Module 3 - Strategic case studies in practice

Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities)

Notes concerning Table 5b The above table is based on the route of synthesis presented in Example 1. The Control for enantiomeric impurity is based on Decision Tree 5 from ICH Guideline Q6A, which allows for control of chiral quality to be established by applying limits to appropriate starting materials or intermediates when justified from development studies. In order for this approach to be acceptable data would need to be provided in 3.2.S.2.6 to demonstrate the stability of the stereocentre under the proposed manufacturing conditions. The table summarises only a portion of the control strategy that would be presented at the time of initial submission and does not include all CQAs of the drug substance. The example control strategy provides for control of some CQAs at stages in the process prior to the drug substance. The elements of the proposed control strategy described in the application would be justified by the applicant and subject to regulatory assessment and approval.

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