ARW's C&G Manufacturing Must-Reads

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 C&G therapy manufacturing, in particular, and/or other C&G 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. But inboxes can be shifty places. (Cue George Carlin on “Losing Things.”)

So, here’s a “permanent” copy of my C&G Manufacturing Must-Reads newsletter that was delivered on October 28th, for all you practical people who, like Carlin, abhor the question, “Where is it?”

The Canterbury Tales — “The Manufacturing Director’s Tale”

• In the second of this 5-part “Choose Your Own Adventure” story, our manufacturing executive — fresh from an unexpected conversation with one C&G expert — finds another new friend in Alexis Melendez, senior director of facilities and engineering at Kite, who wants to make sure our expert is keeping these challenges of “make-to-order” therapies top of mind when designing a new facility.

Wipe That Poker Face Off Your Face: Manufacturing Transparency

• There were a lot of valuable takeaways from the manufacturing-centric panels at the Alliance for Regenerative Medicine’s Meeting on the Mesa. But Sophia Sharp Donaldson’s “secret sauce” was the pièce de la résistance on this dinner table — especially as the lack of transparency in the CGT space stymies our progress towards industrialized CGT manufacturing. 
• Though we’re skittish about sharing our “secret sauce,” the Bespoke Gene Therapy Consortium is a great indication of increasing collaboration and manufacturing standardization. The FDA’s Peter Mark’s has been talking about his hopes for this type of framework since 2020, however the official program only just kicked off in recent weeks, as the NIH announced and STAT reported here (subscription). Here’s what you need to know:  
  • This public-private partnership comprising biotechs/pharma companies, FDA, NIIMBL, ARM, and the NIH (among many others) aims to establish a standardized “playbook” for developing and manufacturing AAV gene therapies for ultra-rare diseases. 
  • This “playbook” will be based on four to six clinical studies, each investigating a different disease using a different AAV vector.   
  • The BGTC will be:  
    • digging into AAV biology to understand vector delivery;  
    • figuring out a standard suite of analytical tools for measuring AAV CQAs; 
    • developing a more cut-and-dry regulatory pathway — one that standardizes preclinical studies to accelerate entry into the clinic. 
• Overall, this is cross-industry collaboration worth celebrating for its dedication to de-mystifying the AAV manufacturing process. 

Yo, FDA — You Forgot To Mention… 

• In the last edition of this newsletter, I “spark-notesed” the FDA’s Interpreting Sameness of Gene Therapy Products Under The Orphan Drug Regulations guidance. (I even threw in a bonus viral vector tongue twister!) I recently found this Morgan Lewis article which asks a great question about how the guidance will be applied to ex-vivo gene-edited cells, which are included in the scope of the guidance but were overshadowed by viral-vector based therapies. 

What’s Under Your Christmas Tree? 

• The responses have been tallied in a new BioPlan annual report, and it looks like 40-plus percent of cell therapy companies are asking Santa for new and improved upstream manufacturing technologies — specifically, cell separation technology and transfection/transduction technology. Personally, I can’t read about buoyancy-activated cell sorting without sharing this gif.  
• Articles that aren’t open access are the worst — but for those of you lucky enough to have institutional access, I’d direct you to this fantastic article from Current Opinion In Biomedical Engineering exploring current and future scale-up, scale-out, and decentralized manufacturing trends for cell therapies. 

Red Fish, Blue Fish, Brown FishField, Green FishField (Or No FishField)   

• What my colleague Louis Garguilo knows at Outsourced Pharma is that manufacturing experts are suckers for content about facility location. So, I offer you his recent article on the construction of a new manufacturing campus that’s coming to Philadelphia faster than you can drown a beefsteak sandwich in melted cheese. 
• My other colleague Matt Pillar of BioProcess Online ushers us into the build vs. buy debate in his recent editorial unpacking the ongoing explosion of growth in the CDMO space and the CGT industry’s interest in the hybrid outsourcing approach.   

“Ancillary Materials” 

• I wish I were as cool and as smart as Derek Lowe, whose latest In The Pipeline column unpacks a nifty imaging technique. Turns out the inside of a HeLa cell is basically an amusement park. 
• Allow me to introduce: The “Wild Swimming Women of Peru”; the history of sushi in the U.S.; and a pianist whose life was changed thanks to bionic hands. Because. Just because.