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Physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1%

Establishing bioequivalence (BE) for dermatological drug products by conducting comparative clinical end point studies can be costly and the studies may not be sufficiently sensitive to detect certain formulation differences. Quantitative methods and modeling, such as physiologically‐based pharmacok...

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Autores principales: Tsakalozou, Eleftheria, Babiskin, Andrew, Zhao, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129718/
https://www.ncbi.nlm.nih.gov/pubmed/33547863
http://dx.doi.org/10.1002/psp4.12600
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author Tsakalozou, Eleftheria
Babiskin, Andrew
Zhao, Liang
author_facet Tsakalozou, Eleftheria
Babiskin, Andrew
Zhao, Liang
author_sort Tsakalozou, Eleftheria
collection PubMed
description Establishing bioequivalence (BE) for dermatological drug products by conducting comparative clinical end point studies can be costly and the studies may not be sufficiently sensitive to detect certain formulation differences. Quantitative methods and modeling, such as physiologically‐based pharmacokinetic (PBPK) modeling, can support alternative BE approaches with reduced or no human testing. To enable PBPK modeling for regulatory decision making, models should be sufficiently verified and validated (V&V) for the intended purpose. This report illustrates the US Food and Drug Administration (FDA) approval of a generic diclofenac sodium topical gel that was based on a totality of evidence, including qualitative and quantitative sameness and physical and structural similarity to the reference product, an in vivo BE study with PK end points, and, more importantly, for the purposes of this report, a virtual BE assessment leveraging dermal PBPK modeling and simulation instead of a comparative clinical end point study in patients. The modeling approach characterized the relationship between systemic (plasma) and local (skin and synovial fluid) diclofenac exposure and demonstrated BE between the generic and reference products at the presumed site of action. Based on the fit‐for‐purpose modeling principle, the V&V process involved assessing observed data of diclofenac concentrations in skin tissues and plasma, and the overall performance of the modeling platform for relevant products. Using this case as an example, this report provides current scientific considerations on good practices for model V&V and the establishment of BE for dermatological drug products when leveraging PBPK modeling and simulation for regulatory decision making.
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spelling pubmed-81297182021-05-21 Physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1% Tsakalozou, Eleftheria Babiskin, Andrew Zhao, Liang CPT Pharmacometrics Syst Pharmacol Reviews Establishing bioequivalence (BE) for dermatological drug products by conducting comparative clinical end point studies can be costly and the studies may not be sufficiently sensitive to detect certain formulation differences. Quantitative methods and modeling, such as physiologically‐based pharmacokinetic (PBPK) modeling, can support alternative BE approaches with reduced or no human testing. To enable PBPK modeling for regulatory decision making, models should be sufficiently verified and validated (V&V) for the intended purpose. This report illustrates the US Food and Drug Administration (FDA) approval of a generic diclofenac sodium topical gel that was based on a totality of evidence, including qualitative and quantitative sameness and physical and structural similarity to the reference product, an in vivo BE study with PK end points, and, more importantly, for the purposes of this report, a virtual BE assessment leveraging dermal PBPK modeling and simulation instead of a comparative clinical end point study in patients. The modeling approach characterized the relationship between systemic (plasma) and local (skin and synovial fluid) diclofenac exposure and demonstrated BE between the generic and reference products at the presumed site of action. Based on the fit‐for‐purpose modeling principle, the V&V process involved assessing observed data of diclofenac concentrations in skin tissues and plasma, and the overall performance of the modeling platform for relevant products. Using this case as an example, this report provides current scientific considerations on good practices for model V&V and the establishment of BE for dermatological drug products when leveraging PBPK modeling and simulation for regulatory decision making. John Wiley and Sons Inc. 2021-03-09 2021-05 /pmc/articles/PMC8129718/ /pubmed/33547863 http://dx.doi.org/10.1002/psp4.12600 Text en Published 2021. This article is a U.S. Government work and is in the public domain in the USA. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Reviews
Tsakalozou, Eleftheria
Babiskin, Andrew
Zhao, Liang
Physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1%
title Physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1%
title_full Physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1%
title_fullStr Physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1%
title_full_unstemmed Physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1%
title_short Physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1%
title_sort physiologically‐based pharmacokinetic modeling to support bioequivalence and approval of generic products: a case for diclofenac sodium topical gel, 1%
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129718/
https://www.ncbi.nlm.nih.gov/pubmed/33547863
http://dx.doi.org/10.1002/psp4.12600
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