21/22 April 2020
The U.S. Food and Drug Administration (FDA) recently made available the International Council for Harmonization (ICH) Q12 draft guidance on "Technical and Regulatory Considerations for Pharmaceutical Lifecycle Management" together with its Annex. The Q12 core guidance is intended to be considered in conjunction with the ICH Q12 Annex document being simultaneously published for comment.
The ICH Q12 guideline is meant to provide a framework for managing post-approval manufacturing and controls (CMC) changes for new and marketed pharmaceutical drug substances (active pharmaceutical ingredients, APIs), drug products (DPs) and drug-device combination products. The draft is intended to demonstrate how increased product and process knowledge (gained by QbD-Development outlined in ICH Q8 / Q11) can contribute to a reduced number of regulatory submissions, leading to a reduction in unnecessary costs and burdens for manufacturers and regulators. The guidance also encourages continual improvements on products which may help reduce variability and mitigate some shortages related to manufacturing and quality issues.
Sections of the draft guideline focus on the categorization of post-approval CMC changes, established conditions (ECs), post-approval change management protocols (PACMPs), product lifcycle management (PLCM), pharmaceutical quality system (PQS) and change management, the relationship between the regulatory assessment and GMP inspection and post-approval changes for marketed products. The draft also deals with life cycle management of analytical methods, a topic so far not covered by ICH Q8 / Q11. Additionally, a decision tree on ECs for manufacturing and control is provided, noting when notification or prior approval is necessary based on the level of potential risk of a proposed change.
As reported before about the ICH Q12 draft the proposed guideline contains the following provision:
"In certain ICH regions, the current ICH Q12 guideline is not fully compatible with the established legal framework with regard to the use of explicit Established Conditions (ECs) referred to in Chapter 3 and with the Product Lifecycle Management (PLCM) referred to in Chapter 5 as outlined in this guideline. These concepts will, however, be considered when the legal frameworks will be reviewed and, in the interim, to the extent possible under the existing regulation in these ICH regions".
In Europe, the EU "Variations Regulation" applies which does currently not exhibit the concept of "ECs". However, FDA introduced the following note in its published Q12 draft: "In the United States, the ICH Q12 guidance is fully compatible with the established legal framework. Therefore, the concept of Established Conditions and supporting Product Lifecycle Management document are fully supported by the U.S. FDA as described in this guidance". The comment deadline for the US is 15 December 2018. The comment deadline for ICH Q12 for EC Europe is December 18, 2018.