent to a high of $180/metric ton of waste for the halogenated waste solvent. Tables
5.4.2.4-A, -B, and -C describe the costs associated with a typical botanical production
operation.
' For operations making widely diverse products in batch operations where many products were made only
once per year with the production lasting anywhere from one day to three months.
141
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5.4.2,5 Drugs from Animal Sources
For our typical plant we have chosen a plant with 20 employees manufacturing insulin.
The hazardous waste stream from this production facility is an aqueous alcohol with organic
solids. It is typically 25% alcohol, 25% solids, and 50% water. This waste is disposed of by
incineration by a contractor off site. The costs average $50/kg of product or $142/metric
ton of waste. Table 5.4.2.5 describes the costs associated with a typical operation in which
drugs are produced from animal sources.
5.4.2.6 Biologicals
Producing plasma protein fractions represents a typical production scenario for a
biological products plant. We have based our estimates of disposal costs on such a plant. The
representative production capacity for this plant is a 500-liter batch of input plasma. The
associated hazardous waste load from this batch is about 2500 liters of aqueous alcohol.
This corresponds to a hazardous waste load per unit of production of 5 liters of waste per
liter of plasma. This results in an average treatment and disposal cost of 40^/liter of input
plasma. Table 5.4.2.6 describes the costs associated with a typical biological operation.
5.4.3 Formulation and Packaging (SIC 2834)
Finished pharmaceutical preparations are made in the formulation and packaging
operation. The hazardous waste stream from this operation consists of a portion of the
returned goods and reject materials. A typical plant would have 200 production employees
and would operate 250 days per year. Because of the variety of products, it is difficult to
assign a representative plant capacity to these operations. We have therefore described the
plant capacity both in terms of the value of shipments and the value added in that
processing operation. The representative plant we have chosen has $11,000,000 value added
and a $14,000,000 value of the shipments. The average product value added annually per
employee is $55,000; the average value of shipment annually per employee is $70,000. The
hazardous waste load from this facility annually is about 18 metric tons of returned goods
and reject material. Under Level I technology, which is described as crushing this material
onsite and having a contractor handle the landfill and the sanitary landfill offsite, the cost
amounts to about $28 per metric ton of waste. Incineration of this waste by a contractor
offsite raises the average treatment and disposal cost to $67 per metric ton of waste.
Table 5.4.3 describes the waste volume and treatment costs of a typical formulation
and packaging operation.
142
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TABLE 5.4.2.1-A
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; ORGANIC MEDICINAL CHEMICALS
WASTE STREAM - NON-HALOGENATED WASTE SOLVENT1"
Plant description: plant with 300 employees
Representative production schedule, days/year: 250
Representative plant capacity: million kg/year: 1.0
Average product value per unit of production, $/kg 22
Process hazardous waste load in million kg/year:
Waste solvent, non-halogenated; 0.7
Waste solvent, halogenated; 0.1
Potentially hazardous high inert content wastes; 0.05
Heavy metal waste —
Organic chemical residues 0.4
Hazardous waste load (Non-halogenated waste solvent)
million/kg year: 0.7
Hazardous waste load per unit of production: kg/kg 0.7
Levels of Treatment
Cost-($) Level I Level)I Level III
Transportation 1,000 as Level I as Level
Contract disposal charges 46,400
Total Annual Costs 47,400
Average Treatment/Disposal Cost
per Unit of Production, $/kg $0.047
per metric ton of waste $68
Level I - Incineration by contractor off-site
Level II — as Level I
Level III — as Level I
Source: Arthur D. Little, Inc., estimates.
143
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TABLE 5.4.2.1-B
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; ORGANIC MEDICINAL CHEMICALS
WASTE STREAM - HALOGENATED WASTE SOLVENT1"
Ptant'description: plant with 300 employees
Representative production schedule, days per year 250
Representative plant capacity: million kg/year: 1.0
Average product value per unit of production, $/kg 22
Process hazardous waste load in million kg/year:
Waste solvent, non-halogenated; 0.7
Waste solvent, halogenated; 0.1
Potentially hazardous high inert content wastes; 0.05
Heavy metal waste —
Organic chemical residues 0.4
Hazardous waste load (halogenated waste solvent)
million kg/year: 0.1
Hazardous waste load per unit of production: kg/kg 0.1
Level of Treatment
Cost - ($) Level I Level II Level III
Transportation 160 as Level I as Level I
Contract disposal charges 18,280
Total Annual Costs 18,440
Average treatment/disposal cost
per unit of production, $0.018/kg
per metric ton of waste $184
Level I — Incineration by contractor off-site
Level II — as Level I; with energy and resource recovery at contractor's site
Level III-as Level II
Source: Arthur D. Little, Inc., estimates.
144
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TABLE 5.4.Z1-C
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; ORGANIC MEDICINAL CHEMICALS
WASTE STREAM: POTENTIALLY HAZARDOUS HIGH INERT CONTENT WASTESt
Plant description: plant with 300 employees
Representative production schedule, days per year
Representative plant capacity: million kg/year:
Average product value per unit of production, $/kg
Process hazardous waste load: million kg/year:
Waste solvent, non-halogenated;
Waste solvent, halogenated;
Potentially hazardous high inert content wastes;
Heavy metal waste
Organic chemical residues
Hazardous waste load (potentially hazardous high inert
content wastes), million kg/year:
Hazardous waste load per unit of production: kg/kg
250
1.0
22
0.7
0.1
0.05
0.4
0.05
0.05
Levels of Treatment
Cost-($)
Transportation Cost
Contractor Incineration Charge
Contractor Landfill Charge
Neutralization Cost
Contractor Secured Landfill Charge
Total Annual Costs
Average treatment/disposal cost
per unit of production
per metric ton of waste
Level I
1,529
1000kg
$26
Level II
163
730
198
—
438
163
730
198
730
438
2,259
$1.53 $2.26
1000kg
$43
Level III
as Level 11
Level I — Incineration by contractor off-site for solvent containing waste; disposal by contractor
in secure chemical landfill for waste containing corrosives or trace amounts of
heavy metal.*\
Level II — Incineration by contractor off-site for sol vent contain ing waste; treatment (neutrali-
zation) by contractor prior to disposal by contractor in secure chemical landfill for
waste containing corrosives or trace amounts of heavy metal.
