When is a BCS-based biowaiver accepted?

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SFDA: “Applying for a BCS-based biowaiver is restricted to highly soluble drug substances with known human absorption and considered not to have a narrow therapeutic index (see section 3.1.9). The concept is applicable to immediate release, solid pharmaceutical products for oral administration and systemic action having the same pharmaceutical form.” (SFDA BE v3.1 · Appendix III – I. Introduction) “BCS-based biowaiver are applicable for an immediate release drug product if • the drug substance has been proven to exhibit high solubility and complete absorption (BCS-class I; for details see section III) and • either very rapid (> 85 % within 15 min) or similarly rapid (85 % within 30 min ) in vitro dissolution characteristics of the test and reference product has been demonstrated considering specific requirements (see section IV.1) and • excipients that might affect bioavailability are qualitatively and quantitatively the same.” (SFDA BE v3.1 · Appendix III – II. Summary Requirements) “The drug substance is considered highly soluble if the highest single dose administered as immediate release formulation(s) is completely dissolved in 250 ml of buffers within the range of pH 1 – 6.8 at 37±1°C.” (SFDA BE v3.1 · Appendix III – III.1 Solubility) EU: “BCS-based biowaivers are applicable to drug products where the drug substance(s) exhibit high solubility and, either high permeability (BCS Class I) or low permeability (BCS Class III).” (ICH M9 · 2) “The BCS-based biowaiver is only applicable to 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 from consideration for a BCS-based biowaiver in this guidance.” (ICH M9 · 1.2) “A drug substance is classified as highly soluble if the highest single therapeutic dose is completely soluble in 250 ml or less of aqueous media over the pH range of 1.2–6.8 at 37±1°C.” (ICH M9 · 2.1) US FDA: “A drug product is eligible for a BCS-based biowaiver provided that the drug substance or substances satisfy the criteria regarding solubility and permeability (BCS Class I and III), the drug product is an immediate-release oral dosage form with systemic action, and the drug product is the same dosage form and strength as the reference product.” (FDA M9 · 3) “A drug substance is classified as highly soluble if the highest single therapeutic dose is completely soluble in 250 milliliter (mL) or less of aqueous media over the pH range of 1.2– 6.8 at 37±1°C.” (FDA M9 · 2.1) “The BCS-based biowaiver is only applicable to 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 from consideration for a BCS-based biowaiver in this guidance.” (FDA M9 · 1.2) WHO: “Following the publication of the WHO guideline on Biopharmaceutics Classification System-based biowaivers, the relevant sections from this guideline have been removed, including the appendix Equilibrium solubility experiments for the purpose of classification of active pharmaceutical ingredients according to the Biopharmaceutics Classification System.” (WHO TRS 1052 Annex 8 · Background) “Guidance providing recommendations to support the biopharmaceutics classification of APIs and the BCS-based biowaiver of bioequivalence studies for FPPs can be found in the WHO guideline on Biopharmaceutics Classification System-based biowaivers.” (WHO TRS 1052 Annex 8 · 10.2)

When is a BCS-based biowaiver accepted?

SFDA Saudi Food and Drug Authority

EU European Union

US FDA US Food and Drug Administration

WHO World Health Organization

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