Minimizing the impact of bioburden and sterility testing on gene therapy batch yield

Gene therapies offer the potential to treat otherwise unmet medical needs. To deliver these therapies to patients, sampling and testing must be performed in a manner that supports manufacturing processes. 

However, gene therapy products are subject to the same regulatory release criteria and expectations as the processes used for biologics/pharma products that produce significantly higher yields. Often, if gene manufacturers were to adhere to current release requirements, the outcome would be little, if any, remaining product for the clinic or the patient.  

This paper makes recommendations for reducing the volumes required for testing and therefore conserving product for patients, while remaining compliant and delivering assay and process information on the microbiological status of gene therapy products. 

Approaches for organizations to consider include:  

• Leveraging existing verbiage in compendia for small-volume products  
• Taking both platform and phase-appropriate approaches  
• Taking matrix-based approaches for suitability testing requirements. 

For this paper, we evaluated strategies for reducing bioburden testing and sterility testing volumes, as these two release tests contribute significantly to the total volume required for release testing. Member organizations completed a benchmarking survey to evaluate common practices, and the results showed no aligned approach for either bioburden or sterility. 

The review included current regulatory requirements, phase-appropriate considerations, qualification and method suitability requirements, and various aspects of testing. It also included a review of a typical gene therapy sampling plan with an evaluation of the impact to yield from example in-process samples.  

• Version
• Download 34
• File Size 637.77 KB
• File Count 1
• Create Date 7th June 2023
• DOI https://doi.org/10.46220/2023CGT006
• Last Updated