Column – The last major technical obstacle for personalized medicine: manufacturability

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Imagine a world in which your loved one is diagnosed with a devastating disease that can be cured with a custom-tailored treatment, specially designed and manufactured for them. The sky is the limit when it comes to the benefits of truly personalized medicine.

For example, the personalization of treatment would ensure a perfect match between the tumor and the immunotherapy, which would make cancer therapy much more effective. It would cure type 1 diabetes using autologous cells, negating the lifelong need for immunosuppressants. And it would help control cystic fibrosis by replacing cells that carry the diseased CFTR receptor with reprogrammed cells from the same patient that now carry the healthy variant. Technically, we are not far from this imaginary being a reality.

CAR-T cell therapy: a success story

One of the most famous and successful examples of personalized medicine is CAR-T cell therapy for the treatment of B-cell lymphoma. In this therapy, some of the patient’s T-cells are temporarily removed from their body . Outside the body (ex-vivo), these T lymphocytes are genetically modified using viral vectors to carry a receptor (Chimeric Antigen Receptor) which recognizes the patient’s cancer cells. Before reentering the body, the modified T cells are activated so that they kill the target that binds to the receptor. It is truly miraculous to think that with the help of ex-vivo genetic programming, the patient’s own cells are able to heal the body of cancerous B cells.

How is this personalized approach unique? Traditionally, drugs have been produced using fairly standardized manufacturing processes in specialized centralized facilities. However, in the case of CAR-T cell therapy, an entire decentralized personalized cell therapy manufacturing infrastructure has been reinvented to allow patients around the world to access a breakthrough treatment. The results so far have been dramatic, and many patients who previously only had years or even months to live are now cured with personalized CAR-T cell therapy.

Personalized medicine: beyond cell therapies

The success of CAR-T cell therapy paves the way for many other personalized treatments. Technologies like CRISPR can now more precisely control the genetic programming of cells. In many ways, we’ve only scratched the surface of what’s possible. Personalized cell therapies are set to further revolutionize the world of medicine. Even more encouraging is the advancement of microfluidic and AI technologies that are bringing sophisticated high-throughput screening approaches for antibody and protein selection into the realm of possibility.

For example, the microfluidic platform technology developed by Abcellera screened a complex sample containing millions of antibody-producing cells to select a specific antibody that was successfully developed into a drug for the treatment of COVID-19. What’s most exciting is that the whole process only took three months instead of the previous 15 to 25 years.

Another recent and successful initiative is 64xBio, a synthetic biology company that just landed a $55 million Series A funding round. 64x Bio is building a platform that dramatically increases the speed and scale of mammalian cell line discovery for viral vector manufacturing. These vectors are used for cell therapies (for example, genetic modification in CAR-T therapy is performed using viral vectors) and gene therapies. In view of these developments, it is not unreasonable to believe that in the near future, personalized medicine will extend beyond cell therapies to therapies using viruses, antibodies and proteins.

Sandy Reid, Bioproduction Equipment, StarFish Medical
Nick Allan (StarFish Medical) manipulates pilot batches of bioengineered materials in an anaerobic environment. Sandy Reid (StarFish Medical) uses confocal laser microscopy to visualize the results of a biofabrication experiment
Images courtesy of StarFish Medical.

Challenges

The future of personalized medicine is exciting, but it also poses real challenges. Never before have we reinvented the way we manufacture and deliver drugs/treatments on such a scale. Each custom treatment comes with its own set of crafting challenges. These include growing a relatively low number of patient-specific cells, monitoring sterility in improvised Class D hospital fabrication rooms (relatively dirty compared to a traditional Class B cleanroom), incorporating drug quality control testing for rapid drug release and controlling the enormous costs associated with custom manufacturing procedures.

The weight of these challenges currently rests on the shoulders of process engineers who use a defined and limited toolbox of manufacturing equipment and single-use consumables. Given the demands of custom manufacturing processes, the limitations of the existing toolkit prevent some of these new therapies from progressing to the clinic. Additionally, the manufacturing tools that exist in the field of personalized cell therapy are dominated by a few large companies with very few new players. This market can absolutely benefit from many other innovative solutions and healthy competition. More collaborative initiatives need to take place between drug manufacturers and developers of manufacturing equipment and consumables.

Given the explosion of new personalized approaches and the need for new, innovative and affordable manufacturing tools and equipment, I expect a severe shortage of equipment and consumables for manufacturing personalized treatments in the short term.

Amazing new personalized treatments from innovative drug development programs deserve to be offered to patients everywhere. Drug manufacturing process engineers should not consider themselves limited by existing tools and equipment. If it doesn’t exist yet, think bigger, reach out to product developers and create a better closed-system bioreactor for adherent cells, or a new small-scale downstream processing solution for drug purification, or a custom valve for aseptic sampling, or any other innovative new equipment deserving of the same celebration as the successes of custom CAR-T cell therapy.

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