CRED Getting the CMC Dossier Right 2024

29/08/2024

Common deficiencies: Polymorphism

⚫ Exemplary MOs

● The polymorphic form of the drug substance is considered as a critical quality attribute which has an impact on the dissolution rate of the finished product. A routine test for polymorphic form should be added to the drug substance specification.

● Unequivocal evidence should be provided to confirm that the obtained form X of the drug substance is the hemihydrate solvate form, with reference to differences in physicochemical characterisation in comparison with other known forms. – A discussion should be provided to address the potential for conversion of the drug substance from the form X to another form (e.g. one or more polymorphs and hydrates/solvates) on storage. – Supporting data should consist of a minimum of TGA/DSC thermograms and XRRD diffractograms.

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Common deficiencies: GMP issues

⚫ The issue:

● Frequently linked to redefinition of synthesis Starting Materials

● Information often out of date

● Critical aspect – needs to be resolved before MA can be granted – Major issue in second half of procedure or MRPs! ● Audit should cover all sites involved in the synthesis of the active substance from the redefined starting material

● Impact on timings

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