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Estimating product bioequivalence for highly variable veterinary drugs.
R Claxton1, J Cook, L Endrenyi
1Schafer Veterinary Consultants, Fort Collins, CO, USA.
Journal of Veterinary Pharmacology and Therapeutics
|March 15, 2012
Summary
This study explores alternative methods for assessing bioequivalence in highly variable veterinary drugs, addressing challenges unique to animal medicine. It proposes modifications to existing human drug bioequivalence approaches for veterinary applications.
Area of Science:
- Pharmacokinetics and Drug Bioequivalence
- Veterinary Pharmacology
- Regulatory Science
Background:
- Large intrasubject pharmacokinetic variability is observed in both human and veterinary drugs.
- The scaled average bioequivalence (SABE) approach, used by the FDA's CDER for human drugs, requires adaptation for veterinary dosage forms.
- Unique challenges in veterinary medicine necessitate variations of the CDER's SABE approach.
Purpose of the Study:
- To discuss highly variable drugs (HVD) and highly variable veterinary drugs (HVVD).
- To present alternative approaches for assessing product bioequivalence (BE) in veterinary medicine.
- To highlight limitations of current crossover study designs and propose statistical analysis strategies for HVVD.
Main Methods:
- Review and discussion of existing bioequivalence assessment methods for highly variable drugs.
- Enumeration of limitations associated with 3- and 4-way crossover study designs in veterinary medicine.
- Exploration of alternative statistical analyses, including parallel study designs, secondary criteria (test-to-reference ratio), definition of σ(0), and average BE with expanding limits.
Main Results:
- Identified limitations in applying standard human bioequivalence study designs to veterinary highly variable drugs.
- Proposed the need for statistical analysis of HVVD in parallel study designs.
- Raised considerations for secondary criteria, defining σ(0), and average bioequivalence with expanded limits for veterinary drugs.
Conclusions:
- Existing bioequivalence assessment methods need adaptation for highly variable veterinary drugs.
- Further discussion and finalization are required regarding regulatory constants and the definition of 'highly variable' in veterinary drug products.
- Collaboration between academicians, industrial scientists, and regulators is crucial to resolve these details.
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