ISPE Members Continue Training Health Authorities on ICH Q12 Implementation

Regulatory Background

The International Council for Harmonization's (ICH) guideline, Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management (Q12), provides a framework to facilitate the management of post-approval chemistry, manufacturing, and controls (CMC) changes more predictably and efficiently across the product lifecycle. Implementing ICH's Q12 guideline is expected to promote innovation and continual improvement in the biopharmaceutical and pharmaceutical sectors, strengthen quality assurance, and help improve the reliability of supply chain management, ultimately benefiting patients.

The guideline was adopted by ICH regulators in November 2019 and is in the process of implementation by ICH member regulators. This implementation is proving challenging, and it is the hope that ISPE can help agencies navigate this potentially transformative guideline through training events like this.

ISPE’s Q12 Implementation Team

ISPE's PQLI initiative was created in 2008 to provide guidance on the practical implementation of the concepts described in ICH guidelines, focusing on Q8, Q9, Q10, Q11, Q12, and Q14 to help ensure product quality throughout a product lifecycle, leading to continual product improvement. PQLI established the Q12 Implementation team to develop a body of knowledge to assist the industry with the global implementation of ICH Q12. This team has delivered articles, webinars, and presentations at ISPE conferences. Most notably, they have delivered ICH Q12 training to four regulatory agencies over a period of four years: Health Canada and Brazil’s ANVISA in 2022, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) in 2023, and Singapore’s (HSA in 2024.

The Q12 Implementation Training Program

ISPE’s Q12 training program was initiated in response to interest expressed by Health Canada in preparing reviewers for their ICH Q12 pilot program and so that reviewers would be ready to review applications with new tools/enablers under the eventual full implementation of ICH Q12 in Canada. ISPE was asked to provide training with case studies. ISPE members from the PQLI Q12 Implementation team worked cooperatively with representatives from Health Canada to develop the initial training agenda to encompass:

• Why ICH Q12 was required
• What the core tools and enablers are
• Using the core tools and enablers in case study examples
• An understanding of companies’ pharmaceutical quality system
• An overview of the US FDA’s Established Conditions pilot study experiences

The ISPE team delivered this in early 2022. The training consisted of a blend of presentations and breakout sessions. The breakout sessions had pre-prepared questions for participants to work on. Where applicable, ICH training material was used without change.

This agenda was essentially the same for subsequent training, with minor changes. For ANVISA, there was a significant emphasis on the construction and use of Post-Approval Change Management Protocols (PACMPs), particularly for small molecules, since this aligned with the phased introduction of Q12 in Brazil. For the MHRA and HSA, the agenda included a short presentation by the US Food and Drug Administration (US FDA) on their experiences in implementing ICH Q12, followed by a Q&A and discussion.

Summary of the Agenda

Session 1

• An introduction to ICH Q12 and its key components
• Pharmaceutical change management system
• Breakout 1: Discussion on Q12
• Feedback and Group Discussion from Breakout 1

Session 2

• Introduction to established conditions with case studies examining:
  • Synthetic drug substance
  • Biological drug substance
  • Analytical procedure
• Breakout 2: Case study work on choosing Established Conditions (ECs)
  • Synthetic drug substance process
  • Large molecule drug substance process
  • Analytical procedure
• Feedback and group discussion from Breakout 2

Session 3

• Product Lifecycle Management (PLCM) Document (ICH material)
• Breakout 3: Presentation and case study work on developing and reviewing PLCMs based on the work done in Breakout 2.
• Feedback and group discussion from Breakout 3
• Presentations specific to agency needs or Experiences with ICH Q12 presented by another regulatory agency (e.g., US FDA)

Session 4

• Best practices for the preparation of a PACMP with examples covering:
  • Biological drug product
  • Synthetic drug product
• Breakout 4: Practice review of mock PACMP documents
• Feedback and group discussion from Breakout 4
• Close and any next steps

Process

The training was delivered live, remotely, to reviewers and inspectors, with as many as 170 attendees split into breakout groups of about ten individuals. ISPE industry experts delivered most plenary presentations; however, some were delivered by experts from the ICH Q12 Expert Working Group (EWG). Breakout group membership was pre-assigned by the agencies, as were breakout group rapporteurs. ISPE Professional Development and Regulatory Affairs staff supported the training.

Feedback

Feedback on the sessions was positive, with participants liking the balance of presentations and breakout sessions and the opportunity to discuss the material presented. The attendees also liked the case studies/examples that were shared and the ability to engage with these in discussion, helping them to contextualize ICH Q12. The attendees provided some points for further improvement, which the team will use to improve the training.

Thanks and Acknowledgements

ISPE expresses deep appreciation to the PQLI Q12 Implementation working group members and their companies for their time, commitment, and access to materials:

• Nina Cauchon, Amgen Inc., former ISPE International Board of Directors member
• Andrew Chang, Novo Nordisk, ICH Q12 EWG representative for PhRMA
• Stuart Finnie, Gilead Sciences (previously AstraZeneca)
• Timothy Graul, Pfizer
• Connie Langer, Pfizer
• Chris Potter, ISPE Technical Projects Advisor
• Saroj Ramdas, Amicus Therapeutics
• Ben Stevens, GSK

Special thanks are due to Nina, Andrew, Stuart, Tim, and Ben, who delivered the training to HSA late into their evenings, including a Sunday evening, and especially to Stuart, who was online from midnight to 0400.

In addition to preparing and delivering material for this training, members of the ISPE team were instrumental in obtaining the participation of regulators more experienced in ICH Q12 implementation to provide summaries and answer questions regarding their experiences with ICH Q12 implementation. ISPE thanks Hugo Hamel, Associate Director, Centre for Blood, Blood Products and Biotherapeutics at Health Canada, who participated in the ANVISA training, and Mahesh Ramanadham, Deputy Director, Center for Drug Evaluation and Research(CDER)/Office of Pharmaceutical Quality (OPQ)/Office of Policy for Pharmaceutical Quality and Q12 lead at the US FDA who participated in the MHRA and HSA training sessions with his team of colleagues providing their input in the late evening. The experience of these regulators provided attendees with their peers’ insights into ICH Q12.

Most especially, ISPE thanks ANVISA, Health Canada, MHRA, and HSA for the opportunity to present this material and provide a forum for cross-agency dialogue, and for their valuable input to the program's design and their facilitation of the training sessions.

ISPE’s PQLI Q12 Implementation team is exploring opportunities to continue this training program with other regulatory agencies to extend the global implantation of all elements of ICH Q12.

For more information contact Regulatory@ISPE.org.