ARW's CGT+RNA Manufacturing Must-Reads (GOOGLE SEARCH 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.

This newsletter was sent on Google Commemoration Day, which is the day we officially celebrate everyone’s favorite research tool, professional assistant, fortune teller, medical professional, and best friend. In honor of this hallowed day, I organized your manufacturing must-reads according to some of the best questions we’ve ever asked Google to answer.

Please note, I didn’t make any of these up; these are all very real examples of what happens — for better or worse — when we get curious about something. So, on that note… Happy Googling!

Why isn’t 11 pronounced onety-one?
[FDA ADCOM: SAREPTA GENE THERAPY]

• This question takes the concept of “quantitative expression” to a whole different level.
• Speaking of which, our ability to quantitatively link protein expression to a gene therapy’s clinical function/effect was one of the biggest sticking points during Sarepta FDA adcom earlier this year. I’ve finally put together an article “expressing” some of my biggest takeaways from this absolutely riveting regulatory case study during which the FDA definitively told Sarepta’s Gene Therapy: “Express Yourself...Maybe?”
• If you’re interested in digging into the FDA’s perspectives on clinical development for ATMPs seeking accelerated approval, this article from The Pink Sheet is well worth a read — CGTs: US FDA Wants ‘Quantitative Correlation’ between Surrogate & Clinical Outcome, Former Reviewer Says. [Free registration required]

What would a chair look like if your knees bent the other way?
[INDUSTRY PERSPECTIVES]

• I dare you to forget this question for the rest of your life.
  • JK you won’t be able to — & you’re welcome.
• Speaking of “interesting perspectives” and “unique angles,” two articles from The Medicine Maker recently caught my eye.
  • I loved this interview with the CSO of Vor Bio, Tirtha Chakraborty, in which he discusses the future of gene editing and ATMP delivery, along with how his background as a visual artist informs his work as a scientist today. I was particularly drawn to his discussion of how the artistic styles of Impressionism/Pointillism relate back to the work of a scientist.
    • ICYMI: I recently shared my own thoughts on how Impressionism and CGT compliance fit together in a recent Cell & Gene Collaborative article.
• If you’re still stuck visualizing (the horrifying) alternate universe in which our knees bend the other way, divert your attention instead to this visionary roundtable offering several ATMP experts’ bold perspectives and predictions on what we should be watching and anticipating for the future of CGTs.

How come cupcake is not considered a mineral?
[COMPARABILITY]

• I respect the &^%$ out of this question.
• Though I’d be first in line to participate in a cupcake/mineral comparability clinical trial, I’d urge you to turn to the amazing “bakers” at BioPhorum when exploring comparability approaches for your CGTs. In particular, they just released this cell-therapy specific document categorizing common cell therapy process changes and the likelihood such changes would significantly impact a product’s quality. [Free registration/download required]
• How we go about integrating new technologies into our manufacturing processes will be a particularly important challenge/comparability consideration facing the CGT industry moving forward. This article by several NIIMBL authors — “Driving Adoption of New Technologies in Biopharmaceutical Manufacturing” — walks us through the high-level barriers to adoption of new technologies, as well as strategies that have proven — and continue to be — important in encouraging ongoing innovation and implementation.

If I ate myself, would I double in size?
[mRNA FUNDING]

• Please stay tuned for my future novel exploring this life altering question — Lord of the Flies II.
• What we do know definitively post-pandemic is that truly seismic innovation/industry growth is possible when there is unfettered public and private funding, infrastructure building, and intellectual generosity.
• Though the funding may pale in comparison to the size of the advance I’ll no doubt receive for Lord of the Flies II, the Biden Cancer Moonshot/The White House just announced a new mRNA initiative known as “Curing the Uncurable via RNA-Encoded Immunogene Tuning” (CUREIT). This new initiative aims to fund and create a “toolbox of mRNA and related technologies” to tackle cancer, autoimmune, and/or infectious disease indications. Project applications will be accepted through March 2024.
  • Now, for those of you who still don’t quite know what all the mRNA fuss is about and just want to go back to basics, I liked this crystal-clear breakdown of all the different ways in which we dream mRNA can be used beyond prophylactic vaccines.

Is it impossible to lick your elbow?
[OUTSOURCING]

• Yes. And this is why outsourcing exists, folks.
• As you commence bending yourself into a pretzel to lick your elbow anyways, perhaps you might instead just relax and listen to the dulcet tones of these best practices to streamline your CDMO RFP process. You can sign up here and stream the first episode of Dark Horse Consulting’s new CGT webinar series.
• I know many would rather bring manufacturing operations in-house. But for the majority of us who cannot afford to build and staff a facility and/or sustain its operations, my colleague Louis Garguilo of Outsourced Pharma is here with this zinger of an editorial on how a CDMO should communicate a form 483 with its clients and how outsourcing partners can productively work together when things don’t go according to plan.

Why do I have no friends?
[COMPATIBILITY]

• People suck. Google is a much better listener, anyways.
• At least we can ensure our drug products experience true compatibility in their lifetimes. This article in Journal of Pharmaceutical Sciences offers us an Excel-based tool we can use to determine when we may need to do a compatibility test in the case of a drug delivery site or component change during a clinical trial. (Please note, this tool is tailored to IV-based drugs; the featured case studies included in this publication are for an Enzyme and mAB product.)

Can I eat my Himalayan salt lamp?
[WORKFORCE CONSIDERATIONS]

• Perhaps an even deeper question we could ask our prospective employees is how they might go about reformulating said-Himalayan salt lamp.
• Over the past few weeks, there have been a few interesting resources published that give us a multifaceted look at:
  • How the ATMP workforce is being fostered — via “Cell & Gene Therapy Workforce Development: The Role of the ISCT in the Creation of a Sustainable & Skilled Workforce in Europe;”
  • How the already employed CMC workforce is being structured internally — via Industry Standard Research Reports’ “The CMC Function at Emerging Pharma;” and,
  • How ATMP experts can support colleagues/the broader industry through participation in professional societies — via this (on-demand) ISPE ATMP Community of Practice Town Hall webinar.