ISPE Team Assists Health Canada with Training on ICH Q12 Implementation

Regulatory Background

The International Council for Harmonization’ (ICH)’s guideline entitled, 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 in a more predictable and efficient manner across the product lifecycle. Implementation of ICH’s Q12 Guideline will promote innovation and continual improvement in the biopharmaceutical and pharmaceutical sectors and strengthen quality assurance and reliable supply of product, including proactive planning of supply chain management. It will allow regulators (assessors and inspectors) to better understand a firm’s Pharmaceutical Quality Systems (PQSs) for the management of post-approval CMC changes.

The guideline was adopted by ICH regulators in November 2019 and is in the process of implementation by ICH member regulators. ICH Q12 does incorporate concepts such as established conditions (ECs), post approval change management protocols (PACMPs) and product lifecycle management (PLCM), and some of these concepts are new to some ICH member countries.

ISPE’s Q12 Implementation Team

ISPE’s PQLI® initiative was created to provide guidance on practical implementation of the concepts described in ICH guidelines, focusing on Q8, Q9, Q10, Q11 and Q12 to help ensure product quality throughout a product lifecycle, leading to continual product improvement.

Under the PQLI umbrella, an ICH Q12 Implementation Team was established with a focus on developing a body of knowledge to assist industry with global implementation of Q12. Recent outputs from this team include two articles and a webinar:

• Introducing ICH Q12: A Transformational Product Life-Cycle Management Guideline
• A Vision for ICH Q12: Current Experience, Future Perspectives
• Challenges and Success of ICH Q12 Related Submissions

Implementation in Canada

As a major part of implementation in Canada, HC issued in July 2021 a revised series of draft guidances for Post-Notice of Compliance (NOC) Changes i.e., post approval changes, with a deadline for stakeholder comments by end of October 2021. As a continuing part of their Q12 implementation, HC announced in November 2021 an opportunity for a limited number of applicants to participate in two pilot programs, one of which is an ICH Q12 Established Conditions and Post Approval Change Management Protocol Pilot Program. In order to prepare HC reviewers for the receipt of applications for the Q12 pilot and to assist with eventual full implementation of ICH Q12 in Canada, HC asked ISPE if it could assist with some training based on case studies and experiences in the FDA pilot on established conditions with the aim of delivering the training before reviewers were tasked with reviewing applications. These case studies had been included in the 2021 ISPE article and webinar.

Training Outline and Process

A subset of members from ISPE’s Q12 Implementation Team, along with ISPE’s Director of Professional Development Brandon Pastore and ISPE Advisor Chris Potter, worked cooperatively with a senior group from Health Canada to develop the training agenda, which had the following objectives:

• Training Health Canada reviewers in Implementation of ICH Q12 so that reviewers are ready for reviewing applications with new tools/enablers
  • Understand why Q12 was required
  • Learn what the core tools and enablers are
  • Use the core tools and enablers in case study examples
  • Hear about companies’ pharmaceutical quality system
  • Learn about FDA Established Conditions pilot study experiences

The training was delivered remotely to approximately 170 reviewers with a small group of inspectors present for some sessions. ISPE team members were home-based in the EU, UK, east and west coast US. Most HC participants were also home-based in Canada.

The training consisted of a blend of presentations and breakout sessions, some using case studies. All breakout sessions had pre-prepared questions for participants to work on. Where applicable ICH training material was used without change. For the convenience of HC participants and to fit in with HC’s Q12 implementation plan, the training was divided into four 3-hour sessions presented on different days in January 2022.

A summary of the training agenda:

Session 1

• Introduction and Workshop Objectives
• Presentation: Summary of why ICH Q12 was needed
• Presentation: Description of pharmaceutical company change management system
• Plenary Discussion on change management system
• Presentation: Introduction to Q12
• Breakout 1: Discussion on Q12, the problem, etc.
• Feedback and Group discussion from Breakout 1

Session 2

• Introduction to Established Conditions and Case Studies
• Presentation: Established Conditions, Case Study 1 to small molecule reviewers
  • Synthetic Drug substance process
• Presentation: Established Conditions, Case Study 2 to biotech reviewers
  • Large molecule drug substance process
• Presentation: Established Conditions, Case Study 3 to all reviewers
  • Analytical method
• Breakout 2: Case study work on choosing ECs
  • Split groups:
    • Synthetic Drug substance process
    • Large molecule drug substance process
    • Analytical procedure
• Feedback and Group discussion from Breakout 2

Session 3

• Presentation of 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
• Presentation: Discussion of PLCM and the Canada-specific Certified Product Information Document (CPID) in the context of Lifecycle Management.
• Group discussion; CPID vs PLCM

Session 4

• Presentation on best practices for preparation of a post approval change management protocol (PACMP)
• Breakout 4: Practice review of mock PACMP documents
• Feedback and Group discussion from Breakout 4
• Close and any Next Steps

Most plenary presentations were delivered by ISPE experts; however, some were delivered by HC experts from the ICH EWG. The training program was chaired by HC. Breakout group membership was pre-assigned as were breakout group rapporteurs. From feedback and group discussion sessions, issues were collected in a “parking lot” for review and collation in the wrap up session. From this session, a series of actions were derived to assist HC with Q12 implementation.

Feedback and Conclusions

Formal feedback from participants was requested, received, and analyzed by HC leadership and shared with ISPE. A formal review meeting was held, and major conclusions were:

• Presentations were well delivered, and case study material was very relevant and welcomed by HC.
• The virtual platform worked well.
• HC facilitation of breakout sessions and feedback presentations were excellent.
• Participants would have welcomed face-to-face training to allow more interaction with ISPE experts particularly informal interaction at breaks. More group discussion time would have been appreciated.

This was judged by all parties to have been a successful training exercise which achieved its objectives. It is intended that the material developed by the ISPE members will become part of ISPE’s training program for industry.

ISPE thanks HC for this opportunity to conduct training as well as the excellent input to the design of the program, and organization and facilitation of the training sessions. Most especially ISPE would like to thank the members of the PQLI ICH Q12 Implementation Team who participated in the training – and their companies - for their time, commitment, and access to materials.

The ISPE participants:

• Nina Cauchon, Amgen and ISPE Board member
• Andrew Chang, NovoNordisk and ICH Exert Working Group (EWG) representative for PhRMA
• Stuart Finnie, AstraZeneca
• Connie Langer, Pfizer
• Saroj Ramdas, Amicus
• Ben Stevens, GSK
• Brandon Pastore, ISPE Director of Professional Development
• Chris Potter, ISPE Advisor, Facilitator