CDMOs Co-Author The RNA Ecosystem

By Louis Garguilo, Chief Editor, Outsourced Pharma

Praise to the innovators, and the innovative service providers.

You’ve brought us a long way, although that progress hasn’t necessarily made it easier to strategize the outsourcing of your RNA-based projects. While we’ve expanded development programs therapeutically, we’ve also dailed up more nuanced production requirements.

It’s still difficult to (a) identify the most suitable external partners at the optimal locations, and (b) network those partners into coordinated supply chains.

Nonetheless, a growing number of CDMOs and a host of specialized suppliers (also see here) have admirably served sponsors on their journey to the clinic.

When looking at all RNA-related modalities combined – including among a growing list, messenger RNA (mRNA) vaccines, mRNA therapeutics, RNA interference (RNAi/siRNA), and antisense oligonucleotides (ASOs) – recent industry tracking data from IQVIA counts over 700 ongoing RNA therapeutic clinical trials worldwide.

The question to ask at his juncture of expanding science and therapeutic application is what will the RNA development and manufacturing outsourcing ecosystem look like in just a few years from now?

Mature People, Maturing Industry

I put that question to John P. Cooke, President, and Andrew Varley, Secretary, at the Society For RNA Therapeutics (SRT). They describe RNA as a multi-pronged scientific discipline much in the process of inventing itself, and its business models.

They iterate that with the expanding potential for future breakthrough therapeutics, new and ancillary fields of application, also comes the need to focus now on the outsourcing matrix of tomorrow.

As much as any component of RNA market maturation, outsourcing models and infrastructure build out is of key significance.

RNA development will continue to mature only as the supporting ecosystems do so as well.

Consider, for example, how today analytical methods are still evolving, quality measurements vary from organization to organization, and manufacturing platforms are still diversifying.

Even experienced developers struggle to determine what “best practices” look like across several critical developoment and manufacturing steps.

None of this should be read as signs of weakness; rather, it’s evidence of technology platforms moving quickly and our working out standards and infrastructure to stay ahead of the curve.

Cooke believes the Society for RNA Therapeutics can help accelerate an industry maturation.

The scientific organization is centered on “professionals and education, workforce development, collaboration between academia and industry, and the exchange of best practices across the field.”

That workforce emphasis is vital, Cooke says. Nearly every advanced therapeutic platform “seems to eventually encounter the same bottleneck – skilled workers.”

There’s a need for scientists to work within organizations that foster understanding of biology, regulatory expectations, analytical characterization and formulation, technology transfers, and manufacturing processes.

Where will these future supply-chain workers come from?

The SRT for one hopes to help build that talent pipeline by bringing together leading academic institutions and programs exposing younger investigators to RNA therapeutics as a business career path.

CDMOs and other outsourcing organizations would be delighted if more skilled students became tomorrow’s process scientists at their facilities.

I for one have said this before: We need a more direct path to CDMOs for these students. This should be an emphasis of workforce development today.

Then there’s the question faced by every industry – automation and AI.

Varley for his part has been pursuing the “understanding of facility needs for the RNA space of today and tomorrow.”

Cooke envisions integrated and automated manufacturing systems producing personalized RNA medicines, those closer to the patient than today’s centralized manufacturing model allows. Those technologies could also dramatically simplify production for individualized therapies. 

But Cooke and Varley see the writing is on the wall; automation will eventually replace large portions of centralized CDMO output.

Perhaps. But it hasn’t worked out quite that way yet. I believe CDMOs and equipment suppliers will continue to evolve to meet market and their own business-model needs.

How about leased, mobile equipment owned and run by professionals deployed from CDMOs, perhaps to hospitals as well as other locations? Perhaps an enlightened leasing-equipment-service model? There are ideas out there.

Cooke acknowledges an impactful l continuing role for CDMOs, while he and Varley both are involved with an alternative service-provider equation: the expanding role of academic and medical centers in providing RNA services. 

Bring In Universities And Medical Centers

Cooke’s work at Houston Methodist and Varley’s organization at the University of British Columbia increasingly resemble expanded translational service organizations.

Theirs and other organizations can manufacture research-grade materials, develop analytical methods, solve formulation problems, and help startup companies move promising ideas closer to clinical development.

These are impressive advancements in the RNA ecosystem. But there is little reason to assume these new areas for practical industry assistance will replace large components of CDMOs.

As noted above, the CDMOs will evolve. For example, why wouldn’t we see the CDMOs and university/medical-based service organizations themselves continue to form new partnerships?

Finally, let's not overlook the large-scale manufacturing needs of many RNA therapies: future mass-market (blockbuster) products anticipate the need for classic large scale and integrated CDMO models.

Also consider national (and global) strategies and stockpiles for pandemic preparedness. History suggests new technologies do not eliminate outsourcing. In fact, they tend to expand and refine it. 

Cooke and Varley are believers in this refinement theory. Once we’ve developed malleable manufacturing platforms/equipment, with human, machine and AI inputs, RNA becomes an even more flexible, programmable therapeutic platform.  

And that maturity will continue to be led by manufacturing flexibility at CDMOs. 

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Part one of our discussion with John P. Cooke, PhD, MD, Director, Center for RNA Therapeutics; Chair, Dept of Cardiovascular Science, at Houston Methodist; and Andrew Varley, Founding Director & Head of R&D, UBC RNA & Formulation Core. Cooke is the President and Varley Secretary of the Society For RNA Therapeutics (SRT)