Animal & Veterinary
ONADE Participates in Bioequivalence Workshop
By Dr. Melanie McLean, Senior Writer/Editor, Communications with contributions from Dr. Marilyn Martinez, Pharmacologist, Office of New Animal Drug Evaluation
CVM’s Office of New Animal Drug Evaluation (ONADE) participated in an international workshop on bioequivalence issues in veterinary medicine in Potomac, MD from June 27 to 30, 2010. The workshop was hosted by three veterinary groups, one based in the United States and two based in Europe:
- American Academy of Veterinary Pharmacology & Therapeutics (AAVPT);
- European College of Veterinary Pharmacology & Toxicology (ECVPT); and
- European Association for Veterinary Pharmacology & Toxicology (EAVPT).
Members of the workshop’s planning committee were from industry, academia, and government. Drs. Marilyn Martinez, Sanja Modric, Ken Harshman, and Eden Bermingham of ONADE were instrumental in organizing the workshop. Drs. Martinez and Modric each chaired a session.
The term “bioequivalence” reflects the pharmacological similarity of different drugs or different formulations of the same drug. Two drugs, or two formulations of the same drug, are “bioequivalent” if they are given at the same dose, contain the same active ingredient, and reach the same level at the site of action. Two bioequivalent drugs, or two bioequivalent drug formulations, are absorbed the same way by the body and result in the same clinical response in the patient.
Bioequivalence is important in evaluating generic animal drugs. A generic animal drug is a copy of an approved brand name animal drug. The approved brand name animal drug is called the “pioneer.” A drug sponsor for a generic animal drug conducts a bioequivalence study to prove that the generic copy is bioequivalent to the pioneer. Bioequivalence is also important in evaluating a formulation change for an approved animal drug. To show that the new formulation is bioequivalent to the original formulation, the drug sponsor generally conducts a bioequivalence study.
The recent workshop was described by Dr. Martinez, a pharmacologist in ONADE, as a way to explore creative solutions to the complex bioequivalence issues seen in veterinary medicine. The typical methods used to evaluate bioequivalence are not always adequate, so new approaches are needed. Because of the diversity of animal species and the variety of animal drugs, there is “no one size fits all” solution, said Dr. Martinez.
Three members of ONADE were speakers at the workshop. Biostatistician Dr. Veronica Taylor, in ONADE’s Division of Scientific Support, discussed a possible new approach to analyze bioequivalence. It involves adjusting the conventional statistical criteria used to assess the similarity of two drugs, or two formulations of the same drug.
Dr. Martinez addressed the challenges of evaluating the bioequivalence of drugs that last in an animal’s body for weeks, months, or even years. The ability of the drug to last for a long time may be due to the drug’s characteristics or how it is formulated. Dr. Martinez stated that the bioequivalence study should be tailored to the method used to analyze the results. Also, the method of analysis should be based on an understanding of how the drug is released into the animal’s body.
Dr. Rebecca Owen, a chemist in ONADE’s Division of Manufacturing Technologies, discussed biomass drug substances. A biomass is an unpurified fermentation product, and some biomass products are approved for use in medicated feeds for animals. For a drug to be approved by FDA, the entire drug substance should be characterized. This characterization includes describing the active molecule and any impurities. Synthetic products are easier to characterize because the impurities are only a small portion of the drug substance. But for biomass products, the impurities make up the bulk of the drug substance. These impurities can include the organism used in the fermentation process, other metabolites produced by the organism, and components of the fermentation media. To determine if a generic biomass product is bioequivalent to the pioneer, the drug sponsor should consider the active molecule and all impurities.
The joint AAVPT/ECVPT/EAVPT workshop provided a good opportunity for biostatisticians, pharmacologists, drug sponsors, and regulatory scientists to brainstorm about solutions to bioequivalence issues in veterinary medicine.
For more information on AAVPT’s Bioequivalence Initiative in veterinary medicine, please visit: http://www.aavpt.org/BEInitiative.shtml.