In the last decade advanced cell therapies are becoming highly commercialized. Industry developers, in general, favor so-called centralized model of cell product manufacturing/ delivery. In centralized model, one big manufacturing plant produces and delivers many many (thousands) products within a country or internationally. In the last few years, Biotech and cell therapy companies (Novartis, Kite Pharma, UniQure…) heavily invested in development of centralized facilities. In the other camp, academics, physicians and tools manufacturers are betting on decentralized or “point-of-care” model of cell therapy manufacturing/ delivery. You can read more about pros and cons of each model in the recent reviews – here and here. But I’d like to focus today on potential catalyst for shifting from centralized to decentralized model.
Proponents of decentralized model of cell therapy delivery would like to use relatively simple/ user-friendly, automated, closed system-based device, which can do many manufacturing processes at once. We call this type of devices “all-in-one”. Of course, “all” is not equal 100% , but combining many major processes, which are usually described in bioprocessing as separate “unit of operations”. Three years ago, German company Miltenyi Biotec has launched new device CliniMACS Prodigy (CE mark in Europe). I’d consider Prodigy’s launch as the first attempt to introduce a prototype of “all-in-one” device to clinical cell therapy world. Unlike previous generation of devices with capability to do more than one process, Prodigy went as far as integration of cell separation, magnetic cell sorting and cell culture.
Since launch, seem like Prodigy is doing well on the market (as much as I can say from attending conferences). Prodigy clinical validation reports are available now for CAR T-cells, mononuclear cells from bone marrow and peripheral blood, CD34 cell selection, NK cells and virus-specific T-cells. The main advantage of Prodigy, of course, is process integration capability. Importantly, it is fully automated, closed system device, which can save a lot on time and labor. I’d like to highlight few disadvantages of Prodigy:
- capability to produce only one batch at time (1 patients –> 1 device)
- high complexity and absence of backup device (equal alternative) underlies high risk
- low flexibility of cell incubation unit (limited volume/ cell concentration)
- relatively high cost.
Now, I’d like to discuss the main potential impact of Prodigy and devices alike. I think, Prodigy could be a catalyst for shifting from currently widely accepted centralized model to “point-of-care” model of cell manufacturing/ delivery. Devices like Prodigy is exactly what most proponents of decentralized manufacturing model were dreaming about. It could, potentially, “democratize cell therapy” by making clean room facilities obsolete and simplifying whole manufacturing process by pushing few buttons and hanging the bags. Single use disposable of multifunctional device is a replacement of class 10,000 clean rooms. Full automation is replacement of labor. Importantly, it will work nicely only for autologous (personalized) cell therapies, where cost of manufacturing is very high and starting material is very variable. In this case, cost of auto- cell product will be equal cost of manufacturing, no profit. Hospitals and patients will love it and jump on it! Allogeneic cell products manufacturing will be taken (almost entirely) by industry into centralized plants.
I think, it may work especially nicely for few processes and few indications (for example, CAR T-cells in B-ALL). If your hospital wants to have multiple cell therapies for multiple indications, Prodigy may not be universal answer. Ideally, big multidisciplinary hospital would have cell therapy facility with both types devices “all-in-one” and “plug-and-play” (multiple devices for multiple processes). But if you’re looking only for getting your CAR T-cell program going in hem/oncology on a budget, Prodigy alone could be the solution.
Finally, I’d like to notice that Prodigy is just at the beginning of its way in clinical cell therapy. We may see more and better “all-in-one” devices in the future. We don’t know for sure if fundamental shift from centralized to hospital-based model will finally happen for some autologous cell products in some indications. Miltenyi’s people firmly believe (based on what I’ve learned from few talks on different conferences) that it may take years, but finally decentralized “point-of-care” model will prevail for autologous cell therapies.
What do you think? Will Prodigy change everything?
Disclaimer: This post is neither advertisement nor endorsement, but invitation for discussion. I’m not a user of CliniMACS Prodigy. I do not have any conflicts, related to Miltenyi Biotec.