Environmental Assessments Human and Animal Drugs Nancy Sager Center for Drug Evaluation and Research...
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![Page 1: Environmental Assessments Human and Animal Drugs Nancy Sager Center for Drug Evaluation and Research Food and Drug Administration.](https://reader036.fdocuments.in/reader036/viewer/2022062320/56649cd55503460f9499c75e/html5/thumbnails/1.jpg)
Environmental AssessmentsHuman and Animal Drugs
Nancy SagerCenter for Drug Evaluation and Research
Food and Drug Administration
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Statutory Framework
• Federal Food, Drug, and Cosmetic Act (FFDCA)
• National Environmental Policy Act (NEPA)– FDA regulations implementing NEPA (21 CFR Part 25) revised in 1997
• Human and animal drugs are exempt from EPA’s Toxic Substances Control Act (TSCA)
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NEPA Process
• Categorical Exclusion (CE)– Extraordinary circumstances provision
• Environmental Assessment (EA)
• Environmental Impact Statement (EIS)
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Categorical Exclusion Examples
• Investigational new (animal) drug applications (IND/INAD)
• Approval of natural substances when approval does not alter significantly the distribution of the substance, its metabolites or degradation products in the environment
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Categorical ExclusionExamples
• Approval of a drug when the approval will not increase the use of the drug
• Withdrawal of approval of a drug
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Categorical ExclusionExamples
• Human drugs: Approval of a drug when the concentration of drug expected to enter the aquatic environment (EIC) is less than 1 ppb
• Animal drugs: Approval of drugs intended for use in nonfood animals
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Environmental Impact Statement
There are no categories of FDA actions that routinely significantly affect the quality of the human environment and that therefore ordinarily require the preparation of an EIS
– FDA has prepared only one EIS directly related to human/animal drug use (CFCs, 1978)
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Environmental Assessment Issues Human Drugs
• EIC 1 ppb (ecotoxicity)
• Use of wild plants/animals (harvesting)
– extraordinary circumstances provision
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Environmental Assessment Issues Animal Drugs
Ecotoxicity
• Feedlots/Poultry Houses/Swine Operations
– Confined animal feed operations (CAFOs)
• Aquaculture
• Pastured Animals
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Ecotoxicity Evaluation
• Fate and Effects
• Follows standard approaches/test methods (OECD/EPA/VICH)
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Fate: Physical/Chemical Characterization
• water solubility
• dissociation constant
• octanol/water partition coefficient
• vapor pressure
• sorption/desorption properties
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Fate: Depletion Mechanisms
• photolysis
• hydrolysis
• biodegradation
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Effects
• Tiered approach: Generally, acute toxicity testing then chronic if data indicate
• Typical number of effects studies
– Human drugs: 2-4
– Animal drugs: 4-5
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Differences: Environmental Compartment
• EAs for human drugs normally focus on the aquatic environment
• EAs for animal drugs may evaluate fate and effects in the aquatic and terrestrial environments
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Differences: Cut-offs
• Human drugs are categorically excluded (CE) if the EIC in the aquatic environment is less than 1 ppb (absent extraordinary circumstances)
• Animal drugs do not have a CE based on an EIC. However, less information can be provided if EICs are:
– less than 1 ppb released from aquaculture facility
– less than 100 ppb in soil
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1 ppb (Aquatic)
• Data on human drugs routinely demonstrated no effects on relevant standard test organisms at concentration less than 1 ppb
• Approximately 90% of the toxicity results were 1 ppm or greater; 10% were between 1 ppb and 1 ppm)
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6 4 51 3 4 0 2 0 1
95
32
12 9 7 610
26
20
53
0
20
40
60
80
100
120
0.001 0.1 0.2 0.03 0.4 0.5 0.6 0.7 0.8 0.9 1 100 200 300 400 500 600 700 800 900 1000
Toxicity test result (ppm)
Retrospective Review of Ecotoxicity Data
Center for Drug Evaluation and Research (CDER)
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100 ppb (Soil)
100 ppb is below the level shown to have effects in ecotoxicity studies conducted on earthworms, microbes, and plants for animal drugs in the U.S
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Sources of Information
• 21 CFR Part 25 (FDA regulations implementing NEPA)
• 40 CFR Parts 1500-1508 (NEPA regulations)
• Retrospective Review of Ecotoxicity Data Submitted in Environmental Assessments available under FOI from Public Docket No. 96N-0057
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Sources of Information
• FDA’s guidance on Environmental Assessment of Human Drug and Biologics Applications (July 1998) available at http://www.fda.gov/cder/ guidance/index.htm
• FDA’s guidance on Environmental Impact Assessments (EIAs) for Veterinary Medicinal Products (VMPs); VICH GL6 (March 7, 2001) available at http://www.fda.gov/cvm/guidance/guide89.doc
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Sources of Information
• After approval of the application, Environmental Assessments are available under the Freedom of Information Act