In 1931, Swiss doctor Paul Niehans injected a preparation of live cells from a parathyroid gland into a dying patient. The patient subsequently recovered, and Dr. Niehans had a eureka moment — that injections of living cells can have tremendous therapeutic value.
Today, there are 13 FDA-approved cellular therapies on the market and over 10,000 clinical trials open for cell therapies. (By comparison, there are approximately 3,000 trials are open for antibodies.) Additionally, the FDA just this month created the new Regenerative Advanced Therapy designation to expedite the development and review of cell therapies for serious or life-threatening conditions. The small number of approved products, large number of trials, and favorable regulatory climate raise the odds of a large gap in manufacturing capacity occurring in the not-so-distant future.
As new cell therapies come to market over the next few years, the industry will need to mobilize rapidly and build commercial production facilities that are dedicated to these therapies yet flexible enough to adapt to evolving needs. Driven by process economics, cell therapies present a unique set of criteria for facility design; needs that vary significantly with factors like the type of therapy, patient population, and process closure.
Autologous Or Allogeneic? Distinct — And Common — Challenges
In the cell therapy process space, the low hanging fruit is in allogeneic cell therapies, which involve harvesting cells from a healthy donor (or donors) and transplanting them into others. Allogeneic therapy production can leverage the development efforts vaccine manufacturers have invested in optimizing adherent cell culture designs. The challenges of handling large numbers of 2D bioreactors and automation of processes have already been addressed by various technology suppliers. For example, the Nunc Cell Factory is a commercial offering from Thermo Fisher Scientific that is already used in several vaccine processes and is fully automated.
For allogeneic processes that rely on manual operations, incubators and biosafety cabinets will be involved. However, manual production operations are not sustainable. Advances in technology will drive the incorporation of robots and “lights out”/human-less modularized factories in the long term, though expanding and improving offerings upon an automated, modular backbone is realizable in the immediate future.
In addition, small, boutique fillers are available from multiple vendors to meet the needs of small batches. With these batch sizes, comparisons should be done to determine if the increased variable cost of closed filled vials outweighs the fixed costs of traditional component preparation.
Autologous therapies — where the patient’s own cells are removed, often treated, and later reintroduced to the donor — require an entirely different process/logistical model. Production of treatments for individual patients may be better suited to more of a pharmacy or doctor environment, because many of these therapies are regionally hosted and time sensitive. This need will drive new execution models. One approach is for the process to be executed via an automated, regulated medical device used by a clinician. Fenwall produces an apheresis device targeted at mononuclear cell collection, and Miltenyi Biotec’s Prodigy system provides automated closed culture and separation in a bench top unit.
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