Even as more cell therapies push past the finish line, questions about how to make the personalized medicines swiftly and dependably persist. For Bristol Myers Squibb, which is standing up two new cell factories, automation and high-tech training will form twin jewels in its production crown, an exec said.
Making cell therapies such as BMS’ recently approved CAR-T meds Breyanzi and Abecma is a highly personal process. There’s apheresis, when T cells are gathered straight from the patient, plus the process of re-engineering the cells and getting them quickly back to patients.
The biggest hurdle, to hear BMS’ vice president of global cell therapy manufacturing Snehal Patel tell it, is maintaining a “good chain of custody” throughout the entire process.
“The last thing we want to do is a mix-up of patients in any way,” he said. “This is a personalized medicine.”
Doing so requires “a good portion of labor” and a whole lot of training because the field is still relatively new, Patel said. With more workers to train than equipment available, BMS is turning to virtual reality.
To start, BMS is developing a VR platform to teach employees the basics of biosafety cabinet operations, Patel said. Biosafety cabinets are enclosed, ventilated lab workspaces where workers handle delicate materials in a controlled environment.
Bristol plans to kick off the program at its future cell therapy factory in Devens, Massachusetts, then the company’s newly unveiled plant in Leiden, Netherlands, and, finally, across the company’s network, Patel said.
To get acquainted with biosafety cabinet essentials like airflow and aseptic technique, trainees simply don a pair of VR goggles and step into the virtual fume hood. Once vetted on the virtual tech, they’d graduate to a real biosafety cabinet in a Bristol Myers’ plant for manufacturing qualification, Patel said.
While the early focus is on biosafety cabinets, the company could consider extending the VR approach to its other equipment—and beyond simply bringing employees up to speed.
The tech could eventually allow BMS’ facilities to “talk” to each other to work through manufacturing problems remotely. For example, a plant in Washington could visualize the exact problem its peers in New Jersey are having, helping the company “navigate … and troubleshoot” the issue, Patel said. That potential application is still a ways out, he acknowledged.
Aside from the virtual reality technology, BMS also hopes to fine-tune its operations by leaving some parts of the production process entirely to machines. The future holds “… more automation and more equipment that is tied together,” Patel said.
Electronic batch records, automated bioreactors and automated flow cytometers are just a few of the advances BMS is blueprinting for its plants in Massachusetts and the Netherlands. By easing the scope of its manual operations, BMS aims to remove variability and potentially slash manufacturing turnaround times.
Shortly after BMS’ February green light for its large B-cell lymphoma CAR-T Breyanzi, the company put the manufacturing pedal to the metal. It laid plans for a 244,000-square-foot cell therapy factory in Devens, Massachusetts, which it will staff with “several hundred” new employees over the next few years. Engineering runs are expected to kick off there in late 2021 or early 2022, Patel said.
Then, just before the company’s second CAR-T approval for Abecma in multiple myeloma in late March, BMS said it would build its first- cell therapy factory in Europe. It recently pegged Leiden as that facility’s home. BMS expects construction on the plant to begin later this year.
The allure of Leiden is twofold: It will enable BMS to tap into the growing life sciences ecosystem coming up around the city, plus the central European locale should ease delivery of BMS’ therapies to patients there, Patel said.
Neither CAR-T therapy is approved yet in Europe, but for patients receiving the treatments in European clinical trials, a manufacturing partner currently performs the initial T-cell collection step.
The partner ships those materials to one of BMS’ existing U.S. plants, which perform the manufacturing and testing. Patel couldn’t comment on how long the process takes in Europe now, but he did say BMS expects turnaround times to decrease once the Leiden plant is up and running.