A Survey of the Regulatory Requirements for BCS-Based Biowaivers for Solid Oral Dosage Forms by Participating Regulators and Organisations of the International Generic Drug Regulators Programme

Abstract

-Purpose:The Biopharmaceutics Classification System (BCS) based biowaiver is a scientific model which enables the substitution of in vivo bioequivalence studies with in vitro data as evidence of therapeutic equivalence subject to certain conditions. Despite being based on the same principles, BCS-based biowaivers are interpreted and regulated differently among international regulatory agencies. In this survey, the Bioequivalence Working Group (BEWG) of the International Generic Drug Regulators Programme (IGDRP) compared the criteria for BCS-based biowaivers applied by the participating regulators and organisations. Methods: Differences and similarities regarding solubility, permeability, dissolution, excipients and fixed-dose combination products, were identified and compared in a detailed survey of each participant's criteria for BCS-based biowaivers. These criteria were determined based upon the participants' respective regulatory guidance documents, policies and practices. Results: This review has, with the exception of two participants who do not accept BCS-based biowaivers, revealed that most IGDRP participants interpret the BCS principles and conditions similarly but notable differences exist in the application of these principles. Conclusion: Although many similarities exist, this review identifies several opportunities for greater convergence of regulatory requirements amongst the surveyed jurisdictions.

Comparison of Dissolution Profiles and Apparent Permeabilities of Commercially Available Metformin Hydrochloride Tablets in Turkey

“…In 2018, the draft ICH guideline M9, on Biopharmaceutics Classification System-based biowaivers (step 2), revealed a validated and standardized in vitro permeability assessment method in Caco-2 cells (22). Some regulatory authorities (e.g., South Korea, USA) accept Caco-2 cell data as primary evidence of permeability; others (e.g., Australia, Canada, EU, New Zealand, WHO) consider it as supporting data (23).…”

Biowaiver for Immediate and Modified Release Dosage forms Scientific summary of the CSPS workshop

“…Post-Workshop Notes: Since the above workshop date, many further reports have been published that are worthy of mentioning; e.g., those by J. E van Oudtshoorn et al (38)…”

A Survey of the Regulatory Requirements for the Waiver of In Vivo Bioequivalence Studies of Generic Products in Certain Dosage Forms by Participating Regulators and Organisations of the International Pharmaceutical Regulators Programme

“…The requirements to waive in vivo bioequivalence studies for immediate release (IR) solid oral dosage forms based on the Biopharmaceutics Classification System (i.e., BCS biowaivers) in IPRP jurisdictions have been previously described (2) and are now harmonised by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) (3). In addition, waivers of in vivo bioequivalence studies may be applied to additional strengths of IR solid oral dosage forms with respect to the strength for which in vivo bioequivalence has been shown (4).…”