ARW's C&G Manufacturing Must-Reads (Valentine's Day 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 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 February 10, for all you practical people who, like Carlin, abhor the question, “Where is it?”

As it is/was almost Valentine’s Day, I put together a sonnet of articles (14 total). Not only are the articles organized as a sonnet (i.e., 3 "stanzas" of 4 articles each plus a final two-line couplet), each section is also introduced by several lines of an obnoxiously cheesy manufacturing-themed sonnet by yours truly. As a bonus, should you need a last-minute gift or declaration of love for your partner [or pets], I have included two of my favorite love poems. Should you be exceptionally cynical, here is the closest thing to a love poem I've ever written. Poems are so much better than a Hallmark card.

How Do I Love Thee, CGT Manufacturing?

How do I love thee? Let me count the ways.
Though you be changeable and imprecise,
The pace at which you advance does entice —
To keep up with you sets my heart ablaze.

• You know what goes great with chocolate? This article that has the links to all five of those CGT manufacturing New Year's resolutions Katy Spink and I discussed. Nothing is sexier than convenience.
• It's been a while since I've shared the wild adventure of our favorite manufacturing director in their quest to build a CGT manufacturing facility. Here, they learn a thing or two about where companies can make a meaningful dent in their COGS.
• Because I wasn't able to make it to Phacilitate's Advanced Therapies Week myself, I'm eternally grateful to BioProcess International for their coverage of this “best of 2021” presentation. #2 & #5 were particularly enlightening.
• What innovations are you watching in the CRISPR world? STAT has three suggestions for you.

I love thee down to your every cell.
Even when you make me sort and edit,
Transfect and transduce you, there is no debt
I wouldn't assume to be under your spell.

• I was intrigued by this discussion in Endpoints about a cell sorting/identification technology that can identify cells (particularly TILs) with a "Goldilocks level of expression." Here's the original Nature publication.
• For the bigger picture manufacturing implications of more specific cell identification & selection, this conversation on transduction efficiency I had with Dr. Bobby Gaspar, CEO of Orchard Therapeutics, connects some dots.
• The grass is always greener on the other side. For those of you who are finding yourself daydreaming about another cell therapy (gasp!), this is a nice write-up of the pros & cons of the different cell types: CAR-T, TCRs, TILs, & NKs.
• This Nature article from December dives into the wide world of allogeneic cell therapies, highlighting the opportunities and risks inherent in the variety of gene-editing approaches companies are taking today.

Just think of where, together, we could go
From clinic to clinic the whole world over
As long as I prove to FDA I know
Your gorgeous CQAs too far won't roam.

• And, just like that, the FDA is back to carrying out domestic facility inspections this week.
• Despite the impassioned debates over auto-vs.-allo, many agree there will always be a place for autologous therapies — but only if the proper infrastructure is established to support decentralized manufacturing. This opinion piece argues that a shift away from centralized manufacturing would enable medical centers to play an even larger, more competitive role in developing and expanding access to CGTs.
• Decentralized manufacturing is the cool kid at school that everyone wants to date. This editorial takes a page from the previous opinion piece, spelling out why shifting to a smaller, more localized manufacturing model is inevitable and in what ways it will benefit overall CGT manufacturing.
• Obviously, to move to a decentralized model, we have to embrace a "just look, don't touch" model of manufacturing. Our friends at BioPhorum have published an extensive analysis outlining a 'mock' ex-vivo CGT manufacturing process, identifying its most prominent contamination risks, and presenting mitigation/potential closure strategies.

If you should stay true, I know in my heart
That I shall love thee from lab to market.

• Because love is all about the little things we do for each other. Here's Gabrielle Calvocorreci in the NYT with "She Ties My Bow Tie."
• Because love is also telling someone you want to "get all up in them" like a vulture does to a dead deer. Here's Traci Brimhall with "Love Poem Without A Drop Of Hyperbole In It."