Meeting Highlights: DIA China 2021

Implementation of ICH Q12 for Post-Approval CMC Changes in China
Fei Zheng

n the International Council for Harmonisation (ICH) Q (quality) series guidance for industry, Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management provides a framework to facilitate management of post-approval chemistry manufacturing and controls (CMC) changes more predictably and efficiently, increase transparency between industry and regulatory authorities, and support continual improvement and innovation in drug lifecycle management.

In joint discussions at ICH Day during DIA China 2021, experts in industry and regulatory agencies from China (NMPA, formerly SFDA), Japan (PMDA), and the US (FDA) agreed that real use cases and experiences with the ICH Q series in more developed regulatory systems will help China implement ICH Q12 from both the policy and technical perspectives.

ICH Q12 provides a framework to facilitate the management of post-approval CMC changes in a more predictable and efficient manner through risk-based management and the use of some advanced change management tools. China has been actively carrying out the implementation of ICH Q12.

At the regulatory level, the NMPA Drug Administration Law (DAL), Drug Registration Regulation (DRR), and Provisions for Post-Approval Changes have provided sufficient support for the transformation and implementation of ICH Q12 in China.

At the technical level, both regulatory authorities and companies continue to recognize and work through various implementation challenges including the identification of risks resulting from such changes, the use of change management tools, and the need to change product management strategies and tools to reflect the different stages of a product’s lifecycle.

Reference Experience for ICH Q12 Implementation in China

All parties recognize that different companies employing different implementation strategies in different regions is inefficient and ineffective, and that global harmonization across industry and regulatory systems is essential to effective worldwide implementation of ICH Q12. FDA has offered both early dialogue and training to share knowledge and experience with industry, providing a good example for other regulators to follow. Industry in China will look to NMPA to help guide and create similar tools for effective implementation based on these and other examples.

Changes to Established Conditions (ECs)

ICH Q12 defines established conditions (ECs) as those elements in an application considered necessary to assure product quality, such as critical manufacturing process parameters for the drug substance or product. These are determined and defined by the Marketing Authorization Holder (MAH) in collaboration with the responsible health authority, who formally approves them. Consequently, any post-approval change to ECs necessitates a submission to the regulatory authority and can only be implemented after regulatory review and approval. (Changing some specific EC parameters within a defined, limited range may not require such reapproval.)

Because Q12 is still in different implementation stages across China, each company is encouraged to take the initiative and open industry-regulatory discussions as soon as possible, and to clearly mark these ECs and the plan for post-approval change management (based upon these discussions) in their application dossier. Open and frequent industry-regulatory communication will enhance consistency and alignment of expectations and processes, and these critical conversations continue in China.

Data and Analytics

Implementation of Q12 has been concurrently helped by the continuous improvement and growth of modern analytical methods, technologies, and tools. The concept of Q12 also supports accumulating and analyzing data in continuous cycles to identify changes to parameters that are not captured within ECs. Coordinating and confirming these data within internal quality management systems will help to improve these data, processes, and products.

Q12 also supports the inevitable changes to sites and equipment for mature products that have been on the market for a long time. For example, when several products are produced on the same production line, knowledge and data accumulated in the change process for the first product can be easily adapted and transferred into this same change for the second, third, and all subsequent products on the same production line. These good supporting data also allow for easier adjustments and refinements to these changes.

ICH Day overviewed the ICH Q (quality) series from the technical, regulatory, and policy levels and deepened expectations, through expert analysis and discussion, that these collaborative efforts of industry and regulators will help deliver safe and high-quality drugs throughout the product lifecycle.