ARW's C&G+RNA Manufacturing Must-Reads (Amusement Park 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.

As this newsletter was sent out on July 28^th, also known as National Waterpark Day, I put together the “pitch deck” for a magnificent new theme park/destination. Each section outlines a proposed ride or park attraction that (loosely) symbolizes the ATMP manufacturing-centric challenges/topics I’ve read about in the past few weeks.  I’ve already received endorsement from Chevy Chase who says this is “the destination to end all destinations.” It’s also possible it will be forced to close its doors due to unsafe conditions and/or your children’s sheer terror and/or boredom. Would you visit?

Attraction #1
Why not start out by admiring the splendor of the whole park from 50 meters above on our legendary Sky Walk entrance? Moving in a single file line, each member of your team will be asked a trivia question. Get it right, you move forward by one tile on this giant bridge; get it wrong and you will plummet into the treacherous Ball Pit of Despair! *Please note, to access all other experiences at the park, you must successfully cross this walkway.

• Ok, so Netflix’s Squid Game may have loosely inspired this attraction... but is it not also a fantastic metaphor for an FDA adcom meeting? Based on the totality of the evidence presented and the company’s ability to answer questions, the advisory committee members can influence a therapy’s path to the market.
• I was happy to read this article by AVROBIO’s CEO, Geoff McKay, sharing his takeaways from the most recent bluebird bio FDA adcom.
• As he pointed out, “Not all lentiviral viral vectors are designed the same,” which was a factor I dug into specifically in part two of my three-part series on the adcom meeting. In addition to showcasing the differences that can exist between vectors, I also thought this meeting nicely portrayed the differences in opinion that can exist between stakeholders as it relates to making significant changes to a therapy’s viral vector.

Ride #2
In this thrilling rendition of a deep-sea dive, your family/friends will suit up in diving gear, enter an underwater cage, and descend into a shark-filled lagoon! As a team, you will have to work together to “shark-proof” the cage and send an SOS up to the surface when it’s time for the cage to be pulled safely up.

• Your development programs will most likely have many “shark sightings” — but how, when, and even IF those dangers are CEO-worthy updates is not always clear.
• You may remember that one of Cell & Gene Collaborative’s 5 CGT Manufacturing New Year’s resolutions was to "Find Balance Between “The Sky Is Falling!” and “Surprise!” In Communicating Risks."
• This resolution led to a Collaborative conversation earlier this year with Poseida’s CEO Mark Gergen, during which we discussed best communication practices between C-Suite and manufacturing execs and what structures must be in place to facilitate open communication as a company expands its headcount and pipeline.

Ride #3
Are you bored by basic roller coasters with just one track that goes up and down? Do you like 12 upside-down loops in a row? Do you want to hang a few inches upside down above a shark-infested lagoon? Well, with 10 cumulative miles of track to choose from, your own car, a single steering wheel, and lightning-fast decision-making, you can chart your own course on this “architectu-roller” marvel!

• If you were thinking, hey, this “create your own roller coaster adventure course” stuff sounds kind of like developing an mRNA therapeutic (or any ATMP, really), well then congratulations: you’ve read my mind.
• This spectacular article by several engineering experts from Imperial College London outlines where we are still coming up short in terms of mRNA manufacturing & quality (despite our mRNA vaccine progress) and, in turn, how Quality by Design principles can be specifically applied to mRNA development.
• I was excited to learn that BioPhorum’s network of brilliant minds is setting its sights on the RNA therapeutic & gene editing space. A few months ago, it released a white paper that outlines the extensive scope of RNA manufacturing challenges its members hope to address in the upcoming years. (Free reg. required to download)
• What are the highest priority challenges, you may ask? I put together a few questions asking just that, and two BioPhorum members — Jimmy Chu of 2seventy bio and Kathryn Black of Lonza — nicely tackled them in this Q&A.
• As you exit the roller coaster, don’t forget to memorialize the experience by taking a picture with your face in the cutout next to these mRNA pioneers, all of whom we can thank for getting us this far scientifically.

Attraction #4
“Step right up” to our “high striker!” No fake mallets and stuffed animal prizes here; You get a real sledgehammer and win cold hard cash. The sledgehammer may get heavier with every successful strike of the bell, but your winnings will skyrocket! The number of times you’re able to ring that bell = the more money you get to “rent” your favorite ride for an hour or “acquire” it for the whole day!

• Unfortunately, you have to do a lot more than swing a sledgehammer and ring a bell to win/secure capacity with an outsourcing partner. But to be fair, CDMOs have been more popular than Disney World over the past few years.
• If the unreturned emails/phone calls, and/or long waiting lines haven’t suggested as much, this article provides a good overview of current CDMO market demand and funding dynamics and the greatest growth/acquisition opportunities in the outsourcing sector.

Ride #5
Have you ever watched a drop tower and thought, “Man, if only I could control when and how fast that sucker drops”? Want to simultaneously thrill and terrify your family and friends? Welcome to “Operation Operator:” We hand over the controls to our legendary drop tower to you — no training necessary!

• Batch failures may not exactly be plunging way down, but they are on the decline in the biotech industry. However, operator error has been implicated as the most common cause of batch failure in both clinical and commercial manufacturing — and given ongoing challenges with hiring, training, and talent retention, it’s expected to remain a common plague in manufacturing programs.
• Speaking of training: I was particularly intrigued to read about this UCSF biotech training program, within which PhD students will be based full-time and complete their degree from inside the (lab) walls of a start-up company. This program is making some academicians antsy, but from a training and experience standpoint, I can’t think of anything more valuable for these potential future industry members.