Outsourcing Challenges For Emerging mRNA Biopharma

By Louis Garguilo, Chief Editor, Outsourced Pharma

Jared Davis is CEO of Calgary-based Providence Therapeutics, an mRNA, personalized-medicine turned COVID-19-vaccine developer.

Davis is a long-time leader in the mRNA process development and manufacturing space. At Providence, he’s played a leading role in the establishment of an independent Canadian CDMO to provide the development and future manufacturing needs of its vaccine, currently in phase one. (see here for more)

In fact, throughout his career in the mRNA space, Davis has seen the challenges emerging mRNA drug developers have had with CDMOs.

Ironically, the COVID-19 vaccine chase, so far won by mRNA developers able to manufacture in large quantities by utilizing CDMOs, has seemed to contradict those persistent challenges.

Still, that success can’t long conceal that CDMOs are not set up to work with emerging mRNA companies like Providence, who until the pandemic was focused solely on precision medicines based on the promise of mRNA therapies.

In fact, the COVID-19 vaccines might have added to the challenges: even less capacity for others where it might have fit into CDMO models, and a more stark comparison to the small batches needed for precision (or personalized) therapies being developed at mRNA biopharma.

For emerging mRNA, as well as any other biotechs with specific needs such as Providence’s, Davis lays down three areas to take under full consideration when forming scientific, business, investment, and overall plans for commercial success.

1. Can’t Be Convinced

Jared Davis, CEO of Calgary-based Providence Therapeutics

“The first challenge is to simply find a service provider with any experience,” David says via video conferencing from the CDMO he’s helping to enable in Calgary (see here and below for more on that).

“In the mRNA field, there're few CDMOs with any experience.

“Early on, what I struggled with was even if they didn't have experience, and I was willing to say my team has the experience, we can train you, they weren’t interested.”

Perhaps they will be more inclined today?

“Even now, getting a CDMO to decide to make mRNA versus what they're making now – even where it could fit their facilities because they are producing plasmid or recombinant protein – is a struggle.

“Most still say we just make plasma. We don't make mRNA.

“So finding a partner – or convincing somebody to say, yes, we'll do this with you – is the first challenge.”

2. Too Fast For Us

“The second is timing … It always comes down to a matter of timing, right? You need to go faster than you're able to within the CDMO’s scheduling,” explains Davis.

On the other hand, he warns: Be careful of “the over-promise and under-deliver” when a CDMO does seem to agree to your timelines. The criticality of meeting your precision-medicine-scheduling needs has to be clear.

Therefore, says Davis, if you do find a CDMO who has met your timelines, and you can enter a trusted relationship, stay with it.

3. Precision Pricing A Problem

The third hurdle is a CDMO that can create a model to deal with your pricing needs and their profitability.

“That's where our precision cancer-vaccine therapies didn't work out for us – and we ended up helping to establish a CDMO from scratch,” says Davis.

“Some CDMOs said maybe they could adjust some elements, but it turned out we’d need to spend half a million dollars per patient-batch.”

“So those are the three challenges your readers getting into mRNA today need to consider,” Davis sums up.

That Sucking Sound

Why mince words? I simply ask Davis:

• Are the COVID-19 vaccines sucking up any existing mRNA interest, capacity and raw materials at CDMOs and suppliers?
• Do you think, on the other hand, this is enticing CDMOs to devote more capability and capacity to other mRNA therapies?

“I think a little of both,” replies Davis.

“For the big-quantity players, the bigger bottleneck is the fill-finish component.

“These mRNAs require complex formulations, and that has to be tied closely to the fill-finish. You almost have to do it all in the same facility.

“But there's not many facilities that can do complex formulation and fill-finish for an injectable. So that capacity has gotten ‘sucked up,’ as you put it.

“The other piece is the raw materials. They are in shorter supply.

“However, to the credit of the suppliers of these materials, they have gone through heroic efforts to stay on top of demand.

“I haven't seen a shortage yet … other than glass.

“And I think you're right, this has created a desire for some CDMOs to perhaps supply mRNA services and material. But we have to keep building out more capacity. Perhaps capable CDMOs are coming online, considering the COVID-19 success, but there still are very few to serve emerging mRNA developers like us.”

Precision Decisions

And what about precision – or personalized – medicine, which mRNA seems so suited for.

“Personalized medicine” seemed on the proverbial lips of an enter industry some years back.

The promise has not nearly lived up to the talk.

Davis – and quite a few others I’ve spoken to – lay much of the disappointment at the feet of the CDMOs.

In an industry now more-or-less built on development and manufacturing outsourcing, does personalized medicine fit the model?

“It really doesn't,” laments Davis.

“I've talked to player after player. The answer always is they’ll work with us, but we’ll need to pay for a full suite for a year, and maybe actually use it maybe ten times at most.

“We have to pay for the staff to have them ready to go on a dime. It just gets very expensive. We have an eight-week turnaround for personalized cancer vaccine. That's our target.

“CDMOs today just can’t work with that.

“And that’s why,” Davis concludes, “emerging mRNA biopharma need to build internally to get going.

“Moderna, for example, had built out quite substantial internal manufacturing. To be successful in this space, its’s pretty much done internally to make it happen.

Otherwise, like Providence, you can always “enable” a new CDMO, as we’ve detailed previously.

But we are an optimistic and opportunist industry.

Services have always evolved to fit our needs. That’s why outsourcing and external supply chains and partnerships have flourished through the years.

Next up, I’ll talk to another experienced professional – this time facing similar challenges in the gene and cell therapy arena. Let’s see if he has evolving solutions to some of these current challenges.