CRED Getting the CMC Dossier Right 2024

29/08/2024

Common deficiencies: Starting materials

⚫ Key Guidance on STM

● ICH Q11 (2011) Development and Manufacture of Drug Substances (chemical entities and biotechnological/biological entities) ● CPMP guideline on the chemistry of new active substances (CPMP/QWP/130/96, Rev 1) ● QWP Reflection Paper (2014) on the requirements for selection and justification of starting materials for the manufacture of chemical active substances. – Reflection Paper - Intention is to clarify expectations of EU regulators on ICH Q11 – Acknowledges – disagreements between applicants and quality assessors – that the guidance is open to interpretation – complex custom-synthesized SMs; commercial drivers etc.

– Expands on ICH Q11 in order to harmonise opinions and clarify requirements ● ICH Q 11 Q&A (2017) intended to provide additional clarification

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Common deficiencies: Starting materials

⚫ How to apply guidance on STM

● Essential to read and fully digest the guidance documents

● Clear that information submitted by applicants to justify the starting materials is very often lacking: – this major deficiency requires special attention – sufficient detailed description of the manufacturing process necessary to allow a full and proper assessment – criticality of all of the manufacturing steps need to be discussed in order to assess which should be carried out under GMP ● Applicants need to consider – if their justification is sufficiently comprehensive, sound, supported, gaps?

● Still not sure? Seek scientific advice before submission

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