From "Wild West" To "Rainforest": Cell & Gene Manufacturing Ecosystem Embraces Symbiosis

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

Last fall, thanks to the rise of the Delta variant, my partner John and I put our long-anticipated return to Brazil on hold, instead heading to Alaska for an expedition through the islands, channels, fjords, and forests of the Inside Passage. Though every landscape in SE Alaska bowled me over, one of my favorite parts of the trip was slowing down and looking down to admire, pet, and poke the hundreds of different mosses and lichens/fungi we’d encounter every step we took.

I’ve been thinking back on these treks into the rainforest lately as the cell and gene manufacturing sector continues to rapidly (and painstakingly slowly) take shape. We often affectionately refer to the CGT manufacturing sector as “The Wild West,” given the diverse patchwork of cell types, technologies, and engineering and manufacturing strategies companies are employing today to safely treat patients and supply the commercial market. However, I’m also starting to see a subtle reformation happening — one that takes us beyond the barren desert full of dueling cowboys and heat-crazed goldminers to that of a lush, productive, and symbiotic rainforest.

We can use the term “symbiosis” to describe a variety of different processes and relationships across the pharma industry. In the broader pharma manufacturing space, look no further than the relationship between a CDMO and biotech; in theory, these relationships should be as symbiotic as the relationship between the mosses/lichens and trees in the forest. Each party — the biotech and CDMO/tech provider — plays some role, however small or large, in helping the other survive. CDMOs and tech providers enable their clients to scale-up/scale-out and/or commercialize pipelines and properly equip in-house labs and facilities. The biotech keeps the CDMO on its toes, so to speak, by providing a development program/product, the unique needs of which will ultimately require the CDMO to continuously explore innovative next-gen development strategies, process efficiencies, and/or platforms to benefit the CGT space as a whole. Of course, this all (hopefully) translates to the long-term financial health of both parties, as well.

But as BioProcess International pointed out in this great article from September 2021, this example of symbiotic “mutualism” has been taking on some different shapes in the CGT manufacturing space. Biotechs and CDMOs aren’t just partnering on development programs these days; we’ve also started to see a number of CDMOs acquiring manufacturing facilities and their staff from CGT players. Last year bluebird bio, Novartis, and Orchard Therapeutics were just a few of the innovators to offload manufacturing capacity to CDMOs.

And, so far, 2022 remains no exception.

Without any ado or formal announcement (that I could find, anyways), National Resilience snapped up Tmunity’s manufacturing operations and some of Tmunity’s own in-house manufacturing experts.

Atara Biotherapeutics, which opened its own manufacturing facility in 2018, announced it is selling said facility to Fujifilm Diosynth Biotechnologies. The two companies also entered into a long-term supply agreement, guaranteeing Atara capacity for clinical and commercial manufacturing.

On the AAV gene therapy side of things, Homology and Oxford BioMedica entered into a joint-venture. Oxford BioMedica acquired a majority stake in Homology’s manufacturing expertise and in-house capabilities, which will henceforth be known as Oxford BioMedica Solutions. In return, Homology received $130 million from Oxford Biomedica to put towards Homology’s ongoing clinical development. Naturally, the company will also have access to the necessary manufacturing capacity for future clinical/commercial development.

Of course, such strategic shifts and acquisitions are hardly unheard of given the bedeviling nature of drug development. But I’d also argue that these aforementioned CGT examples are solid depictions of some much needed symbiotic “mutualism” taking place in the CGT space. Just as moss provides fertile ground for new trees to grow and lichens protect trees and rocks from the elements, the CGT biotechs selling off their facilities are providing a critical service to the CGT ecosystem.

We currently live in a world in which companies are struggling to gain access to external capacity. In articles and panel discussions, we hear quite a few companies passionately explaining that capacity crunch delays have been a huge factor in their decisions to build. But figuring out why and when it’s the right time to build isn’t the only critical decision companies need to make; it’s equally important for companies and their COGS to know if, when, and in what ways their own internal capacity could be better utilized. This may mean selling or spinning off said capacity — whether it be underutilized or just too costly to maintain — in exchange for further development funds and guaranteed access to capacity and talent. In return, the technological gains and manufacturing expertise of that biotech becomes available for those who either don’t have their own manufacturing capacity and in-house expertise or simply need more of it.   

I really liked this quote from Tmunity’s founder Bruce Levine because it best captures the “symbiosis” challenges ahead for the CGT industry:

“Key components of the next-generation of cell-based immunotherapies are being developed in university laboratories or biopharma research facilities around the world. But these components are only as good as the other essential technologies and methods with which they must be combined for success.”

To Levine, the success of the CGT industry will come from finding ways to bring all of these isolated pieces together into one functioning, productive whole. One critical way we can do that is by bringing some of the technological advancements made within the privacy of a company’s own internal manufacturing capacity out into the light for the benefit of the entire industry — whether it be through licensing agreements, development partnerships, or the aforementioned acquisitions.

It’s rarely socially acceptable to call anyone or anything a fungus (outside of lichens or mushrooms, of course). But at the risk of sounding irreverent, I’d venture to say that the examples taking shape in the CGT manufacturing field prove that, sometimes, we all just have to be more like fungus.