Cell therapy manufacturing: Where is the process control?

The Cell Therapy [CT] sector has reached a critical point. Recent years have seen significant milestones reached with the approval of CAR-T therapies for treatment of specific cancers as well as adult stem cell-based treatments, like Takeda’s Alofisel for Crohn’s complications. Yet these ground-breaking therapies come with a hefty price tag and significant delivery challenges. To realise the promise shown by clinical trials, we must improve Cell Therapy manufacturing.

CT operates in two modes. Autologous therapies, like CAR-T, harvest a patient’s own cells, manipulate and expand them, then administer these cells back to the same patient. Allogeneic therapies on the other hand, are developed using healthy donor cells that can be administered to multiple patients.

These modes have distinct process economics. Allogeneic products can tap the economies of scale we see in Biologics manufacturing. Autologous products cannot. The discrete small volumes involved require near-patient manufacturing within clinics. 

Many predict that industry will favour allogeneic therapies in the future due to their ‘off the shelf’ potential. Until both safety and efficacy of this strategy can be proven, however, autologous therapies will prevail, especially for the treatment of life-threatening diseases, but the economics are challenging. Our goal is to make autologous manufacturing accessible to all.

“IF YOU CANNOT MEASURE IT, YOU CANNOT IMPROVE IT” Lord Kelvin

Regardless of manufacturing mode, fundamental analytical challenges exist when manipulating and expanding cells ex vivo for therapeutic treatment. 

Wider manufacturing makes extensive use of Process Analytical Technology [PAT] to control process parameters that determine product yield and quality. A typical CT bioprocess will monitor simple physical and chemical quantities (temperature, pH, dissolved gases, etc.), and generally strive to hold these at set values, but biological assays speaking to cell identity and functional potential – the very core of both bioprocess performance and clinical impact – do not exist in any useful form.

Current practice uses an array of different laboratory assays to monitor and confirm product identity and function. Some of these assays can take weeks to complete. As a result, important information on product quality is often only available after the manufacturing process is complete. This leaves the entire process under-sampled and under-controlled. Practically no information on cell quality is fed back into the system to keep manufacturing on course. Without this feedback there can be no process control

This same slow assay challenge exists in cell culture media development. Manufacturing cells in chemically-undefined media containing animal- or human-derived components does not make for reproducible and safe production. We urgently need to develop fully-defined, consistent, animal- or human-derived component-free CT media. Yet slow and laborious cell assays are again a considerable pain point for CT media developers. 

To develop better CT bioprocessing, we need faster and more informative cell assays

Process controllers and media developers could achieve so much more with faster cell assays. Better bioanalytics will enable assessment of critical process parameters to boost yield and quality for both CT modes. In autologous manufacturing, fast and rich cell analytics will allow us to tailor both the culture media and process itself to the patient’s own cells. Decentralised smart CT manufacturing in clinics, directed by advanced bioanalytics and process controllers, will deliver truly Personalised Medicine.

OUR VISION

We believe Data will drive the next wave of bioprocessing. Valitacell’s commercially available products embed rich analytics right across Biologics manufacturing. Our flexible analytical technologies enable faster, cheaper and more robust biomanufacturing. With our partners, we are applying our advanced analytics to the currently intractable process of CT manufacturing. Our CT R&D programme is developing novel analytics to enable a data-driven approach to CT manufacturing, targeting core challenges such as donor cell functional characterisation and media design with our ChemStress, Quantum, Enhance and Cell-AI technology platforms. Our technologies will power the closed, fully automated, near-patient CT manufacturing systems of the future. 

Dr. Stephanie Davies, Head of Science (Cell Therapy) & Dr. Paul Dobson(Head of Data)

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