ARW's C&G + RNA Manufacturing Must-Reads (Acting Class 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 out on Sept. 8^th, it was National Actors Day. So, naturally, I decided to craft each section of this newsletter in the voice of a particularly demanding and eccentric acting coach/director. This director has some specific instructions, acting exercises, & reading materials for an aspiring actor — in this case, you — to bring their cinematic vision (a.k.a. an ATMP-filled universe) to life on the big screen. Break a leg!

 

“Picture Yourself In A Manufacturing Facility In A Universe Far, Far Away”
Look, I really didn’t want to suspend you from the ceiling. But you just weren’t embodying the energy that you should be. You are an astronaut with bioprocessing skills: you’re UNTOUCHABLE! This new universe is your playground! Where is your sense of awe?

• There are companies making in-space manufacturing technology — space grown crystals! — to help improve future drug discovery, design, and purity.
• mRNA manufacturers are exploring a variety of plug-and-play manufacturing approaches to automate, speed up, and even create point-of-care mRNA therapies. [mRNA Printers Kick-Start Personalized Medicine For All]
• And yes, believe it or not, we are learning more everyday about mRNA’s higher-order structure and stability once encapsulated in an LNP — especially when we compare and contrast mRNA’s structure to that of a biologic’s structure. [A Biopharmaceutical Perspective on Higher-Order Structure and Thermal Stability of mRNA Vaccines]

There you go — look at that smile! We’re in outer space now!“

 

Scientific Tongue-Twisters Are No Excuse For Mumbling Your Lines”
In fact, I’ve found nothing quite improves your diction like reciting gene editing vocabulary five times fast.

• NIST and ISO published just the thing to help you: a list of 42 agreed-upon gene editing terms and definitions. [ Genome Editing Terminology Is Standardized In NIST-Led Effort]
• For bonus points, repeat after me: “Additional control data for a cytokine independent growth assay;” “further analyses of certain off-target editing experiments,” and “additional control data for genomic rearrangement assessments.”
• According to the FDA & Beam, these are important things to spell out in an IND application, too. [Beam Therapeutics SEC filings (briefly) outline FDA hold on base-editing medicine]

Now, say it all again, but this time, pretend you’re British.

Remarkable. You sound so much smarter.

 

“Understand The Conflicts That Drive Your Character (Insane): Waste, Contamination, & Patents — Oh, My!”
Now that we’ve fixed your chronic mumbling, stand up and show us just how much your character cares about single-use technology and sustainability.

   *deer-caught-in-the-headlights-stare*

   ...I think some homework is in order.

• Grab a white-board, a marker, and all the current research around the environmental impact of fixed-facility batch manufacturing processes and flexible facilities with continuous manufacturing [CM] processing. You’re going to want to take down some figures:
  • What’s The Environmental Impact of Biopharma CM? Part One & Part Two
  • Yes, the data showcased in these articles is for mAbs, which don’t quite compare to ATMPs scale- and facility-wise. But USP’s continuous manufacturing of biologics workshop in early December will have some discussions around CM in the advanced therapies sector — and your character would totally go to this.
• Secondly, for next class, come dressed to recite all your lines while in a split. If you’re going to embody a character who truly understands “flexible facilities,” you should be flexible, too.
  • If your brain also happens to need some yoga, this article defining what we actually mean by “flexible facilities” is well worth the time. [A State of Flex: Finding Clarity In Pharma’s Quest To Attain Ultimate Flexibility]

*nail biting*

Talk about contamination! You know what, add these articles to your homework, too:

• Points to Consider for Microbial Control in ATMP Manufacturing (Free to PDA Members only)
• Contamination Control for Cell & Gene Therapies Needs New Analytics
  
  *eyes shift towards the table with the donuts*

Nope — eyes over here; those donuts are only for the crew.

• How did the crew win “exclusivity” over the donut table, you may be wondering?
• Well, as anyone in biotech knows, exclusivity/IP are the rainbow sprinkles on the donut for any company. But the increasingly dense patent landscape is turning the mRNA LNP space into a highly entertaining soap opera. [The Current mRNA/LNP Patent Litigation Landscape]

 

“The Mood We’re Going For Is: ‘Stuff Is Hard, But It’s Cool, Too,’ Not: ‘I Hate You, Science’”
Now, when you throw down the batch records and say, “Will I ever understand what this #$%^&*@! means?!” I need you to precisely convey both apprehension and excitement over the challenging but limitless opportunities facing you. Think about your first day of high school!

Or, if that’s too traumatizing, put yourself in the shoes of these grown up and well-adjusted, NIIMBL-funded project planners & participants. [NIIMBL Announced $15.8M To Fund 14 New Biopharmaceutical Manufacturing Projects].

Two ATMP-centric projects worth noting received funding, including:

• University California-Davis and partners Eli Lilly, Pall Corp/Cytiva, & Solano College are launching this incredibly important program: “Public-Private Partnership Strategy for Workforce Training in CGT Manufacturing.”
• Together, University of Delaware, MilliporeSigma/EMD Serono, and Agilent are tackling: “Innovative Scalable Technologies for Production of Cell Therapies.”

 

“Dig Deep — But Regulate Your Emotions; Less Is Always More...”
Right now, your face should be saying, “I’m an inquisitive engineer,” not “I like you, but I want to kill you.” Turn that “Joker” smile down notch.

• Finding a good balance emotionally — and scientifically — can leave anyone feeling unhinged. That’s why I’d like to remind you that the FDA is going to be hosting a virtual Gene Therapy CMC Town Hall Meeting on Sept. 29, at 11:30 AM ET to provide some sweeping guidance and address your biggest questions, concerns, confusions, grievances, etc., etc.
  • And when you feel you’re losing your grip overall, you can always turn to the long-anticipated and newly released EU GMP Annex 1 revision to keep your (manufacturing) performance under control. [Download Annex 1 here.]
• All the best actors study the performances of their idols — why should drug developers be any different? Dark Horse Consulting penned this in-depth piece asking important questions about what bluebird bio’s Zynteglo approval and the FDA’s AdCom format for Zynteglo/eli-cel could mean for future regulatory thinking/decision-making.
  • If you wish to re-experience the bluebird bio AdCom, I humbly offer 3 of my own takeaways, one of which includes some Shakespeare who knew a thing or two about how to present one’s self on the stage.