The importance of viral vector-based gene therapies continues to grow as they have demonstrated promising clinical results and gained regulatory approval for treating genetic diseases, and different types of cancers.
However, the small batch sizes and high costs associated with their manufacture limit their supply and therefore patient access to treatments. At the same time, most regulatory guidance is for small molecules and protein therapeutics, causing high material demand for various gene therapy batch-release tests and stability studies – meaning little may remain for clinical trials or, ultimately, for the patient.
Container closure integrity testing (CCIT) is one of the major factors affecting batch yields, which is why we have published Minimizing the impact of container closure integrity testing on gene therapy batch yield.
With a focus on CGT, the paper looks at:
- This challenge and its impact on the CGT sector
- The CCIT methods available and their pros and cons
- Strategies for how to minimize the impact of using those methods
- Other strategies that can be used to reduce the impact of CCIT on the batch so there is more product left for delivery to the patient while maintaining regulatory compliance.
It focuses on the CCIT of viral vector gene therapy drug product. However, the proposed CCIT strategies apply to all advanced therapy medicinal product (such as cell therapy, ex vivo gene therapy, and mRNA therapeutics) that are manufactured in small lot sizes, typically <500 vials. We hope the paper will be equally useful for companies producing other advanced therapeutic modalities.
If industry doesn’t address this area, then it will continue producing gene therapy batches at a high cost and will need to produce more batches to cover doses for patients. Although companies may create their own solutions, these would not have the influence of BioPhorum’s cross-industry consensus view and options – which is incredibly useful if you are faced with challenges from a regulatory body or inspector to justify your CCIT strategies.
Our paper will be useful if you are involved in the production, analytical development, and QC testing of a small batch-sized product, e.g., a gene therapy. It is especially relevant if you are part of a CMC team generating your strategy for QC testing for the batch release of your product.
With various strategies available for CCIT, our paper summarizes and compares these in line with existing regulatory guidance. This will help your selection of an appropriate strategy for a cell and gene therapy product that balances the reduction of testing overhead with maximizing the detection of container closure defects.
This paper is a companion to our other papers that will be published very soon – Minimizing the impact of stability testing on gene therapy batch yield and Minimizing the impact of bioburden and sterility testing on gene therapy batch yield.