Two "Spicy" Takeaways On The FDA's Platform Designation Guidance

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

I first heard Peter Marks broach the concept of the “platform designation” at a gene therapy conference in March 2023. Like most FDA initiatives and/or guidances, the concept of the platform as a regulatory designation appeared out of thin air and within a few short months had become the very air we were breathing in the RNA space.

Fast forward to the (rather stealthy) release of the first draft guidance and, at least so far, industry reception has been a bit…lackluster. Over the past few weeks since the guidance was released, I’ve spent some time listening to industry conversations and reading the guidance and related articles (some of which have been published on Advancing RNA — namely, here and here).

In the following series of articles, I’ll share a few general impressions and (slightly spicy) thoughts I’ve been mulling over in response to the draft guidance. Obviously, this is only the first draft of the guidance, and there are quite a few industry comments to sift through that will provide alternative arguments and directions for us to discuss in the future. But in the meantime…  

Between “The Guidance Of Our Dreams” & “Duh,” This Guidance Is The Latter

Perhaps one of my favorite summaries of this guidance was the following statement: “Boon for Companies With Approved Products & A Bummer for Everyone Else.” (This was a subhead taken from this article.) For the mRNA space, in particular, this guidance certainly feels premature. Given that such a designation will only be applicable to companies that have products on the market (which amounts to three mRNA companies today), most of us with preclinical/clinical RNA products are left wondering how the heck we can take advantage of such a guidance.  

Well, we are in luck and, also, not quite. Those of you who have read the guidance will know that the FDA was very careful to specify throughout that sponsors can and should be relying on “prior knowledge,” regardless of whether they are granted designated platform technology. (To reiterate: While not everyone will be granted a platform designation, everyone can and should rely on prior knowledge to make their RNA product development more efficient over time.)

All in all, for those of us (all of us…) without commercialized products, this guidance serves more as a “dream” for the future, as opposed to a tool we can be utilizing right now. Of course, this guidance certainly gives us a glimpse into what the FDA may consider worthy of a platform designation, as well as what the platform is not (i.e., a ticket to an expedited approval designation/pathway,). But for most of us, this guidance is essentially advising us to do what we already know and hopefully, would already be doing/planning to do instinctually: to engage the FDA in discussions on where our prior knowledge may be applicable across products.

In fact, the argument could be made that the more useful guidance for the current mRNA field would be one that provides examples of prior knowledge and/or approaches on how we can go about relying on prior knowledge specifically in the development of our RNA products. After all, the RNA world is a “new” space full of early stage biotechs, some of which may be emerging from academic environments. Ironically, the “prior knowledge” to rely on “prior knowledge” may not exist. Likewise, the novelty of our products and our current lack of knowledge around their clinical functions makes it more difficult to bridge our knowledge across products/platforms. This becomes even less straightforward as some of us explore alternative RNA modalities and/or work in both autologous and in vivo therapy spaces — all under the same roof.

This leads me to my next brief but still important point to note —

Regulators Are Not Aligned On The FDA’s Platform Terminology/Designation

It’s not unusual for industry and regulators to have differing ideas of what is or is not necessary in the development of a product. Likewise, we’re no strangers to instances in which our interactions with regulators can be stymied thanks to a lack of scientific alignment around data requirements for global approvals. We’re starting to see/hear some of these alignment issues cropping up between regulators over the FDA’s idea/definition of “platform.”

In the industry, the term “platform” is typically used to describe standalone pieces of technology or a set of technologies/operations that we use to characterize and/or develop and manufacture our products. However, it’s also safe to say that “platform” can mean something different to each individual company. It’s thanks, in part, to the often-limited and/or varied “platform” definitions between sponsors that other international regulators are much more comfortable using/applying the phrase “prior knowledge” as opposed to “platform” when describing the FDA’s expectations for its platform designation. On the one hand, as one regulator argued, prior knowledge is a (at least more) clear-cut term with which most of the industry has experience. Similarly, as Advancing RNA LIVE panelist Melanie Cerullo nicely explained in this clip from our RNA regulatory discussion earlier this year, the term “platform” does not necessarily encapsulate the totality of the evidence (spanning all functional areas, not just CMC) that may be necessary to demonstrate/justify our future platform designations. At the end of the day, we wouldn’t want differences in terminology to stymie development/knowledge sharing between products in the future should regulators and sponsors not be on the same page on what is/is not a “platform.” 

However, I’d argue there’s another important factor at the root of some regulators’ hesitance with all this talk of “platforms” today — and that has to do with the nascence of the mRNA space clinically, along with the sheer breadth of our therapeutic approaches with the technology. Yes, to reiterate: The FDA’s platform designation will only applicable to products following in the footsteps of a commercialized product. So, by the time most of us reach that stage, we will obviously know infinitely more about our products than we do today. But as one regulator pointed out at a conference earlier this year, the mRNA “platform” designation is currently “breaking down on the scientific side” as we start to advance into a variety of different therapeutic pursuits. Though we’re starting to see some commonalities emerging “under the hood,” if you will (e.g., on the quality/CQA front), we’re entering a time that promises great clinical diversity. And, as we all know, the function and safety of our products remains a critical piece of our justification for such a platform designation (beyond that of the COVID vaccine model). This ultimately begs the question: Are we attempting to “solidify” the concept of the “platform” too early?

Stay tuned for part 2 in which I’ll continue to share more context and thought/rumination on the FDA’s guidance.