ARW's CGT+RNA Manufacturing Must-Reads (Weird Contest 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 week, August 6-12, is Weird Contest Week. So, I’ve sorted your must-reads according to a made-up slogan for some of my absolute favorite contests in existence, along with a link to each so you can start planning your trips immediately. Though I came up with the “slogans” for these contests, I had nothing to do with the brilliance of the contests themselves. Stay weird.

“#Resurrected!” @ Hunky Jesus & Foxy Mary Contest
[COMPLIANCE]

• What exactly are the “[s]pecs” of a high-quality savior-hunk? (Asking for a friend.)
• If you can forgive my extreme blasphemy long enough to read something, I put together a much classier article from the PDA ATMP conference using my love of art history to explore what the CGT industry currently “looks like” and how it fits into existing regulatory and compliance frameworks.
• As I mentioned in the article above, one of the debates brought up at the PDA conference is the applicability of the EU’s Annex 1 to ATMP products/facilities. In fact, PDA wants to hear from you via this anonymous survey on your Implementation of the New EU GMP Annex 1 & Implementation of Barrier Systems. Responses are due by (TOMORROW) Friday, August 11, so get thee to the nunnery survey post-haste.

“World’s #1 Pallbearer” @ Frozen Dead Guy Days
     *no death certificate required for entry
[mRNA/LNP CRYOPRESERVATION]

• You carried the winning coffin in a casket race, you say? ...
• Speaking of unstable... this is an older article (January 2023), but still presents a well-rounded look at strategies for mitigating mRNA’s instability. Outside of the inherent instability of the molecule itself, I particularly appreciated this article’s attention to the unique handling challenges of working with mRNA in your/your partners’ facilities.
• Likewise, we’re still trying to understand how storage conditions (temperature) and cryoprotectants (particularly sugars) impact the stability and efficacy of our LNPs. This study in Advanced Healthcare Materials unearths some answers for us on how multiple freeze-thaw cycles and temperature fluctuation can impact the stability, encapsulation, and transfection efficiency of LNPs and receptor-targeted nanocomplexes.

“It’s a bird! It’s a plane! It’s a... Bathtub Regatta?”
[COMPARABILITY]

• Like you’ve never dreamt of taking your bathtub out into the open (Belgian) waters.
• Sometimes things change, whether we’re retrofitting our bathtubs, or we’re changing our manufacturing processes to make them more “seaworthy.” In one of my latest editorials, I emphasize the importance of well-reasoned changes in our mindsets and manufacturing processes to ensure our industry can venture safely out of the harbor and meet more patients’ needs in deeper waters.
• Though this article is not written with ATMPs in mind, it does a nice job of summarizing existing regulatory expectations and best practices for biologics’ comparability studies — some of which are broadly applicable to ATMPs.

“Truckles will roll” @ Cooper’s Hill Cheese-Rolling & Wake
[REGULATORY]

• Most of us love cheese — but would you really go running & rolling down a mountainside to catch a wheel of cheese that’s going 65 mph?
  • Put your (delightfully unbroken) hand down.
• Nothing in pharma moves quite as fast as a cheese wheel downhill or into your mouth on a Tuesday night. But that doesn’t mean it shouldn’t. Here, Raz Eliav of Beyond CMC outlines “The Digital Future of CMC Regulatory Affairs,” showcasing recent technological initiatives the FDA has implemented to get the current document-heavy industry-agency communication schemes rolling more swiftly toward a digital future.

“My milkshake brings all the worms out of the yard” — @ World Worm Charming Championships
     *Hoeing encouraged
[OUTSOURCING]

• Just when we thought the Brits couldn’t bring us anything sexier than ‘007, they go and offer us this.
• Far be it from me to decry your CDMO’s soil-patting, grunting, and fiddling abilities. But I loved this article from my colleague Louis Garguilo on some of the most important questions you should be asking your CDMO to ensure that they’re relevant and actually living up to the innovation they proclaim in their marketing materials.

“My phalanges are more swole than your biceps” — @ World Toe Wrestling Championship
[LNP MANUFACTURING]

• This world clearly has more to offer us than boring old “eeny, meeny, miny, moe” when it’s time to make our equipment purchasing decisions.
• For those of us looking for nanoparticle manufacturing equipment, this article boasts a list of vendors/models/technology types/GMP-applicability, etc. But even beyond that helpful compilation, it provides what I can only characterize as a “muscular” discussion on the nuances of encapsulation efficiency and the pros and cons of various methods of nanoparticle formation — namely micromixing and solvent injection.