ARW's Cell & Gene + RNA Manufacturing Must-Reads (Chef's 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.

When this newsletter was sent, it was October 20^th, or International Chef’s Day. As those of you in manufacturing are the “cooks in the kitchen” (so to speak), I’ve included below several quotes from famous chefs that are complementary to the themes of this week’s batch of ATMP manufacturing reads. Bon Appetit.

A great chef is first a great technician. If you are a jeweler, or a surgeon or a cook, you have to know the trade in your hand. You have to learn the process. You learn it through endless repetition until it belongs to you. — Jacques Pepín

• I can’t think of a more perfect quote to accompany my latest article featuring Paul McCormac, CTO of gene therapy company LEXEO Therapeutics: “Science Over Steel: Exploring The Foundations Of The Hybrid Outsourcing Strategy.” Here, he explains how companies insourcing their process development ultimately do own their “own their manufacturing destiny,” even if they’re relying on CDMOs for the majority of their manufacturing.
• I’d like to believe that article with Paul above is the more grown up (and perhaps wiser) continuation to this article I wrote last year exploring in what other ways facility-less companies can own their manufacturing destinies. (Writing, like cooking and manufacturing is a repetitive process through which you are constantly learning, questioning, and reevaluating.)
• Now, in the case you just can’t afford to own anything right now and are annoyed that all the counter space in CDMO kitchens is taken, I hear you, and offer the following article, “Biomanufacturing Capacity Crunch: It’s The Supply Chain’s Fault.” Based on a panel discussion at Bioprocess International, this article identifies the root causes of our current manufacturing capacity challenges, what vendors are doing to overcome these limitations, and how biotechs can/are currently protecting themselves from such disruptions.

Food is maybe the only universal thing that really has the power to bring everyone together. No matter what culture, everywhere around the world, people eat together. — Guy Fieri

• You know what also brings people together? Pharma conferences — which sometimes also involve food. There are a few events worth keeping on your radar.
  • Next Wednesday, Oct. 26, USP will be hosting a free live/virtual Stakeholder Forum on CAR-T CMC. Check out the agenda and register here.
  • As luck would have it, I will be speaking (gasp) on what the future holds for mRNA at AGC Bio’s (in-person) 2022 CMO Summit in Boulder, CO Nov. 7-10. In addition to presentations on a variety of cell/gene/mRNA manufacturing topics, there will also be a tour of AGC’s Longmont (CGT-specific!) facility. I’d love to see/meet you there!
    • (Also, I dare say you want to hear what Michelangelo sculptures and the game Exploding Kittens can tell us about the future of the mRNA industry. 😉)
  • It’s not actually an upcoming live event, per se, but my colleague’s (virtual) panel discussion BioPharma PAT: Gateway To Continuous Manufacturing is now available to stream on-demand. (Free registration required).

The only time to eat diet food is while you’re waiting for the steak to cook. — Julia Child

• Certainly, not all foods are created equal — and the same can be said about the infrastructure and tools we’re using, or waiting to rely upon, today in the ATMP space.
• In my recent editorial from the mRNA Therapeutics Summit, I share some thoughts from Pfizer’s Jane True, VP mRNA Commercial Development, who identifies in which ways mRNA development could and should shake up traditional operational and commercial models.
• A few must-reads ago, I shared an intriguing article posing a controversial question: “Did short-term solutions for COVID-19 stifle long-term [mRNA] success?” One of the authors of that article recently shared some of his thoughts in this newer editorial: “People, Pipelines, and Projections: What Can Be Done To Help Emerging Therapeutics Get To Market?” I’d direct your attention in particular to his (Carl Schoellhammer) thoughts on why we need better tools/assays in the CGT space, and how firms can better focus their current analytical efforts.

I’ve been a cook all my life, but I am still learning to be a good chef. I’m always learning new techniques and improving beyond my own knowledge because there is always something new to learn and new horizons to discover. — Jose Andrés

• Jose’s quote can certainly be applied to the endlessly iterative work we’re doing in the ATMP manufacturing sector, in which one of these “new horizons to discover” is decentralized/Point-of-Care (POC) cell/gene therapy manufacturing.
• Much like biotechs are dedicated to evolving their science, processes, and practices, the FDA, too, regularly demonstrates its desire to improve its own knowledge/guidance.
• The FDA’s CDER recently released a critically important new discussion paper entitled: “Distributed Manufacturing & POC Manufacturing of Drugs.”
  • As a quick reminder, this discussion paper follows in the footsteps of the UK’s MHRA Consultation On POC Manufacturing [Aug. 2021].
• Please note, while the FDA paper’s initial scope is primarily products regulated by CDER, such manufacturing approaches are also relevant to products under CBER’s oversight. As such, BLA holders/hopefuls are asked to contribute their thoughts/feedback, as well.
• Specifically, the agency is seeking your feedback on 20 questions (pp.11;15-16.) In addition, the FDA and PQRI will be hosting a virtual workshop on DM & POC manufacturing from Nov. 14-16 to gather further feedback and spark intra-industry conversation around adoption challenges, quality systems operation, and GMP expectations for DM/POC manufacturing.
• In case reading an FDA document is a horizon you just can’t motivate yourself to mentally broach today, RAPS has put together a nice summary of the ins-and-outs of this discussion paper.
• If you’re looking to understand more deeply the implications of such manufacturing strategies specific to the CGT space, this well researched article spells out the big picture straight away in its title, “Decentralized CAR-T Manufacturing Reduces Costs & Complexity, Expands Access.”

Always serve too much hot fudge sauce on hot fudge sundaes. It makes people overjoyed and puts them in your debt. — Judith Olney

• I feel as though this quote could be a subtle piece of advice from the industry to the FDA... if, by “hot fudge,” Judith actually means “more in-depth and specific guidance.”
• Over the past few months, there’s been some buzz around the FDA’s Voluntary Consensus Standards Recognition for regenerative medicines draft guidance. Once more, RAPS saves the day by providing us a nice summary of some of the industry comments/concerns about this guidance. Some of the comments/questions offered were around how the FDA is defining a consensus standard, how standards could be included in this program, and to what extent the agency will leave room/permit flexibility given the diversity of/variability between ATMPs under the guidance’s scope (e.g., auto/allo cell therapies, gene therapies, etc.).
• For those of you who didn’t attend Meeting on the Mesa last week, this article provides a nice breakdown of Peter Mark’s keynote at the conference. Topics covered included regulatory harmonization, the new FDA “Super Office,” expanded access programs, and strategies for improving small-scale manufacturing commercial viability.