Travis Byrd, PhD
Junior Associate Editor, ISCT Telegraft
The Ohio State University Wexner Medical Center
United States
Earlier this month, I attended a local immuno-oncology symposium as a representative of our cell therapy lab’s process development team. I presented a poster showcasing some of the Chemistry, Manufacturing, and Controls (CMC) data our lab generated for several IND submissions this year. As I explained to interested attendees that our cell therapy lab does far more than bone marrow and stem cell processing, a recurring question emerged: “So what exactly does the process development (PD) team do?” Great question!
The field of cell and gene therapy is built on scientific creativity and innovation, as we rely heavily on academic discovery to push the field forward. These innovations thrive under flexibility, rare reagents, bespoke culture conditions, open systems and protocols that depend on expert hands. However, many of the technologies entering the preclinical pipelines today were never designed with GMP manufacturability in mind, as we all too often see the familiar pattern of a product with strong, small scale preclinical data that stalls during scale-up, regulatory review, or early clinical manufacturing. This is not criticism, as this model is the foundation for discovery science, but the transition from promising concept to a reproducible, regulatory compliant cell therapy product remains one of the fields greatest bottlenecks.
The PD teams sit at the critical intersection between innovation and implementation. PD is often the first to identify whether a new technology or concept is scalable and even plausible. Translational success can often be determined by these two questions:
- Are the raw materials available, qualifiable, and sustainable for clinical use?
Research grade materials, such as cytokines, custom plasmids or vectors may be irreplaceable in discovery but create challenging GMP barriers
- Does the process produce cells that perform consistently across donors and scales?
What works in an open BSC, with manual manipulations may not translate, as reproducibility in a single lab is not the same as reproducibility in large scale GMP manufacturing or even across a multi-site clinical trial.
As the number of cell and gene therapeutics explodes, so does the pressure…the timeline pressure, the budget pressure, the regulatory pressure.
Even if a cell therapy product shows strong clinical promise, it will struggle to succeed unless it can be manufactured consistently, safely, and at a reasonable cost. In the coming years, the next generation of cell and gene therapy products will demand that innovation and manufacturability evolve together, not in sequence. I may be a little biased, but it is my belief that it is the PD teams, operating as the cornerstone of clinical translation, who will bridge these academic innovations into GMP realities.