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

By Anna Rose Welch, Director, Cell & Gene Collaborative
Subscribe to my blog ARW on CGT here!

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.

May 17 was “send an electronic greeting card day.” So, below, you’ll find that each section of manufacturing must-reads is prefaced by a greeting card-esque saying that the CGT industry would send — if the industry were a snarky person that actually could send a greeting card.

You’re welcome. For literally everything.
[mRNA REGULATORY]

• The leading mRNA companies have never and would never actually say this, but I felt immense gratitude and awe for the people that make this industry what it is as I listened to one first-hand perspective on the mRNA vaccine development and approval process.
• In particular, I loved hearing how Moderna’s Chris Kelly & his regulatory team at Moderna tackled this lesser proclaimed supply-chain & regulatory hurdle.
• Speaking of regulatory documentation nuances that drive us crazy: this article from Nature Nanotechnology laying bare the nuances of the ongoing active ingredient vs. excipient debate for nanomedicines is one to read and share widely across the nonviral gene therapy space. (Be sure to say “you’re welcome” before your colleagues even say thank you).

My sympathies for making your day job so difficult.
[CELL THERAPY MANUFACTURING]

• The industry isn’t the only one that owes us this card — we should also be getting one from the cells we work with. I’m sure it’ll be here any day now...
• This LinkedIn post shares an article on risk factors for CAR-T manufacturing failure (particularly in DLBCL patients). Regardless of the indication in which you’re working, this study is worth a look. In particular, the authors determined the rates at which treatments (particularly bendamustine) administered prior to apheresis increased the risks of manufacturing failures.

Thinking of you during this difficult time. You’ve really earned this picture of David’s abs.
[FUTURE OF mRNA]

• David’s just a sculpture — calm down.
• Though you may think I’ve finally fallen of the deep end here, I thought there was a clever metaphor to be made about the history of Michelangelo’s famous sculpture of David and mRNA as a past, present, and future modality. Check out Episode 4 of ARW on RNA: Michelangelo Meets mRNA to figure out how I see the mRNA space chiseling out its own impressive “six-pack” a.k.a. line-up of therapeutic products in the future.

Thanks for being my friend (and not a jerk).
[INDUSTRY COLLABORATION]

• I dare say if we boil down the legal jargon behind every industry partnership, this is what each partner is really saying to each other.
• Luckily for the mRNA space, there’s a new “club” in the works in which companies can come together and advocate for mRNA-specific scientific, regulatory, and policy-related advancements. As this LinkedIn post shares, the groundwork is being laid for the Alliance for mRNA Medicines — the future mandate for which will be discussed at the upcoming BIO convention.
• To stay in the loop on AMM’s future goals/purview/and projects, apply to join its newly launched LinkedIn group.

Thank you for your question(s). Please refer to the guidance for the answer(s) you seek.
[FDA TOWN HALLS/AD COMS]

• Your latest regulatory communication may (seemingly) be winging its way to you via carrier pigeon as opposed to email, but we really do have to applaud the FDA for the sheer amount of work it has been doing for the space in the past few weeks.
• You may have caught word that the agency just hosted a highly anticipated gene therapy adcom for Sarepta’s AAV gene therapy in DMD. I fully intend to write something about the discussions that led to this nail-bitingly close 8-6 vote recommending accelerated approval in the upcoming weeks. But for the truly impatient among us, you can watch/rewatch all your favorite moments of the 8-hour event here.
• If you’re saying, “been there, watched all that,” then can I interest you instead in the April 25th Gene Therapy CMC Town Hall? The recording and transcript are available here for you to watch (or re-watch if you’re an overachiever).
  • If you’re short on time and just want a few of the main highlights from this latest Town Hall, RAPS published a write-up here.
• For all my “cellebrities” on the cell therapy side, the FDA just announced a cell therapy CMC-dedicated town hall forthcoming on Thursday, June 8th. You can register here.

AI probably won’t kill us, but just in case, I wanted to send you this note letting you know I’ll never forget you.
[AI/ML]

• Disclaimer: This greeting card was created using AI. Please report any errors or grievances back to the sender.
• In 2021, the FDA received more than 100 drug and biologics applications containing AI/ML elements. This is just one of the many reasons the FDA released two papers on AI/ML in recent weeks:
  • AI in Drug Manufacturing; and, most recently,
  • Using AI/ML In The Development of Drug & Biological Products
  • Please note, the commentary period has ended for the AI in Drug Manufacturing paper, but the FDA is seeking commentary on the second paper. The agency has posed discussion questions pertaining specifically to 1.) human-led governance, accountability, and transparency; 2.) quality, reliability, and representativeness of the data; and 3.) model development, performance, monitoring, and validation.
• If writing (or using ChatGPT to write comments for you) isn’t your thing, the FDA and Product Quality Research Institute (PQRI) will be hosting a workshop on AI in drug development on Sept. 26-27th. You can register to attend and join the discussion here.

Congratulations on the birth of your new manufacturing technology!
[INNOVATIVE MANUFACTURING APPROACHES]

• A few months, the FDA hosted a workshop on Advanced Manufacturing & Analytical Technologies for Regenerative Medicine Therapies. You can watch the video for the cell therapy-/tissue engineering-specific session here and the viral vector GT-specific session here.
• But why stop at just two?
• Duke-Margolis Center for Health Policy and FDA have put together a particularly robust agenda to continue the discussion on innovative manufacturing.
• “Advancing the Utilization & Supporting The Implementation of Innovative Manufacturing Approaches” will take place in Washington D.C. on June 8th, from 9 AM-4:30 PM ET. You can register here.

What is that you express in your eyes? It seems to me more than all the words I have read in my life.
[INDUSTRY COMMUNICATION]

• Yes, sometimes even the industry feels sentimental enough to quote Walt Whitman’s poetry.
• Though your eyes are undoubtedly two of your best features, the depths of your expression won’t exactly help the FDA in its efforts to standardize the electronic submission of quality and CMC documentation. So, in addition to laser staring at your computer screen, please also write/submit your commentary to the FDA’s request for comments on chapter two of its draft pharmaceutical quality/CMC data elements and terminologies document.
• We don’t just have to communicate across the industry and with the FDA; we also need to reach our patients and the broader public. A few months ago, I’d emphasized the importance of education and communication — particularly more creative, relatable communication — about the complex science of mRNA.
• This is why I was thrilled to hear that Moderna has just launched its first global mRNA campaign. The poetic and beautifully done first campaign video can be found in this article.
• In addition to Moderna’s example, I loved this explainer video by medical education company Sketchy creatively explaining how mRNA works using the metaphor of a medieval village.