Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized immunotherapy, offering innovative solutions for cancer treatment. Allogeneic CAR-T therapies utilize T cells from healthy donors or such sources as umbilical cord blood and induced pluripotent stem cells, providing scalable, off-the-shelf treatments with broader applicability and reduced waiting times compared with autologous CAR-T therapies. The manufacturing process includes T-cell activation, genetic modification using viral vectors to express CARs, cell expansion, rigorous quality control testing, and cryopreservation for storage and shipment. These therapies demonstrate clinical efficacy in hematologic malignancies, making them cost-effective and accessible to patients who are unsuitable for autologous approaches. In contrast, autologous CAR-T therapies leverage a patient's own T cells to create personalized, highly targeted treatments. Beginning with T-cell collection via apheresis, the process involves activation, genetic engineering to express CARs targeting specific cancer antigens, cell expansion, and thorough quality control. Despite challenges in T-cell quality and manufacturing complexity, autologous CAR-T therapies have shown remarkable success in treating acute lymphoblastic leukemia and non-Hodgkin lymphoma, offering hope to patients who have exhausted other treatment options. Together, both approaches highlight the transformative potential of CAR-T therapies in cancer treatment.
This second part of a two-part article provides a clear understanding of microbiological load reduction during cleaning processes in the non-sterile pharmaceutical manufacturing. Different microbiological test methods are used to get to an outline if the cleaning process can already be seen as a microbiological risk reduction step. Finally, cleaning validation considerations using different cleaning chemistries are discussed in this paper.
A critical function of container closure systems-defined as one vial, one stopper, one seal, or one press-on cap-used for the packaging of injectable drug products is to maintain closure integrity over the life cycle of the drug product when exposed to a range of storage and transportation temperature conditions. Many injectable drugs are packaged in glass vials affixed with an elastomeric closure secured by an aluminum seal using sufficient crimping seal force to obtain the target residual seal force to assure container closure integrity (CCI). And more recently, interest in closures comprised of press-on caps pre-assembled with stoppers. The development of advanced therapy medicinal products (ATMPs), vaccines, insulins, and many biologics requiring extreme cold storage management pose CCI challenges not encountered at ambient and base cold storage temperatures impacted by differences in packaging component coefficients of expansion and elastomer viscoelastic transition to a glass-like state beyond -50 degrees C. ATMPs, including cell, gene, and RNA therapies, are collectively defined as a class of highly innovative novel drugs requiring complex cold chain logistics, driving sustained growth of the cold chain medicine market and a need for injectable primary packaging capable of maintaining CCI at extreme cold storage (-80 degrees C) temperatures. This study evaluates the best-in-class elastomer compounds, formulations, and coatings, affixed with aluminum seals and press-on caps to Type I borosilicate tubular glass vials conforming to the International Organization for Standardization (ISO 8362) injection containers requirements.