Level 111 — as Level 11
*lf this plant were to landfill the solvent containing waste (as described in Table 4.5.3-A) and
landfill the waste containing corrosives or trace amounts of heavy metal, then the associated
costs for treatment and disposal would be $0.77 per 1000 kg product ($13 per metric ton of
waste).
^Source: Arthur D. Little, Inc., estimates.
145
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TABLE 5.4.2.1-D
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; ORGANIC MEDICINAL CHEMICALS
WASTE STREAM - ORGANIC CHEMICAL RESIDUES*
Plant description: plant with 300 employees
Representative production schedule, days/year: 250
Representative plant capacity: million kg/year: 1.0
Average product value per unit of production: $/kg 22
Process hazardous waste load in million kg/year:
Waste solvent, non-halogenated; 0.7
Waste solvent, halogenated; 0.1
Potentially hazardous high inert content wastes; 0.05
Heavy metal waste —
Organic chemical residues 0.4
Hazardous waste load (organic chemical residues)
million kg/year: 0.4
Hazardous waste load per unit of production: kg/kg 0.4
Levels of Treatment
Cost - ($) Level I Level II Level III
Transportation 600 as Level I as Level I
Contract disposal charges 39,400
Total Annual Costs 40,000
Average treatment/disposal cost
per unit of production $0.04/kg
per metric ton of waste $100
Level I — Incineration by contractor off-site*
Level II — as'Level I ,
Level III - as Level I
*lf this plant were to landfill these wastes as described in Table 4.5.2, the associated costs
for treatment and disposal would be $0.0034 per kg product ($8.50 per metric ton of waste).
Larger facilities, such as the one described on this page, do not landfill these residues.
Source: Arthur D. Little, Inc., estimates.
146
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TABLE 5.4.Z3-A
ACTIVE INGREDIENT PRODUCTION; FERMENTATION PRODUCTS; PENICILLIN
WASTE STREAM - WASTE SOLVENT CONCENTRATE (50%SOLIDS)t
Plant description: small plant (with solvent extraction)
Representative production schedule, days per year: 350
Representative plant: 200,000-gallon fermentor capacity.
Product, million kg/year: 0.95
Average product value per unit of production, $/kg 22
Hazardous waste load (waste solvent concentrate, 50% solids),
million kg/year: 1.14
Hazardous waste load per unit of production: kg/kg 1.20
Levels of Treatment
Cost - ($)
Transportation
Contract disposal charges
Total Annual Costs
Average treatment/disposal cost
per unit of production
per metric ton of waste
Level I — Incineration by contractor off-site
Level II — as Level I
Level III — as Level I
* Source: Arthur D. Little, Inc., estimates.
Level I
Level II
1,730 as Level I
133,000
134,730
$0.14/kg
$120
Level III
as Level I
147
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TABLE 5.4.2.3-B
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; FERMENTATION PRODUCTS; PENICILLIN
WASTE STREAM - WASTE SOLVENT CONCENTRATE (50% SOLIDS)1"
Plant description: large plant (with solvent extraction)
Representative production schedule, days per year: 350
Representative plant: 600,000-gallon fermentor capacity
Product, million kg/year: 2.9
Average product value per unit of production, $/kg 22
Hazardous waste load (waste solvent concentrate, 50%
solids), million kg/year: 3.48
Hazardous waste load per unit of production: kg/kg 1.20
Levels of Treatment
Cost - ($) Level I Level II Level III
Transportation 5,280 as Level I as Level I
Contract disposal charges 406,000
Total Annual Costs 411,280
Average treatment/disposal cost
per unit of production $0.14/kg
per metric ton of waste $120
Level I — Incineration by contractor off-site
Level II - as Level I
Level 111 - as Level I
Source: Arthur D. Little, Inc., estimates.
148
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TABLE 5.4.2.4-A
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; BOTANICALS; ALKALOIDS
WASTE STREAM - AQUEOUS SOLVENT WITH SOLIDS (30% SOLVENT, 20% WATER,
50%SOLIDS)t
Plant description: typical size industrial plant with 20
employees
Representative production schedule, days per year: 250
Representative plant capacity, kg/year: 680
Average product value per unit of production, $/kg 11,000
Process hazardous waste load in thousand m3/year:
Aqueous solvent with 50% solids 0.09
Halogenated waste solvent 0.005
Non-halogenated waste solvent 0.020
Hazardous waste load (aqueous solvent with solids 30%
solvent, 20% water, 50% solids) thousand m3/year: 0.09
Hazardous waste load per unit of production: m3/kg 0.13
Levels of Treatment
Cost - ($) Level I Level II Level III
Transportation 160 as Level I as Level I
Contract disposal charges 12,500
Total Annual Costs 12,760
Average treatment/disposal cost
per unit of production $18.8/kg
per metric ton of waste $144
Level I — Incineration by contractor off-site
Level II — as Level I
Level 111 - as Level I
* Source: Arthur D. Little, Inc., estimates.
149
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TABLE 5.4.24-B
TREATMENT AND DISPOSAL COSTS
ACTIVE INGREDIENT PRODUCTION; BOTANICALS; ALKALOIDS
WASTE STREAM - HALOGENATED WASTE SOLVENT*
Plant description: typical size industrial plant with 20 employees
Representative production schedule, days per year: 250
Representative plant capacity: kg/year: 680
Average product value per unit of production, $/kg 11,000
Process hazardous waste load in thousand m3/year:
Aqueous solvent with 50% solids 0.09
Halogenated waste solvent 0.005
Non-halogenated waste solvent 0.020
Hazardous waste load (halogenated waste solvent, thousand
m3/year): 0.005
Hazardous waste load per unit of production: m3/kg 0.007
Levels of Treatment
Cost - ($) Level I Level II Level III
as Level I as Level I
Transportation 20
Contract disposal charges 1,000
Total Annual Costs 1,020
Average treatment/disposal cost
per unit of production $1.5/kg
per metric ton of waste $180
Level I — Incineration by contractor off-site
Level II — as Level I
Level III — as Level I
Source: Arthur D. Little, Inc., estimates.
