Issue link: https://www.e-digitaleditions.com/i/1520859
10 Pharmaceutical Technology ® Trends in Manufacturing eBook May 2024 PharmTech.com Biologics In t h is perspect ive, rapid ster i l it y test i ng ca n provide a substantia l level of assurance that the product is sterile in a short time frame. If the shelf life of the product does not allow waiting for the results from final product testing, representative intermediate products can be tested using a rapid sterility method to support the release of the batch for administration. To ensure maximum safet y, it is recommended to use t he con ser vat ive approach of combi n i ng BACTEC testing with the compendial method. The conditional release for administration is based on five days of BACTEC testing; however, the compen- dial sterility test (after 14 days) is required for final release. T h is combi ned met hod ca n shor ten t he time to drug application but assures safety for the patient. It enables drug administration or clinical preparator y activities (e.g., transpor t of the dr ug and low-density lipoprotein chemotherapy) while results from the gold standard method—compen- dial direct inoculation—are acquired. As required by the regulatory guidelines, when product admin- istration has been cleared using rapid sterility test- ing, procedures of informing medical staff at the clinical site should be in place if contamination is later detected. Outsourcing CAR T-cell drug manufacturing Partnering with a specialized contract development and manufacturing organization (CDMO) can help mitigate the risks involved when manufacturing a CAR T-cell therapy. A CDMO can provide access to new technologies, infrastructure, and expertise, while freeing up internal resources to focus on other aspec ts of d r ug development. Pa r t ner i ng w it h a CDMO also reduces costs and the risk of failure and speeds up time to market. Specia l ized CDMOs have t he exper t ise a nd ex- perience in aseptic processing, which is critical for maintaining sterility throughout CAR T-cell therapy manufacturing. This involves specialized facilities, equipment, and trained personnel to minimize the risk of contamination. CDMOs implement rigorous quality control proce- dures throughout the manufacturing process. This includes testing for sterility at various stages to en- sure the final product is free from contamination and adhering to GMP stands, ensuring that ATMPs are consistently produced and controlled according to regulatory quality standards. CDMOs have established sterilit y testing pro- cedures specific to cell and gene therapies but are a lso implementing new met hods like BACTEC FX40 to speed up drug production and get ther- apies to patients more quickly. These processes consider factors like limited sample volumes and the need for rapid turnaround when handling CAR T-cell products. Conclusion Pat ients rema in in cr it ica l need, so t he indust r y needs to eva luate and promote sterilit y methods t hat en su re qu ick deploy ment of sa fe t herapies. The rapid sterility test using the BD BACTEC FX40 device proved to be a suitable method for sterilit y testing of CAR T-cell drug products. Notably, it ful- filled the comparability criteria to the compendial method outlined by European Pharmacopoeia and the US Pharmacopeia, highlighting its ability to address regulatory compliance, improve efficiency, mitigate risks, and integrate innovative technology making it a pertinent topic within the realm of ATMPs and quality control. To ensure ma x i mum sa fet y, a n approach com- bining the BACTEC method with the industry stan- dard compendial method is recommended. Af ter five days of the BACTEC sterility testing, the condi- tional release is done, followed by compendial ste- rility testing (after 14 days) for the final release. The testing and validation of other cleanroom-specific environmental bacterial or fungal species is encour- aged. It is expected that rapid methods such as BAC- TEC will become commonplace solutions in the near future as more CAR T-cell therapies are developed and gain approval by FDA. Using a CDMO partner that has specialist knowl- edge and expertise can be beneficial when develop- ing CAR T-cell drug products. Their experience of working with time-sensitive therapies can remove t he r isk , reduce costs, a nd help get cr ucia l d r ug products to market more quick ly, while adhering to st r ic t reg u lator y g u idel i nes a nd m a nu fac t u r- ing processes. References 1. Phillips C. Lif ileucel First Cellular Therapy Ap- proved for Cancer. National Cancer Institute, Can- cer Current Blogs, March 5, 2024. 2. Johnson & Johnson. CARV YKTI is the First and Only BCMA-Targeted Treatment Approved by the US FDA for Patients with Relapsed or Refractor y Multiple Myeloma who have Received at Least One Prior Line of Therapy. Press Release, April 6, 2024. 3. US Code of Federal Regulat ions Tit le 21, sec t ion 610.12: sterility (21CFR610.12). 4. USP. USP General Chapter <71>, "Sterility Tests," USP 32-NF 27 (Rockville, MD, 2016). 5. England, M.R.; Stock, F.; Gebo, J.E.T.; Frank, K.M.; Lau, A.F. Comprehensive Evaluation of Compen- dial USP<71>, BacT/Alert Dual-T, and Bactec FX for Detection of Product Sterilit y Testing Contami- nants. J. Clin. Microbiol. 2019, 57 (2), e01548-18. ■