Comparability assessment plays a pivotal role in ensuring the safety and efficacy of Cell and Gene Therapy (CGT) products during manufacturing process changes. While the principles outlined in the ICH Q5E guidance provide a foundation for comparability assessment, the unique complexities associated with CGT products warrant a more tailored approach. This presentation outlines key considerations for a comprehensive comparability assessment, emphasizing the need for rigorous risk-based evaluations, analytical comparability, and detailed reporting to support Investigational New Drug (IND) and Biologics License Application (BLA) submissions.
Risk-Based Comparability Assessment The draft guidance issued by the FDA underscores the importance of adopting a risk-based approach when assessing manufacturing changes for CGT products. Due to their inherent complexity, predicting the impact of such changes can be challenging. The guidance recommends integrating statistical methods into the risk assessment process, with a focus on critical quality a (CQA). For minimally manipulated CGT products affected by manufacturing changes, graphical representations and visual comparisons are suggested to complement statistical analyses, especially when higher risks to CQA are involved.
Analytical Comparability Prior to commencing a comparability study, the FDA advises submitting a comprehensive comparability protocol, seeking feedback on study design and statistical methodologies. This protocol should include a forward-looking plan to assess the effects of post-approval manufacturing changes on product quality and safety. The extent of the comparability study should align with the conclusions drawn from the risk assessment, encompassing relevant quality attributes, suitable test methods, and acceptance criteria. Furthermore, the study should encompass quality attributes not routinely used for product release. Special considerations are also provided for CGT products derived from variable cellular starting materials, vectors used for ex vivo cell modification, potency assessment, and analytical methods.
Tissue-Engineered Medical Products (TEMPs) The draft guidance recognizes the unique challenges posed by manufacturing changes to TEMPs, which often incorporate viable cells and scaffolds. Changes to TEMPs can impact cells, scaffolds, or the combined product in unpredictable ways, requiring specialized evaluation methodologies beyond current measurement technologies. The guidance outlines the need for meticulous analysis and assessment when dealing with TEMPs.
This presentation highlights the essential components of a robust comparability assessment for CGT products, emphasizing the significance of a risk-based approach, analytical comparability, and tailored reporting to ensure product safety and efficacy. These considerations are vital for supporting IND and BLA submissions in the dynamic field of CGT.
Learning Objectives:
Define the key principles and regulatory guidance for comparability assessments of cell and gene therapy (CGT) products after manufacturing changes.
Analyze the importance of risk-based approaches, analytical comparability studies, and detailed reporting when evaluating CGT manufacturing changes.
Evaluate unique considerations for comparability assessments of complex CGT products like tissue-engineered medical products (TEMPs).
