ARW's CGT+RNA Manufacturing Must-Reads (‘TWAS THE NIGHT BEFORE CHRISTMAS' 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.

For this final must-reads roundup of 2023, I figured I’d help us get into the holiday spirit by revitalizing the famous Christmas story — “A Visit from St. Nicholas” a.k.a. “Twas the Night Before Christmas”— to make it more applicable to the ATMP world. But should you already have your “CGT fanfiction” needs met elsewhere (somehow...), this batch of must-reads will, no doubt, provide way more value than my terrible rhyming.

 

‘Twas the night before Christmas and all through the house, four CEOs were stirring —
[2024 RNA OUTLOOK]

• ...you don’t quite know how they got into your house.
• But, since it’s the season of polite cohabitation, perhaps you’ll be interested in hearing what they have to say about the past and future of the RNA therapeutics space? In my latest editorial, executives from Ethris, Replicate Biosciences, Combined Therapeutics, and Orbital Therapeutics share their visions of what’s to come both scientifically and commercially for RNA in the new year.
  • Please also note that this article is featured on one of Life Science Connect’s newest editorial communities, Advancing RNA, which (*spoiler alert*), is set to become my new editorial home in 2024. Stay tuned for more information in the new year!

You would’ve been tucked all snug in your bed, but out on the market there rose such a clatter,
[BIOPHARMA MARKET TRENDS]

• you sprang to the window to see — was it the funding you’d asked for?
• Sadly, no. But before you collapse, exasperated, face first into “the breast of the new-fallen snow,” this piece from Deloitte lists 3 big factors shaping priorities at biopharma companies — plus a few extra “stocking stuffers” worth keeping on the periphery.
• Likewise, Nature put together a quick profile of the biggest CGT partnerships and deals that defined 2023 (through Sept.) — most of which have been inked around companies’ underlying technologies/platforms, as opposed to single therapeutic candidates.

When what to your wandering eyes should appear, but Peter Marks — with a beard! —
[REGULATORY]

• and a sack full of regulatory updates for you to keep near.
• In case you didn’t observe the reindeer in the room... the agency is investigating the risk of lymphoma in patients following treatment with CAR-T therapies.
  • To be clear, the benefits of CAR-Ts continue to outweigh the risks, and the incidence of lymphoma remains low. The only figure I could find was 19 cases out of the 20,000 patients treated with CAR-T to-date.
• Overall, Marks remains highly positive about the growth of the CGT space. In this Q&A, he discusses the agency’s progress over the past year with industry guidance and hiring, as well as which initiatives he anticipates will bring greater maturity to the field in 2024. [Free registration required]
  • Speaking of hiring, Marks provided a bit more color around the hiring needs for the Support for clinical Trials Advancing Rare disease Therapeutics (START) pilot program — which could result in higher industry user fees in the future.

Marks whistled and shouted and called each platform by name:
[PLATFORM DEVELOPMENT]

• On AAVs, LNPs, LVVs, Go! On cell therapy, gene therapy, in & ex-vivo, let’s roam!
• A few weeks ago, ARM & NIIMBL hosted a scientific exchange meeting between the industry and FDA on “Building Blocks & Platform Development for CGT Development.” In case you couldn’t nerd out for the whole day (or at all), ARM released this helpful summary sheet sharing high-level information about the FDA’s platform technology provision and the scope of the scientific exchange meeting.
  • A much more comprehensive whitepaper is forthcoming, in which we’ll become privy to the specific building blocks each working group outlined for AAV, IPSC, and LNP technologies respectively.

And then, in a twinkling, down the chimney there came a pair of Marks’ Merrell footwear
[STANDARDS]

• and a sack of best practices, packaged with care.
• In late November, the British Pharmacopeia hosted a free webinar to “unwrap” best practices from two guideline documents on ATMP characterization — specifically Vector Copy Number & Characterization of the Vector Particle Population of AAV Products.
• Speaking of guidance, USP just announced a call for candidates to be part of an expert panel on mRNA vaccines. Candidates can apply through January 31, 2024, and those selected will pen a future chapter on manufacturing and testing best practices for mRNA vaccines.
• If the promise of future guidelines isn’t enough of a present for the mRNA space, here’s a friendly reminder that USP will also be hosting an mRNA Open Forum on February 28 and 29 from 9 AM-1 PM EST to further discuss additional much-needed developments for mRNA vaccines and therapeutics.

He spoke not a word but went straight to his work, unloading gift after gift —
[TECHNOLOGY/SUPPLY CHAIN]

• No supply chain impediments to drive him berserk.
• If visions of sugar plums dancing in your head is getting dull, perhaps you can substitute in single-use systems and modular technologies. You won’t be alone; as a recent editorial from BioPlan Associates explains, interest in modular bioprocessing units/modular facilities remains evergreen — particularly in the personalized medicine sector.
• President Biden just announced two big supply-chain-centric initiatives:
  • The new cabinet-level Council on Supply Chain Resilience will review the state of the U.S. supply chain to identify products (per sector) that are critical to national and economic security.
  • As per the Defense Production Act, the White House/HHS will be investing in the domestic production of starting materials for essential sterile injectable medicines.
• As your favorite Hallmark movie cuts to commercial, perhaps turn your attention (3 minutes at a time) to this quick, 30-minute presentation, during which an executive at Roche delves into a few supply chain strategies the company has implemented to better control ATMP raw material COGS and to streamline personalized medicines’ delivery to clinics. (BTW, Roche has a very heterogenous pipeline of in- and ex-vivo viral vector-based AND mRNA therapies.)

And then up the chimney that right jolly regulator rose,
[AI/ML]

• Was he real or just a hologram — oh dear, will you ever know?
• Though resources on AI/ML can leave the non-digital experts among us feeling like we drank a bit too much spiked eggnog, I still appreciate this (Nov. 2022) no-nonsense article from McKinsey on how AI can accelerate R&D for CGTs. In particular, the authors walk us through the specific use-cases for AI in the R&D for mRNA cancer vaccines, CAR-Ts, and AAV gene therapies.
• Though my partner who attended the AWS re:Invent Keynote did not manage to secure me an introduction to Pfizer’s Chief Digital & Technology Officer after her keynote, I appreciated this quick (albeit rah-rah Amazon!-heavy) write-up of takeaways from her presentation on Pfizer’s data management and AI strategy. A video of her keynote is available here from the 1:09:30-1:19:00 mark.

But you heard him exclaim, ere he hiked out of sight: “The highest quality therapies for all —
[AAV QUALITY]

• and to all a good night!”
• Because it’s way more fun to open lots of small presents (as opposed to just one big present), I’ve broken my latest panel discussion with two AAV experts — Are We There Yet? Roadmap(s) To Higher Quality AAV — into 8 shorter snippets on AAV CQAs, common impurities, and the state of current upstream and downstream processing innovations, to name a few. Check them out and/or redistribute them to your colleagues during your upcoming “white elephant” gift exchanges.
• Sure, you can just keep shaking your presents to try to figure out what’s in them — but FYI, that’s not one of the go-to methods your colleagues at BioPhorum recommend in this latest whitepaper on the characterization and/or release of full, empty, or partial AAV capsids.