Module 3 Presentations

14/05/2024

A Disaster in the Making?  Is it highly desirable to have pure starting materials and specific transformations? Maybe but help is at hand to increase or control purity: o Solid intermediates can be recrystallised o Liquids can be distilled o A detailed knowledge and understanding of the synthesis can identify early-stage impurities that will not participate in the downstream process and can thus be discounted (removed by some means)

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3.2.S.2.4 Control of Critical Steps and Intermediates - 1  What are ‘critical steps’ in the synthesis?  Critical Quality Attributes (CQAs) are DS and DP properties that could affect clinical safety and efficacy: o A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality (ICH Q8(R2) ANNEX)  Critical steps are those steps that can affect the DS/DP CQAs  Need to have CQAs identified and justified in dossier comes from ICH Q7: Validation: Defining the API in terms of its critical product attributes  ICHQ8(R2): At a minimum, those aspects of drug substances [...] that are critical to product quality should be determined and control strategies justified  ICH Q11: Manufacturing process development should include, at a minimum, the following elements: Identifying potential CQAs associated with the drug substance [...]  FDA MaPP Applying ICH Q8, Q9, Q10 Principles to CMC Review: Applications should include the following minimal element [...]: - Critical Quality Attributes (CQAs) of the drug product - CQAs of the drug substance and excipients 18

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