There is no mistaking the sure but steady revolution happening in cell therapy.  With the long-held promise now rewarded with greater funding, investment and belief, the change in gear has been dizzying.

However, this is merely the end of the beginning and the hurdles we must overcome in disseminating clinical manufacturing are surely the next beach-head. Not just for now but how cell products can be produced as the scale of cell therapy matures through its adolescence. Miltenyi Biotec has been involved in cell therapy development for nearly twenty years. It has always been clear that cell manufacture will require a closed-system, independence from higher-grade operating backgrounds, automation, standardisation and single-device processing. This will be increasingly obvious and of vital concern as cell therapy progresses to Phase III trials and on to commercialisation.

Miltenyi Biotec’s vision has thus evolved to provide closed-system cell manufacture in one device with all required GMP materials. With larger-scale GMP cell manufacturing becoming real, the advantages of having one experienced partner providing all requirements in a facilitating manner are becoming clear, exclusive licencing being another growing concern in this changing market. The CliniMACS Prodigy® is one of the first truly closed, automated end-to-end GMP cell processing devices and its potential is now beginning to be realised.

The unmistakable poster boys of cell therapy right now are undoubtedly CAR T cells, with such promise in the clinic and burgeoning interest from Big Pharma and private investment. However, production of these cells is long and complex with many different steps, including the utilisation of genetically modified viral vectors. To encompass this process into a closed automated device is perhaps the key to any organisation wishing to lead the field in this arena. It is thus exciting that the CliniMACS Prodigy T Cell Transduction Process is about to be released – a fully integral manufacturing solution in a closed-system. A process comprising preparation, isolation, activation, viral transduction, expansion and final formulation, closed and automated, which is flexible enough to allow subtleties in differing protocols and optimisations but rigid enough to maintain GMP fidelity. An end-to-end solution that can be monitored and controlled.

While the field becomes aware of the requirement of such processing, we believe the CliniMACS Prodigy is leading the way. As cell manufacturing progresses, the main difference we shall see will be in scale. Many processing solutions for allogeneic cells (e.g. MSCs) have necessarily focused on increasing cell numbers and establishing cell banks. However, personalised autologous applications, such as CAR T cells, rather need an increasing number of individual products. This is where such a system comes into its own, particularly where viral vectors are concerned. A fully closed device providing an end-to-end process can give independence from facility capacity. Currently, only one product is usually produced in one cleanroom at a time, but a closed-system means that multiple devices can operate in the same room simultaneously. Capacity then becomes a mere factor of how many automated devices are running, with all the associated benefits to operational costs and management.

The benefits of device-based manufacturing are clear over any production line using multiple facilities and varying devices. A centralised production model is then easier to establish, but because the devices are automated and so easily transferable it also applies to a localised or point-of-care model. A smaller number of devices at local units enables manufacture of personalised cell products in the same standardised way. The CliniMACS Prodigy is a GMP cell manufacturing platform made truly integral with our GMP raw materials, which include now, thanks to our new colleagues from Lentigen Technology Inc., lentiviral vectors.

GMP cell processing also requires thorough QC and analysis of cell products. For a complete solution we developed the MACSQuant® Flow Cytometers and flow reagents, bracketing the closed-system manufacturing with high-performance analysis. It is exciting to see cell therapy finally begin to blossom and to see what comes next. We believe that in the CliniMACS Prodigy we have a complete, compact solution, easily transferable and instantly scalable, for the needs of ATMP production just now being perceived.

By Jason Jones

Manager, Cell Therapy, Miltenyi Biotec Ltd.