The FDA alerted the public about issues related to amniotic eye drops last year and now the agency just warned the manufacturer of one such product called Regener-Eyes.
The manufacturer is Regenerative Processing Plant, LLC. The warning letter was addressed to its owner, Carl R. Harrell, MD.
What’s the deal with this warning?
Let’s start with some brief background.
Regener-Eyes review
Regener-Eyes is a firm and also a series of biological eye drop products. The eye drops are made from amniotic materials.
The clinical goal is to relieve dry, irritated eyes.
In looking on-line I see a mixed bag of Regener-Eyes reviews. Some patients feel it helps, while others report no effect or things getting worse.
As a stem cell biologist, I have concerns about using allogeneic eye drops including potential risks of absorption of material into the bloodstream. I don’t see sufficient published clinical trial data to warrant their use yet.
Even so, eye drops are a big business.
There have been some challenges with many eye drop products. As a result, the FDA has also issued other advisories more broadly about non-biological eye drops as well.
FDA warning to Regener-Eyes
One key factor with amniotic eye drops is that they are a drug.
Since there is no FDA approval for any amniotic eye drop drug, the agency states in the warning letter that Regener-Eyes is an unapproved drug.
The letter further identifies other concerns including some related to CGMP: “This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals.”
The warning letter is not the first FDA action related to these products The FDA sent an untitled letter to Regener-Eyes in 2022, which became public in 2023.
In the new, full-blown warning letter, the FDA seems concerned about how things have continued in the intervening period:
“FDA sent you a copy of the Untitled Letter dated October 5, 2022 issued to your subsidiary, Regener-Eyes, LLC, notifying you that your product, Regener-Eyes® Ophthalmic Solution, derived from “placental-derived biomaterial” and intended to mitigate or treat dry eye disease appeared to be a drug and a biological product requiring a valid biologics license under 42 U.S.C. § 262(a) in order to lawfully market the product. During the inspection, your Chief Strategist claimed that your firm discontinued manufacturing Regener-Eyes® Ophthalmic Solution containing amniotic fluid in approximately June 2021, and represented that any remaining amniotic fluid at your facility is used for research purposes.”
I also find the CGMP concerns in the letter quite concerning. For more details on the concerns in the inspection report see this post on the site Biologic Eye Drops.
FDA is being too slow on unapproved biologics
Overall, this story reflects a broader, relatively slow, and incremental FDA oversight approach to unapproved biological drugs. Here is the typically pattern:
- Untitled letter.
- A few years go by.
- Warning letter. (possibly repeat)
- The firm becomes compliant or switches products, or continues under a new name and maybe a new location.
There have even been cases where firms got multiple warning letters over a few years, extending periods of potential risks to consumers without definitive action or resolution.
I don’t know that such slowness is workable in a fast-moving area like regenerative biologics.
FDA more active in 2024?
Still, this is the second warning letter from CBER in just a few weeks so maybe we’ll see more action from the agency moving forward. See: FDA warns Mother Stem Institute & Alvaro Skupin. In addition, in June the FDA warned Neobiosis via a letter to its leader Ian A. White, Ph.D. Then earlier in January both Kimera Labs and MiMedx got warning letters.
In the past, CBER has issued only one or two warning letters for entire years.
This eyedrop warning fits with my prediction for 2024 that there would be further action on biological eye drops. You might be interested in the other predictions.
For more background, see this explainer post: What is an FDA warning letter & how should firms respond?
Also, more generally, now in late 2024 it is clear that the FDA’s oversight of cell and tissue biologics has taken off this year with 12 warning letters.