FDA issues final guidance on BCS-based biowaivers

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The US Food and Drug Administration (FDA) has published final guidance on ‘M9 Biopharmaceutics Classification System (BCS)-Based Biowaivers’. The guidance was prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), formerly the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

Guidance V13F21

The final guidance was announced in a Federal Register post-published on 12 May 2021. The guidance provides recommendations to support the biopharmaceutics classification of drug substances and the BCS-based waiver of the in vivo bioequivalence study requirement for certain drug products.

M9 Biopharmaceutics Classification System-Based Biowaivers
Date: 12 May 2021

Two drug products containing the same drug substance or substances are considered bioequivalent if their bioavailability (rate and extent of drug absorption) after administration in the same molar dose lie within acceptable predefined limits. These limits are set to ensure comparable in vivo performance, i.e. similarity in terms of safety and efficacy. In in vivo bioequivalence studies, the pivotal pharmacokinetic parameters area under the concentration time curve (AUC) and maximum concentration (Cmax), are generally used to assess the rate and extent of drug absorption.

The final guidance replaces draft guidance issued back in October 2018. The aim of the guidance, and the BCS-based biowaiver approach, is to reduce the need for in vivo bioequivalence studies, i.e. to provide a surrogate for in vivo bioequivalence.

The BCS categorizes drug substances into one of four BCS classes as follows:

  • Class I: high solubility, high permeability
  • Class II: low solubility, high permeability
  • Class III: high solubility, low permeability
  • Class IV: low solubility, low permeability

The BCS-based biowaiver can only be used for immediate release, solid orally administered dosage forms or suspensions designed to deliver drug to the systemic circulation. Drug products having a narrow therapeutic index are excluded. Fixed-dose combination products are only eligible when they meet certain criteria, including being of the same dosage form and strength and when their excipients and dissolution properties meet the criteria outlined in the guidance.

Comments on the guidance can be posted to the Dockets Management Staff under Docket HFA-305. This can be done via the website www.regulations.gov or written comments can be mailed to Division of Dockets Management (DDM) under Docket FDA-2019-D-5473.

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To further enhance the objectives of GaBI in sharing information and knowledge that ensure policies supportive of safe biosimilars use, we are pleased to announce that we will be launching a new section on GaBI Online and GaBI Journal, the ‘Latin American Forum’ (in Spanish) featuring the latest news and updates on research and developments in generic and biosimilar medicines in Latin America.

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Para fomentar los objetivos de GaBI sobre la difusión de información y conocimiento sobre las políticas de apoyo que garantizan el uso seguro de medicamentos biosimilares, nos complace anunciar el lanzamiento de una nueva sección en GaBI Online y GaBI Journal, el ‘Latin American Forum’ (en español), que presentará las últimas noticias y actualizaciones en investigación y desarrollo sobre medicamentos genéricos y biosimilares en Latinoamérica.

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Source: Federal Register, US FDA

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