In mid-December, the Food and Drug Administration (FDA) issued a murky and confusing notice saying that companies intending to submit a new premarket approval application (PMA) or supplement to a PMA for a new or changed use of injectable hyaluronic acid (HA) “are encouraged to obtain an informal or formal classification and jurisdiction determination through a Pre-Request for Designation (Pre-RFD) or Request for Designation (RFD)” before submitting.
Historically, HA has been regulated as a device. However, this notice seems to imply (but does not actually say) that if the sponsor of the HA application doesn’t submit an RFD or Pre-RFD, then, for the purposes of new applications or amendments, FDA will consider the new HA use to be as a drug, not a device.
The notice of “Intent to Consider the Appropriate Classification of Hyaluronic Acid Intra-Articular Products Intended for the Treatment of Pain in Osteoarthritis of the Knee Based on Scientific Evidence,” was published in the December 18 Federal Register.
The implication that HA might be regulated as a drug in the future (absent a case-by-case designation as a device in response to an RFD or Pre-RFD) arises from the body of the FDA announcement, which says (summarized) that originally, HA was classified as a device because it has a cushioning effect, which doesn’t last, but that now (in FDA’s view), the principal way it acts on the joint is by creating chemical reactions in the joint. Impliedly, that would seem to make it a drug.
Here’s another strange detail: In response to our attempt to get clarification, an FDA spokesperson said the agency isn’t answering any questions beyond the text of the notice “until we evaluated comments submitted.” However, the notice doesn’t make any mention of a comment period or how to submit a comment.
Her email adds, “You may want to consider reaching out to experts outside of FDA to see if they wish to comment.”
We did.
Enter Outside Expert
We found that we’re not alone in wondering what FDA intends.
Attorneys Jeffrey K. Shapiro & Jeffrey N. Gibbs of the Washington law firm Hyman Phelps & McNamara PC, wrote in a December 19 posting in the firm’s FDA Law Blog, “This document is quite unusual, to say the least. Without fanfare, FDA has suddenly announced that products regulated as Class III devices for 23 years ‘may’ actually be drugs.”
The blog opines:
“As a procedural matter, this approach does not seem sensible. 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….”
“Instead, FDA has expressed doubt about the classification of all these products but only ‘encourages’ PMA holders to seek classification decisions via the Pre RFD or RFD processes…. Nothing in the notice suggests that the science FDA is citing would apply to some HA products but not others. If so, why bother with case by case decision making at all? Why not take a class wide approach, and solicit comments?”
Injectable HA is a controversial treatment. The American Academy of Orthopaedic Surgeons (AAOS) pulled its recommendation to use HA in its clinical practice guidelines in 2017 after many years (“AAOS Issues New OA Clinical Practice Guidelines,” Elizabeth Hofheinz, M.P.H., M.Ed. May 1, 2017).
The FDA evidently doesn’t know what they are regulating, so perhaps they should remove, rather than add, further confusing regulations.
I am very frustrated that the FDA has chosen to approve coverage for the HA injectables in the knee and hip, however, has not improved it for the shoulder. When will that be considered – why allow for some areas of the body to have coverage and other areas it does not. That leaves those in a lot of shoulder pain to pain for the HA injections out of pocket.