Biowaiver Based on the Biopharmaceutical Classification System: Regulatory Basis and Limits of Scientific Interpretation (Review)

INRODUCTION. Biowaiver procedure based on the biopharmaceutics classification system (BCS) is widely used in regulatory practice when assessing the bioequivalence of generic medicinal products (GMPs). The use of the biowaiver is aimed at reducing the rate of in vivo studies while maintaining the requirements for GMP quality, safety, and efficacy. Over the recent years, additional analytical and modeling tools used in bioequivalence assessment have been actively discussed in the scientific literature. This requires a clear distinction between regulatory requirements and research approaches, including in vitro / in vivo correlations (IVIVC), physiologically based pharmacokinetic (PBPK) modeling, and artificial intelligence (AI) algorithms.

AIM. This study aimed to compare the existing regulatory approaches to the application of the BCS-based biowaiver procedure, with an emphasis on current requirements used to assess GMP bioequivalence.

DISCUSSION. In all considered regulatory systems, the use of the biowaiver procedure is limited to active pharmaceutical ingredients (APIs), BCS classes I and III, with strict adherence to solubility criteria and comparability of dissolution profiles. The division of Class II into subclasses IIa and IIb is not stipulated in any official guidelines and is used exclusively in the scientific literature for the research purposes. It has been established that IVIVC, PBPK models, and AI technologies are considered by regulatory authorities as supporting scientific tools and do not have independent status as an evidence base used to renounce the use of in vivo studies.

CONCLUSIONS. The findings confirm the lack of fundamental regulatory differences between approaches to the biowaiver application. Proposals for expanding biowaiver practice identified in the references relate to scientific controversy without reflecting current regulatory practice. The work forms a methodologically correct basis for the interpretation of regulatory requirements and further research in the area of biopharmaceutical GMPs evaluation.

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