The session included presentations from four speakers, followed by a panel discussion with regulatory experts from different countries. The speakers included Stuart Finnie, PhD, Senior Director, CMC Regulatory Affairs, Gilead Sciences; Eli Zavialov, PhD, Senior Director, CMC Regulatory Affairs, GlaxoSmithKline; Timothy Graul, Director, Global CMC Advisory Office, Pfizer, Inc.; and Qinggang Wang, PhD, Director, Chemical Process Development, Bristol Myers Squibb.
Finnie discussed the geographical coverage and future of ICH Q12. He highlighted the heterogeneity in its global implementation, noting that the US Food and Drug Administration (US FDA) has been the most successful thus far. He also touched on the concepts of established conditions and supporting information that some health authorities find challenging because of local regulations and guidelines. This underscores the need for a supportive legal basis for Q12 implementation. He also highlighted that the legal framework within the US is broad enough to accommodate concepts of ICH Q12, thus contributing to its successful implementation by the US FDA. The existing reporting categories at US FDA are consistent with the risk base classification outlined in Q12 and its implementation has been further supported by organizational changes within US FDA that have promoted close interactions between reviewers and inspectors. He concluded with insights into the future of Q12, including its potential unlocking in Europe and engagement with China.
Zavialov focused on industry experiences with implementing ICH Q12. He discussed the results from a survey of implementation status of various concepts within Q12 across companies. The results highlighted the challenges faced in the slow adoption of concepts like established conditions, while showing good adoption of PACMP approaches. He also shared lessons learned from interactions with FDA that underscore the importance of providing robust justification for designating process parameters as non-established conditions for process control and for defining only analytical procedure parameters that are fundamental to the underlying principle of the method. He highlighted the benefits of this guideline to the industry and health authorities, along with real-life examples and challenges in its application.
Graul talked about advancing Q14 concepts related to lifecycle management of analytical procedures. He discussed the overall objectives of ICH Q14 that describe the science and risk-based approach of developing and maintaining analytical procedures, outline minimal and enhanced approach for analytical procedure development, support change management of analytical procedures, and provide submission consideration to facilitate communication between sponsors and regulators on analytical procedures lifecycle. Graul covered the tools described in ICH Q12 for post-approval change management and lifecycle management, and how Q14 incorporates these tools along with newer concepts like the Analytical Target Profile (ATP) and risk management principles from ICH Q9. Graul also shared a case study to describe a risk-based approach to defining established conditions and supportive information for a dissolution procedure for a solid oral product. He built on this example further to illustrate considerations for identifying the reporting categories for the established conditions when changing the dissolution analysis technique from liquid chromatography and ultraviolet (LC-UV) to inline UV. He also discussed how principles of ICH Q2(R2) can be applied to implement abbreviated validation testing of an established platform analytical procedure when it is used for a new purpose, if scientifically justified.
Wang focused on discussing the readiness of the pharmaceutical industry to implement ICH Q14. He shared the results from a recent ISPE survey of companies in the pharmaceutical industry. Overall industry response to ICH Q14 and Q2(R2) has been very positive. Survey data showed that only a small fraction of respondents was ready to implement Q14; most were either not ready or were in the process of getting ready. Comments indicated that lack of experience, cost and resources, lack of global regulatory acceptance, and lack of value were among the top barriers to Q14 implementation.
The presentations were followed by a panel discussion with regulatory experts, Yasuhiro Kishioka, PhD, Review Director of the Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency (PDMA); Jayda Siggers, PhD, Senior Scientific Evaluator, Health Canada; and Joel Welch, PhD, Deputy Office Director, Offices of Product Quality Assessment (OPQA) I, II, & III, US FDA.
Kishioka shared that in Japan, the ICH Q12 (Step 5) guideline was published in October 2021. He also shared that they are working on the translation of ICH Q2(R2)/Q14 guidelines into Japanese and he expects to see them implemented in Japan soon.
Siggers noted that while Health Canada is committed to the implementation of ICH Q12 and Q14, there have been some internal obstacles to the full implementation of both guidelines. She discussed the need for regulatory and operational changes prior to full implementation of both guidelines. She shared that while the Biologics Directorate is planning a partial implementation of Q12 that will include the acceptance of Post-Approval Change Management Protocols (PACMPs) in regulatory filings for biologic drugs only, the acceptance of established conditions will require a regulatory change. She further noted that Health Canada’s Therapeutic Products Directorate requires the regulatory change to fully implement Q12 and will not go forward with a partial implementation at this time.
Welch shared that the US FDA is receiving increasing number of Q12 based submissions and taking action on them. He noted that while biologics have been the focus of Q12 submission at US FDA, they have started receiving a good number of small molecule submissions as well. Welch highlighted that US FDA is receiving some repeat Q12 submissions, suggesting that sponsors are seeing value in this approach. Welch added that US FDA published the ICH Q2(R2)/Q14 guidelines in March 2024 and is starting to see submissions with analytical target profiles and meeting packages with proposals for validation of platform analytical procedures. He also encouraged industry to continue sharing their experiences with the application of these guidelines.
Disclaimer
This is an informal summary of a presentation on 15 October 2024 at the 2024 ISPE Annual Meeting & Expo in Orlando, Florida, USA. It has not been vetted by any of the agencies or regulators mentioned in this article, nor should it be considered the official positions of any of the agencies mentioned.
