John Tomtishen, Global Head Cell Therapy, Field Application Scientists and Strategic Alliances at Catalent, shared on LinkedIn:
“Over the past few weeks, I have been asked to share my perspective on some of the recent challenges that have impacted various CAR-T programs. While the news has not been great, the sky is not falling! Progress in cell therapy – really, throughout biopharma – has never been linear.
The root cause for some of the recent issues may never be public, but they may relate in some fashion to new manufacturing approaches.
What I can say for sure is that with CMC, every action has a reaction. Extended manufacturing cycles, especially for autologous CAR-T therapies, come with a set of issues that the whole field has had to address in order to develop robust, commercial-ready manufacturing processes.
There are advantages to shortening the manufacturing process – for example, you might end up with more active and potent T cells. The reaction might be that you need to account for safety issues that come with a stronger immune response. Changes in cell phenotypes might need to be offset, for example, by adjusting the dosing strategy.
To state the obvious: you do not want to have to make these adjustments in later stages of development and well into clinical trials or after receiving authorization. Avoiding that takes extensive early characterization. The more characterization data you have, the better your understanding will be of any required CMC changes during the drug development lifecycle and, ultimately, the downstream impact on the final therapeutic product.
None of the challenges cropping up in headlines seem insurmountable. But CMC is tied directly to the commercial potential of cell therapies. The later it gets into development, the more expensive it gets to address manufacturing issues – and patients will be exposed to increasingly higher risk. Both can create challenges in bringing these therapies to the market, which is why CMC is so critical to their success.”