ARW's C&G+RNA Manufacturing Must-Reads (International Women's Day 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.

March 8 was International Women’s Day. So, to keep honoring the brilliant women that have shaped our industry — and many other industries and the world — the manufacturing must-reads below are accompanied by a quote from a famous woman throughout history.

[COGS]
“With money in your pocket, you are wise and you are handsome, and you sing well, too.” — Muriel “Mickie” Siebert

• As the first woman to own a seat on the NY Stock Exchange, Mickie would know better than anyone the sheer magic of having ample funding.
• While we may not be singing a whole lot these days in the CGT space, my latest article — Cell & Gene Therapy COGS: Progress & Pitfalls In Our Quest for Affordability featuring the brilliant Katy Spink of Dark Horse Consulting — adds a bit more color around where the ATMP industry stands in terms of funding and economic security. Most importantly, Spink explores the nuanced ways in which the current financial landscape could simultaneously benefit and threaten our CMC initiatives in the long-term.

[mRNA MANUFACTURING STANDARDIZATION]
“How else would God speak to me, if not through my imagination?” — Joan of Arc

• God probably isn’t who/what comes to mind when you think about mRNA standardization… but I think Joan’s quote speaks to the broader role imagination could play in making long-term improvements to the mRNA manufacturing paradigm.
• In Episode 2 of my new creative video series, “ARW on RNA,” I allowed my imagination to run a bit wild (shocking, I know) in order to explain why “The Game of Risk” serves as a good example for the mRNA therapeutics space on its quest for manufacturing standardization.

[STANDARDS]
“‘Um’ is not an answer!”— Judge Judy

• Judge Judy tells it like it is — and I imagine answering the FDA’s/your patients’/your boss’ questions with a long protracted “um” probably wouldn’t go over well, either.
• Fortunately, the good folks at The Standards Coordinating Body have created the perfect vehicle for you to verbalize all the exquisitely crafted thoughts/opinions that I know you have. Be sure to take their 15-minute survey to help SCB determine which standards are most urgently needed in your sector of the CGT space and which future initiatives SCB should prioritize.

[REGULATORY]
As you get better at developing your product, your shots on goal will become more accurate. — Denise Gavin

• As we already know, Denise Gavin, FDA’s GT Branch Chief (plus ~12 other titles), is thankfully alive and well and playing an indelible role in shaping the FDA’s CGT regulatory paradigm. And the FDA has been busy lately.
• For starters, we know things are getting a lot more structured at the agency following the announcement of the new super office, Office of Therapeutic Products (OTP). If you’re curious about what that structure will look like and how the reorg will impact your interactions with the agency, check out this recent FDA post which clearly breaks down the new structure and offers an FAQ section.
• As I mentioned in a previous must-reads, the FDA will be hosting a workshop on advanced manufacturing and analytical technologies for regenerative medicines next week.
• But to deepen their focus on “next-gen” technologies, the agency just released a discussion paper on Artificial Intelligence in Drug Manufacturing. (This paper is applicable to NDA/ANDA and BLA products.)
  • In particular, the FDA is seeking industry feedback (here) on the role AI can play in several key areas, including process design and scale-up, advanced process control, process monitoring and fault detection, and trend monitoring.
  • If reading is exceptionally hard today, regulatory guru Daniela Drago lists the eight questions CDER & CBER would like stakeholders to address in her recent LinkedIn post. Comments are due by May 1.
• In another momentous occasion, the FDA, in alignment with ICH, released its Q13 Continuous Manufacturing of Drug Substances & Drug Products final guidance.

[SMART MANUFACTURING]
“Some things will always drop out of the public eye and will go away. But there will always be science, engineering, and technology.” — Katherine Johnson

• This (thankfully no longer) “hidden figure” in NASA’s history says it best — the critical building blocks of our industry will always be en vogue.
• In addition to the FDA’s efforts to stimulate discussion and adoption of novel manufacturing technologies, I’d also call out this recent ISO white paper on Smart Manufacturing.
  • Because reading hasn’t gotten any easier since the previous section, we can thank Jeff Winter for this accompanying LinkedIn post, which succinctly outlines the “enablers” and “enhancers” of smart manufacturing discussed in the ISO white paper that will help us chip away at our long-term Industry 4.0 goals.

[CDMO SELECTION/MANAGEMENT]
“Longed for him. Got him. Shit.” — Margaret Atwood

• ^^A poem you never want to use to describe your relationship with your CDMO.
• To save you from writing future “breakup” poems, the kind folks at Halloran Consulting provide us with this great breakdown on CDMO selection criteria for small or early-stage biopharma — including the biggest quality, supply chain, raw materials management, and starting materials considerations that demand a sponsor’s due diligence.
• Speaking of healthy CDMO-sponsor relationships, I also liked this article by two helpful “relationship counselors” at ValSource, spelling out how the most recent revision to Annex 1 could change your existing relationship(s) with your CMO(s) — hopefully, for the better.

[mRNA PANEL DISCUSSION]
“Look to your colleagues because one day you will need them, you will need their work, follow them, study what they do, and they will help you.” — Katalin Karikó

• When the “Mother of mRNA” speaks, we listen.
• I can think of no better opportunity to look to and learn from your mRNA colleagues than by attending my upcoming BioProcess Online LIVE panel discussion on 3/28/23 @ 11 AM ET. I am very excited to pick the brains of John Stubenrauch, COO, Nutcracker Therapeutics, and Hari Pujar, COO, Tessera, about where the greatest inefficiencies, questions, and opportunities for optimization/innovation exist within the current mRNA drug substance and product manufacturing paradigm.
• You can sign up to attend for free here. (FYI, this panel will also be available to stream post-event.)

[REIMBURSEMENT POLICY]
“I’ve got cash, but I don’t deal with the monkey.” — Lara Croft

• Yes, this quote is bizarre, and no, Lara Croft is not a real person. But she was the reason I wanted to be an archaeologist from the tender ages of 8-15. (I still want to be her.)
• Though there are many “screeching monkeys in the room” fighting for our attention, it’s worth singling out reimbursement policy. After all, making manufacturing more efficient and cost-effective won’t matter if patients/health systems can’t or won’t pay for our therapies.
• A few weeks ago, the Centers for Medicare & Medicaid Services (CMS) announced that the CMS Innovation Center will be testing two new reimbursement schemes that will impact CGTs. These include The Cell & Gene Therapy Access Model and The Accelerating Clinical Evidence Model.
• But just as potency assays, regulatory requirements, and the phrase “the process is the product” get folks all fired up, reimbursement policy is an equally special breed. For example, though we can all agree we want broader, more cost-effective access to CGTs, the Alliance for Regenerative Medicine points out a few potential ways these CMS models could get us into trouble.