Environmental Assessments Human and Animal Drugs

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Environmental AssessmentsHuman and Animal Drugs

• Nancy Sager
• Center 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 EPAs
  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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Retrospective Review of Ecotoxicity Data
Center for Drug Evaluation and Research (CDER)
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)
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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

• FDAs guidance on Environmental Assessment of
  Human Drug and Biologics Applications (July 1998)
  available at http//www.fda.gov/cder/
  guidance/index.htm
• FDAs guidance on Environmental Impact
  Assessments (EIAs) for Veterinary Medicinal
  Products (VMPs) VICH GL6 (March 7, 2001)
  available at http//www.fda.gov/cvm/guidance/guide
  89.doc

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Sources of Information

• After approval of the application, Environmental
  Assessments are available under the Freedom of
  Information Act