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International Guidelines for Bioequivalence of Systemically Available Orally Administered Generic Drug Products: A Survey of Similarities and Differences

  • Review Article
  • Theme:Human and Veterinary Therapeutics: Interspecies Extrapolations and Shared Challenges
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Abstract

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.

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ACKNOWLEDGMENTS

The authors wish to thank the following for valuable contributions to this manuscript: Gary Condran, Craig Simon, Bindu Islam, and Mike Ward of Health Canada; Silvia Arteaga Hernandez of the Federal Commission for the Protection Against Sanitary Risk, Mexico; Jun Kitahara and Nobumasa Nakashima of the Japanese Pharmaceuticals and Medical Devices Agency; Cordula Landgraf and Gabriela Zenhaeusern of SwissMedic; and Matthias Mario Stahl of the World Health Organization; and Xiaofei (Sophie) Wang of FDA’s Office of Generic Drugs.

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  1. Merck Pharmaceuticals, Rahway, New Jersey, USA

    Barbara Davit

  2. Office of Generic Drugs, Center for Drug Evaluation and Research, US-FDA, Rockville, Maryland, USA

    April C. Braddy, Dale P. Conner & Lawrence X. Yu

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  1. Barbara Davit
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  2. April C. Braddy
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Correspondence to Barbara Davit.

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Davit, B., Braddy, A.C., Conner, D.P. et al. International Guidelines for Bioequivalence of Systemically Available Orally Administered Generic Drug Products: A Survey of Similarities and Differences. AAPS J 15, 974–990 (2013). https://doi.org/10.1208/s12248-013-9499-x

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