ICH M9 - Biopharmaceutics Classification System-Based Biowaivers

What it says

ICH M9 establishes when a Biopharmaceutics Classification System-based biowaiver can substitute in vitro dissolution testing for an in vivo bioequivalence study, applicable to highly soluble, highly permeable BCS Class 1 drug substances formulated as rapidly dissolving immediate-release products, provided the formulation meets specific similarity criteria to the reference product.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• This guideline provides a scientifically justified pathway to avoid an in vivo bioequivalence study entirely for certain well-characterised, well-behaved drug substances, connecting directly to the dissolution testing principles under USP <711> and the broader bioequivalence framework under 21 CFR Part 320.
• Eligibility depends on specific, demonstrated drug substance characteristics, high solubility and high permeability under the Biopharmaceutics Classification System, meaning a biowaiver is a scientifically earned exception applicable only to specific compounds meeting defined criteria, not a general alternative pathway.
• Dissolution similarity between the test and reference products, demonstrated using an appropriately discriminating method, is the critical evidence supporting the biowaiver, placing significant weight on dissolution method quality exactly as described in USP <711> and <1092>.

What inspectors look for

• Whether a claimed BCS-based biowaiver genuinely meets the specific eligibility criteria for the drug substance's classification and the formulation's dissolution behaviour.
• Whether dissolution similarity data supporting the biowaiver was generated using a method with adequate discriminating power, connecting back to the same principles described in USP <1092>.
• This is primarily a product development and regulatory submission strategy framework rather than a specific manufacturing practice inspected directly, though its scientific foundation depends on manufacturing and testing data quality.

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