By Anna Rose Welch, Editorial & Community Director, Advancing RNA
This article is the fourth in a five-part series unpacking the Top 5 Cell & Gene Therapy Manufacturing Evolutions in 2021— counting down from #5 to #1. In the three previous installments, we covered the talent crunch (#5), the push towards next-generation delivery efforts (#4), and our ongoing war with cell culture (#3). Here, we progress ever closer to #1 — but starting first with #2.
But heaven forbid anything be straightforward. As I was working on this series, it struck me just how nicely the lyrics to some of Taylor Swift’s biggest hits complement the larger themes I’ve noted in the CGT manufacturing space. So, in addition to providing the big CGT picture, each article will offer an accompanying song recommendation (and lyrics!), if only to add a touch of levity to the important discussions at hand.
Music & Lyrics: “Dancing With Our Hands Tied”
I loved you in spite of/ deep fears the world would divide us/
So baby, can we dance on/ through the avalanche?
Like all of the other black and white questions we’ve posed in the CGT industry over the year, the answer to “Build or buy?” that emerging most regularly in 2021 was, “Why not both?” or, “There is no one right answer…” (Le sigh.)
Of course, there have been a wide array of players who have proudly chosen — in the words of T-Swift — to not let the world divide them from their manufacturing destiny and “to dance on through the avalanche” of facility construction and the many pluses and minuses of corporate expansion. Tenaya, Jaguar, Biogen, Poseida, PTC, Capsida, and Spark — to name only a few — all announced new facility launches or investments in 2021. (And don’t get me started on the movement we saw in the CDMO space — thankfully, this BioProcess International sums that up nicely for me and saves you guys from another Taylor-Swift themed manufacturing article.)
On the flip side, there continue to be many new and established CGT players that don’t have the financial or personnel resources and/or the pipeline and operational needs for their own facility. They continue to dance on with their CDMO partners.
But, as many of you are intimately aware, this is hardly the whole story. There have been a variety of arrangements made over the course of the year that fit into that fluid “hybrid” category. Whether it’s renting a clean room, garnering a coveted spot an Elevate Bio or Cell & Gene Therapy Catapult-type model, or keeping some element of expertise strictly in-house, or outsourcing AND building, the industry has been resilient in fording through the capacity and expertise crunch. (For more depth on the nuances of the hybrid model, be sure to check out some work from my colleagues, in particular this Outsourced Pharma event by Louis Garguilo and this BioProcess Online article by Matt Pillar.)
All of this talk about hybrid models, however, speaks to two even larger trends and challenges that have come to the forefront in the advanced therapies manufacturing space over the past year — and that’s knowledge management and transparency.
Companies navigating a hybrid model will continue to be challenged beyond finding the right partners for these unique products and determining which aspects of development they may wish to keep in-house. They will also need to determine how much insight into and ownership of the outsourced processes they need — and make sure each partner is willing and able to provide that desired amount of collaboration and transparency. (I really liked this expert’s thoughts on what this might look like, as well as the importance of keeping at least one aspect of development in-house.)
Though I argued that we need to expand our definition of “controlling our manufacturing destiny" as it pertains to the in-house/outsourcing debate, my thoughts on this advanced as 2021 progressed. We can and currently are talking about knowledge management and transparent collaboration on an outsourcing level; but I also think we’ve become (incrementally) more aware that we, as individual companies, just can’t solve all of our problems on our own. We also need to begin to suss out which parts of our manufacturing processes are truly deserving of the phrase: “I could tell you, but then I’d have to kill you."
To date, the industry has been quite closed-lipped — after all, IP is essential. But the shift is starting amongst some of the first-wave leaders in the space, as one Kite exec shared at Meeting on the Mesa.
Other trends from the past year that suggest the “veil of secrecy” is being raised include the growth in organizations like BioPhorum; the various collaborative initiatives of the Cell & Gene Therapy Catapult; the publication of ARM's ambitious Project A-Gene: a case study on gene therapy CMC; the rise of end-to-end manufacturing platform companies and their collaborative partnership models; the dialogue around AAV full empty-capsid ratios; and the FNIH’s Bespoke Gene Therapy Consortium, in particular its Platform Vector Gene Therapy pilot program. I’d also argue that the FDA’s 2021 gene therapy “sameness” guidance is the agency’s first step towards acknowledging that the industry needs a clearer understanding of which elements of a gene therapy (i.e., vector, transgene) make it unique from its “highly similar” competitors — the development processes of which may ultimately demand the most confidentiality.
We're almost there! You know you want to continue on to Number One...