Novartis has been advancing CTL019, an investigational chimeric antigen receptor T cell (CAR T) therapy for relapsed/refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL) through clinical trials.
Novartis shared insights from the development of the therapy in an opinion manuscript, as a global perspective on the considerations and challenges of manufacturing CAR-T therapies.
Titled Global Manufacturing of CAR-T Therapies, the manuscript discusses, comprehensively, every step of the manufacturing of these potential cures: from vector selection, to genetic modification, scale up considerations when moving from development to manufacturing, and the regulatory landscape.
Novartis, alongside their manufacturing and vendor, Oxford Biomedica, and scientists at University of Pennsylvania’s Department of Pathology and Laboratory Medicine, published the paper in Molecular Therapy Methods & Clinical Development.
Particularly, the manuscript discusses critical control considerations in terms of deployment of external manufacturing sites and vendors, who have to maintain critical quality attributes including cellular phenotype and functionality to result in a consistent product. At the same time, these processes are drawn up within the constrains of the product, which, for CARs, means that positivity, viability, phenotype, and potency will vary from product to product. These differences result mostly from differences in starting apheresis material, rather than variations in the manufacturing process. Moreover, such considerations are particularly difficult for products, such as CTL019, which are to be commercialized globally.
Vendor agreements, it is further discussed, are critical for maintaining a controlled manufacturing process.
Finally, as an emerging class of therapies, the authors recognize the lack of harmonization across the regulatory landscape. While this is something that will change as this and competing therapies reach the market, the manuscript recommends awareness and caution of the varied, and varying, regulatory positions.