150
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TABLE 5.4.2.4-C
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; BOTANICALS; ALKALOIDS
WASTE STREAM- NON-HALOGENATED WASTE SOLVENT*
Plant description: typical size industrial plant with 20
employees
Representative production schedule, days per year: 250
Representative plant capacity, kg/year: 680
Average product value per unit of production, $/kg 11,000
Process hazardous waste load in thousand m3/year:
Aqueous solvent with 50% solids 0.09
Halogenated waste solvent 0.005
Non-halogenated waste solvent 0.020
Hazardous waste load (non-halogenated waste solvent,
thousand m3/year): 0.020
Hazardous waste load per unit of production: m3/kg 0.03
Levels of Treatment
Cost - ($) Level I Level II Level III
Transportation 80 as Level I as Level I
Contract disposal charges 1,040
Total Annual Costs 1,120
Average treatment/disposal cost
per unit of production $1.60/kg
per metric ton of waste $68
Level I — Incineration by contractor offsite
Level II — as Level I
Level 111 — as Level I
* Source: Arthur D. Little, Inc., estimates.
151
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TABLE 5.4.2.5
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; DRUGS FROM ANIMAL SOURCES; INSULIN
WASTE STREAM - AQUEOUS ALCOHOL WITH ORGANIC SOLIDS
(25% ALCOHOL, 25%SOLIDS, 50% WATER)T
Plant description: typical size industrial plant with 20
employees
Representative production schedule, days per year: 250
Representative plant capacity, kg/year: 284
Average product value per unit of production, $/kg 11,000
Hazardous waste load (aqueous alcohol with organic solids,
25% alcohol, 25% solids, 50% water), thousand m3/year: 0.10
Hazardous waste load per unit of production: m3/kg 0.35
Levels of Treatment
Cost - ($) Level I Level II Level III
Transportation 400 as Level I as Level I
Contract disposal charges 13,900
Total Annual Costs 14,300
Average treatment/disposal cost
per unit of production $50/kg
per metric ton of waste $142
Level I — Incineration by contractor off-site
Level 11 - as Level I
Level III - as Level I
Source: Arthur D. Little, Inc., estimates.
152
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TABLE 5.4.2.6
TREATMENT AND DISPOSAL COSTS:
ACTIVE INGREDIENT PRODUCTION; BIOLOGICAL PRODUCTS;
PLASMA PROTEIN FRACTIONS
WASTE STREAM - AQUEOUS SOLVENT*
Plant description: typical size industrial plant
Representative production schedule, days/year 250
Representative production capacity: 500-liter batch of
input plasma
Average product value per unit of production, $/kg N.A.*
Hazardous waste load (aqueous alcohol, liters/batch) 2,500
Hazardous waste load per unit of production: liters/liter
of plasma 5
Levels of Treatment
Cost-($) Level I Level II Level III
I
Contract disposal charges per batch 200 as Level I as Level
Average treatment/disposal cost $0.40/1 iter of
per liter of plasma input plasma
Level I — Incineration by contractor off-site
Level II - as Level I
Level III — as Level I
*N.A. = not available
Source: Arthur D. Little, Inc., estimates.
153
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TABLE 5.4.3
TREATMENT AND DISPOSAL COSTS:
FORMULATION AND PACKAGING (FINISHED PHARMACEUTICAL PREPARATIONS)
WASTE STREAM- RETURNED GOODS AND REJECT MATERIAL*
Plant description: plant with 200 employees
Representative production schedule, days/year: 250
Representative plant capacity: $11 million value added
$14 million value of shipments
Average product value added per employee, $/year $55,000
Average value of shipments per employee, $/year $70,000
Hazardous waste load, returned goods and reject material,
metric tons/year 18
kg/year/employee 90
Levels of Treatment
Cost-(S) Level I Level II Level
Crushing 100 - as Level II
Transportation 200 200
Landfill Charge 200 -
Incineration Charge — 1,000
Total Annual Costs 500 1,200
Average treatment/disposal cost
per metric ton of waste $27.80 $66.70
per pound of waste $0.013 $0.03
Level I - crush on-site and landfill in sanitary landfill off-site by contractor
Level II — Incineration by contractor off-site
Level III-as Level II
Source: Arthur D. Little, Inc., estimates.
154
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APPENDIX A*
DESCRIPTION OF HAZARD GRADES
HAZARD CATEGORY I - FIRE
Grade 0 Insignificant Hazard: Includes chemicals that are essentially noncombustible.
Grade 1 Slightly Hazardous: Includes chemicals having a closed-cup flash point
above 140°F (60°C).
Grade 2 Hazardous: Includes combustible chemicals having a closed-cup flash point
below 140°F (60°C) and above 100°F (37.8°C).
Grade 3 Highly Hazardous: Includes flammable liquids having a closed-cup flash
point below 100°F (37.8°C) and a boiling point under standard conditions
above 100°F (37.8°C).
Grade 4 Extremely Hazardous: Includes volatile liquids or liquefied gaseous materials
having a flash point below 100°F (37.8°C) and a boiling point below 100°F
(37.8°C).
*National Academy of Sciences Hazard Classification Scheme.
155
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HAZARD CATEGORY II - LIQUID CONTACT WITH SKIN AND EYES
Grade 0 Insignificant Hazard: Liquids in this category are all those not described
below.
Grade 1 Slightly Hazardous: Liquids that are corrosive to the eyes according to the
definition in 16 CFR 1500.3(c) (3) and the test procedure in 16 CFR
1500.42
Grade 2 Moderately Hazardous: Liquids in this category are:
a. Liquids that are corrosive according to the test procedure described in
46 CFR 146.23-1.
b. Materials that are transported as liquids at 140°F (60°) or above.
c. Liquefied gases that are capable of causing freeze burns.
Grade 3 Highly Hazardous: Liquids in this category have an LD50* of more than
20 mg/kg of body weight when administered by continuous contact for 24
hours or less with the bare skin of rabbits, according to the test procedure
described in 21 CFR Section 191.10 of the Code of Federal Regulations.
