A modern compendial automated and rapid sterility testing technology for cell and gene therapy products

Abstract

Background & Aim Cell and Gene Therapies are currently being developed to treat different diseases. By design, those therapies have very short shelf lives compared to traditional sterile pharmaceutical drugs. Besides, Cell and Gene Therapies can not be sterilized by filtration, therefore the historical compendial sterility test methods that takes 14 days to complete as defined in USP : “Sterility Tests” is not compatible. In order to assess the sterility of these therapies prior to transfusion, the BacT/ALERT Dual-T, an automated and more rapid technology, has been developed to reduce the time to result while keeping the highest level of perfomance and compliance. This method has now been recognized as compendial and can be used in lieu of the traditional 14 day sterility test to assess the sterility of cell-based products as defined in the EP Chapter 2.6.27 Microbiological Examination Of Cell-Based Preparations. The objective of this work is to present the pathway to making an alternative test compendial for the specific cellular products. Methods, Results & Conclusion Method: The BacT/ALERT Dual-T will be presented and discussed as a compendial test replacing the traditional culture-based 14 day incubation sterility test, and other alternative technologies will also be discussed in comparison to compendial testing. A review of all major litteratrue and scientific articles will be presented that demonstrates the use and applicability of the BacT/ALERT Dual-T to assess the sterility of cell-based products. Different real-cases of implementation of the BacT/ALERT Dual-T within the Cell and Gene Therapies field and the biotechnology industry will be discussed, with recently adopted implementation strategies for different type therapies. And finally a regulatory update will be given, specifically on the recent advancements in several regulations and Pharmacopoeia Chapters, encouraging the use of more Modern, Rapid and Automated Sterility Testing solutions. Conclusion: Several validation studies have provided data comparing the BacT/Alert System to the compendial sterility test method and enabled the adoption of this technology as a compendial method for sterility testing of cell-based therapies. This enables the industry to replace the historical 14 day incubation historical compenidal sterility test by a much more modern and rapid automated method, which results in greater patient safety by providing final sterility results in less than 14 days.