Minimizing the impact of stability testing on gene therapy batch yield

It is widely recognized that gene therapy manufacturing processes result in low yields, particularly in early product development stages. Gene therapy products, however, are largely subject to many of the same regulatory requirements and expectations as other large molecule biopharmaceuticals that are produced at significantly larger scales. Often, if gene therapy manufacturers were to adhere to common paradigms for stability studies, the outcome would be little, if any, remaining product for patients or studies to support investigational new drug applications.  

This paper outlines strategies for reducing the volumes required for stability studies with the goal of conserving product for patients, while remaining compliant and delivering data on critical quality attributes across the shelf life of gene therapy products. The recommendations provided include considerations for both drug substance and drug product. 

It is based on a survey of industry participants and was used to identify ways to reduce the impact of routine stability testing on batch yield. Approaches for organizations to consider, include (in order of impact):  

• Performing product development studies on representative non-GMP material  
• Including expanded storage conditions and time points in research stability studies  
• Limiting drug substance stability time points to one year  

• Using container closure integrity testing in place of sterility  
• Implementing low-volume methods (e.g., osmolality, pH, titer, % full capsids, and potency)  
• Sharing samples and concurrent scheduling of common analyses at common testing sites. 

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• Create Date 5th July 2023
• DOI https://doi.org/10.46220/2023CGT010
• Last Updated