Grade 4 Extremely Hazardous: Liquids in this category have an LD50* of 20 mg/kg
or less or body weight when administered by continuous contact for 24
hours or less with the bare skin of rabbits, according to the test procedure
described in 21 CFR Section 191.10 of the Code of Federal Regulations.
*LD5o: that dose likely to kill one-half of a group of animals within 14 days.
156
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Grade 0
HAZARD CATEGORY III - INHALATION OF VAPORS
(Occasional Short-Term)
Insignificant Hazard: Liquids in this category are all those not described
below.
Grade 1 Slightly Hazardous: Liquids in this category cause dizziness and unsteadiness
in 30 minutes or less upon exposure to an atmosphere saturated with vapor
at 122°F(50°C).*
Grade 2 Moderately Hazardous: Liquids in this category have an LC50** in air of
more than 200 ppm, but not more than 2000 ppm by volume of vapor; or
more than 2 mg/1, but not more than 20 mg/1 of mist when administered by
continuous inhalation for one hour or less to both male and female albino
rats (young adults), provided the Coast Guard finds that such concentration
is likely to be encountered by man under any reasonably foreseeable condi-
tion of transportation.*
Liquids in this category may produce sufficient irritation of the eyes or
respiratory tract to cause temporary incapacitation. This includes lachryma-
tors and those corrosive liquids as defined above in Hazard Category I that
have a vapor pressure at 122°F (50°C) or 10 mm Hg or more.*
Grade 3 Highly Hazardous: Liquids in this category have an LC50** in air of more
than 50 ppm but not more than 200 ppm by volume of vapor, or more than
0.50 mg/1, but not more than 2 mg/1, of mist when administered by con-
tinuous inhalation for one hour or less to both male and female albino rats
(young adults), provided the Coast Guard finds that such concentration is
likely to be encountered by man under any reasonably foreseeable condi-
tion of transportation.*
Grade 4 Extremely Hazardous: Liquids in this category have an LC50** in air of
50 ppm by volume or less of vapor, or 0.5 mg/1 or less of mist when admin-
istered by continuous inhalation for one hour or less to both male and
female albino rats (young adults), provided the Coast Guard finds that such
concentration is likely to be encountered by man under any reasonably
foreseeable condition of transportation.
'During transportation emergencies involving liquids (ruptures, spills, etc.) the degree of personnel hazard
is increased by rapid evaporation. If the ratio of the evaporation rate for the test material to that of
n-butyl acetate at 122°F (50°C) under the same test conditions is 0.8 or less, the test material should be
given the next higher rating with a notation to this effect. An appropriate test procedure has been
described.
**LC50: that concentration which, over a given period of time, is likely to kill one-half the test animal
species.
157
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HAZARD CATEGORY IV - GAS INHALATION
Grade 0 Grade 0 is not applicable since no gas has an insignificant hazard.
Grade 1 Slightly Hazardous: Gases in this category are all those not described below,
since the release of a gas into a confined space may displace sufficient
oxygen to create a significant hazard to life.
Grade 2 Moderately Hazardous: Gases in this category have an LC5 0 * in air of more
than 200 ppm, but not more than 2000 ppm, by volume of gas when admin-
istered by continuous inhalation for one hour or less to both male and fe-
male albino rats (young adults). Gases in this category may product suffi-
cient irritation of the eyes or respiratory tract to cause temporary incapacita-
tion. This includes lachrymators.
Grade 3 Highly Hazardous: Gases in this category have an LCSO* of more than 50
ppm, but not more than 200 ppm as described in Grade 3 of Hazard
Category III.
Grade 4 Extremely Hazardous: Gases in this category have an LC5 0 * of 50 ppm or
less as described in Grade 4 of Hazard Category III.
HAZARD CATEGORY V** - HAZARD RATING FOR PREPARED
INHALATION OF GASES AND VAPORS
Grade 0 Insignificant Hazard: Materials in this category are all those not described
below and having standards established by the U.S. Department of Labor,
Occupational Safety and Health Administration (OSHA), as in 29 CFR Sub-
part G, Section 1910.93, of 1000 ppm or more.
Grade 1 Slightly Hazardous: Materials in this category have standards established by
OSHA of 100 ppm or more, but less than 1000 ppm.
Grade 2 Moderately Hazardous: Materials in this category have standards established
by OSHA of 10 ppm or more, but less than 100 ppm.
Grade 3 Highly Hazardous: Materials in this category have standards established by
OSHA of 1 ppm or more, but less than 10 ppm.
Grade 4 Extremely Hazardous: Materials in this category have Occupational Safety
and Health Standards established by OSHA of less than 1 ppm.
*LC50: that concentration which, over a given period of time, is likely to kill one-half the test animal
species.
*OSHA standards are applicable to a normal working situation, i.e., 8 hours per day, 5 days per week.
158
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Grade
0
1
2
3
4
HAZARD CATEGORY VI - WATER POLLUTION RATING -
HUMAN TOXICITY
Description
Insignificant Hazard
Slightly Hazardous
Moderately Hazardous
Highly Hazardous
Extremely Hazardous
LD
so
Above 5000 mg/kg
500-5000 mg/kg
50-500 mg/kg
5-50 mg/kg
Below 5 mg/kg
HAZARD CATEGORY VII - AQUATIC TOXICITY RATING
Grade
0
1
2
3
4
Description
Insignificant Hazard
Practically Nontoxic
Slightly Toxic
Moderately Toxic
Highly Toxic
TLm Concentration
>1000mg/l
100-1000 mg/1
10-100mg/l
1-10 mg/1
<1 mg/1
HAZARD CATEGORY VIM -WATER REACTION RATING
Grade 0 Insignificant Hazard: No known hazardous reaction with water.
Grade 1 Slightly Hazardous: Chemical or physical reaction with water may occur.
Unlikely to be hazardous under conditions of water transportation.
Examples are chlorine, bromine, ethylene oxide, propylene oxide, propionic
anhydride, stabilized benzoyl chloride, and acetic anhydride.
