Scientific Publications by FDA Staff

AAPS J 2013 Oct;15(4):974-90

International guidelines for bioequivalence of systemically available orally administered generic drug products: a survey of similarities and differences.

Davit B, Braddy AC, Conner DP, Yu LX

The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Association, Japan, Mexico, Singapore, South Korea, Switzerland, the USA, and the World Health Organization. We began with a comparison of how the various jurisdictions and organizations define a generic product and its corresponding reference product. We then compared the following bioequivalence approaches: recommended bioequivalence study designs, method of pharmacokinetic calculations and bioequivalence acceptance limits, recommendations for modifying bioequivalence study designs and limits for highly variable drugs and narrow therapeutic index drugs, provisions for waiving bioequivalence study requirements (granting biowaivers), and implementation of the Biopharmaceutics Classification System. We observed that, overall, there are more similarities than differences in bioequivalence approaches among the regulatory authorities surveyed.