COGS crisis: Cell therapy sector must rethink CMC says expert

The cell therapy sector faces a cost of goods sold (COGS) crisis and needs to get beyond the “product is the process” mind-set says Anthony Davies, CEO of Dark Horse Consulting.

Cell and gene therapies have attracted a lot of attention in recent years. In part this is because drugs like Yescarta, Kymriah and Zolgensma have been approved as one-off cures.

However, their cost – $373,000, $475,000 and $2.1m per vial in the US, respectively – has also seen them talked about in less than glowing terms.

Image: AdobeStock/dizain

But the pricing debate is not the only challenge the sector faces. According to Anthony Davies, CEO of Dark Horse Consulting, all cell therapy firms would benefit from better manufacturing methods.

“For the last several years, cell and gene therapy has been driven by a tail wind of terrific clinical data. This has thrust commercial licensure on complex products which have spent a relatively short amount of time in pharmaceutical development.

“Approvals out of, effectively, Phase II clinical trials are becoming likely for products with even less than Phase II grade CMC,” Davies told Bioprocess Insider.

The impact of this underdevelopment on cost can be significant Davies says.

“These under-developed manufacturing processes can have exorbitant costs of goods (COGs), due to both their manual and/or bespoke nature and the complexity and cost of starting materials, raw materials and unit operations.

“This leads to a situation where products can be ‘cost effective but unaffordable” he said, adding “Dark Horse’s experience can enable clients to develop their way out of this COGS crisis.”

Better analytics, no magic

The keys to developing improved manufacturing process are better data and a QbD-based approach, according to Davies.

“Analytical methods need to deepen and improve – you can’t develop and scale processes if you don’t have a deep, precise and accurate understanding of both process intermediates and final product.

“Classical Quality by Design (QbD) principles, especially processes developed by Design Of Experiment (DOE), need to permeate the field.  And people need to believe that there really does not need to be any magic in these processes.”

Process not the product?

In cell therapy development there is a widely held belief the “process is the product.” In other words, product characteristics depend on the process.

In the small molecule drug sector manufacturing processes are tweaked and optimized. In contrast in the cell therapy sector – and to an extent in the wider biopharmaceutical industry – once processes are established changes are seldom made.

While this approach helps ensure consistency, the lack of optimization means most manufacturing processes are more expensive then they need to be.

But production could be optimized if industry had access to better analytical technologies says Davies.

“We believe strongly, contrary to historical wisdom in the field, that the process need not be the product, as long as the process is well enough analyzed and developed.

“When this becomes the modus operandi of cell and gene therapy sector, manufacturing will have become cost-effective and routine.”

Expertise in demand

And Dark Horse is not the only organisation to have noticed the surge in demand for cell therapy expertise. In July the consulting firm attracted an investment from private-equity firm Arcline Investment Management.

Davies declined to detail the scale of the investment, but did tell us the funding will “ensure our continued ability to attract and retain world class talent with real-world experience, in a marketplace which abounds in opportunities for such individuals.

“We are also increasing our rate of expansion in our London office, and looking seriously at opening offices in locations such as the Pacific Rim, perhaps Japan or South Korea and Toronto.  Opportunistically, we are always alert to opportunities to acquire other consulting organizations in and adjacent to our space.”