Patient-specific cell therapies have the potential to cure cancers when other treatments have failed. Unfortunately, a global lack of production capacity and a paucity of skilled production staff are limiting access.
The seven autologous CAR T therapies approved by the FDA to date—Abecma, Aucatzyl, Breyanzi, Carvykti, Kymriah, Tecartus, and Yescarta—have two things in common: they are made from patient-specific cells, and they are complex to produce.
And, for traditional manufacturing models, these characteristics are a major challenge, says B. Wayne Bequette, PhD, a professor from the Department of Chemical and Biological Engineering at Rensselaer Polytechnic Institute in New York.
“The current manufacturing mode of operation is centralized, with only a few manufacturing sites available. There are currently many manual manufacturing steps and a limited number of operators and technicians with the background and skills to operate them. And there is substantial variability in the number and quality of cells available from patients.
“Analysis by Bristol Myers Squibb [which makes Abecma] shows that the major contributor to therapeutic product variability is the cells from the patient. Indeed, they propose that patient-specific product specifications should be used.”
Patient-specific product specs aside, to really address the production challenges, the industry needs to take a multifaceted approach, with the development of faster manufacturing and more efficient logistical methods being obvious starting points.
Bequette tells GEN, “Production times can be reduced using several strategies, from decentralized capacity that could eliminate cryopreservation steps and shipping delays, to rapid manufacturing that results in fewer but more viable product cells, and finally reduced product release testing times by using more in-process monitoring.”
Innovation
The burgeoning autologous cell therapy industry would also benefit from embracing innovative production technologies and methods, Bequette says, citing automation and AI as examples.
“More complete manufacturing automation helps in many ways, by enabling closed systems that do not require as expensive cleanroom environments and enable a reduction in the number of operators/technicians and the facility space required.
“AI can be implemented at many levels, from learning algorithms that better operate expansion bioreactors to assisting with planning and scheduling production lines between manufacturing sites,” he says.
Bequette, who set out a blueprint for faster, more efficient production in recent research, believes AI can help even earlier in the process.
“Although technically not associated directly with manufacturing, I feel AI-based decision support systems could assist a clinician in choosing between alternative treatments for a particular patient. For example, product A may have a higher expected efficacy for a particular patient, but product B may currently have a shorter expected vein-to-vein time, so a clinician could use this information to make a treatment recommendation.”
Skills shortage
Industry also needs more engineers with the specialist skills needed to manufacture CAR T therapies, Bequette says, citing study programs at the Rensselaer Polytechnic Institute as a potential source.
“It is important that we have a well-educated workforce to expand production of life-saving therapeutics. For example, our Center for Engineering in Precision Medicine (CEPM) is linked with the Mount Sinai School of Medicine in New York City.
“One CEPM activity involves a PhD program in Health Sciences Engineering (HSE), where students spend their first year on the engineering campus in Troy, NY, followed by clinical and translational research at Mount Sinai.
“In my courses, in addition to developing mathematical algorithms, I motivate students to consider the human element throughout the process—from maintaining the safety of the process operators to the quality of the therapeutics being manufactured and delivered to patients,” he adds.
