The advancements in CAR-T makes the immunotherapy a key for a range of cancer treatment applications, However, there is a range of challenges that are still faced around the manufacture, release testing, and quality assurance of these potent therapies that must be resolved between regulatory agencies and manufacturers, prior to optimal patient solutions, challenges that can enable broader use and commercialization of this effective therapy. Developments in CAR-T therapy must be followed carefully by researchers, to ensure that they are staying on top of the crucial changes and advancements in the field.
Quality Control Practices in CAR-T Therapy Manufacturing
Developing effective, cost-effective technologies and processes for CAR-T’s commercialization and clinical trials is difficult, because the quality of the products is not only subject to variation between donors but also manufacturing conditions, quality and available sources of reagents and raw materials. Manufacturers need to consider these requirements, their platforms and logistics to ensure quality at every stage of manufacturing.
To stay in compliance, manufacturers need to include numerous technologies, including air handlers, 24/7 alarm monitoring, environmental monitoring, nonviable particle counters, cell washers, bioreactors, automatic cell counters and flow cytometers. They must keep this equipment properly maintained while supporting the manufacturing process and operating a skilled workforce that has extensive knowledge and experience with GMP manufacturing, including sufficient quality control testing.
Creating and Maintaining Quality in the Manufacturing Platform
Biologics require controlled, robust, reproducible manufacturing platforms integrating the readiness of the facility, utilities, environmental monitoring, equipment qualification, raw material choice, standard operations methodology, batch production-control records, in-method and end-of-method sampling, highly-trained manufacturing workers, quality control and analytics. These aspects should be tested individually, while the qualification process makes it easier to identify unanticipated challenges. Data can be collected throughout the process to understand challenges and inconsistencies in quality control.
Ancillary Component Quality Control
There are several ancillary components in CAR-T cell manufacturing, including one-time-use disposables, reagents for genetic editing, formulation mediums, cytokines, culture medium, and cryopreservation reagents. Approval of raw materials or components in manufacturing is needed, while certificates of analysis from your vendors needed and acceptance criteria met and reviewed for every lot. Routine testing of the raw materials ensures integrity of the product, so having backup vendors already be in place to reduce supply chain disruption risk is vital to success.
Therapy Release Testing for CAR-T
The differences in patient cell population samples and the response to processing creates a high level of variability. The complex production process requires researchers to provide release tests on every lot while CAR-T therapies are under clinical assessments. The complex production process requires high levels of operator skills and complicated biological materials, so testing analyzes the purity, safety, potency and identity as an essential part of CAR-T testing, to help reduce side effects.
Autologous cell-based therapies are personalized, requiring many manufacturing challenges in scaling production while maintaining quality control. There’s potential for parallel independent production lines, but the platforms are labor-intensive, with the surrounding quality control and single-lot release making the process even more complex and expensive. As the shift to commercial production increases, testing must not fall by the wayside in the overall process, with some companies moving to decentralized models for production, an approach that requires more sophistication in in-line testing while minimizing sampling and manual transfer to off-line testing.
As the technology continues to advance and a regulatory framework solidifies, the testing itself will evolve. This has allowed manufacturers and regulators to work together to determine quality control testing standards. Testing technology also advances, creating faster, more cost-effective testing.
