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Pharmacokinetics-Based Approaches for Bioequivalence Evaluation of Topical Dermatological Drug Products

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Abstract

The pharmacokinetic approach has accelerated the development of high-quality generic medicines with extraordinary cost savings, transforming the pharmaceutical industry and healthcare system in the USA. While this is true for systemically absorbed drug products, the availability of generic versions of topical dermatological products remains constrained due to the limited methods accepted for bioequivalence evaluation of these products. The current review explores the possibility of developing appropriate bioequivalence approaches based on pharmacokinetic principles for topical dermatological products. This review focuses on the strengths and limitations of the three most promising pharmacokinetics-based methods to evaluate the performance and bioequivalence of topical dermatological products, which include in vivo skin stripping, in vivo microdialysis, and in vitro permeation testing (IVPT) with excised human skin. It is hoped that recent advances in pharmaceutical and regulatory science will facilitate the development of robust bioequivalence approaches for these dosage forms, enable more efficient methodologies to compare the performance of new drug products in certain pre-approval or post-approval change situations, and promote the availability of high-quality generic versions of topical dermatological products.

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Notes

  1. Drug products approved by the US FDA are coded to reflect the nature of their therapeutic equivalence (or lack thereof). According to the preface of the 34th edition of the Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations [7], the therapeutic equivalence rating of AB for a generic drug product indicates that it is considered to be therapeutically equivalent to its pharmaceutically equivalent reference listed drug product, and that actual or potential bioequivalence problems have been resolved with adequate in vivo and/or in vitro evidence supporting bioequivalence.

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Acknowledgments

No sources of funding were used to assist in the preparation of this review.

Conflict of interest

S. G. Raney, T. J. Franz, P. A. Lehman, R. Lionberger, and M.-L. Chen have no conflicts of interest to declare.

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Authors and Affiliations

  1. Office of Research and Standards, Center for Drug Evaluation and Research, United States Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA

    Sam G. Raney & Robert Lionberger

  2. 10716 SE Forest View Lane, Happy Valley, OR, 97086, USA

    Thomas J. Franz

  3. QPS Holdings, LLC, Newark, DE, USA

    Paul A. Lehman

  4. Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA

    Mei-Ling Chen

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  1. Sam G. Raney
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  2. Thomas J. Franz
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  5. Mei-Ling Chen
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Correspondence to Sam G. Raney.

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This article reflects the views of the authors and should not be construed to represent the United States Food and Drug Administration’s views or policies.

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Raney, S.G., Franz, T.J., Lehman, P.A. et al. Pharmacokinetics-Based Approaches for Bioequivalence Evaluation of Topical Dermatological Drug Products. Clin Pharmacokinet 54, 1095–1106 (2015). https://doi.org/10.1007/s40262-015-0292-0

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