ARW's CGT+RNA Manufacturing Must-Reads (CHOCOLATE MOUSSE 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 CGT and RNA therapy manufacturing, in particular, and/or other ATMP 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.
November 30th was National Mousse Day. As you are, no doubt, already planning your menu for the upcoming holidays, I’ve taken the liberty of preparing (some quite insubstantial) SOPs to make the mousse of your choice. Should my instructions leave you wanting, however, I have no doubt the accompanying must-reads will satisfy your appetite for more in-depth industry insights and best practices. Bon appétit.
Research (at least) 20 different recipes, identifying potential flavor variations and shared cooking techniques and ingredients.
[PLATFORM DEVELOPMENT]
- I’m going to pretend I didn’t just hear you say there is no difference between making a dark chocolate peppermint and a white chocolate raspberry mousse.
- In the gene therapy world today, we can’t quite assume that our CMC efforts will carry over between products when it comes to submitting regulatory documentation. But the FDA does see a future for “official” gene therapy platforms (AAV & mRNA) — a concept which Peter Marks has been increasingly vocal about this year. Check out some of Marks’ thoughts on this nascent platform designation in one of my latest editorials.
Immediately eliminate all mousse recipes containing fish or meat.
[REGULATORY]
- Seriously, though. What the *&^% is wrong with you.
- Though some regulation is in good taste, there is a healthy balance and, according to this spicy op-ed by former U.S. Senator Richard Burr, the FDA hasn’t yet achieved a “balanced diet” of appropriate caution/risk aversion and regulatory innovation in the face of our ATMPs. (Subscription required)
- Not all mousse is created equal — and neither are comparability exercises. Beyond Burr’s constructive criticism for the FDA, the industry also joined him in expressing their thoughts, concerns, and polite grievances about the long-awaited CGT comparability guidance. As this summary from RAPS explains, not only do we want additional info on phase-appropriate approaches to comparability, we also want modality-specific comparability guidance.
Scale your recipe for your family and holiday guests. Then, quadruple that scale.
[MARKET ACCESS]
- Cheers to a new age of (plentiful) personalized mousse!
- If only. A new MIT model/study estimates that annual spending on currently approved (and some late-stage) gene therapies will be upwards of $20.4 billion — conservatively. This article gets “math-heavy,” but the results and their potential implications on payer and Medicare coverage towards the end of the article are worth looking at more closely.
- Speaking of fancy, new (expensive) gene therapies, you may have caught word that the UK’s MHRA approved the world’s first CRISPR-based gene therapy. But as this brief blog reminds us, the MHRA is only one of two parties that must be heard from. NICE, the UK’s cost watchdog, still must approve the therapy for coverage via the NHS.
Amass all necessary ingredients.
[SUPPLY CHAIN]
- Secret (creativity inspiring) hip-flask optional.
- As that optional “liquid creativity” rapidly “transfects” your brain cells, perhaps you’ll find yourself even more blitzed by this brand-new BioPhorum whitepaper proposing a standardized control strategy for your therapy’s transfection reagents. [Free registration required]
- However, as BioPhorum also mentioned, LNPs are another common transfection reagent, and I’ve been coming across more research lately on this very topic — particularly as it relates to the use of LNP-mRNA-based cell engineering. Feast your eyes on:
When you realize making the chocolate from scratch was a ghastly mistake and you’re in over your head, recruit help.
[OUTSOURCING]
- Tis the season of teaching your loved ones about the importance of good kitchen practices (GKP).
- You will undoubtedly face growing pains in passing on your “tribal process knowledge” to the additional “cooks in the kitchen”/CDMO facility. This article walks us through the biggest, most important steps in tech transferring our knowledge, processes, and products into a CDMO’s facility — with a special focus on analytical method transfer.
- If you’re still just trying to identify a suitable partner for your product, ISCT will be hosting a webinar on CDMO selection for AAV, LVV, or LNPs on Dec. 6 at 12 PM ET.
Gently fold whipped cream into your (finally completed) chilled chocolate mixture.
[GENE EDITING]
- Congratulations: With this critical step, you’ve successfully transformed the genome of your chocolate pudding into that of a mousse. (!)
- Obviously, with the recent CRISPR therapy approval in the UK, gene editing has (almost) made it to commercial “prime time.” But base editing has increasingly been appearing on the menu over the past few weeks, too.
- In an editorial this fall, my colleague Tyler Menichiello sat down with several executives from Beam Therapeutics & Prime Therapeutics to give us this helpful primer on the basics of Base and Prime Editing for monogenic diseases and in multiplex editing.
- In the research world, two scientific publications caught my eye:
- Autolus Therapeutics/Imperial College London: Large-scale Manufacturing of Base-Edited CAR-T Cells (with circular RNA!)
- UPenn: A Base-Editing Strategy Using mRNA-LNPs for in vivo Correction of the Most Frequent Phenylketonuria Variant
- Of course, the success of our gene editing relies on a good guide. Luckily, the artisans at Genentech dish out their strategy for characterizing sgRNA in this new paper, and yes, I know, it sounds absolutely delicious: “Characterization of Synthetic Guide RNA Through Hydrophilic Interaction Chromatography Coupled With Mass Spectrometry.” (Institutional access required)
Garnish mousse with candy, berries, cocoa powder, nuts, peppermint, more whipped cream...
[RNA INDUSTRY DEVELOPMENT]
- Or perhaps several different flavors of RNA.
- There’s quite a bit to salivate over in the RNA therapeutics space, including the many ongoing efforts Nobel-winner Drew Weissman outlines in this Forbes article. Cancer vaccines, in vivo CAR-Ts, targeted delivery — it’s a pretty tempting dessert cart, if I do say so myself.
- If you’d also enjoy a sprinkling of oligonucleotides (a word which, in and of itself, is a delightful gobstopper), this is a great write-up on the state of and future outlook for the oligo market.
Hide Betty Crocker’s name and claim it’s a secret family recipe forever and ever until death do you part.
[PATENTS]
- Master chefs don’t kiss and tell.
- Cooking Tip: Avoid mistletoe.
- In my last edition of must-reads, I shared a long document from the European Patent Office on the growth of patenting in the mRNA space. But if bite-sized visuals are more appealing to you, patent intelligence firm KnowMade has kindly made its poster on mRNA and self-amplifying RNA patent & industry trends from the 11th annual mRNA Health Conference available for mass consumption.
- Speaking of the European Patent Office: The EPO invalidated one of Moderna’s patents, freeing BioNTech (at least at present, pre-appeal) from having to pay damages for using Moderna’s alleged technology in Pfizer/BioNTech’s vaccine.
- FYI, the patent revoked was the EP 565 patent covering the “betacoronavirus mRNA-LNP vaccine,” NOT the EP 949 patent protecting modified mRNA (i.e., “ribonucleic acids containing n1-methyl-pseudouracils and uses thereof”).