Assessing Environmental Impacts of Veterinary Products: Lessons from VICH

In 1996, the Steering Committee of the VICH (International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Products)1 selected ecotoxicity as one of the five initial topics2 for harmonization under this joint government-industry program. This topic was selected for harmonization by the principal parties to VICH (viz., European Union, United States, and Japan) because of the gulf in drug registration requirements that existed among these regions at the time. A working group (VICH Ecotox Working Group or VICH EWG) was formed in 1997 to develop harmonized guidelines, taking into account any existing guidance documents and legislative/regulatory requirements. The VICH EWG included representatives from industry and regulatory authorities from the European Union, United States, Japan, Australia, New Zealand, and Canada. The VICH EWG held nine face-to-face meetings over a 7-year period that ended in 2004. The task of developing the guidelines was split into two phases: phase I and phase II. For drugs that qualify for a VICH phase I assessment only, environmental fate and effects data are not required for evaluation of the potential risk of drug residues on nontarget species in the environment. For products that require a full assessment (VICH phase II), environmental fate and effects study data are required to assess the potential impact of veterinary drug residues (parent and metabolites, in certain situations) on nontarget species in aquatic and terrestrial ecosystems. A phase II assessment of a given veterinary drug residue includes studies of (1) physicochemical properties (eg, water solubility, octanol/water partitioning), (2) binding to soils, (3) biodegradation in soil or aquatic test systems, and (4) effects of the drug residue on select aquatic (algae, daphnia, fish) and terrestrial species (soil microflora, plants, earthworms, and possibly dung beetles and flies). The studies recommended for a phase II assessment are to be done in accordance with Organization for Economic Cooperation and Development (OECD) protocols (found at www.oecdwash.org/PUBS/PERIOD/per-chemical.htm). Alternatively, International Organisation for Standardization (ISO) protocols (found at www.iso.ch/iso/en/CatalogueListPage.CatalogueList) are used if final OECD protocols do not exist. Whether these studies are to be done in accordance with good laboratory practices (GLPs) is a region-by-region matter, and hence it is not recommended in the VICH phase II guidance document. As of 2006, the VICH phase I and II guidelines have been adopted officially in the European Union, United States, Japan, Australia, and New Zealand. They have been formally adopted in the European Union, United States, Australia, and New Zealand.3 These documents are available on various Web sites (Food and Drug Administration’s Center for Veterinary Medicine [FDA/CVM] at www.fda.gov/cvm, European Medicines Agency [EMEA] at www.emea.europa.eu, and VICH4 at www.vichsec.org). Algorithms to calculate worst-case predicted environmental concentrations (PECs) could not be harmonized by the VICH EWG, ostensibly because of the differences in the animal husbandry and land-use practices of the respective VICH regions. Development of PEC calculation algorithms was left to the individual regions5 to develop, and several approaches have emerged that may be used by regulators and applicants alike. The effort to develop harmonized ecotoxicity testing guideines under the VICH program was largely concluded to be successful by regulators and many in the pharmaceutical industry. It opened channels for meaningful dialogue between regulators and industry personnel on appropriate approaches to assessing the potential risks of veterinary drug residues on nontarget species in the environment. But, the true measure of how successful this 7-year effort was will be determined in the coming years as experience is gained using these guidelines in the regions where they were adopted.