Autologous cell therapies are unique because they are made in small, individual batches, bespoke to each patient.

This places new demands on the manufacturing and logistics infrastructure needed to deliver product. The industry is well aware of these challenges but, as yet, this hasn’t precipitated a coherent solution.

Should cell therapy developers find solutions to these problems or would this be better addressed by equipment manufacturers? Who should lead the charge?

How has it been tackled so far?

Dendreon is an example of a company who took on the cell therapy manufacturing challenge. Unable to develop an integrated manufacturing solution, they went to market with a largely manual manufacturing process. However, this was not well suited to the demands of cost and quality that are placed on serial production of a product. Whilst Dendreon was in many ways a leading pioneer in cell therapy manufacture, without equipment well suited to the unique demands of cell therapy manufacturing, they were arguably doomed from the start.[1]

There have been attempts to create better cell therapy manufacturing platforms by the equipment manufacturers. Companies such as Miltenyi with Prodigy and Octane with Cocoon have developed “all in one” systems, whilst some suppliers have created broader offerings such as GE with its acquisition of Biosafe.[2] These may yet prove to be part of the solution but there remains significant uncertainty as to the ultimate outcome. Against this backdrop, you could argue the success and timeliness of the first commercial therapies will be heavily dependent on the progress made by manufacturing equipment companies.

Should we be expecting equipment manufacturers to be releasing a steady stream of new equipment for the autologous cell therapy industry?

The evidence from the trade halls of any cell therapy conference suggests that there is not an explosion of new offerings. 2016 saw the release of GE’s Sefia platform and we expect 2017 to bring electroporation to Prodigy, but this is far from rapid progress.  In many ways the limited enthusiasm of equipment manufactures is understandable. There is a risk that therapies currently under development are still years away from significant manufacturing volumes. Worse still, cell therapies’ longevity and other side effects may mean they never become mainstream. Then there is an uncertain regulatory landscape that could easily lead to an equipment manufacturer developing the wrong equipment. Finally, there is a significant therapy cost of goods challenge which could yet see the industry stall. In a way this is a chicken and egg situation. If we don’t develop the manufacturing equipment, the cost of goods will never be low enough to make therapies successful, but until we have developed the hardware, economic manufacture won’t be possible.

Alongside this is the question of what the specification should be for the first generation of cell therapy manufacturing equipment.  This is not just about the processes it must be able to perform, but also the nature of the environment in which it will be installed; anything from in a biologically clean factory to a relatively poorly controlled near patient facility. Uncertainty around the winning specification coupled with an industry that is generally conservative, presents further barriers to adoption.

This combination of factors makes it tempting to watch and wait, but in an industry with such significant potential this is a risky strategy. Perhaps equipment manufacturers may therefore have to move outside of their comfort zone and seek help from those used to working against an uncertain backdrop.

How much of a lead should the cell therapy developers take?

Clearly the therapy developers are best placed to define the requirements of the equipment, both at a process level and from the perspective of how the requirements align with their longer term manufacturing strategy.  In an industry where “the process is the product”, therapy developers have more interest than many in securing long term access to the hardware. In particular, the world of single use bioprocess equipment recognises that security of supply of the consumables is mission critical. However, therapy developers’ core expertise is unlikely to cover hardware development. It may well be time for this lack of expertise to be addressed; the unique challenges of cell therapy manufacture will likely require much more of a sea change in the industry than previous therapies have demanded.

Can’t everyone just work together?

There are examples of collaborations between the therapy developers and the equipment manufactures.  Kite have a relationship with GE, GSK has one with Miltenyi.[3] It is certain that closer working relationships, whatever the parties involved, will be needed than are required in traditional pharmaceutical manufacturing. Cell therapy will not only challenge us to find solutions to technical, economic and regulatory problems but it will also require us to develop new relationships and new ways of working together.

How should we move forward?

As an industry we need to move beyond simply acknowledging the challenge of manufacturing. One way or another, we must ensure that progress in developing new manufacturing equipment keeps pace with the development of new cell therapies. This may mean we need to think differently about how new equipment is realised. We are not in a world of catalogue products and we cannot rely on somebody else finding an answer to our problem.

So what is the solution? Dendreon has shown that a unilateral approach is risky. It is likely collaboration is needed. However, we may need to look beyond just the therapy developers and equipment manufacturers if the industry is going to successfully move into this exciting new territory.

Dr Edwin Stone