Hyaluronic Acid: Drug or Device?

The medical device industry relies on consistency and trusted decisions that take into account the development cycle’s extremely long lead times. It takes years to get a product to market, so getting advance notice of any changes that could impact that timeline is not only critical, but a requirement to successfully conduct business. Recently, I learned of a situation impacting the orthopedic industry that ran counter to this.

Further, the change came from an entity every single medical device manufacturer must interact with—the U.S. Food and Drug Administration (FDA).

Hyaluronic acid (HA) is an intra-articular injection solution used to address the pain resulting from osteoarthritis (OA). It is an opioid-free source of pain relief that can last up to six months following a series of one to five weekly injections. HA can help put off a total knee replacement for some time without the concerns about addiction that can result from pharmaceuticals used to alleviate pain.

From 1997 through 2018, the FDA viewed HA as a device and it was regulated as such. For more than 20 years, the agency recognized the mechanical aspects of the treatment as the primary mode of action for relief of pain caused by OA. Then in December 2018, the agency issued a Notice in the Federal Register that it was considering a change in how HA was classified; it believed the solution may act more like a drug than a device. This announcement came with no prior warning or announcement. Further, no additional clarity was provided on a decision, but the FDA did suggest sponsors of future HA submissions submit a Request for Designation.

This information was brought to my attention by Mike Daley, the CEO of OrthogenRx, via a contributed article (The FDA’s Flip-Flop on Hyaluronic Acid) and as a guest on my podcast, Medtech Matters. I thought the information important enough to call out in this issue’s letter as well (since neither of the previous items appeared in print for readers of the magazine). So should you have interest in gaining more information about this FDA action, I encourage you to check out both on the ODT website.

Beyond the obvious confusion this causes for HA manufacturers, there are several concerning aspects to this situation that extend well beyond this specific technology.

The FDA published this notice of the potential change in how it views the technology without prior warning or announcement. The notice mentioned the change in thinking was due to “current published scientific literature” indicating HA’s treatment of pain was accomplished through chemical action within the body. While it’s understandable the published information would give cause for a reevaluation of the technology, it does not explain the process in which it was performed.

In an entry on fdalawblog.net, Jeffrey K. Shapiro and Jeffrey N. Gibbs stated, “If FDA believes that new science requires the agency to re-classify HA injectables for the knee as drugs, then it would make more sense to announce the concern, conduct a public proceeding to gather all the appropriate information and views, and make a class wide decision, with clear guidance on the transition and implementation of the decision. The sudden change without public input will deprive FDA of receiving broad feedback.”

Putting HA before a public review committee would eliminate what looks like a unilaterally made backdoor decision without any input from industry. Given safety isn’t a concern with this decision (no products I’m aware of have been removed from the market as a response to this decision), why the need to abruptly change the course of review without any opportunity for stakeholders to comment?

This action should also raise some concern to companies who have required similar decisions in the past, or those who may need such a decision in the future. As more orthopedic products come out of the biologic space, might these face a similar decision after being well established on the market for years? A number of biologic products, regulated as devices, have a pharmaceutical component. Could the FDA change its mind on the primary mode of action of these technologies, possibly again without warning?

Similarly, orthopedics is entering a new realm of technologies that will involve development of new tissue, muscle, and bone for patients. Might these be classified one way, then reevaluated in 20 years? The lack of public input and warning on the HA decision is concerning for a multitude of reasons.

Should anyone want to comment on their experience with this or a similar agency action, please reach out to me. And, of course, I welcome comment from the FDA itself on the HA (in)decision too. 

Sean Fenske, Editor-in-Chief
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