Be Wary of Amniotic Fluid Eye Drops, FDA Says

In its ongoing battle against companies selling unapproved stem cell products, the FDA issued a safety communication earlier this month about amniotic fluid eye drops being improperly marketed for dry eye disease.

The communication links to earlier letters to two manufacturers -- makers of Regener-Eyes and StimulEyes -- warning that the products would need an approved Biologics License Application (BLA) to stay on the market, or healthcare providers would need an investigational new drug (IND) application to deliver them to patients.

"There are no assurances that the products are safe and effective for any disease or condition," FDA said in its safety communication, adding that there are "currently no FDA-approved amniotic fluid eyedrops to treat, mitigate, or cure eye diseases or conditions."

Both products appear to be readily available for sale on the internet, with plenty of options on Google Shopping. Although StimulEyes maker M2 Biologics states on its homepage that online ordering of the product is currently unavailable, the product appears to be available for purchase through other channels. Neither Regener-Eyes CEO Randall Harrell, MD, nor M2 Biologics returned a request for comment.

It's not clear if the companies made other changes to their products or their marketing following the FDA's earlier letters. The original "untitled" letter to Harrell and Regener-Eyes from October said the company made claims on its website that it was a "biological product" composed of "placental-derived biomaterials" and used for the treatment of dry eye disease. The untitled letter to M2 Biologics sent in November said its website claimed StimulEyes was a "regenerative medicine" product also used for treatment of dry eye disease.

In both cases, the FDA said the products appeared to be a drug and a biological product and would need a valid biologics license to be marketed.

"Your product is not the subject of an approved biologics license application (BLA), nor is there an IND in effect for your product," the FDA stated in both letters.

FDA has been getting tougher on "birth tissue" companies, which market products that allegedly contain stem cells and other biological materials that are derived from the placenta and umbilical cord. The agency has argued that these are biological products that need to be regulated as such.

Leigh Turner, PhD, executive director of the bioethics program at the University of California Irvine, who has long been tracking stem cell companies, said that while "hundreds" of businesses sell such allogeneic birth tissue-derived stem cell products, a "much smaller number of companies advertise purported 'regenerative' amniotic fluid eye drops for dry eye disease and other indications."

"The problem with such commercial activity is that such companies haven't tested their products in controlled clinical trials and the safety and efficacy of such amniotic fluid products in the treatment of individuals with dry eye disease and other diseases have not yet been established," Turner told MedPage Today. "These untested or inadequately tested products pose risks to patients, as the recent public safety notification issued by the FDA notes."

In its letter to Regener-Eyes, FDA noted that the company described its product as an "acellular" biological product, meaning it does not contain stem cells, Turner said, adding that it's "not clear what businesses are claiming when they assert such products have regenerative properties."

"It appears to be another example of using the hype and buzz associated with regenerative medicine to sell purported treatments," he added.

Paul Knoepfler, PhD, of the University of California Davis, who has also been tracking the stem cell industry, said that these products still could contain growth factors and other substances that could have activity in the eyes.

"The drops likely contain hundreds of different fetal proteins and other substances, which don't necessary just do helpful things, so there are definite risks," he told MedPage Today. "For example, I could imagine a risk of abnormal blood vessel or other undesired tissue growth in the eye after using such drops due to growth factors in the drops."

He warned that such possible tissue changes "may not be entirely reversible after stopping the drops. We just don't know."

Knoepfler added that any drug placed into the eye could end up "in systemic circulation so there could be risks outside of the eye. I'd also worry about risks of infection."

"There are good reasons to treat these products as drugs and require robust clinical trial data before marketing," he said.

Turner noted that FDA's use of untitled letters to the two companies may not have enough teeth to force any real change, especially as the products appear to be readily available for purchase online.

"More robust regulatory responses are likely needed to curtail such activity," he said.

In its notice, FDA said healthcare providers should report any adverse events associated with amniotic fluid eye drops to its MedWatch program.

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