ISPE’s ICH Q12 Team Trains Singapore’s HSA on Regulatory Guideline

The team, which is part of the ISPE Product Quality Lifecyle Implementation (PQLI)^® committee, has been conducting training events worldwide to assist regulatory agencies in implementing the International Council for Harmonization’s (ICH) Q12 guideline, “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management.”

The guideline offers a framework for biopharmaceutical and pharmaceutical manufacturers to manage post-approval changes in the chemistry, manufacturing, and controls of pharmaceutical products more predictably and efficiently across the product lifecycle. Implementing ICH’s Q12 guideline is expected to promote innovation and continual improvement in production, strengthen quality assurance, and help improve the reliability of supply chain management, ultimately benefiting patients.

The training in Singapore was held virtually over four days with approximately 70 attendees. The program included sessions on key components of ICH Q12, established conditions, and Post-Approval Change Management Protocol (PACMP), also known as a Comparability Protocol in the United States. US Food and Drug Administration (FDA) representatives were on hand, providing valuable insights into the practical application of the guideline.

Implementing ICH’s Q12 guideline is expected to promote innovation and continual improvement in production, strengthen quality assurance, and help improve the reliability of supply chain management, ultimately benefiting patients.

REGULATORY BACKGROUND

The guideline, which was adopted by ICH regulators in November 2019, is in the process of being implemented by ICH member regulators. To date, ICH Q12 has been adopted by the FDA, the Pharmaceuticals and Medical Devices Agency in Japan, the National Medical Products Administration (NMPA) in China, and the European Medicines Agency (EMA). Health Canada is in the process of integrating the guideline, as are Brazil, Mexico, Singapore, Republic of Korea, United Kingdom, Switzerland, and Chinese Taipei1.

ICH Q12 has been adopted by the FDA, the Pharmaceuticals and Medical Devices Agency in Japan, the National Medical Products Administration (NMPA) in China, and the European Medicines Agency (EMA). Health Canada is in the process of integrating the guideline, as are Brazil, Mexico, Singapore, Republic of Korea, United Kingdom, Switzerland, and Chinese Taipei.

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. However, it has proven to be challenging. ISPE’s goal is to help agencies navigate this potentially transformative guideline through training events.

THE Q12 IMPLEMENTATION TRAINING PROGRAM

PQLI® 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, Q13, and Q14.

The Q12 Implementation Team was established to collect 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. In addition to Singapore’s HSA in 2024, it has conducted training sessions for Brazil’s Agência Nacional de Vigilância Sanitária (ANVISA) in 2022, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) in 2023, and Health Canada in 2022.

The ISPE Q12 training program was created after Health Canada expressed interest 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. The PQLI Q12 Implementation Team worked with representatives from Health Canada to develop the training program which addressed:

• 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 A
• 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 in the UK and HAS in Singapore, the agenda included a short presentation by the FDA on their experiences in implementing ICH Q12, followed by a Q&A and discussion.

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 small breakout groups. ISPE industry experts delivered most plenary presentations and were augmented by the FDA’s experts in implementation of ICH Q12 who were able to add a session on their expertise in this area. 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 enhance future training.

Acknowledgments

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 04:00.

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.

ISPE extends its gratitude to the PQLI ICH Q12 Implementation Team members and their companies for their dedication and support, as well as to the US FDA representatives and HSA liaison Dr. Subin Sankarankutty for their contributions to the training’s success.

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