WHO TRS (Technical Report Series) 1019, 2019 Annex 4

WHO TRS (Technical Report Series) 1019, 2019 Annex 4

Protocol to conduct equilibrium solubility experiments for the purpose of Biopharmaceutics Classification System-based classification of active pharmaceutical ingredients for biowaiver

1. Scope:

The objective of this document is to provide guidance on the design and conduct of equilibrium solubility studies undertaken for the purpose of active pharmaceutical ingredient (API) classification within the Biopharmaceutics Classification System (BCS) (1, 2).

Notably, the definition and guidance given in this document for performing solubility studies apply to APIs and there might be differences in requirement with respect to the conditions for dissolution studies that are applicable to solid finished pharmaceutical products (FPPs).

A study protocol has been developed to provide a harmonized approach when performing solubility studies; however, alternative approaches to determining the solubility of an API, such as phase solubility analysis (3), can also be valid if the appropriate test conditions are employed.

The aim of the WHO biowaiver guidance is to reduce the risk of bioinequivalence to an acceptable level when granting biowaivers supporting pharmaceutical development. 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.

Equilibrium solubility profiles of APIs contained in medicines in the WHO Model List of Essential Medicines (EML) (4) can be used in conjunction with absorption/permeability data, FPP dissolution studies, and comparative consideration of FPP excipient content, to enable an informed decision on whether a biowaiver could be granted safely.

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WHO TRS (Technical Report Series) 1019, 2019 Annex 4:

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