PII-190 - GLOBAL HARMONIZATION OF IMMEDIATE-RELEASE SOLID ORAL DRUG PRODUCT BIOEQUIVALENCE RECOMMENDATIONS AND THE IMPACT ON GENERIC DRUG DEVELOPMENT.

J. Kotsybar¹, S. Hakeem¹, L. Zhang¹, W. Jiang¹; ¹U.S. Food and Drug Administration.

Background: Immediate-release (IR) solid oral drug products constitute a significant portion of approved drug products and products under development globally. 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.

Methods: U.S. FDA-approved IR oral products were obtained via the Orange Book and Drugs@FDA from Jan 1938 to Dec 2022. These products are categorized as solids, liquids, or semi-solids. Published product-specific guidances (PSGs) for solid oral IR products were obtained via the FDA’s PSG database (Sept 2008-Dec 2022) and the EMA’s website (Jan 2009-Dec 2022).

Results: 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. Over 80% of all oral IR product NDAs fall within the scope of ICH M13A. For 1,051 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 both fasting and fed BE studies, while only 15.9% EMA PSGs recommended both fasting and fed BE studies. Of the available 63 PSGs for IR solid oral products by EMA, ~6% had no corresponding PSG by U.S. FDA. For PSGs from EMA and FDA that matched in API, dosage form, and route of administration, Table 1 shows ~26% of the PSGs aligned on fasting/fed study recommendations and 84% aligned on study population between the two agencies (Table 1).

Conclusion: This study helps clarify the scope of U.S. solid oral IR products impacted by the new ICH M13A draft guideline and demonstrate how recommendations in draft ICH M13A could significantly harmonize BE recommendations for IR oral products to facilitate global drug development.