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Supercharged T-Cells Battle Cancer But Will GxP Compliance Be Their Kryptonite?

What if your company had to sign off on hundreds of unique product batch releases a year; each a therapeutic for a specific individual, and where a “mix-up” could be fatal? This is the challenge facing developers of chimeric antigen receptor T-cell (CAR-T) therapeutics and other autologous cell therapies.

Results of clinical trials for CAR-T leukemia treatments have shown stunning outcomes. In a trial at Children’s Hospital of Philadelphia 27 of 30 pediatric patients had a complete remission of their cancers. Similarly, in the Memorial Sloan-Kettering Cancer Center Trial, 14 of 20 adult patients experienced comparable remission results and even more early phase trials have reported similar outcomes. Using the CAR-T approach each patient receives his or her own modified T cells as the active therapeutic agent. The commercialization hurdle for this therapy and other autologous cell therapies is creating a GxP compliant cell culture system for every patient. This unprecedented situation presents a number of unique analytical challenges for our industry:

  • T-cells harvested from each patient represent a unique “production cell bank” that must be fully characterized;
  • Robust bioassays are required to evaluate the health and potency of transfection appropriate T-cells; and
  • Cell stability assays will be required to monitor, as with any cell bank, the frozen and stored expanded cells of each donor master cell bank (MCB).

Despite these and other commercialization challenges, CAR-T technology continues to attract the attention of venture capitalists and big pharma. Several partnerships around CAR-T therapies have been announced, including Immunocore’s agreements with AstraZeneca, Hoffmann La Roche (Genentech), and Eli Lilly, Juno Therapeutics’ 10-year collaboration with Celgene, Kite Pharma’s agreement with Amgen, and Pfizer’s investment in Cellectis. Novartis announced the intent to establish a cGMP CAR-T manufacturing facility under its partnership with the University of Pennsylvania. And just recently, Sorrento Therapeutics announced that its subsidiary, TNK Therapeutics, had acquired preclinical and clinical stage CAR-T programs and associated technology from two privately held companies.

Clearly, the promising early clinical outcomes are driving the flurry of ventures between the CAR-T technology innovators and big pharma. However, many process and regulatory hurdles lay ahead before the CAR-T approach becomes a standard of care in cancer treatment. Bringing these therapeutics to the market will require cooperation between industry and regulators as new methods and processes are developed to overcome the unique challenges for this class of therapeutics.

 

Blog article by: Sheila G. Magil