Your C&G Manufacturing Must-Reads (Super Mario 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 March 10, for all you practical people who, like Carlin, abhor the question, “Where is it?”

As March 10 is also known as Super Mario Day (Mar10), this Manufacturing Must-Reads has a Super Mario theme. As someone who gets slain by Goombas literally three seconds into any level of Super Mario, I’m far from an expert on the Mario universe — but I certainly respect it, if only because I’m so terrible at it.

In the CGT “Mushroom Kingdom,” Our Manufacturing Facilities Are Symbiotic

• Over the past year — and especially the last few months — I’ve noted several of the first CGT companies to invest in their own manufacturing capacity have decided to sell off that capacity to CDMOs. Here’s my take on what these strategic redirects mean for the CGT manufacturing and outsourcing ecosystem.

Step Aside, Princess Peach — Queen CMC Needs Us More

• Figuring out how to get a thumbs-up from the FDA may feel like beating your head against a brick wall and hoping a coin pops out. This "biobusiness brief” published in Nature Reviews Drug Discovery by McKinsey & Co. (subscription required) highlights the extent at which CMC — particularly comparability and analytics — are plaguing late-stage CGT companies. If the subscription is an issue, here’s an accompanying infographic that’s been all over LinkedIn.

Like The Best Video Games, Cells Have A Lot Of “Levels,” Too

• Back in January, this outlook article posited that allogeneic NK cells could be the CGT industry’s secret weapon in oncology. But like every other cell type being explored today, there are a lot of unique manufacturing challenges to figure out. I got a great look into how Wugen’s VP of CMC Ken Chrobak is approaching some of these challenges in a recent article. 
• Delving into the world of analytical characterization and determining CQAs may seem as harrowing as crossing “The Butter Bridge(s)” and entering “The Forest of Illusion.” That’s why the NIH Regenerative Medicine Innovation Project (RMIP) is launching the In-Depth Cell Characterization (IDCC) Platform Hub at Georgia Tech to determine the “cell fingerprints” of stem cells and the impact these “fingerprints” have on clinical effect.

Don’t Get Caught In The Piranha Plant: Decentralize Manufacturing Instead

• A Caring Cross whitepaper entitled, “Centralized vs. Decentralized Manufacturing of Personalized Cell Therapies: CAR-T Cell Product Manufacture, Quality, and Release” makes a well-supported argument demonstrating that high quality manufacturing is currently possible at the point of care (POC) — and will only be helped with greater automation, a POC regulatory framework, and harmonization of reagents and instrumentation.

Mario=Red, Luigi=Green; If Only Characterizing Your Viral Vectors Was That Easy

• Several Regeneron experts have published analytical characterization data revealing the impact of multiple freeze-thaw cycles on AAV8 (and several other serotypes). Turns out what happens to AAV in “Ice World” unfortunately doesn’t stay in “Ice World.” [Subscription required]
• Step aside PCR, there’s a new(ish) character on the block. This roundtable is a thorough primer on implementing ddPCR in viral vector manufacturing— including its benefits; best practices for implementation and standardization; future use cases; and potential improvements.
• Unfortunately, throwing mechakoopas will not help you beat back or eliminate any of your viral vector impurities — let alone your empty or half-full capsids. Luckily, MIT and BioMarin have teamed up on a new orthogonal method to quantify these light capsids using a suspended nanochannel resonator.

“Back-Integrated Outsourcing:” The “Secret Exit” From Supply-Chain Woes

• While the war in Ukraine hasn’t impacted outsourced manufacturing, my colleague at Outsourced Pharma has written a timely editorial on the importance of “back-integrated outsourcing”— especially as this war raises interesting questions about what would happen to pharma should a similar conflict emerge between Taiwan and China. 

Who Captured The CRISPR Castle?

• MIT & the Broad Institute of Harvard were crowned the big winners after sparring with Jennifer Doudna and Emmanuelle Charpentier (aka the CVC group) in court for 7 years over the patent for guide RNA. STAT+ raises three questions about the impact this will have on the companies that licensed their CRISPR tech from the CVC Group and whether shiny next-gen versions of CRISPR will actually be “new enough” to garner their own patents.