FDA Bans Marketing of Two More Groups of Unapproved Drugs

Cheryl A. Thompson

BETHESDA, MD 23 September 2008—None of the approximately 35 papain-containing topical drug products sold in the United States have FDA's approval and neither do ophthalmic balanced salt solutions other than those from Alcon Laboratories Inc. and Akorn Inc., regulators announced today.

Those unapproved products, which have been linked to serious adverse events, are the latest targets in FDA's ongoing effort to stop companies from marketing and shipping drug products that lack the agency's approval.

More than 300 reports received by FDA since 1969 have implicated ophthalmic balanced salt solution products in serious adverse events, the agency reported in today's Federal Register (PDF). Some of these events resulted in patients permanently losing the ability to see objects clearly.

FDA said one manufacturer's unapproved ophthalmic balanced salt solution product a couple years ago was contaminated with endotoxins, resulting in several hundred reports of adverse events, some of which were serious. In some patients, exposure to the contaminated product led to a noninfectious inflammation of the anterior segment of the eye.

Alcon's and Akorn's ophthalmic balanced salt solution products are marketed for use as irrigation solutions during ocular surgery. Alcon markets BSS and BSS Plus. Akorn markets Endosol Extra and a generic version of BSS.

Deborah M. Autor, director of the Office of Compliance at FDA's Center for Drug Evaluation and Research, told reporters during a media briefing today that three companies make unapproved ophthalmic balanced salt solution products: B. Braun, Baxter, and Hospira.

Those unapproved products, she said, accounted for about 1% of the ophthalmic balanced salt solution products used in 2007.

About a dozen firms sell papain-containing topical drug products with labeling claiming that they debride wounds and promote wound healing, Autor said. "But the firms marketing these products have not shown them in a reliable, scientific way to be safe and effective."

FDA, since 1969, has received 37 reports (PDF) of adverse events related to papain-containing topical drug products, said Charles Lee, an FDA medical officer. Four of the reports described anaphylaxis, necessitating emergency medical care.

Lee said FDA is also concerned about cross reactions between latex and papaya, the source of papain. Patients who are sensitive to latex could react to papain, he explained.

"We can't put up with adverse events of this severity . . . when we have no evidence that the product is effective," Lee said.

Autor said companies must stop manufacturing the unapproved products within 60 days and stop shipping the products within 120 days.

Michael Levy, with the Office of Compliance, said FDA's Unapproved Drugs Initiative has resulted in the removal of about 400 unapproved products, including the products affected by today's announcement.