Grade 2 Hazardous Reaction: Examples are anhydrous ammonia, hydrogen fluoride,
and hydrogen chloride.
Grade 3 Highly Hazardous (Vigorous Reaction): Examples are oleum, 72%-98% sul-
furic acid, ethyl trichlorosilane, and chloroacetyl chloride.
Grade 4 Extremely Hazardous (Violent Reaction): Likely if mixed with water.
Examples are sulfur trioxide, chlorosulfonic acid, aluminum triethyl, unstab-
ilized benzoyl chloride, methyl trichlorosilane, and acetyl chloride.
159
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HAZARD CATEGORY IX - SELF-REACTION RATING
Grade 0 Insignificant Hazard: No appreciable self-reaction.
Grade 1 Slightly Hazardous: Chemicals known to undergo polymerization or other
self-reaction under certain conditions. Due to low reactivity or low heat
evolution, they are unlikely to lead to a hazardous situation in bulk water
transportation.
Grade 2 Hazardous: Chemicals that may undergo polymerization or other self-
reaction if contaminated-by an initiator for such process. The results may be
hazardous. They are not considered to require a stabilizer or inhibitor for
safe shipment under normal conditions.
Grade 3 Highly Hazardous: Chemicals that may underto a hazardous self-reaction and
are considered to require special handling, such as incorporation of a sta-
bilizer or polymerization inhibitor to ensure safety in bulk water transporta-
tion.
Grade 4 Extremely Hazardous: Chemicals that can undergo self-oxidation, and/or
polymerization, possibly causing explosions or detonations.
160
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APPENDIX B
PROPERTIES OF HAZARDOUS CONSTITUENTS
EXPLANATION OF SPECIAL TERMS
Several of the terms used in the following tables may not be clear to the average reader.
Therefore, we have prepared short explanations that will be useful in interpreting the data.
• Physical Form - The statement indicates whether the chemical is a solid,
liquid, or gas after it has reached equilibrium with its surroundings at
"ordinary" conditions of temperature and pressure (15°C and 1 atmo-
sphere).
• Specific Gravity - The specific gravity of a chemical is the ratio of the
weight of the solid or liquid to the weight of an equal volume of water at
4°C (or at some other specified temperature).
• Flash Point — The flash point is defined as the lowest temperature at which
vapors above a volatile combustible substance will ignite in air when exposed
to a flame. Depending on the test method used, the values given are either
Tag closed cup (C.C.) (ASTM D56) or Cleveland open cup (O.C.)
(ASTM D93). The values give an indication of the relative flammability of
the chemical. In general, the open-cup value is about 10° to 15°F higher
than the closed-cup value.
• Boiling Point at 1 Atmosphere — This value is the temperature of a liquid
when its vapor pressure is 1 atmosphere. For example, when water is heated
to 100°C (212°F), its vapor pressure rises to 1 atmosphere and the liquid
boils.
• Melting Point — The melting point is the temperature at which a solid
changes to a liquid.
• Chemical Composition — This has been limited to a commonly used one-line
formula.
• Molecular Weight - The value given is the weight of a molecule of the
chemical relative to a value of 12 for one atom of carbon.
• Heat of Combustion - The value is the amount of heat liberated when the
specified weight is burned in oxygen at 25°C. The products of combustion,
including water, are assumed to remain as gases; the value given is usually
161
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referred to as the "lower heat value." The negative sign before the value
indicates that heat is given off when the chemical burns. Units are calories
per gram.
• Solubility - The value represents the grams of a chemical that will dissolve
in 100 grams of pure water. Solubility usually increases when the tempera-
ture increases. The following terms are used when numerical data are either
unavailable or not applicable:
"Miscible" means that the chemical mixes with water in all proportions.
"Insoluble" usually means that 1 gram of the chemical does not dissolve
entirely in 100 grams of water.
• TL (Aquatic Toxicity) — TLm (Median Tolerance Limit) means that ap-
proximately 50% of the fish will die under the conditions of concentration
and time given. The form of data presentation used by the Environmental
Protection Agency's "Oil and Hazardous Material-Technical Assistance Data
System (OHM-TADS)" is used here. Reading from left to right and separated
by slashes (/) are the following data:
Concentration in parts per million by weight (or milligrams per liter) at
which the chemical was tested;
Time of exposure in hours;
Name of the aquatic species studied (only data on fish are given here);
• TLV (Threshold Limit Value) — The threshold limit value is usually ex-
pressed in units of parts per million (ppm) — i.e., the parts of vapor (gas) per
million parts of contaminated air by volume at 25°C (77°F) and atmospheric
pressure. For a chemical that forms a fine mist or dust, the concentration is
given in milligrams per cubic meter (mg/m3). The TLV is defined as the
concentration of the substance in air that can be breathed for five consecu-
tive eight-hour workdays (40-hour work week) by most people without
adverse effect.* As some people become ill after exposure to concentrations
lower than the TLV, this value cannot be used to define exactly what is a
"safe" or "dangerous" concentration.
• LDSO (Oral Toxicity) - The term LDSO signifies that about 50% of the
animals given the specified dose by mouth will die. All LDS 0 values listed
are for rats.
'American Conference of Governmental Industrial Hygienists, "Threshold Limit Values for Substance in
Workroom Air, Adopted by ACGIH for 1972."
162
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TABLE B-1
PROPERTIES OF ACETONE
Physical & Chemical Properties
Physical form: Liquid Chemical composition: CH3COCH3
Specific gravity: 0.791 Molecular Weight: 58.08
Flash Point: 4°F O.C., 0°F C.C. Heat of Combustion: -6808 cal/g
Boiling point at 1 atm: 56.1°C Solubility: Complete
Melting point: -94.7°C Odor: Sweetish
Biological Properties
Toxicity:
TLm: 1 3,000 ppm/48 hr/mosquito fish
TLV: 1000ppm
LD50: >5000 mg/kg
TABLE B-2
PROPERTIES OF ACETONITRILE
Physical & Chemical Properties
Physical form: Liquid Chemical composition: CH3CN
Specific gravity: 0.787 Molecular Weight: 41.05
FlashPoint: 42°F O.C. Heat of Combustion: -7420 cal/g
Boiling point at 1 atm: 81.6°C Solubility: Miscible
Melting point: 45.7°C Odor: Sweet, ethereal
%CI:
Biological Properties
Toxicity:
TL : 1150 ppm/24 hr/fathead minnow
TLV: 40 ppm
LD5 o : 500-5000 mg/kg
163
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TABLE B-3
PROPERTIES OF AMYL ACETATE
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.876
Flash Point: (n-) 91°F, C.C., (iso-) 69°F C.C.
