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.
Minimizing the impact of bioburden and sterility testing on gene therapy batch yield 637.77 KB 415 downloads
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.
This paper is a companion to the Minimizing the impact of container closure integrity testing on gene therapy batch yield and Minimizing the impact of stability testing on gene therapy batch yield.
For more information, download the paper below and contact Simon Walker, Global Change Facilitator, at simon.walker@biophorum.com
Abstract
The purpose of this paper is to assess and provide recommendations for reducing volumes required for testing of bioburden and sterility of gene therapy products including considerations for clinical stage and process stage (i.e. in-process vs bulk drug substance (BDS)). 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.Â
I question the commonly used strategy of benchmarking to obtain industry practice when a risk-based approach with a statistical analysis to determine the probability of detection of microbial contamination based on sample volume would be a superior approach. Also risk should be mitigated as prevention is better than testing. See Cundell, T., S. Drummond, I. Ford, D. Reber and D. Singer 2020 Risk Assessment Approach to Microbiological Controls of Cell Therapies PDA J. Pharm. Sci. & Technol. 74 (2) 229-248