ARW's CGT+RNA Manufacturing Must-Reads (Safari Edition!)

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

Day-in and day-out, I write, read, listen to, and watch as much content as I can about CGT and RNA therapy manufacturing, in particular, and/or other ATMP industry-related topics that you should at least be aware of in the manufacturing facility. Every two weeks, I compile the articles and industry updates I think are most worthy of your time into an unconventional newsletter format (below) and send them out via email.

September 22, when this newsletter was sent, was National Elephant Appreciation Day and World Rhino Day, both of which — along with the leopard, cape buffalo, and lion — are known as Africa’s “Big Five.” To become a member of this elite group of the biggest and baddest animals, each was highly ranked according to four key criteria: They all embody power and danger, boast unique features, and have a certain charisma that keeps safaris in business. As I reviewed the manufacturing must-reads for the week, I realized that each article also fit under/could speak to one of these four criteria. In other words, enjoy this safari through the “Biggest and ‘Baddest’” ATMP articles around. Safe travels!

“Home, Home On The Range, Where The Funding And Biotechs Roam”

• First things first: before we start looking for the “Big Five,” it’s always good to take stock of your surroundings — not only to avoid being mauled by a cheetah, but also to appreciate the vastness of the view.
• There’s no way you missed the news out of the White House about the National Biotechnology and Biomanufacturing Initiative (NBBI); it was as prominent as a stampede of giraffes across a treeless plain.
• But what does it all really mean for biotechs? In his latest column, my colleague Matt Pillar provides us with a comprehensive look at how Biden’s initiative could impact several NIST, NIIMBL, FDA, and HHS projects in the broader biotech sphere — including but not limited to the ATMP space.
• If you just want to focus your binoculars in on the smaller (but still vibrant!) stretch of grass that is the ATMP industry’s stomping grounds, be sure to check out this article from PA Consulting which is an abridged field guide on the CAR-T landscape/its leading players and other cell types/companies showing promise (both in and outside of the CAR-technology). But if a full-blown encyclopedia or bestiary is more your speed, you can download PA Consulting’s Cell & Gene Therapy in 2040 report.

Giggling Like A Hyena Is Just One Way To Snag An ATMP Partner

• I’ll be the first one to say that a laughing hyena is oddly delightful — even when they’re running around with a carcass. But that’s not exactly the type of charisma I’m talking about that will make your company, your science, and/or your capabilities turn heads and be named the “Big Five” of the ATMP space.
• Being open to new scientific ideas and modalities from outside your own company is going to be a critical best practice to advance an mRNA pipeline. Check out my latest article series showcasing the biggest takeaways/best practices shared at the Hanson Wade mRNA Therapeutics Summit, starting with Takeaway #1: Don’t Get Uppity: Match mRNA Science To Your Capabilities — And Vice Versa.
  • The grand rivalry between a cackle of hyenas and a pride of lions at dinner time makes for an entertaining Animal Channel special, but the pharma industry should probably model itself more so after the generous folks at Ultragenyx who recently served us this open access feast of an article: Double Stranded RNA Reduction By Chaotropic Agents During The IVT Process of mRNA.

“A Regulator A Day Keeps The Danger (Noodles) Away”

• Calling a snake a “danger noodle” is almost cute enough to make stumbling upon the highly dangerous “bushmaster” less daunting. (Almost...)
• Unlike the “Big Five” animals which get their recognition from being highly dangerous, in the pharma world, our therapies need to be as far from “dangerous” as possible — and that’s where our partnerships with regulators come in. But, like a snake, regulations can get a bit long and twisty and strike concern into the hearts of those who need to integrate that guidance into their own programs.
• A few weeks ago, we caught word that the long-awaited revision of Annex 1 was finally upon us. But knowing what is new in the guidance may not be apparent. That’s why I liked this article by several ValSource consultants who lay out six practical steps for tackling the known unknowns and unknown unknowns (etc.). Zoom your camera in on the state of your quality risk management program and appoint a contamination control strategy lead who can keep you from stepping on (or into) anything undesirable on the trail.
• I also appreciated the resources posted here by the Standards Coordinating Body (SCB), which put together a handy power point presentation on the FDA’s recent draft guidance on voluntary consensus standards. If you’re short on time and want the big picture of this guidance, check out SCB’s slide deck from pages 23-27, or you can watch SCB’s entire webinar.
• As I am writing this newsletter from the sidelines of this week’s mRNA Process Development Summit, the perilousness of venturing into the wild with scant or no regulatory guidance is also intimidating. As companies struggle to decide in which use-cases, phases, and for which raw materials GMP is the be-all-end-all, one speaker wisely urged attendees to supplement their approach with tips from this 2019 BioPhorum white paper, "Raw Material Risk Assessments: A Holistic Approach To Raw Material Risk Assessments Through Industry Collaboration."

Which Is More Awe Inspiring — A Lion, Or A (FDA-Accepted) Potency Assay?

• Yes, these are very different “animals,” per se, but they both embody a certain level of power — be it brute, muscular/physical strength or, well, potency.
• If you want to learn how Kite Pharma and USP have/are working to tame the potency assay beast (and other big cats), mark this upcoming USP stakeholder forum on your travel log for September 26th: Collaborating To Solve CMC Challenges & Support Efficient Development of Lenti-Viral Mediated Car-T Cell Therapies. You can register here.
• Though it’s not for ATMPs, NIIMBL announced another initiative worth watching; it is seeking project proposals for the development of in vitro potency assays for mRNA vaccines and viral-vector-delivered vaccines.

The One Feature Our Products Could Stand To Adopt From A Flamingo

• Your delivery vehicles might not be as flashy as a flamboyance of flamingos, but to move beyond the liver and/or achieve more targeted delivery, we certainly need our delivery methods to grow some longer legs.
• On October 4 at 1 PM ET, I’ll be moderating a conversation on what the future holds for mRNA delivery with Strand Therapeutics’ Aalok Shah, director of delivery & formulation, and Russell Johnson, RVAC’s VP of formulation research. Together, we’ll be looking back at the evolution of the LNP; the scientific, supply-chain, and operational-level challenges facing companies today; and what delivery would look like if all of Shah’s and Johnson’s wildest dreams were to come true. Register to join us here!
• If in vivo gene editing is more your speed, several MIT experts have penned this review of the pros and cons of viral and non-viral delivery methods of gene editing agents and where improvements could be made. [Subscription required]
• Like a flamingo’s "invisible" knees (which are not actually that visible bend on their legs, btw), there’s a lot going on behind the scenes to improve AAV process development. This interview with Vertex’s director of upstream process development is worth a closer look.