CMC Strategy Forum North America Summer 2021

Efforts are underway to update and expand the applicability of ICH Q2(R1), Validation of Analytical Procedures, the authoritative guidance on analytical method validation. In parallel, the ICH Expert Working Group is drafting Q14, Analytical Procedure Development, to provide guidance on modern approaches in analytical method development and method lifecycle management. Q2(R1) and Q14 are intended to provide a roadmap for efficient communication between applicants and regulators on the approaches and expectations of advancing an analytical procedure from the definition of intended use through development, validation, and routine use through the lifecycle of the product. The session will include a brief overview of the workplans and current progress for the revision of Q2(R2) and the development of Q14, including regulator and industry perspectives on the value the new documents and case studies to demonstrate innovative approaches to analytical method development. A panel discussion will follow, providing an opportunity for audience engagement with the speakers and other experts. Finally, breakout sessions to allow for strategic dialogue and open exchange regarding specific topics relevant to these guidelines, such as expectations for robustness and use of Analytical Target Profiles.

Since the publication of the Q5A(R1) Guideline in 1999, there has been advances in biotechnology product development and manufacturing that are not reflected in the original guideline. Additionally, emergence of new virus detection technologies and evolvement of strategies for virus clearance strategies based on manufacturing experience and scientific consensus has occurred. The revision of ICH Q5A(R2) was endorsed as a new topic for ICH harmonization in June 2019 and the concept paper was published in Nov 2019. The following areas were proposed for updating the ICH Q5A(R1):

• New classes of biotechnology products (e.g., virus-like particles (VLPs), subunit proteins, and viral-vectored products)
• Additional validation approaches for virus clearance (e.g., modular validation)
• New virus assays and alternative analytical methods (e.g., PCR, NGS)
• Virus clearance validation and risk mitigation strategies for advanced manufacturing (e.g., continuous manufacturing)
• Aspects of virus clearance validation that have emerged or evolved

This session will include brief presentations to describe the context for revisions to the guideline, and then provide opportunity for discussions related to their incorporation. For example:
1. How will the updates support or impact your current manufacturing process and practices?
2. Do you think the updates will address current gaps? Do you have additional suggestions within the scope of the updates?
3. What are the most challenging topics within viral safety validation for continuous / advanced manufacturing?

ICH Q13, Continuous Manufacturing of Drug Substances and Drug Products, is progressing through document development with endorsement of Stage 1 expected in May 2021. This document is expected to provide guidance to industry and regulatory agencies regarding regulatory expectations on the development, implementation, and assessment of CM technologies used in the manufacture of drug substances and drug products. This session will feature perspectives from regulators, industry and the ICH Q13 Expert Working Group (EWG) on the motivation for ICH Q13, the perceived benefits, progress, and challenges to-date. Participants will have an opportunity through the panel discussion to share their hopes and concerns with those directly involved with the development of the document.

New guidelines versus additional updates, flexibility versus detailed expectations, statistical tools versus application of knowledge, modeling versus specific data… what is your position? Proposals to revise ICH Q6B (Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products) and ICH Q5C/Q1 (Quality of Biotechnology Products: Stability Testing of Biotechnological/Biological Products and related Q1 stability guidances) are currently on the table. Further guideline revisions and/or new guidelines will be added to the ICH agenda periodically. The timing of this conference presents an opportunity for strategic dialogue and open exchange regarding challenges and opportunities related to the current specification and stability guidelines prior to drafting of the revisions and an opportunity to reflect on additional challenges that could be addressed through novel ICH guidelines. This session will engage participants in discussions regarding next steps in the development of ICH Quality guidelines in support of harmonization, modernization, and use of scientific and regulatory best practices to advance the future of medicines globally.