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Global harmonization of immediate‐release solid oral drug product bioequivalence recommendations and the impact on generic drug development

Journal Article · · Clinical and Translational Science
DOI:https://doi.org/10.1111/cts.13670· OSTI ID:2471318

Immediate-release (IR) solid oral drug products constitute a significant portion of approved drug products and products under development. Bioequivalence (BE) assessment for these oral products is important for establishing therapeutic equivalence for generic products to their respective comparator products. In December 2022, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published the first new draft guideline on BE for IR solid oral dosage forms (M13A). To support the development of ICH M13A, we comprehensively reviewed the landscape of oral IR products approved by the U.S. Food and Drug Administration (FDA) and compared BE recommendations for these products in the current U.S. FDA and European Medicines Agency (EMA) BE guidances. We utilized databases including Drugs@FDA, Orange Book, and product-specific guidances (PSGs) published on the U.S. FDA and EMA websites to collect information. Oral IR products account for 46% of all FDA-approved new drug applications currently listed in Orange Book with 82.5% solids, 0.9% semi-solids, and 16.6% liquids. For all published U.S. FDA PSGs for solid oral IR products, in vivo BE studies with pharmacokinetic (PK) endpoints account for 88% of BE approaches recommended. Of these PK BE studies, 86.5% recommended fasting and fed BE studies, while only 15.9% EMA PSGs recommended both fasting and fed BE studies. This review helps clarify the scope of U.S. solid oral IR products impacted by the new ICH M13A draft guideline and demonstrates how recommendations in draft ICH M13A could significantly harmonize BE recommendations for IR oral products to facilitate global drug development.

Research Organization:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC); USFDA
Grant/Contract Number:
SC0014664
OSTI ID:
2471318
Journal Information:
Clinical and Translational Science, Journal Name: Clinical and Translational Science Journal Issue: 12 Vol. 16; ISSN 1752-8054
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English

References (3)

The Global Bioequivalence Harmonization Initiative: Summary report for EUFEPS international conference journal January 2018
The Global Bioequivalence Harmonisation Initiative (GBHI): Report of the fifth international EUFEPS/AAPS conference journal November 2023
International Guidelines for Bioequivalence of Systemically Available Orally Administered Generic Drug Products: A Survey of Similarities and Differences journal July 2013

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