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By Barbara Davit and Yu Chung Tsang

Barbara Davit-finalYu Chung Tsang-finalPharmaceutical drug products are commonly available in multiple strengths, either for immediate release (IR) or modified release (MR) formulations. Pivotal bioequivalence (BE) studies, whether used for bridging formulations during new drug development or for establishing therapeutic equivalence between a generic drug and its corresponding reference product, are usually required by regulatory agencies to be conducted on the highest strength of the product line.

If the formulations of the lower strengths in the product line are linearly proportional to that of the highest strength and the dissolution characteristics of all the dosage strengths are similar, then the in vivo BE study requirement can be waived for the low strengths (i.e., a biowaiver can be granted). However, if various strengths are not linearly formulated, then the waiver of BE studies may not be granted, depending on the degree of deviation from linearity. The development of proportional formulations can be challenging for MR products and combination drug products with more than one active ingredient.

Currently, biowaiver criteria from various jurisdictions (e.g. U.S., EU, and Canada) are different, resulting in significant challenges in the development of same formulations for global marketplaces. A harmonization of the criteria will provide a clear direction to the formulator in developing the global formulations that minimize the number of required BE studies.

At the 2015 AAPS Annual Meeting and Exposition on October 25, the AAPS Bioequivalence Focus Group and the Generic Pharmaceuticals Focus Group will jointly present a short course titled Global Criteria for Biowaiver of Various Dosage Strengths of a Drug Product. The objectives of this short course are to:

  • examine the differences in criteria triggering requests for BE studies versus biowaivers among the major regulatory authorities; and
  • discuss strategies commonly employed by formulators to produce proportional formulations among various strengths of IR as well as MR products in order to minimize the number of required BE studies.

This short course is an important forum for scientists from both innovator and generic drug companies to learn the challenges in developing proportional formulations and possible strategies in dealing with them in order to save time and cost for formulation development. Such strategies to be discussed in this short course are especially relevant for MR products and combination drug products, both of which present biowaiver challenges. The unique opportunity to hear from and interact with regulators from the U.S., EU, and Canada in this short course is timely in aiding drug developers to understand the differences in requirement among these major jurisdictions. Such understanding of similarities and differences in global requirements can in turn pave the path for possible harmonization which is essential for developing global formulations, as global product development is increasingly desired for multinational drug companies.

Barbara Davit, Ph.D., J.D., is an executive director in the Biopharmaceutics Team at Merck Research Laboratories (MRL), where she is responsible for directing clinical bioavailability/bioequivalence studies worldwide as deemed necessary during Phases 1, 2, and 3 of new drug development. Prior to joining MRL, she worked at FDA’s Center for Drug Evaluation and Research for 22 years, where she held positions of increasing responsibility in both the Office of Clinical Pharmacology and Biopharmaceutics and Office of Generic Drugs.
Yu Chung Tsang, B.Sc. Phm., Ph.D., is the chief scientific officer in Biopharmaceutics and Biostatistics at Apotex Inc., Canada. He has been working there for 25 years and his current responsibilities include the provision of scientific expertise and strategic direction in the design of bioequivalence/clinical endpoint studies, and statistical support in clinical trials of new chemical entities as well as biosimilar products in the Apotex group of companies.