The FDA has made available a draft guideline by the International Council for Harmonization (ICH), Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, which seeks to facilitate the management of post-approval chemistry, manufacturing and controls (CMC) changes for new and marketed pharmaceutical drug substances, drug products, and drug–device combinations.

The FDA’s release of this draft guideline marks Step 2 in the ICH procedure for the harmonization of a new ICH topic. At Step 2 of the ICH procedure, a consensus draft text or guideline, agreed by the appointed ICH Expert Working Group, is transmitted by the ICH Assembly to the regulatory authorities of the ICH regions for internal and external consultation according to national or regional procedures.

The draft guideline provides guidance on a framework to facilitate the management of post-approval CMC changes in a more predictable and efficient manner across the product lifecycle. ICH says that adoption of the guideline will promote innovation and continual improvement and strengthen quality assurance and reliable supply of product, including proactive planning of supply-chain adjustments. It will allow regulators (assessors and inspectors) to better understand companies’ pharmaceutical quality systems (PQSs) for management of post-approval CMC changes. The draft guideline is intended to complement the existing ICH Q8 to Q11 guidelines and includes a core guideline as well as annexes. The ICH Q8 to Q11 guidelines respectively include: Pharmaceutical Development, Quality Risk Management, Pharmaceutical Quality System, and Development and Manufacture of Drug Substances.

ICH Q8 and Q11 guidelines focus mostly on early-stage aspects of the product lifecycle (i.e., product development, registration, and launch). ICH said in the draft guideline that “experience with implementation of recent ICH guidelines has revealed technical and regulatory gaps that limit the full realization of more flexible regulatory approaches to post-approval CMC changes as described in ICH Q8 (R2) [Pharmaceutical Development] and Q10 Annex I [Potential Opportunities to Enhance Science and Risk Based Regulatory Approaches].

The draft guideline outlines topics, including the categorization of post-approval CMC changes, established conditions, post-approval change management protocols, product lifecycle management, pharmaceutical quality system and change management, the relationship between the regulatory assessment and inspection, and post-approval changes for marketed products. The draft also includes a decision tree to guide the identification of established conditions to say when prior approval or notification is required based on criticality and risk assessments.

Source: ICH (draft guidance), ICH (annex)