CGT myth-busting: ‘The process is NOT the product’

Deeper characterization and quality-by-design (QbD) approaches demonstrate the cell and gene therapy space has outgrown the lazy ‘process is the product’ rhetoric, say experts.

Journalists and industry alike have clung onto the concept that ‘the process is the product’ when it comes to cell and gene therapies (CGTs). For years, the catchy phrase has been banded around convention centers and company boardrooms but as the field matures – 10 CGTs won approval in the US and Europe last year – such rhetoric needs to be dropped.

This was the opinion of experts at last week’s Advanced Therapies Week (ATW) in Miami, Florida, where it was stressed by numerous experts that the product is, in fact, the product, rather than a manifestation of the process mechanisms used to produce it.

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“The process does not need to be the product anymore, we’ve outgrown that,” Anthony Davies, founder & CEO of Dark Horse Consulting Group succinctly said to Brad Loncar, CEO at Loncar Investments, at the event.

However, “we need to outgrow it more because it implies these products are incredibly fragile, can never be moved, can never be altered, can never be biosimilar-ed, and we do not believe that any of those things are going to be true.”

Davies pointed to better characterization of these complex products to drive the next wave of CGTs. The need for deeper characterization is “one of the Achille’s heels of this field,” he said, and looked to new analytical tools and methods – omics, deep sequencing, etc. – to transform the sector.

His view rang through the conference, with multiple presentations and sessions focused on how best to characterize these life-saving medicines. However, it was the first muttering of potential CGT biosimilars along with evidence of progress in manufacturing scale-up that further blew the doors off ‘the process is the product’ concept.

For example, Lior Raviv, chief technology officer at Israeli-based biotech Pluri, told delegates while the process directly affects the product and changes in manufacturing will, of course, change the product, his company is taking an ‘engineering-by-design’ approach to its allogeneic stem cell candidates “to change the art of growing cells into an industrialized process.”

He said: “We build a black box about every step of the operation to truly learn what are the inputs and what are the outputs, and how they are connected to the critical quality attributes.”

This parallels the widely recognized and employed QbD approach used to maximize the efficacy and safety profile of biologics while enhancing their manufacturability. Biologics are, compared to CGTs, highly characterized and this shift towards a QbD model is further evidence the process equals product slogan is close to obsolete.

Luca Alberici, managing director at contract development and manufacturing organization (CDMO) AGC Biologics in Milan, Italy, further busted the CGT process myth, telling delegates while the future of CGTs is unclear “we do know that in 10 years’ time the processes that we have today are not the processes we are going to use.”

Therefore, he said, as the sector blooms, manufacturers are implementing flexible systems, technologies, and facilities to accommodate different processes with robust analytics capability to manage evolving product characterization.