Biopharmaceutical Classification System (BCS)

A BCS-based biowaiver for generic drugs requires high drug solubility throughout the physiological pH range plus identical product quality and near-identical reference product content to meet recommendation standards outlined by the 2017 FDA Guidance. The International Council for Harmonization gave its authorization to these procedures during 2018. The FDA employs identical terms while discussing BCS-based biowaiver approvals for BCS class III medications (highly soluble but partially permeable substances). The development of IVIVC using traditional mass balance deconvolution methods becomes improbable for BCS III medicines when extremely rapid dissolution occurs. Physiologically based pharmacokinetic models separate different processes which shape the given function by analyzing dissolution and gastrointestinal transit and permeation. IVIVC development through various compartmental absorption and transit model modifications enables drug companies to obtain biowavers for BCS III medications. Some questions about this topic continue to remain unanswered. A systematic assessment of PBPK model development for IVIVC and biowaiver applications leads to identifying essential challenges and gaps in this area through this review. The paper advocates for further research on excipient dissolution alongside penetration effects alongside development of virtual clinical study simulations that unite in vitro data with in vivo bioequivalence confirmation.