CRED Getting the CMC Dossier Right 2024

28/08/2024

Supporting ICH guidelines (2)

● ICH Q7 – Good Manufacturing Practice – Clinical and commercial – ICH Q7 Q&A provides useful clarifications ● ICH Q8: Pharmaceutical Development (DP focussed, but discusses the Concept of Design Space and enhanced development ) ● ICH Q9: Quality Risk Management & ICH Q10: Pharmaceutical Quality Systems: More relevant for quality and manufacturing organisations ● ICH Q11 – Development and Manufacture of Drug Substances – ICH Q11 Q&A on Starting Material Selection and Justification is essential ● ICH Q13 – Continuous Manufacturing of Drug Substances and Drug Products

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ICH Q11: Traditional vs. Enhanced [1]

Traditional Approach

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▪ Defined set points and operating ranges for process parameters

▪ Drug Substance control strategy typically based on

▪ Demonstration of process reproducibility ▪ Testing to meet established acceptance criteria

▪ Enhanced Approach- (might also be referenced as Quality by Design)

▪ Risk management and more extensive scientific knowledge to select process parameters and unit operations

▪ Evaluation in studies to establish control strategies (which could include a design space) applicable over the lifecycle of the drug substance

▪ These approaches are not mutually exclusive. Company can choose:

▪

Traditional to Enhanced

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Most likely a combination of both

▪ Risk assessments determine steps / unit operations of highest risk to API quality (CQAs)- it is not uncommon to see, for example, earlier steps that have no quality impact leveraging traditional approaches to understanding; and later steps leveraging enhanced approaches to understanding

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