ISPE Assists Health Canada with ICH Q13 Guidance Training

Continuous manufacturing has been used for decades across various industry sectors. Some common pharmaceutical manufacturing unit operations like tableting and automated liquid filling are inherently continuous but often run in batch mode due to limited input material. Interest in fully continuous pharmaceutical manufacturing—linking operations like powder granulation and tableting—emerged in the early 2000s, aiming for regulatory approval. Progress followed, with the first regulatory approval for continuous granulation in 2015,1 and additional product approvals in 2016, 2017, 2018, and 2020.2

Although literature reports indicated that the early product approvals were accepted in many regions,1 individual regions started to draft guidelines between 2016 and 2019. A proposal was made and accepted by the ICH in a concept paper in November 2018 as ICH Q13 “Continuous Manufacturing of Drug Substances and Drug Products” with the aim of introducing a harmonized guideline to facilitate global introduction of continuous manufacturing. An expert working group was established that produced a Step 2 draft document for public comment in July 2021.

A finalized guideline was issued in November 2022.3 This guideline describes scientific and regulatory considerations for the development, implementation, operation, and life cycle management of continuous manufacturing. Building on existing ICH Quality guidelines, this guideline provides clarification on continuous manufacturing concepts and describes scientific approaches and regulatory considerations specific to continuous manufacturing of drug substances and drug products. A comprehensive set of training videos was issued in November 2024.4 The guideline is in the process of implementation by ICH member regulators.

ISPE’s Product Quality Lifecycle Implementation (PQLI)^® initiative was created to provide guidance on practical implementation of the concepts described in ICH guidelines, focusing initially on Q8, Q9, Q10, and Q11. These guidelines promote enhanced science- and risk-based approaches to product development, technology transfer, and manufacturing, with the goal of fostering innovation and continuous improvement. One such innovation is the adoption of continuous manufacturing in the pharmaceutical industry.

Under the PQLI^® umbrella, a continuous manufacturing team5 was established in 2017 to develop a body of knowledge supporting global implementation of continuous manufacturing. Over the past three years, the team has:

• Published seven articles on continuous manufacturing
• Conducted an Expert Exchange webinar
• Responded to the ICH Q13 Step 2 draft guideline with a series of well-constructed technical comments, many of which were incorporated in the final Step 4 document
• Drafted an ISPE Good Practice Guide on control strategy development for continuous manufacturing, scheduled for release later in 2025.

Implementation of ICH Q13 in Canada

After the final ICH Step 4 document was issued, the ICH Q13 Implementation Working Group (IWG) continued to work to produce training material. During preparation of the ICH training material, Health Canada approached ISPE to assist with the implementation based on the positive experience with previous ISPE training for ICH Q12 implementation.6 Health Canada’s request was to establish ISPE’s interest in providing some industry virtual sessions for their staff to understand industry perspectives as well as potentially facilitating some visits to manufacturing sites.

Leadership of ISPE’s PQLI^® and Continuous Manufacturing teams interacted with Health Canada’s small and biological molecule review leadership to establish requirements and timescales. Given that this virtual training would complement the ICH training material, there was sufficient time to develop the agenda and prepare material using industry case studies and highlighting industry “pain points.” Consequently, ISPE agreed to form a Q13 Training sub team to deliver the training and take account of ICH training material.

During discussions between Health Canada and ISPE it was agreed that invitations to this virtual training could be made to other regulatory agencies. For the training itself, invitations were sent to 16 UK Medicines and Healthcare products Regulatory Agency (MHRA) quality reviewers, three UK MHRA inspectors, and four Singapore Health Sciences Authority (HSA) reviewers. The Q13 training was conducted in four half-day sessions. ICH Q13 was implemented in Canada earlier this year.

The training agenda was jointly developed by senior small molecule and biologics reviewers from Health Canada and ISPE’s PQLI^® and Continuous Manufacturing teams. The training aimed to prepare Health Canada assessors and inspectors for ICH Q13 implementation by deepening their understanding of industry practices in continuous manufacturing, sharing real-world challenges to encourage dialogue with regulators, offering flexible, on-demand access for participants with varying expertise, and aligning with ICH IWG training efforts. While continuous manufacturing of biologics is less advanced than for small molecules, industry requested inclusion of case studies—particularly on monoclonal antibody production—to reflect current experience. Training combined presentations, Q&A, and listen and learn sessions using case studies and published industry materials. Case studies—covering process dynamics, control strategy, and disturbance handling—were developed for both small and biological molecules. Each session included a plenary presentation followed by breakout discussions with pre-set questions, culminating in a final Q&A. The remote training, delivered via Microsoft Teams, reached ~170 Health Canada reviewers and inspectors, with notable participation from MHRA and HSA. ISPE experts from the US and EU led plenary case study presentations and chaired the program. Participants joined from Canada, the UK, and Singapore. Breakout groups, leaders, and rapporteurs were preassigned, and the sessions were effectively facilitated by Health Canada. Formal feedback is being collected and will be analyzed. Early responses indicate strong engagement and praise for the clear, high-quality presentations. ISPE thanks Health Canada for the opportunity, their input on program design, and expert facilitation. Special thanks go to the training group members and their companies for their time and materials. Participants agreed the training was successful and met its objectives.