The Hidden Challenge Holding Back CAR-T Growth: Scaling Out Patient-Specific Manufacturing

An analysis found that the hidden constraint holding back CAR-T cell therapy growth is not "mass production," but the difficulty of "scaling out" by running the entire process anew for each patient.

According to BioPharmaDive on the 2nd (local time), commercial supply of autologous CAR-T therapies is tied not to a particular product but to an individual patient. As the number of patients grows, the model requires adding thousands of individualized manufacturing processes rather than producing large batches.

Carvykti, a multiple myeloma treatment marketed by Legend Biotech and Johnson & Johnson (J&J), recorded second-quarter net sales of $657 million, up 50% from the same period a year earlier, after its first approval in 2022. It is now prescribed at 348 institutions in 19 markets.

Yet the fundamental constraints have not changed years after launch. Patient cells, manufacturing slots, quality testing, release dates, logistics and treatment center schedules all have to move in sync.

Mike O'Mara, chief operating officer (COO) of Cellipont Bioservices, explained by email that "when you scale autologous cell therapies, you scale out, not up."

In early clinical development, a small number of experienced staff can handle a limited number of patients, but commercialization requires multiple teams to reproduce patient-specific processes simultaneously. That is why manual steps and variation among operators become more consequential.

"The real question isn't, 'Can you make one more batch?' It's, 'Can you consistently manufacture, test, release and ship on the timeline required?'" O'Mara said.

Legend has established a model in which U.S. patients are treated with product manufactured in the United States and European patients with product manufactured in Europe. All four sites are operational: the expanded Raritan facility, a Novartis contract manufacturing organization (CMO) facility, and the Obelisk and Tech Lane facilities in Ghent, Belgium.

According to Legend, the expanded Raritan facility can support treatment for up to 10,000 patients annually. In the first quarter, the manufacturing success rate in the United States was 99%, the median turnaround time was 29 days, and the on-time release rate for final product shipments exceeded 95%.

Finished CAR-T doses must pass testing and quality review, and manufacturing uses specialized raw materials that have their own supply constraints. At the commercial stage, a bottleneck at any one step can slow the entire process.

Treatment centers are also part of the system. Patient enrollment and scheduling for clinical trials must align with manufacturing slots booked by contract development and manufacturing organizations (CDMOs), and canceled or delayed procedures leave reserved manufacturing resources idle.

In June 2025, the U.S. Food and Drug Administration (FDA) eliminated risk management requirements for several approved CAR-T therapies, including Carvykti. The agency expected that simplifying post-treatment monitoring and reducing the required period of staying near a health care facility and avoiding driving to 2 weeks would improve access for patients in rural areas.

"The most common misconception is that there will always be time to optimize the manufacturing process later," O'Mara said, advising companies to design processes with scale in mind before commercialization.

Next-generation CAR-T therapies address the problem by eliminating some ex vivo manufacturing steps. Legend is testing LB2501, an in vivo CAR-T candidate that uses a gene vector to directly modify immune cells in the body.

LB2501 is designed to generate CD19/CD20-targeted CAR-T cells in the patient's body with a single infusion. Initial phase 1 data released in June from 12 patients with relapsed or refractory B-cell non-Hodgkin lymphoma reported no dose-limiting toxicities, serious adverse events or deaths.

However, a study of 12 patients is only an early evaluation. Alan Bash, Legend's interim chief executive officer (CEO), said long-term follow-up must confirm safety and demonstrate efficacy competitive with existing treatments.

The in vivo approach could shift the burden from running an external cell-processing workflow for each patient to standardized vector production. The vectors themselves would still need to be manufactured reliably at commercial scale, but the process could be simpler.

O'Mara predicted that as cell therapy manufacturing models diversify, CDMOs will need flexible systems to support multiple approaches and a broader role in helping design processes.

With autologous CAR-T, each additional patient adds another manufacturing process. How well individualized processes can be industrialized or partly replaced is expected to determine how widely these therapies can reach.