Higher-Tier Environmental Exposure Assessments for Veterinary Medicines
October 10, 2018
Requirements for evaluating the environmental impact of human and veterinary medicines as part of the drug approval process exist across various regulatory authorities in North America, Europe, and Asia-Pacific. In recent years, as the possible effects of pharmaceuticals in the environment have come under increasing scrutiny, these requirements have become more complex, often resulting in fewer exemptions, and more complex exposure and risk assessments. The processes and methods for conducting environmental assessments (EAs, also referred to as environmental impact assessments, or EIAs) for human and veterinary pharmaceuticals can therefore be a significant challenge—both in terms of estimating potential environmental exposure and in utilizing toxicity data generated on non-target organisms to assess possible risks.

Under the National Environmental Policy Act (NEPA), the U.S. Food and Drug Administration (FDA) is required to evaluate all major agency actions, such as approval of a drug, to determine whether they will have a significant impact on the human environment. For animal drugs in particular, the FDA’s Center for Veterinary Medicine (CVM) requires applicants submit either an EA or a claim for categorical exclusion to demonstrate that a drug does not individually or cumulatively have a significant effect on humans or the environment. In the EU, Directive 2001/82/EC, as amended by Directive 2004/28/EC as well as Regulation (EC) 726/2004, requires an EIA for each new and renewal application for any veterinary medicinal product (VMP).

In both the United States and the EU, the environmental risk posed by the use of veterinary medicines is assessed according to the VICH1 harmonized guidelines for Phase I2 and Phase II3 assessments. Further detailed guidance for EU assessments is provided in the European Medicines Agency (EMA) guidelines4, and U.S. assessments may also rely on procedures in the EMA guidelines. These guidelines provide information concerning the structure and content of the EAs/EIAs required for VMPs, and they detail initial exposure assessment methodologies that provide basic worst-case exposure calculations for use in first-tier risk assessments. Where calculations do not indicate an acceptable risk at the first tier, more complex higher-tier exposure assessment can be used to refine the exposure and risk assessment.

One such refinement option is the use of more realistic and mechanistic environmental exposure models to refine the environmental exposure. For the United States, FDA/CVM encourages the use of more advanced models for risk refinement, for example, the U.S. Environmental Protection Agency’s (EPA’s) Pesticides in Water Calculator (PWC). This model was developed for predicting potential exposure of pesticides and, therefore, needs adaptation for assessment of VMPs; however, it incorporates information about soils, climates, crop scenarios and other factors pertinent to the United States.

Exponent has extensive experience with PWC and with the adaptation of this model to predict environmental exposures from VMPs. Exponent performed even further exposure refinement using a unique watershed-level exposure assessment, in which we successfully applied EPA’s BASINS/HSPF5 models6. For the EU, the FOCUS7 models are recommended for higher-tier refinements of exposures through surface water, sediment, and groundwater. These models were developed to examine potential exposure following application of agricultural pesticides and incorporate soil, climate, and crop scenarios specific to the EU. However, as with the PWC model, adaptations of the FOCUS model inputs are required to make the modeling appropriate to the use pattern for a VMP.

How Can Exponent Help?

Exponent scientists have many years of experience using and adapting the VICH, EPA, and FOCUS tools and models for environmental assessment of VMPs to fulfil drug approval requirements. In addition to the refinement of risks on a watershed scale that was accomplished with the BASINS/HSPF models, Exponent has also successfully refined surface water and sediment exposures following applications of a VMP to livestock for intensively reared and pasture-reared animals. In these situations the exposure refinement and subsequent environmental assessment led to a successful regulatory outcome.

These capabilities exist within our European and North American Chemical Regulation and Food Safety and Ecological and Biological Sciences practices. The group can be contacted for further information using the details listed below.

References

  1. VICH refers to International Cooperation on Harmonization of Technical Requirements for Regulation of Veterinary Medicinal Products: https://vichsec.org/
  2. VICH. 2000. Environmental Impact Assessments (EIA’s) for Veterinary Medicinal Products (VMP’s) – Phase I. VICH GL 6.
  3. VICH. 2004. Environmental Impact Assessment for Veterinary Medicinal Products – Phase II Guidance. VICH GL 38.
  4. EMA. 2016. Committee for Medicinal Products for Veterinary Use (CVMP). Guideline on Environmental Impact Assessment for Veterinary Medicinal Products in Support of the VICH Guidelines GL6 and GL 38. European Medicines Agency EMEA/CVMP/ERA/418282/2005-Rev.1-Corr. 24. June 2016.
  5. BASINS/HSPF refers to Better Assessment Science Integrating Point and Non-point Sources (BASINS) and Hydrologic Simulation Program-Fortran (HSPF): https://www.epa.gov/ceam/better-assessment-science-integrating-point-and-non-point-sources-basins.
  6. https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadEA/1
  7. [1] FOCUS refers to the Forum for Co-ordination of pesticide fate models and their use: https://esdac.jrc.ec.europa.eu/projects/focus-dg-sante.

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