environmental assessments human and animal drugs
DESCRIPTION
Environmental Assessments Human and Animal Drugs. Nancy Sager Center for Drug Evaluation and Research Food and Drug Administration. Federal Food, Drug, and Cosmetic Act (FFDCA) National Environmental Policy Act (NEPA) FDA regulations implementing NEPA (21 CFR Part 25) revised in 1997 - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/1.jpg)
Environmental AssessmentsHuman and Animal Drugs
Nancy SagerCenter for Drug Evaluation and Research
Food and Drug Administration
![Page 2: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/2.jpg)
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)
![Page 3: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/3.jpg)
NEPA Process
• Categorical Exclusion (CE)– Extraordinary circumstances provision
• Environmental Assessment (EA)
• Environmental Impact Statement (EIS)
![Page 4: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/4.jpg)
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
![Page 5: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/5.jpg)
Categorical ExclusionExamples
• Approval of a drug when the approval will not increase the use of the drug
• Withdrawal of approval of a drug
![Page 6: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/6.jpg)
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
![Page 7: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/7.jpg)
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)
![Page 8: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/8.jpg)
Environmental Assessment Issues Human Drugs
• EIC 1 ppb (ecotoxicity)
• Use of wild plants/animals (harvesting)
– extraordinary circumstances provision
![Page 9: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/9.jpg)
Environmental Assessment Issues Animal Drugs
Ecotoxicity
• Feedlots/Poultry Houses/Swine Operations
– Confined animal feed operations (CAFOs)
• Aquaculture
• Pastured Animals
![Page 10: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/10.jpg)
Ecotoxicity Evaluation
• Fate and Effects
• Follows standard approaches/test methods (OECD/EPA/VICH)
![Page 11: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/11.jpg)
Fate: Physical/Chemical Characterization
• water solubility
• dissociation constant
• octanol/water partition coefficient
• vapor pressure
• sorption/desorption properties
![Page 12: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/12.jpg)
Fate: Depletion Mechanisms
• photolysis
• hydrolysis
• biodegradation
![Page 13: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/13.jpg)
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
![Page 14: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/14.jpg)
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
![Page 15: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/15.jpg)
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
![Page 16: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/16.jpg)
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)
![Page 17: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/17.jpg)
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 DataCenter for Drug Evaluation and Research (CDER)
![Page 18: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/18.jpg)
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
![Page 19: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/19.jpg)
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
![Page 20: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/20.jpg)
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
![Page 21: Environmental Assessments Human and Animal Drugs](https://reader035.vdocuments.us/reader035/viewer/2022062501/568160cb550346895dcffc23/html5/thumbnails/21.jpg)
Sources of Information
• After approval of the application, Environmental Assessments are available under the Freedom of Information Act