Biowaivers

Biowaivers are regulatory provisions that allow a pharmaceutical product to be approved without conducting a full in vivo bioequivalence study, provided that robust in vitro tests demonstrate equivalence to a reference product. In practice, this means relying on dissolution performance and pharmaceutical characteristics rather than human BE trials.

The rationale for biowaivers is to reduce unnecessary human testing, accelerate access to medicines, and conserve resources while ensuring therapeutic equivalence. They are endorsed by major regulatory frameworks and guided by international standards that link in vitro performance to in vivo bioavailability where appropriate.

Regulatory guidance for biowaivers exists in several jurisdictions, with principles drawn from ICH guidelines and national agencies such as the FDA and EMA. In general, biowaivers apply most clearly to immediate-release solid oral dosage forms and are based on drug substance properties and dissolution behavior rather than on new BE studies alone.

Conditions commonly considered for a biowaiver include: the drug substance is highly soluble and highly permeable (BCS Class 1), or in some cases highly soluble and low permeability (BCS Class 3); the product exhibits rapid dissolution across physiologically relevant pH media; dissolution profiles of test and reference products are sufficiently similar (often assessed by f2 similarity); the drug is not a narrow therapeutic index substance and there are no major suspected food effects or complex release mechanisms.

Biowaivers are not universally applicable and are limited for modified-release products, NTI drugs, or formulations with complex or highly variable absorption. Decisions are region-specific and rely on formal regulatory guidelines.