Spring Intro 2023

28/03/2023

Choice of Regulatory starting materials:

Industry perspective - Prefer to see RSMs defined later in synthetic scheme - Want to have flexibility on supply - Increased burden and cost to validate and characterise, demonstrate impurity purge - Increased burden to apply GMP at earlier point - Downstream processes may be highly capable of addressing upstream impurity risk

Regulator’s perspective - Prefer to see RSMs defined early in synthetic scheme - Want to see transparent supply chain - Want high level of assurance that impurities are not carried through to final DS - Want to see GMP at all critical points of synthesis

The Organisation for Professionals in Regulatory Affairs

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3.2.S.2.5 Process validation/evaluation

Demonstrates consistency and robustness of the commercial manufacturing process to deliver a Drug Substance meeting all Critical Quality Attributes • Traditionally 3 consecutive full-scale batches • Other approaches now accepted – Process verification, continued process verification • Special attention needs to be paid to sterile Drug Substances or low bioburden – refer to decision trees on sterilisation and Annex 1 of the GMP guide • Note – there is a difference in emphasis between Europe and other regions when it comes to choice of sterilisation • Aseptic processing is a “last resort” in Europe, generally accepted outside EU

The Organisation for Professionals in Regulatory Affairs

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