Blog | May 9, 2022

ARW's C&G Manufacturing Must-Reads (The Simpsons Edition!)

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By Anna Rose Welch, Editorial & Community Director, Advancing RNA

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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 May 5 for all you practical people who, like Carlin, abhor the question, “Where is it?

As May 5 is known as “Cartoonist’s Day,” I was left with little choice but to present to you the CGT manufacturing articles/updates worth noting with a little bit of wisdom (and some clips) thrown in from everyone’s favorite cartoon family, The Simpsons. (Sorry, NOT sorry.) If you require further inspiration, please feel free to accompany your reading with The Simpsons’ opening theme song. 

“Why You Little...”: A Lesson In Not Losing It Over Your CGT COGS

  • If you look closely enough, there are some fantastic parallels that can be made between Homer’s [failed] attempt to design the “Ultimate American Car of the 90s” for the “every man” (it was only $82,000!) and cost-effectively scaling up a gene therapy.
  • I dare say we all want our CGTs to be “powerful like a gorilla yet soft and yielding like a nerf ball.” But we also don’t want the extreme sticker-shock that will keep these critical therapies away from the “every man/woman.”
  • That’s why I really enjoyed my conversation with Tenaya Therapeutics’ CTO, Kee-Hong Kim, unpacking the COGS in gene therapy development. In particular, we discussed how CGT companies can embrace the “engineer’s mindset” and ensure COGS is top of mind when transitioning from R&D to manufacturing for current and future product generations.

Even Blinky The Three-Eyed Fish Didn’t See This Coming

“I used to be with “it” but then they changed what “it” was, and now what I’m with isn’t “it.” And what’s “it” seems weird and scary to me.” - Grampa Simpson

  • Grampa’s quote is a definite mood these days as the biotech stock market enters a period of what some analysts are calling “the deepest and longest correction we’ve seen in the biotech indices since their inception.”
  • That said, it’s all about perspective. Yes, investors have gotten a bit more risk averse than in 2020-2021, when funding exciting ideas (as opposed to the business) was as contagious as the "monorail song". But as one analyst reminds us, the lows we’re experiencing now are simply a return to pre-pandemic levels — which were still quite high, historically speaking, for the biotech industry.
  • Sadly, the industry hasn’t reached the end of its painful layoff season yet. But what doesn’t necessarily make the headlines as often as layoffs are companies’ efforts to alter their technical strategies to extend their financial runway. For example:
    • It’s not an option for companies with unused capacity to just tack a cardboard sign to the doors saying “abandoned.” As I shared previously, this Wild West-style industry is becoming more akin to the rainforest and selling off facilities to CDMOs in exchange for long-term development partnerships, or they’re launching joint ventures.
    • “Donuts — and possibly more donuts to come” isn’t the only solid motivational technique to improve productivity. As I shared on LinkedIn, one biotech’s recent change in strategy speaks to the importance of evaluating how an outsourcing strategy can better work for you. This may also mean relying on more mature technologies (e.g., transient transfection) to streamline operations.

DO’H!-tency Assays…

  • As proud as I am over my new Simpson’s-themed name for the dreaded potency assay, this write-up defining the goals and challenges of putting together a matrixed potency assay for in-vivo and ex-vivo gene therapies is also worth reading.
  • The news out of Pfizer this past week that the FDA finally accepted its potency assay matrix for its DMD gene therapy is certainly worthy of Homer’s other signature sound effect: “Woo hoo!”
  • However, as I posted on LinkedIn, the FDA’s concerns with Pfizer’s potency matrix were not shared by several other regulators from highly regulated territories who signed off on the assay and permitted Phase 3 trials to begin. Now that the FDA and Pfizer have reached agreement, Phase 3 trials are allowed to begin in the U.S.
  • We don’t want analytical and regulatory affair professionals to follow in Krusty the Klown’s footsteps and embrace a life of extreme cynicism, burnout, and chain smoking, That’s why I penned an article a few months ago arguing the importance of regulatory alignment for the efficiency of CGT development and patient access overall. [That this article happens to draw inspiration from another cartoon — Disney’s Cinderella — is just a delightful coincidence.]

It's A Bird! — It’s Marge’s Blue Hair! — No, It’s...

“Kids, you tried your best and you failed miserably. The lesson is:”

  • “Never try.”
  • Just kidding. For those bad days when your brain feels as though it’s emerging from a particularly violent episode of “Itchy & Scratchy” (perhaps, Scratchtasia?), I’d urge you to ignore Homer and instead take a page from Robert Langer's book. His extreme dislike of giving up ultimately paved the way for mRNA delivery.