Solubility Variability – Even BCS Class 1 drugs may exhibit pH-dependent solubility, impacting dissolution across GI conditions.
Permeability Concerns – Variability in permeability assessment (Caco-2 cells vs. human data) can create regulatory challenges.
Excipient Impact – Certain excipients may alter drug permeability or solubility, requiring additional justification.
Dissolution Profile Similarity – Regulatory bodies demand strict similarity, rapid, very rapid dissolution; failure requires further justification.
Regulatory Variations – Different agencies (USFDA, EMA, WHO) have distinct biowaiver acceptance criteria, adding complexity.
Food Effect Considerations – Biowaivers focus on fasting conditions, but food can alter drug absorption and bioavailability.
Batch-to-Batch Consistency – Manufacturing variability can lead to differences in dissolution profiles, impacting approval.
Limited Predictability – In vitro dissolution may not always correlate with in vivo performance, leading to uncertainties.
BCS Class III Drugs – These drugs are highly sensitive to excipient effects, making permeability data critical for approval.
Narrow Therapeutic Index (NTI) Drugs – Biowaivers are often unsuitable for NTI drugs due to bioequivalence risks.
Read also: Online BCS Classification Database
Resource Person: Vijay Agrawal
