CRED Getting the CMC Dossier Right 2024

28/08/2024

Europe: 3AQ11a Specifications and Control Tests on the Finished Product

• Excipients which affect the bioavailability of an active substance must be the object of a quantitative determination in each batch, unless bioavailability is guaranteed by other appropriate tests, established on a case by case basis as a function of development studies. • In the case of preservatives, content limits of 90-110% at release should be acceptable without further justification except in special cases. On expiry the lower limit of antimicrobial preservatives may be reduced subject to the results of satisfactory preservative efficacy testing. For chemical preservatives (antioxidants), the lower limit may be considerably lower than 90% during the shelf life, because of the preferential degradation of these agents.

The Organisation for Professionals in Regulatory Affairs

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Europe: Guideline on Excipients in the Dossier for Applications for Marketing Authorisation of a Medicinal Product

EMEA/CHMP/QWP 396951/2006 Guideline on Excipients in the Dossier for Applications for Marketing Authorisation of a Medicinal Product

• The medicinal product release specifications should include an identification test and a content determination test with acceptance criteria and limits for each antioxidant and antimicrobial preservative present in the formulation. The medicinal product shelf-life specification should also include limits for antimicrobial preservatives when present. • Where antioxidants are used during the manufacture of the medicinal product, the release limits should be justified by batch data or a sound justification has to be provided, if the proposed specifications do not include an identification test and a content determination test for the antioxidant. If needed, the adequacy of the specified limits should be justified on the basis of controlled conditions and (in-use) stability testing, to ensure that sufficient antioxidant remains, to protect the medicinal product throughout its entire shelf-life and during the proposed in-use period.

The Organisation for Professionals in Regulatory Affairs

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