Selection of Starting Materials (SM) for commercial manufacture of an Active Pharmaceutical Ingredient (API) is an important matter for industry and regulators. This starting material, once approved, becomes the starting point for application of current Good Manufacturing Practice (cGMP), and manufacturing process and control commitments.

Regulatory expectations in ICH countries for selection of SMs are provided in Q11 “Development and Manufacture of Drug Substances.” In Q11, a set of “principles” are provided for an applicant to consider as part of justification of proposed SMs. These principles provide a set of considerations that can support the proposal of an SM, but do not establish an algorithm for decision-making, so every applicant who considers a process will not immediately be led to the same SM proposal. This flexibility is appropriate as different approaches to manufacturing, supply and control can support different SMs and means that the SM proposal requires justification. The justification becomes a matter for review and approval. A regulator can question proposed SMs and may require the applicant to redefine their proposed SM, usually earlier in the synthesis. As this decision is clearly linked to the supply of the API, the refusal of a proposed SM can have significant impact on the applicant’s supply intentions and thus, is worthy of careful attention and risk management.

Starting Materials Selection and Life Cycle Management article considers the principles established in Q11 and examines the implementation challenges for industry and regulators. The article also provides insights into how an applicant might address such challenges.

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