The CMO Dilemma

The dilemma is not whether to use a CMO. For many therapies, CMOs are the natural pathway to commercial manufacture. The dilemma is how to preserve therapeutic intent while taking advantage of their expertise and infrastructure.

As a proponent of cell therapy automation, a well-known CMO president once challenged our conversation with the observation:

“I cannot work out if you are a competitor or an ally.”

It is a perceptive question.

Cell therapy developers frequently engage CMOs to avoid the need to build in-house teams capable of supporting clinical trials, manufacturing and regulatory submissions. This approach makes a great deal of sense, and there are many excellent organisations providing these capabilities.

Having observed the outcomes of these interactions on several occasions, one concern repeatedly emerges: the process developer can gradually lose control of the methods used to conduct their process.

This is understandable. CMOs naturally employ methods that align with their existing facilities, quality systems and preferred procedures—methods for which they already possess experience, documentation and validation.

Over time, however, pragmatic adjustments may subtly change the therapeutic strategy itself.

The challenge is not that CMOs make poor decisions. Rather, development pragmatism may progressively shape the process in ways that were never part of the original therapeutic intent.

In my view, process developers should remain firmly in the driving seat. Pragmatic solutions should be embraced where appropriate, but developers must also be prepared to push their manufacturing partners beyond established comfort zones when the therapy demands it.

Paradoxically, CMOs become even more valuable when considering commercial scale-out.

CMOs already possess qualified facilities, trained personnel and established quality systems. When manufacturing must be transferred to another country or region, engaging an experienced local CMO is often the only sensible approach.

The key requirement is that the manufacturing process itself can also be transferred robustly and reproducibly, without dependence upon local “preferred methods.”

By way of example, a seemingly simple operation such as manually mixing a bag prior to sampling may vary between facilities, operators and organisations. Standardised, automated unit processes reduce this variability and preserve process intent during technology transfer.

For developers considering whether to build their own facilities, a simple cash-flow analysis can be illuminating. Not only may a CMO accelerate time to market, but the capital that did not need to be spent on facilities and infrastructure can instead remain available to support development and growth.

So, are automation platforms competitors or allies to CMOs?

In many respects, they are both.

Standardised, automated manufacturing methods may reduce dependence on local practices, but they also strengthen the ability of CMOs to reproduce processes consistently across facilities and geographies.

Ultimately, CMOs may be the most effective route to manufacturing at global scale. The responsibility of process design is therefore not to eliminate CMOs, but to ensure that processes can be transferred robustly between them.

References

1. Investment Insights for Cell Therapy Manufacture