The World Health Organization (WHO) is seeking input on the fourth set of medicines to prioritize for biopharmaceutics classification system (BCS)-based biowaivers to ease in vivo study requirements for generic drugs.
The 12 medicines the agency is proposing to prioritize include several cardiovascular and anti-infective medicines, as well as the antidepressant drug amitriptyline.
Since piloting an approach to characterizing the solubility profile of medicines in its WHO Biowaiver Project in 2018, WHO has gone through several cycles of active pharmaceutical ingredients (APIs) to study for BCS-based biowaivers for medicines in the WHO List of Essential Medicines (EML) based on public health prioritizes. To be considered for the project, an API must be on the EML, formulated as an immediate-release, solid oral dosage form, belong to a therapeutic area of major public interest and its specific physical-chemical properties must be known.
“WHO recognizes the possibility to waive in vivo bioequivalence studies for immediate-release, solid oral dosage forms for APIs belonging to classes I and III according to the BCS, using comparative dissolution studies as surrogate proof of bioequivalence,” the agency writes. The BCS classifies drugs into four classes based on the aqueous solubility and intestinal permeability of the drug substance, with classes I and III representing drugs with high solubility/high permeability and high solubility/low permeability, respectively.
The practice of issuing BCS-based biowaivers was furthered last year with the adoption of the International Council for Harmonisation’s (ICH) M9 guideline, which aims to streamline the development of generics for eligible products by providing a harmonized approach to BCS-based biowaivers.
“The aim of the WHO biowaiver guidance document is to reduce the risk of ‘bioinequivalence’ to an acceptable level when granting biowaivers supporting pharmaceutical development and access to medicines. In this context, the solubility, the release from the drug product and the subsequent absorption phase are considered critical processes underlying the equivalence of the test and reference product,” WHO writes.
Comments on the proposed list of medicines for prioritization for BCS-based biowaivers are due by 30 October 2021. Following the public consultation, WHO will present a list of APIs for study in the next cycle to its Expert Committee on Specifications for Pharmaceutical Preparation (ECSPP).
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