CAR-T Therapy Manufacturing: Lessons from the Automotive Industry

Although chimeric antigen receptor (CAR) T-cell cancer therapies have the potential to cure cancer, they rely on complex drug customization for each patient. CAR-T manufacturers have spent years trying to personalize manufacturing processes, but their strategies rely on technicians with extensive immunology and scientific experience. Companies have struggled to achieve success using that model.

Despite abundant venture investment, CAR-T developers often encounter delayed schedules and excessive expenditures while they try to refine complicated and difficult-to-scale manufacturing processes to generate clinical proof of concept. Prominent CAR-T companies recently announced high-profile staffing cuts and have narrowed the reach of their clinical programs.

Fortunately, CAR-T manufacturing is similar for all companies, differentiated mostly by how they genetically modify cells. Over 90% of production is virtually identical for each patient, which enables companies to use paradigm-shifting techniques that the automotive industry relied upon to transform car production.

Comparing CARS with Cars

Making an automobile actually is more complicated than making a CAR-T drug, but unlike CAR-T manufacturing, automobile manufacturing is highly systematized in an assembly-line fashion. Thousands of components are built into hundreds of subassemblies that roll up into a final commercial product. Automobile manufacturers control their processes to maintain optimal efficiency, tracking essential variables to catch mistakes throughout and build high-quality cars.

CAR-T companies must follow in the footsteps of the automotive industry rather than rely on scientists who lack manufacturing backgrounds to lead manufacturing design. In good manufacturing practice (GMP) processes, scientists should be replaced or augmented by personnel who understand the principles and methods of high-throughput manufacturing. Such a transformation could bring assembly-line processing to CAR-T manufacturing, inherently improving scheduling, quality control, and overall manufacturing efficiency. A widespread transition to an assembly-line model will enhance the long-term business viability of CAR-T companies.

Put simply, CAR-T manufacturing involves a series of liquid-handling operations. Manufacturing technology’s reliance on continuous fluidic connections to capital equipment must be limited to enable parallel processing at a large scale, similar to operations in a bottling factory. CAR-T manufacturers should collaborate closely with equipment and critical-material suppliers. Together, they can create standardized process-sized packaging systems with sterile connections.

Manufacturers then could use equipment within standardized facility layouts that enable efficient workflows using low-skill unit-operation processes. Such companies also should use well-timed subassembly manufacturing processes to prepare critical reagents in closed-system–compatible delivery systems. That step would help to minimize downtime and enable optimal scheduling and manufacturing line efficiency during drug-substance processing. By exercising strict control of reagent-supplier quality and process variables, manufacturers can ensure repeatable outcomes from lot to lot.

The variability of starting cell material can present difficulties that do not exist in automobile manufacturing. However, to address these problems, CAR-T manufacturers once again can look to the automobile industry. Although apparently identical car components look the same, slight dimensional differences often can distinguish some parts. Auto manufacturers implement statistical process controls to ensure that those parts fall within a bell curve distribution of tolerance to fit their mating components. Similarly, CAR-T manufacturers can use proven small-scale models in process development to represent large-scale manufacturing. Historical data can help to create bell curves of tolerance for different unit operations.

Outside industry manufacturing experience should be leveraged to create highly repeatable, controlled, and simple CAR-T–manufacturing processes. By drawing inspiration from the automotive industry, we can revolutionize production of CAR-T therapies. Such a paradigm shift would help us make advanced cancer treatments accessible to patients. By leveraging the creativity, methods, and personnel that have propelled seemingly unrelated products to mass production, we can scale CAR-T manufacturing to enable facilities to produce hundreds of thousands of runs per year.

Josh Ludwig is the global director of commercial operations at ScaleReady LLC, 2100 Old Highway 8 NW, New Brighton, MN 55112. For inquiries, contact Suzanna Muggleton at [email protected].