Striking The Right Balance: The Critical Discussions Driving The mRNA Industry's Next Chapter
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
As 2025 winds down here at Advancing RNA, I’ve been feeling infinitely more retrospective and introspective, as is typical for this time of year. In turn, I wanted to revisit a few notable conversations that stuck with me over the course of the year that nicely set the stage for where we currently are and where we are headed in 2026.
Earlier this year, I had the privilege of speaking at and attending the inaugural CASSS mRNA symposium. I kicked off the festivities with a presentation unpacking the lessons the mRNA industry can learn from the life and work of the artist Picasso (follow-up articles here & here). But I was only a small part of an incredible program which went on to unpack progress being made on the clinical, CMC, and regulatory fronts. In particular, there were two panel discussions — one on analytical development & the other on manufacturing — through which we got a realistic view of how far we’ve come as an industry, and just how far we have yet to go.
Now, I cannot claim that I or any of the panelists at CASSS have or had access to a real crystal ball that will show us the future. However, what did come through these discussions loud and clear is that the future of our industry must include “balance.” Here, I’ll unpack a few ways the theme of “balance” presented itself — and no doubt will continue to present itself in the future — as well as how the panelists see us achieving this necessary balance.
The Balance Between Vaccines & Therapeutics: Avoiding the “One Size Fits All” Trap
If there is one thing to call out about 2025, it’s the year we saw more animal data released demonstrating the promise of our therapeutic candidates. This suggests that as we head into 2026, we’re on the cusp of seeing a lot more companies receiving INDs and heading into the clinic. As we continue to learn more about our drug candidates, it’s only natural that the regulatory paradigm and regulators’ recommendations would also be undergoing similar evolutions alongside our knowledge.
As each of the speakers on the manufacturing panel at CASSS affirmed, there is greater understanding (or at least more clarity) around what our molecules need to comprise as well as the quality/release specs for raw materials and the release panel for our drug products. However, given the different therapeutic goals we have for our mRNA products, it’s also important we don’t fall into the mindset of “one size fits all,” especially when it comes to something as important as a release panel.
While we may have a better understanding of what is ultimately needed for success thanks to our work with vaccines, we cannot become complacent and always accept the status quo, especially as we move into next-gen modalities and therapeutic approaches.
As one speaker explained, “I’m wondering whether we are translating too much from what we have done and creating a rigid framework without thinking where we can simplify and better control our processes based on current understanding, and, ultimately, have a more refined or slimmed down release panel in the end.”
Achieving The Balance Between Too Much & Too Little Analytical Data
In every industry I’ve had the privilege to cover, the conversation about analytical development always ends up circling around to the same point: How do we arrive at a well-balanced analytical package? The more we learn, the better we get at identifying which attributes are most important to measure. However, the more we learn, the more we find ourselves (and regulators) asking much deeper questions — questions that often require more complicated and/or thorough analytical exercises to answer.
As you can imagine, a good portion of the conversation ‘drifted’ (biologic pun fully intended) to the growth we’ve observed over the past few years in the analytical realm. Whether it be regulatory expectations over the quality of the enzymes, the quality of our starting materials, or what we must demonstrate analytically about our products, there have been a handful of “huge shifts.” For starters, as one speaker pointed out, the potency assay is increasingly in the spotlight as our therapeutic goals advance. Likewise, alternative RNA modalities — namely saRNA and circRNA — naturally dignify their own analytical considerations.
“Analytical challenges have grown exponentially with mRNA since the pandemic,” one speaker qualified. “Before the pandemic, most of the analytical methods were informed by biologics or protein production. Now, we need to have an analytical panel that is catered to the features of mRNA. It used to be that an agarose gel was enough to characterize the fragmentation of mRNA. Now, we need at least capillary electrophoresis and LCMS. Our analytics are growing more complicated and need to be adapted to the product and the product’s application.” Look no farther than this example presented at a conference back at the beginning of 2024, in which the speaker of an mRNA-based gene editing company revealed that each platform (i.e., the mRNA, sgRNA, LNP) required 15-20 assays for release.
That’s not to say that our past in biologics and the analytical advancements of the biologics sector cannot be influential to those of us in the RNA space. Afterall, as one speaker went on to emphasize, our end goal would be to adopt inline analytics to improve the turn-around time, particularly for personalized medicines.
“I’m wondering whether we can borrow from the biologics field to ensure that we can stick with only three rapid measurements — for example UV, DLS, temperature — and sterility tests to go forward,” the speaker went on to explain. “We’re not there yet, but this is what we need to grow towards.”
Not surprisingly, there was also much conversation about the process of developing platform methods to significantly compress development times. Though this is inevitably in the cards for our long-term future, it’s difficult to accomplish today — particularly on the CDMO side of the industry — because each sponsor has its own analytical “wish lists.”
For starters, several members of the panel emphasized that sequence agnostic/independent assays are prime candidates for “platformization” with the appropriate justification (i.e., data demonstrating an in-depth understanding of the method/which factors influence its performance).
“If we can keep parameters consistent, then we can really have a platform method,” a speaker added. “In cases where we cannot maintain these parameters and know we need to make changes, our goal should be to minimize the parameters that have to change. At least this way, we can minimize the burden of additional validation and studies.” (For more on the topic of analytical platforms, please refer to my previous article: Britney Spears’ Take On Building Platform Analytics For mRNA Therapeutics.)
Balancing Perspectives: Aligning Industry and Regulatory Definitions of “The Platform”
It’s likely no surprise to anyone that aligning around the definition of the ‘platform’ will be a big challenge moving forward — especially if we look at the “platform” through the lens of the FDA’s platform technology designation. On the one hand, arriving at a more clear-cut definition will require “balancing” perspectives. As one speaker went on to articulate, “We have to appreciate how difficult it might be for regulators to settle on the definition of ‘a platform’ and to articulate which changes move us out of the realm of a platform technology.”
As the speaker went on to argue, however, our desire to innovate will inevitably lead to iterative changes, which will also require a bit of give and take from the regulators, as well.
“It’s not just the definition we need to align around,” they concluded. “We need to help regulators — and each other — understand how we validate a platform to not have to revalidate to totality as we continue to innovate. We need to make it easier for regulators to accept those changes and have the next version of the platform.”
For more on the concept of “the platform,” please check out the following articles: