Evolving QC for Cell & Gene Therapy – What’s new in the cell and gene therapy landscape?
What’s new in the cell and gene therapy landscape? What is the role of quality control in efforts to scale up manufacturing of CGT products and alleviate talent constraints?
“For me the most exciting thing is the rapid approval we are seeing for new indications and the expansion to second-line use for existing cell therapy products,” explains Tom Jones.
This year, the US Food and Drug Administration (FDA) approved Bristol Myers Squibb’s Breyanzi® (lisocabtagene maraleucel) and Kite’s Yescarta® (axicabtagene ciloleucel) for second-line treatment of adult patients with large B-cell lymphoma.
Studies are already underway for frontline use, which Tom notes would mean a rapid rise in patients treated with these therapies.
“Kite alone has announced they are looking to treat 25,000 patients a year by 2025. So, if you add to that, the Alliance for Regenerative Medicine’s forecast for regulatory decisions on 17 new cell and gene therapy products by the end of 2023, you can see the potential for an explosion in the number of patients that could be treated with these therapies,” Tom adds.
The role of QC in efforts to scale up manufacturing of cell and gene therapies
Félix Montero Julian discusses trends in manufacture of cell and gene therapies, including the move to decentralised manufacturing, efforts to integrate manufacturing processes and initiatives to reduce lead times.
“The manufacturing of autologous products takes about three to four weeks…until the patient is infused with the CAR-T product. Companies are trying to reduce these lead times…to one week or even a few days,” Félix says.
“Quality control can be the hold up,” adds Tom. “Probably the most pressing need now is to increase the speed of these QC tests…”
Cell therapy products need the full range of safety, environmental, and cellular quality attribute (CQA) tests. Safety testing includes sterility, mycoplasma testing and endotoxin testing to ensure a product is not contaminated. CQA testing, including identity, viability and potency tests are also critical, to help ensure that patients are getting dosed correctly, Tom explains.
Félix and Tom then go on to discuss efforts to reduce the time of sterility testing and mycoplasma testing, as well as to reduce the complexity for QC for CGT.
“Pharmacopeia chapters describe the detection of mycoplasma in 28 days. That is incompatible with the speed that is required for cell therapy products,” explains Félix.
Nucleic acid testing is one of the means that is used to speed up the detection of mycoplasma in these products. But even assays can be cumbersome and require highly skilled personnel.
Similarly, traditional flow-cytometry – used for CQA testing – require an extremely-dedicated and highly-trained workforce to operate.
“Many of the existing solutions were developed for applications that are less time sensitive and don’t meet the needs for cell and gene therapy manufacturers,” says Tom.
Addressing talent constraints with innovative QC for CGT
Thomas Jones has been Cell & Gene Therapy Business Senior Director for bioMérieux since 2020
The cell and gene therapy field is booming and there is already fierce competition for QC talent, according to Tom.
“Companies face high turnover and the lack of sufficient skilled personnel to perform complex QC testing…”
“As the number of patients grows and the batches grow with them, this talent crunch is really going to threaten the growth of the industry,” he adds.
A key solution to this talent constraint, Tom believes, is to make the QC tests themselves easier to use, so that deep training is not required.
“As an additional benefit…that lessening of complexity, reduces the chance for errors, so you wind up getting to a more consistent QC process,” he adds.