Boiling point at 1 atm: 146°C
Melting point: <-100°C
% Cl:
Biological Properties
Toxicity:
TLm:
TLV: 100ppm
LD50: >5000 mg/kg
Chemical composition: C
Molecular Weight: 130.19
Heat of Combustion: -7423 caI/g
Solubility: Insoluble
Odor: Banana-like
TABLE B-4
PROPERTIES OF BENZENE
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.879
Flash Point: 12°F C.C.
Boiling point at 1 atm: 80.1°C
Melting point: 5.5°C
% CL:
Biological Properties
Toxicity:
TLm: 20 ppm/24 hr/sunfish
TLV: 25 ppm
LDSO: >5000 mg/kg
Chemical composition: C6H6
Molecular Weight: 78.11
Heat of Combustion: -9698 cal/g
Solubility: Insoluble
Odor: Aromatic
164
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TABLE B-5
PROPERTIES OF CHLOROFORM
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 1.49
Flash Point: -
Boiling point at 1 atm: 61.2°C
Melting point: -63.5°C
%CI: 89.09
Biological Properties
Toxicity:
TLm: -
TLV: 25 ppm
LD5 o : >5000 mg/kg
Chemical composition: CHCI3
Molecular Weight: 119.39
Heat of Combustion: —
Solubility: Insoluble
Odor: Ethereal
TABLE B-6
PROPERTIES OF CHROMIC ANHYDRIDE
Physical & Chemical Properties
Physical form: Solid
Specific gravity: 2.70
Flash Point: -
Boiling point at 1 atm:
Melting point: —
Chemical composition: Cr03
Molecular Weight: 100.01
Heat of Combustion: —
Solubility: Very soluble
Odor: -
Reactivity: Reacts with organic materials rapidly; may cause ignition
Biological Properties
Toxicity:
TLm: 52 ppm/96 hr/goldfish
TLV: -
LD5 o : 50-500 mg/kg
165
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TABLE B-7
PROPERTIES OF COPPER SULFATE
Physical & Chemical Properties
Physical form: Solid
Specific gravity: 2.29
Flash Point: -
Boiling point at 1 atm:
Melting point: —
Chemical composition: CuS04-5HaO
Molecular Weight: 249.7
Heat of Combustion: —
Solubility: Soluble
Odor: -
Biological Properties
Toxicity:
Tl_m: 3.8 ppm/24 hr/rainbow trout
TLV: -
LDSO: 50-500 mg/kg
TABLE B-8
PROPERTIES OF ETHANOL
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.790
Flash Point: 55°F C.C., 64°F O.C.
Boiling point at 1 atm: 78.3°C
Melting point: -114°C
Chemical composition: C2HSOH
Molecular Weight: 46.07
Heat of Combustion: -6425 cal/g
Solubility: Miscible
Odor: Like whiskey
Biological Properties
Toxicity:
TLm: 250 ppm/6 hr/goldfish
TLV: 1000 ppm
LD50: >5000 mg/kg
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TABLE B-9
PROPERTIES OF ETHYLENE DICHLORIDE
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 1.253
Flash Point: 60° F O.C., 55° F C.C.
Boiling point at 1 atm: 83.5°C
Melting point: -35.7°C
%CI: 71.66
Biological Properties
Toxicity:
TLm: 150 ppm/*/pin perch
TLV: 50 ppm
LD50: 500-5000 mg/kg
*Time of exposure unknown.
Chemical composition: CICH2CH2CI
Molecular Weight: 98.96
Heat of Combustion: 1900cal/g
Solubility: Insoluble
Odor: Ethereal
TABLE B-10
PROPERTIES OF ETHYLENE GLYCOL MONOMETHYL ETHER
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.966
Flash Point: 120°F O.C., 107°F C.C.
Boiling point at 1 atm: 124.5°C
Melting point: -85.1°C
Chemical composition: CH3OCH2CH2OH
Molecular Weight: 76.10
Heat of Combustion: 5,500 cal/g
Solubility: Miscible
Odor: Mild ethereal
Biological Properties
Toxicity:
TLm: -
TLV: 25 ppm
LD50: 500-5000 mg/kg
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TABLE B-11
PROPERTIES OF HEPTANE
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.6838
Flash Point: 250°FC.C.
Boiling point at 1 atm: 98.4°C
Melting point: -90.6° C
Chemical composition: CH3(CH2)sCH3
Molecular Weight: 100.21
Heat of Combustion: -10,650 cal/g
Solubility: Insoluble
Odor: Gasoline
Biological Properties
Toxicity:
TLm: 4924/24 hr/mosquito fish
TLV: 500 ppm
LD50: >15000mg/kg
TABLE B-12
PROPERTIES OF ISOPROPYL ALCOHOL
Physical & Chemical Properties
Physical form: Liquid
Specif ic:gravity: 0.785
Flash Point: 65° F O.C., 54° F C.C.
