ARW's CGT+RNA Manufacturing Must-Reads (Post Card 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.

The first week of October is International Post Card Week. As someone who loves collecting old postcards with fun messages written on them, I decided to draft a few “postcards” to introduce/describe the latest batch of CGT/RNA manufacturing content. Hopefully, the Safari you went on for your last Manufacturing Must-Reads was just as post card-worthy.

After three flights, a four-hour car ride, 2 boat rides (down different rivers), and a donkey-drawn cart, we FINALLY made it to our first layover.

• After many years of hard work, those of you in CMC may feel that your uphill journey has led you finally to a clearing beyond the trees and above the cloud cover. At least, this whitepaper from McKinsey entitled “Out of the Shadows: A Brighter Future For Pharma Technical Development” argues as much.
• However, if we want to keep transforming CMC — and not get stuck in an extended layover at base camp — the authors highlight five key areas where firms should be investing today.
• Most notable — though hardly surprising — is their discussion around why the CMC “lab of the future” must have a fit-for-purpose digital infrastructure — including in silico modeling, advanced analytics, and automation in a few key areas.
• Their emphasis on all things digital nicely explains the “why” behind this recent headline from a Fast Company article entitled: “Laid Off By Big Tech? Big Pharma Wants You.” (However, thanks to hackers, the site/article is currently unavailable.)
  • I know we’re trying to get away from paper. But you know what can’t be hacked? Post cards. Just saying.

This trip has been everything we anticipated it would be — and more.

• I suppose this post card could’ve been sent by an extreme pessimist, meaning the trip was a hijinks-laden disappointment.
• But we can’t say the same for the emerging predictions about what the rest of the year holds for the cell and gene therapy space. As we approach the end of the year, Katy Spink of Dark Horse Consulting revisits some of her predictions for CGT progress in 2022, sharing which are still on track to come true and which will take more time to be realized.
  • In particular, she homes in on the lack of significant inflection points in the allogeneic cell therapy space during 2022. But just as numerous connections/layovers are necessary to get around a big country, progress is made incrementally. I thought this piece from the CEO of Poseida Therapeutics was a thoughtful examination of what the current allo clinical data is telling us and where scientific finessing can be done to get us closer.
• If you wish to weigh the progress you and your team have made this year (or to see if you’ve been focusing on the most meaningful things) be sure to revisit this collection of 5 CGT Manufacturing New Year’s Resolutions that Spink and I put together earlier this year.

We’ve been thinking about you every day. But we can’t fit anything else in our suitcases, so this post card is your souvenir. Sorry.

• We just can’t escape capacity woes, can we? Or… can we?
• My colleague is going to be tackling the current capacity outlook with several folks on the front lines of external alliance management. Register for this Outsourced Pharma Live event on October 25th to learn more about where we might be realizing some breathing room in the outsourcing world and where we’ll continue to be hard-pressed to fit anything — even something as small as a fridge magnet.
• If you actually do have room to spare in your suitcase, you may wish to purchase a copy of BioPlan’s latest "Manufacturing Capacity & Production Annual Report and Survey" and keep it next to your Lonely Planet travel guide.
• For those enterprising folks among us who will go so far as to buy a whole new suitcase to supply presents to the whole family, I’d refer you back to my (older but still relevant) Choose-Your-Own-Adventure-style article about building a cell therapy manufacturing facility. It is a wild (post card-worthy) reading experience if I do say so myself.

How did people travel before Google Translate? Last night, I almost ordered a bowl of boiled tuna eyeballs. I miss McDonald's.

• Yes, mRNA and Google Translate are entirely different tools. But we can’t celebrate such a “life-saving translation” tool like Google Translate without giving a nod to mRNA and our ribosomes (our internal translation machinery).
• In the mRNA therapeutics world, there have been a few academic papers published lately discussing alternative approaches/frameworks and emerging technologies that promise to bolster the efficiency of the IVT process; LNP production/RNA encapsulation; and continuous manufacturing.
  • Say goodbye to Design of Experiments methods and say hello (bonjour, olá, ciao, etc.) to these machine learning techniques in Maximizing mRNA Vaccine Production With Bayesian Optimization
  • Learn how Microfluidic Technologies and Devices for Lipid Nanoparticle-based RNA Delivery are a much-needed alternative in the realm of LNP production/RNA encapsulation.
  • Check out these folks’ design for continuous, end-to-end sterile mRNA production/formulation in Pharma 4.0 Continuous mRNA Drug Products Manufacturing [Aug. 2021; Subscription required]

Wish you were here!

• Whether you actually wish your cousin thrice removed was standing next to you on that salt flat in Bolivia, you probably do wish you had an FDA representative at your beck and call.
• Well, news on the ATMP block is that the FDA is undergoing welcome changes to bolster its infrastructure to handle more industry “tourism.”
  • PDUFA VII was finally approved, and CBER should be feeling pretty good about itself.
  • For one, CBER’s hiring budget has been quadrupled from 32 hires under PDUFA VI to a whopping 228 anticipated hires (over the next 5 years) under PDUFA VII.
  • In addition to the passage of PDUFA VII, the FDA announced a new name and reorganization for CBER’s OTAT, now a “Super Office” called the Office of Therapeutic Products (OTP).
  • This reorganization adds several CGT-product specific offices to better manage the FDA’s ATMP workload, along with more supervisory positions to improve the agency’s long-term organization and employee retention efforts.
  • Though user fees will be increasing, scroll down in this article to check out some of the CGT-specific efforts the agency plans to implement for the broader benefit of the ATMP industry.
  • With these increased user fees, employee numbers, and new structure, the agency should have the tool kit for implementing some cool policies in the future. For example, earlier this year, Marks expressed dreams of an Operation Warp Speed-style pilot for gene therapies.
• However, because I’m aware these incremental improvements don’t meet your current needs for the agency “to be right here with you right now,” you can at least stream the recording of their Sept. 29th FDA Gene Therapy CMC Town Hall — with an audio transcript — to (hopefully) get a few more immediate answers today.