CRED Getting the CMC Dossier Right 2024

29/08/2024

Common deficiencies: Other concerns

⚫ The issue (contd.):

● Many OCs could be MOs – Could be upgraded later in the procedure if responses are not satisfactory! – Examples: – All potentially occurring genotoxic impurities should be controlled in the drug substance specification in line with TTC. – The impurities limit in the specification for X is wide (5.0 %) and not supported by the provided CoA (0.2 %). The specification should be tightened or it should be demonstrated that this level of impurities does not impact on the drug substance quality. – Polymorphic purity should be tested with a suitable limit of detection for unwanted polymorphs. – Stability/conversion of the polymorphic form under storage or stress conditions should be discussed. – Justifications should be provided for the tests and acceptance limits for particle size and tapped density applied by the finished product manufacturer.

The Organisation for Professionals in Regulatory Affairs

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General hints & tips

Regulatory awareness

⚫ Dossier presentation

● New developments / state of the art

● Quality not quantity

– Rolling review, conditional MAs (CMA) ● New guidance

● Is information easy to find? – Hyperlinks / bookmarks – Quality of scans – Spelling – Table of changes ● Is terminology used correctly and consistently? ● Are conclusions supported by data? – Are data included in the dossier? ● If data are conflicting – Don’t ignore – Discuss – Question: Is the submission premature? ● Is guideline deviation justified (with data)?

● Orphan status of DS?

● Regulatory issues of debate (e.g. STM)

● DS currently approved in the MS? – Old DS can be considered as “NAS” by CA! – Are the same salts used in that MS?

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