Reducing Lentiviral Vector COGS: A Love Story

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

When it comes to the world of viral vectors, it’s would seem that AAV is the best-dressed Belle of the C&G industry’s current ball. It’s rare that I stumble upon thought leadership and/or conversations around the future of AAV’s (seemingly but not really) homely best friend, the lentiviral vector. 

So, when I fortuitously stumbled across the article in Biochemical Engineering Journal entitled, “Lentiviral Vector BioProcess Economics for Cell & Gene Therapy Commercialization,” I was a bit starstruck. Not only did it put lentiviral vectors into the spotlight, for once, but it was also about reducing COGS, which is at the center of our manufacturing universe.

It goes without saying that you should carve out some time to read the full article linked above. But here are the bare-bones, no frills (or assumptions-laden) takeaways from this lengthy tome if you just want the big picture right now:

• The authors analyzed the performance of five different cell culture platforms, including: 10-layered vessels and hollow-fibre, fixed bed, rocking motion (with microcarriers), and single-use stirred tank bioreactors (SUB). The first four are adherent processes, while the SUB is a suspension-based process.
• Specifically, the authors determined the cost/dose to produce LVV for a CAR-T/TCR product at a dose of 2 x 10⁹ TU. They explored the costs per platform for both early/late clinical trials (10-300 doses/trial) and at commercial scale (500-10,000 doses/year).
• Using the tool, the authors ranked each technology’s impact on COGS, arriving at the determination that the SUB was the most impactful on COGS — particularly at larger scale. In early clinical trials, it was only 8 percent cheaper ($85,000/dose) than the 10-layered vessel; however, it spikes to 90 percent cheaper in late-phase trials ($4,300/dose). For commercial scale, the SUB was 95 percent more cost effective than the 10-layered vessel ($1,200/dose).
• Of the adherent processes, fixed bed and rocking motion bioreactors were ranked the most meaningful in COGs reduction (compared to 10-layered vessels) at late-phase and commercial scale (94 percent and 92 percent respectively).
• When evaluating the reduction in COGs for the SUB when compared with the fixed bed and rocking motion bioreactors, it’s important to note that the reduction was a bit more modest — 17 percent and 32 percent respectively for late-phase/commercial scales.

Now, heaven forbid I let it rest at just that.

Given the scalability and cost challenges associated with producing viral vectors today, I took the liberty (for better or, most likely, for worse) of (very loosely) translating this information into a Shakespearean sonnet. 

To My Darling Lentiviral Vector: A Practical Love Poem

If I could, I’d ply you with wine and steak;
there’d be bed upon bed to rest your head
and as many plasmids as it would take
for you to feel fully completed.

Though my generosity knows no bounds,
my millions of dollars are too meager
to treat you like you’re wearing a crown.
There’s a future for which I’m all too eager

where you won’t eat me out of house and home
& James Bond is just wrong on “shaken-not-
stirred;” our future is STRs, less “Rom-
ancing the Stone.” Your stinginess isn’t hot;

For any hope that our love will survive
I need you to not be so one of a kind.