Boiling point at 1 atm: 82.3°C
Melting point: -88.5°C
Chemical composition: CH3CH(OH)CH3
Molecular Weight: 60.10
Heat of Combustion: -7,201 cal/g
Solubility: Soluble
Odor: Like ethyl alcohol
Biological Properties
TLm: 900-1 000 ppm/24 hr/chab
TLV: 400 ppm
LDSO: >5000 mg/kg
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TABLE B-13
PROPERTIES OF MERCURY
Physical & Chemical Properties
Physical form: Liquid Chemical composition: Hg
Specific gravity: 13.55 Molecular Weight: -
Flash Point: - Heat of Combustion: -
Boiling point at 1 atm: 357°C Solubility: Insoluble
Melting point: -38.9°C Odor: -
Biological Properties
Toxicity:
TLm: 0.29 ppm/48 hr/marine fish
TLV: 0.05 ng/m3
LDSO: -
TABLE B-14
PROPERTIES OF METHANOL
Physical & Chemical Properties
Physical form: Liquid Chemical composition: CH3OH
Specific gravity: 0.792 Molecular Weight: 32.04
Flash Point: 59°F C.C., 61°F O.C. Heat of Combustion: -4677 caI/g
Boiling point at 1 atm: 64.5°C Solubility: Miscible
Melting point: -97.8°C Odor: Faintly sweet
%CI: -
Biological Properties
Toxicity:
TLm: 250/4 hr/goldfish
TLV: 200 ppm
LDSo >5999mg/kg
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TABLE B-15
PROPERTIES OF METHYL ISOBUTYL KETONE
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.802
Flash Point: 73° F C.C., 75° F O.C.
Boiling point at 1 atm: 116.2°C
Melting point: -84° C
Chemical composition: (CH3)2CHCH2COCH3
Molecular Weight: 100.16
Heat of Combustion: -5800 caI/g
Solubility: 2%
Odor: Pleasant ketonic
Biological Properties
Toxicity:
TLm: >1000ppm
TLV: 100 ppm
LD50: 500-5000 mg/kg
TABLE B-16
PROPERTIES OF METHYLENE CHLORIDE
Physical & Chemical Properties:
Physical form: Liquid
Specific gravity: 1.322
Flash Point: -
Boiling point at 1 atm: 39.8°C
Melting point: -96.7°C
%CI: 83.49
Biological Properties
Toxicity:
TLm: -
TLV: 500 ppm
LD5 o: 500-5000 mg/kg
Chemical composition: C
Molecular Weight: 84.93
Heat of Combustion: -
Solubility: Insoluble
Odor: Aromatic
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TABLE B-17
PROPERTIES OF NAPHTHA (STODDARD SOLVENT)
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.78
Flash Point: 110°FC.C.
Boiling point at 1 atm: 160-199°C
Melting point: —
Chemical composition: (mixture)
Molecular Weight: —
Heat of Combustion: -10,100cal/g
Solubility: Insoluble
Odor: Like kerosene
Biological Properties
Toxicity:
TLm: -
TLV: 200 ppm
LD50: 500-5000 mg/kg
TABLE B-18
PROPERTIES OF n-BUTANOL
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.810
Flash Point: 84°F C.C., 97°F C.C.
Boiling point at 1 atm: 117.7°C
Melting point: -89.3°C
Chemical composition: CH3(CH2)2CHOH
Molecular Weight: 74.12
Heat of Combustion: -7906cal/g
Solubility: Slightly soluble
Odor: Alcohol-like
Biological Properties
Toxicity:
TLm: 1000ppm/29hr/goldfish
TLV: 100 ppm
LD50: 500-5000 mg/kg
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TABLE B-19
PROPERTIES OF n-BUTYL ACETATE
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.875
Flash Point: 99° F O.C., 75° F C.C.
Boiling point at 1 atm: 126°C
Melting point: -73.5°C
Chemical composition: CH3COO(CH2)3CH3
Molecular Weight: 116.16
Heat of Combustion: -7294 cal/g
Solubility: Insoluble
Odor: Fruity in low concentrations
Biological Properties
Toxicity:
TLm: -
TLV: 150-200 ppm
LDSO: >5000mg/kg
TABLE B-20
PROPERTIES OF o-XYLENE
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.880
FlashPoint: 63° F C.C., 75° F O.C.
Boiling point at 1 atm: 144.4°C
Melting point: -25.2°C
Chemical composition: o-C6H4(CH3)2
Molecular Weight: 106.16
Heat of Combustion: -9754.7 cal/g
Solubility: Insoluble
Odor: Benzene-like
Biological Properties
Toxicity:
TLm: -
TLV: 100ppm
LD50: 50-500 mg/kg
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TABLE B-21
PROPERTIES OF TOLUENE
Physical & Chemical Properties
Physical form: Liquid
Specific gravity: 0.867
Flash Point: 40°F C.C., 55°F O.C.
Boiling point at 1 atm: 110.6°C
Melting point: -95.0°C
Chemical composition: CgHjCHs
•Molecular Weight: 92.14
Heat of Combustion: -9686 cal/g
Solubility: Insoluble
Odor: Aromatic
Biological Properties
Toxicity:
TLm: 1180ppm/96hr/sunfish
TLV: 100 ppm
LD5 o : > 5000 mg/kg
TABLE B-22
PROPERTIES OF ZINC CHLORIDE
Physical & Chemical Properties
Physical form: Solid
Specific gravity: 2.91
Flash Point: -
Boiling point at 1 atm: —
Melting point: 283°C
%CI: 52.03
Biological Properties
Toxicity:
TLm: 7.2 ppm/96 hr/bluegill
TLV: 1 mg/m3 (dust)
LD50: 50-500 mg/kg
Chemical composition: ZnC12
Molecular Weight: 136.28
Heat of Combustion: —
Solubility: Soluble
Odor: -
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GLOSSARY OF TERMS
Activated Sludge Treatment - A wastewater treatment process in which biological orga-
nisms convert soluble and insoluble pollutants to biological mass (activated sludge)
which is then usually removed from the treated wastewater by settling.
Active Ingredient - The chemical constituent in a medicinal which is responsible for its
activity.
Analgesics — Pain-relieving medicinals.
Ataraxics — Tranquilizers
Alkaloids - Basic (alkaline) nitrogenous botanical products which produce a marked physio-
logical action when administered to animals (or humans).
Ampoule — A small, sealed-glass container for one dose of a sterile medicine to be injected
hypodermically.
Antibiotic — A substance produced by a living organism which has the power to inhibit
multiplication of, or to destroy, other organisms, especially bacteria.
Biological Products — In the pharmaceutical industry, medicinal products derived from
animals or humans, such as vaccines, toxoids, antisera and human blood frac-
tions.
Blood Fractionation — The separation of human blood into its various protein fractions.
