Gene therapy products are subject to the same regulatory release criteria and expectations as those used for biologics/pharma products with significantly higher yields. However, if gene therapy manufacturers were to adhere to current release requirements, there would be little, if any, remaining product for the clinic or the patient.
There is limited guidance on how to perform bioburden and sterility testing on low-yield products. The most recent updates to bioburden chapters in pharmacopeia were performed more than a decade ago and do not account for new and novel products.
To provide up-to-date guidance in this area, we have published Minimizing the impact of bioburden and sterility testing on gene therapy batch yield.
This paper outlines strategies 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. It provides you with an industry perspective and framework for how you could evaluate your bioburden and sterility testing strategies.
Our 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 on yield from example in-process samples.
The paper is targeted at your QC and QA teams who will be part of designing sampling plans and executing testing in general. It will also interest your regulatory affairs teams with primary interactions with health authorities and writing submissions. It will be especially useful if you are a smaller cell and gene therapy organization that is preparing your first product filing or production runs, as it will help guide your thinking and provide data that will be meaningful throughout your clinical program.
When looking at the overall impact on yield and clinical supply and planning, conserving product means there is an opportunity to increase the number of patients dosed with every batch, reduce the costs of goods sold, and reduce the time to clinic. Our paper will help you do this.
If you have some production in-between large and small scales, you may not be able to use a one-size-fits-all approach. Leveraging some of the concepts in the paper will help you align internally on how to proceed when scaling up a process or working with one that remains low yield. It gives you an important framework and context around alternative sampling plans.
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 way that supports manufacturing processes. Using the recommendations outlined in our paper will help you reduce the impact of testing for bioburden and sterility while still achieving the goals of safety testing.