CASSS Welcome and CMC Strategy Forum 2025 Introductory Comments & Workshop I - Approaches to Developing an Enhanced Understanding of Product Quality Expectations

Forum Co-Chairs: Fiona Cornel, Health Canada, JR Dobbins, Eli Lilly and Company, Doug Richardson, Merck & Company, Inc., Shawn Novick, BioPhia Consulting

Quality standards is a term which encompasses management of quality from prior to manufacturing through patient dosing. Quality standards are applied in facility design, process design, product release, storage, and dosing. Quality standards are essential to develop and execute appropriate manufacturing process and product control strategies, that ultimately ensure that biopharmaceuticals remain safe, effective, and of consistent quality. A patient-centric quality standard (PCQS) has previously been defined as a set of patient-relevant attributes and their associated acceptance ranges to which a drug product should conform within the expected patient exposure range (see A. Mire-Sluis et al., J. Pharm. Sci. 2024, Vol 113, 837-855).

New tools and enhanced understanding of biopharmaceuticals, including prior knowledge, allow Sponsors to identify and better understand the safety and efficacy profiles for many critical quality attributes (CQAs). This understanding provides an opportunity to set requirements and ranges for manufacturing and release that are patient-centric rather than mainly reflecting manufacturing experience. Therefore, achieving patient-centricity is understanding patient-relevance, which is defined as the level of impact that a quality attribute could have on safety and efficacy within the potential exposure range.

By using a patient-centric approach to setting quality standards, batches of drug product (DP) will not be rejected due to an explainable shift in a quality attribute, if the shift is within the range determined to be safe and effective for the patient. Additionally, this can increase the flexibility of sponsors to explore newer or novel technologies during product life-cycle management.

This forum will explore the tools available to understand and set patient-centric quality standards including control strategies which ensure safety, efficacy, and product availability for the patient. Advancements, challenges and case studies in the development and application of patient-centric quality standards will be presented. Regulatory considerations and how to apply them in a fashion which is consistent with regulatory guidance to ensure a robust, safe and efficacious patient experience will also be explored.

The session will explore approaches towards developing enhanced product understanding that supports the establishment patient centric quality standards and control strategies.

Speakers will present recent advances on nonclinical tools that inform criticality of quality attributes (CQAs), such as use of biotransformation data for biotherapeutics and in vivo/ in vitro models for vaccines. In addition, the application of a structured CQA assessment will be discussed, to provide insights on risk assessment strategies to ensure appropriate knowledge of product safety and efficacy, and consequent establishment of effective control strategies. The session will conclude with sharing the regulatory perspective on these approaches.

Session Speakers:

What is Meant by Patient-Centric Quality Standards

Phil Krause, Independent Consultant

Patient-Centric Control Strategy Development: Principles, Tool, and mAb Examples

Claudia Gributs, Eli Lilly and Company

Leveraging Biotransformation Data to Refine Bioprocesses and Derisk PQAs

Maribel Beaumont, Merck & Company, Inc.

Defining CQAs Impacting Vaccine Efficacy: The Role of in Vitro and in Vivo Models

Barbara Capecchi, GlaxoSmithKline

Enhanced Approaches to Setting Specifications – A Regulatory Perspective

Jayda Siggers, Health Canada