FDA Posts ICH Q11 Q&A Guideline

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The ICH Q11 Q&A discusses the development and manufacture of drug substances and the selection and justification of starting materials.

On Feb. 17, 2017, FDA published the International Council for Harmonization’s (ICH) Q11 Development and Manufacture of Drug Substances, Questions and Answers on the agency’s website. The draft Q&A document is currently in Step 3 of the ICH process, and comments from international regulators are due in March 2017.

The ICH Q&A document provides clarification on the selection and justification of starting materials. It also clarifies information that should be provided in marketing authorization applications and/or master files.

The Q&A document states that API starting materials already accepted by regulatory authorities for use in authorized medicinal products “would not need to be re-justified against the ICH Q11 general principles or the recommendations included in this Q&A document, unless significant changes are made to the manufacturing processes and controls. However, a starting material accepted for one manufacturer's process may not be considered acceptable for a different manufacturer's process, if the proposal does not comply with the guidance in ICH Q11.”

Some questions addressed in the Q&A document include the following:


  • “How should an applicant determine which manufacturing steps impact the profile of mutagenic impurities in the drug substance as part of the selection and justification of starting materials?”

  • “Do all steps that involve mutagenic reagents, impurities, or establish regio- or stereochemical configurations, need to be included in the process description in Section 3.2.S.2.2?”

  • “Should all the ICH Q11 general principles be considered and met in selecting starting materials?”

  • “What considerations are important for starting material specifications?”

The document also states, “Designation of starting materials should be based on process knowledge for the intended commercial process. It is emphasized that all of the general principles in ICH Q11 Section 5 should always be considered holistically, together with the clarifications in this Q&A document, rather than applying a single general principle or Q&A clarification in isolation.”

Source: FDA and ICH