Clinical supplies & logistics
White blood cells collection
T-cells isolation and activation
CAR gene implementing
T-cells multiplication Engineered T-cells infusion
cells to do battle against the disease in the bodies of patients, they use various cytotoxic mechanisms to eliminate the cancer cells. These mechanisms include the release of perforin and granzymes, which create pores in the cancer cell membrane and induce apoptosis (programmed cell death). CAR T-cells can also express cell surface receptors that directly induce apoptosis in the cancer cells. The results of this customised approach are still being evaluated in clinical trials, with one academic paper finding 1,087 CAR T-cell clinical trials were in operation according to
ClinicalTrials.gov as of February 2023. According to work by Acumen Research and Consulting, for instance, the CAR T-cell therapy industry is set to enjoy CAGR of 24% through 2032. That’s shadowed by growth in specific countries: In the United States, researchers expect the sector to reach $7bn over the next decade. But while interest in CAR T-cell therapies abounds, they equally cause vast challenges in the supply chain. That’s not hard to understand. Rather than drawing a straight line from factories to patients like with small molecule drugs, CAR T-cell therapies must instead travel from patient to manufacturer – and back again. And if that inevitably causes bottlenecks, there are other problems too. From a lack of trained staff to a bewildering variety of extraction protocols, insiders must overcome a range of hurdles before patients can finally enjoy the benefits of personalised cell therapy. Even then, the costs involved remain eye- wateringly high for many, particularly when such a booming field leaves little space for collaboration.
Blood supply
Few people are better placed to explore the difficulties of the CAR T-cell therapy supply chain than Quezada. An industry veteran of more than three decades, he began his career overseeing the technical operations of a blood bank. Since then, he’s worked on everything from stem cells to quality control. Now a self-employed transfusion medicine and cell therapy consultant, he well understands the
Clinical Trials Insight /
www.worldpharmaceuticals.net
strengths of CAR T-cell therapies. Yet if his enthusiasm at “second chances” speaks vividly to the medical miracles these technologies promise, he is equally conscious that none of it is easy. Most fundamentally, the issues start with the supply chain. Compared to regular medications, Quezada explains that the latest blood therapies add “one more step to the chain, because you have to collect the cells first from the patient, and then send them to the manufacturing facility like any other raw material”.
The complex pipeline of production for CAR T-cell therapies involves multiple steps.
Unfortunately – in the US, obviously – many of the pharmaceutical companies are trying to reimburse their shareholders.”
Dr Jeffrey Winters
In practice, that predictably slows down the time it takes for patients to get treatment. Depending on the precise manufacturing method, that can take about a month, hardly ideal when early treatment is crucial to survival. Nor is this back-and-forth supply web the only bottleneck. For one thing, the machines to extract blood samples, known as apheresis units, are often hard to use. This isn’t so much down to the devices themselves as it is to the demands of manufacturers – though it doesn’t help that nursing courses normally don’t cover them. From extracting different blood volumes to specific counts of white blood cells, Dr Jeffrey Winters says that nurses are expected to master a bewildering range of extraction methods. As the Mayo Clinic specialist continues, that means nurses need about six months of training before they can use apheresis machines confidently – a number that rises to twelve months for more complex procedures.
There are troubles at the other end of the supply chain, too. While demand is soaring, CAR T-cell therapy manufacturers are struggling to keep up. This is unsurprising: Quezada warns that with the best will in the world, it can take months or even years to build new facilities, while the needs of
19
Olha Pohrebnyak/
Shutterstock.com
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41