BOD — Biochemical Oxygen Demand — A measure of the amount of oxygen required (and,
therefore, the concentration of the pollutants present) in the destruction of pollu-
tant^) by microorganisms (i.e., activated sludge).
Botanicals — Drugs made from a part of a plant, such as roots, bark, or leaves.
Capsules — A gelatinous shell used to contain medicinal chemicals; a dosage form for admin-
istering medicine.
Chemical Residues - Waste materials, such as still bottoms and chemical process "muds"
or waste slurries.
Control Technology — Method for treatment or disposal for wastes such as neutralization,
landfill, and incineration.
Diatomaceous Earth — A fine material of uniform particle size used to aid in filtration.
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Ethical Products - Pharmaceuticals promoted by advertising to the medical, dental, and
veterinary professions.
Fermentation — Decomposition or conversion of complex substances to other substances
by enzymes produced by microorganisms.
Fermentor Broth - A slurry of microorganisms in water containing'nutrients (carbohydrates,
nitrogen) necessary for the microorganism's growth.
Filter Cakes - Wet solids generated by the filtration of solids from a liquid. This filter cake
may be a pure material (product) or a waste material containing additional fine solids
(i.e., diatomaceous earth) that has been added to aid in the filtration.
Halogenated Solvent — An organic liquid chemical containing an attached halogen (chlorine,
fluorine, etc.) used for dissolving other substances.
Hazardous High-Inert Content Wastes — Those high inert content wastes which contain;
corrosives, trace amounts of heavy metals, or flammable solvents.
Hazardous Wastes — No final judgments are intended by such a classification. Additional
information will be required before a definition of hazardous waste can be made.
Heavy Metals — Originally defined as a group of metals including lead, zinc, arsenic, mer-
cury, selenium, cadmium, and copper which have an atomic weight greater than iron.
In more recent usage, the toxic metals, chromium and vanadium, are also considered
to be "heavy (toxic) metals."
High-Inert Content Wastes — Waste materials such as filter cakes which contain large
amounts of diatomaceous earth, filter aid or activated carbon used to remove color or
trace impurities.
Hormone - Any of a number of substances formed in the body which activate specifically
receptive organs when transported to them by the body fluids.
IMCO System - Intergovernmental Maritime Consultative Organization hazardous material
determination system.
Incineration — Burning under controlled combustion conditions.
Injectables - Medicinals prepared in a sterile (buffered) form suitable for administration by
injection.
Iso-FJectric Precipitation - Adjustment of the pH (hydrogenion concentration) of a solu-
tion to cause precipitation of a substance from the solution.
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Land-Destined Process Wastes — Solids, slurries and liquids currently or previously disposed
on land. The term is used to distinguish these wastes from water or air effluents.
Land Disposal - Placing waste materials into the land in a specific manner as a method of
treatment, storage, or disposal.
LDSO - A dosage level that is lethal to 50% of the test animals to which it is administered.
Medicinal Chemicals — Chemicals which have therapeutic value.
Mycelia — A mass of filaments which constitutes the vegetative body of fungi. In the indus-
try, the term is commonly used to designate the mixture of cells, filter aid, undigested
grain solids, etc., that is filtered off and discarded from all types of fermentations.
Pharmaceutical — A medicinal chemical which has been processed into a stable useful dosage
form.
Plasma — The fluid part of the lymph and of the blood, as distinguished from the coi •
puscles.
PMA — Pharmaceutical Manufacturers Association, which represents 110 pharmaceutical
manufacturing firms which, in turn, account for approximately 95 percent of the
ethical Pharmaceuticals sold in the United States.
Priority I — Hazardous Waste — Includes all "elementary" toxic materials, viz., materials
which are potentially harmful, regardless of their state of chemical combination. This
also includes materials which owe their hazardous properties to their molecular
arrangement — and which fall in hazard grades 3 or 4 in Table 3.1.2A.
Priority II — Hazardous Waste — These wastes owe their hazardous properties to their
molecular arrangement and fall in hazard grades 1 or 2 in Table 3.1.2A.
Proprietary Products — Pharmaceuticals promoted by advertising directly to the consumer.
Sanitary Landfill — A sanitary landfill is a land disposal site employing an engineered
method of disposing of solid wastes on land in a manner that minimizes environmental
hazards by spreading the wastes in thin layers, compacting the solid wastes to the
smallest practical volume, and applying cover material at the end of each operating
day.
Secure Chemical Landfill — A landfill that is lined and limited to chemical wastes.
Serum — Blood serum containing agents of immunity, taken from an animal made immune
to a specific disease by inoculation; it is used as an antitoxin.
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SIC Codes - Standard Industrial Classification. Numbers used by the U.S. Department of
Commerce to denote segments of industry.
Steroid — Any one of a large group of multicyclic ring chemical substances related to
various alcohols occurring naturally in plants and animals.
Still Bottom - The residue remaining after distillation of a material. Varies from a watery
slurry to a thick tar which may turn hard when cool.
Tablet — A small, disc-like mass of compressed medicinal powder used as a dosage form for
administering medicine.
Technology Level I - A waste treatment or disposal method that is the broad average of
technologies which are currently used in typical facilities.
Technology Level II - A waste treatment or disposal method which is the best technology
from an environmental and health standpoint that is currently used in at least one
pharmaceutical facility.
Technology Level III — A waste treatment or disposal method that provides adequate health
and environmental protection.
TLm — Median Tolerance Limit — This measure of aquatic toxicity means that approxi-
mately 50 percent of the fish will die under the conditions of concentration and time
given.
Toxoid — Toxin treated to destroy its toxicity, but still capable of inducing antibody forma-
tion.
Vaccine — A preparation of dead or modified live virus or bacteria introduced into the body
to produce immunity to a specific disease by causing the formation of antibodies.
Virus — Any of a group of ultramicroscopic or submicroscopic infective agents that cause
various diseases; viruses are capable of multiplying in connection with living cells.
Wastewater — Process water contaminated to such an extent it is not reusable in the process
without repurification.
Also please note terms appearing in Appendix B.
ua!318
SW-508
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U. S. GOVERNMENT PRINTING OFFICE : 1976 623-300/498
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