Blog | April 6, 2023

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

Source: Cell & Gene Collaborative
ARW Edit Headshot 2

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.

Though there were a lot of great holidays to choose from for this newsletter’s creative theme, I just couldn’t tear myself away from the truly bizarre “Plan Your Epitaph Day.” As you ponder the legacy for which you’d hope to be celebrated in the far future, I’ve grouped each of your manufacturing must-reads under several 100% real epitaphs that also — believe it or not — nicely describe the themes and challenges we’re facing in the ATMP manufacturing space today. May you read in peace.

“COGS: Spent, But Never Forgotten”

  • Ok, I made this one up. But if we want patients to benefit from all our hard work, we must take this “epitaph” to heart and never forget the importance of achieving greater cost efficiencies.
  • It’s hard to get too deep in the weeds on COGS given the intricacies of our individual products. But this certainly didn’t stop Dark Horse Consulting’s Katy Spink from drilling into the topic a bit more deeply with me in a recent conversation. In one of my latest columns, I share a few of Spink’s “words of wisdom” on how to evaluate your COGS levers throughout development.

“Grace, dignity, and elegance personified.”

“Goddamn you all: I told you so.”

  • Please note, H.G. Well’s words here are (probably) not the best way to justify our efforts to our FDA CMC reviewers.
  • This statement will also (most likely) not come up during the FDA’s next Gene Therapy CMC Townhall, which will be taking place on April 25, 2023 from 11:30 AM-1 PM ET.
  • As of last Saturday, the FDA’s CMC Development and Readiness Program (CFRP) is open for applicants. For those of you craving additional FDA interaction, be sure to review the scope of this pilot to see if your program is eligible.
  • In general, efficiency has been top-of-mind for the FDA as of late. As Peter Marks explained in one of his slides at the Gene Therapy for Rare Disorders conference last month, accelerated approvals for gene therapy, concurrent submission and product review with regulatory authorities, and the Operation Warp Speed for Rare Diseases communication pilot are three of CBER’s main focuses these days.
    • Speaking of concurrent submission/product review: if you’re hoping to work with both EMA and FDA but don’t quite know how to make the EMA-FDA Parallel Scientific Advice (PSA) program work for you, check out this fantastic publication explaining the “why” and “how” of the PSA, as well as several best practices for sponsors applying for the program.

“[Moderna] did it the hard way.”

  • Ok, yes, I took a few creative liberties here with Bette Davis’ epitaph... but if Bette had heard Moderna’s presentation on the work it took to document, submit, and amend the regulatory documentation for its mRNA vaccine, I daresay she’d be cool with my amendment.
  • Of course, we won’t all have to do it the same way Moderna did. In fact, as I argue in my first of three takeaways from Moderna’s regulatory CMC-centric presentation, it’s probably a blessing that one of our challenges ahead will be bracing for more realistic post-pandemic regulatory interactions.

“To see a world in a grain of sand/ and a heaven in a wildflower/hold infinity in the palm of your hand/and eternity in an hour.”

“Let ‘er rip!”

  • In addition to letting regulatory and cost-related efficiencies “rip” (Preach, Leslie Nielsen), here are a handful of journal articles I’ve found lately showcasing the technological/process-related improvements being explored today:
    • “Toward Autonomous Production of mRNA Therapeutics in the Light of Advanced Process Control and Traditional Control Strategies for Chromatography” (
    • “Process Improvement of AAV Production” [to support large-scale preclinical animal studies in labs] ( [Jan. 2022]
    • “Machine Learning & Metabolic Modeling-Assisted Implementation of a Novel Process Analytical Technology in CGT Manufacturing” (i.e., LVV production) (
    • “Process Intensification for LVV Manufacturing Using Tangential Flow Depth Filtration” (