Your C&G Manufacturing Must-Reads (Mixologist 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 24, for all you practical people who, like Carlin, abhor the question, “Where is it?

As February 24th was National Bartender's Day, I put together a "Mixologist Edition" of Manufacturing Must-Reads. Each article is one of the key ingredients in a specific cocktail I picked to be the most suitable accompaniment to each reading list. Please read responsibly.

 

Bottoms Up! Cheers To The Many Futures Of Cell Therapy Manufacturing
Best read with a Salted Maple Old-Fashioned

45 ml single malt Scotch whiskey

• Just as you each have your own favorite whiskey you will also likely have different questions about how to best construct your own CGT facility. Choose your own CGT manufacturing facility adventure!

2 tsp. Canadian maple syrup

• Allogeneic cell therapies are certainly the maple twist to the classic autologous cell therapy recipe. I had a great conversation with Ken Chrobak, VP of CMC at Wugen, to talk through what the up-and-coming allogeneic space has learned from the "old fashioned" autologous realm (part 1 of 4).

2 dashes angostura bitters

• Overcoming supply constraints and logistical and scalability challenges in the autologous CAR-T space aren't optional endeavors (though you may be bitter about them). Learn how these two Atara Biotherapeutics manufacturing & supply chain execs are wholeheartedly embracing these challenges.

A pinch of salt & a twist of an orange peel (to garnish)

• Building an in-house manufacturing facility — let alone two — may be a "garnish" your company can't yet afford or fit into its strategy. But for Cellectis, building two facilities in Paris and Raleigh during the pandemic was well worth the effort. To finish off your cocktail, here's a Q&A on the challenges the company overcame and the podcast from which the Q&A was derived.

 

Pop The Cork! Elevating Viral Vectors To New Heights
Best read with Sparkling Winter Punch

1 bottle of Champagne or Prosecco

• The future staple ingredient of the LV and AAV vector spaces is likely to be the stable cell line. Here, I talk with Orchard's CEO Bobby Gaspar about the steps Orchard is taking to achieve this long-term manufacturing goal in the lentiviral space.

1 cup orange juice

• Tim Kelly, COO of Homology Medicines offers four of his biggest lessons learned in constructing an AAV gene therapy facility/platform. (FYI: Homology's in-house manufacturing organization will now become Oxford Biomedica Solutions.)

1 cup vodka

• Just like the vodka in this cocktail, the quality of your AAV vector could get you into big trouble. Luckily, USP is on it — be on the lookout for a whitepaper this summer comprising best practices, challenges, and recommendations for AAV QC/potency that came to light during a December USP expert panel.

1 cup honey-rosemary simple syrup

• Novel capsids are pretty sweet. ASGCT published a research-laden (and colorful!) blog post sharing the most promising directed evolution approaches to novel capsid design.

 

Straight, No Chaser: These 2 Manufacturing Trends Speak For Themselves
Best read with SHOTS!

shot of Fireball

• The CDMO market is on fire, according to a new report. The North American CDMO market is projected to grow 41 percent by 2026. However, don't expect the capacity crunch to lift, thanks to continued single-use supply shortages. Downstream purification costs aren't going to go down as easily as fireball, either.

1 shot of Limoncello

• Like Limoncello, nothing quite screams "sophistication" in manufacturing like "Industry 4.0." On Feb. 28th, CPI will be hosting a webinar explaining the goals of a pre-competitive, collaborative effort called the "Digital Grand Challenge" and how industry and tech providers can join the initiative.

 

Industry To FDA: "There's No Walking A Straight Line After Reading These Guidances"
Best read with Buttered Rum Hot Chocolate

4 cups homemade hot chocolate (recipe included above!)

• Industry has responded to the FDAs "Umbrella" trial guidance, which enables multiple versions of a CGT product targeting the same disease to be studied in parallel in a single early-phase trial. In particular, commenters asked for greater clarification on the size and scope of the manufacturing changes that would result in a new "version" (and, in turn, require a new IND) of a product.

¾ cup spiced rum

• The FDA once again reminds drug makers that none of their recommendations — including its ask for data on manufacturing volume — are strict requirements... Just like hot chocolate is fantastic with or without the rum. (FYI autologous therapy makers or those without commercialized therapies, this request wouldn't apply to you.)