FDA Warns Companies to Stop Marketing Unapproved Ophthalmic Balanced Salt Solution Drug Products

FDA Warns Companies to Stop Marketing Unapproved Ophthalmic Balanced Salt Solution Drug Products and Topical Drug Products Containing Papain

The U.S. Food and Drug Administration (FDA) today announced that companies marketing unapproved ophthalmic balanced salt solutions (BSS) and unapproved topical drug products containing papain must stop manufacturing and marketing these products or risk enforcement action.

FDA is taking these actions because it has received reports of serious adverse events associated with their uses.

Companies must stop manufacturing unapproved BSS products on or before Nov. 24, 2008, and must stop shipping such unapproved products on or before Jan. 21, 2009. After these dates, all topical products containing papain must have FDA approval to be manufactured or shipped in interstate commerce.

Companies that continue to market unapproved topical papain products after these dates may be subject to immediate FDA enforcement action, such as seizure and/or injunction against the company.

Today's action does not affect approved ophthalmic BSS products.

Companies marketing any unapproved topical drug products containing papain must stop manufacturing them on or before November 24, 2008. Companies or others engaged in shipping these products must stop shipping these products on or before Jan. 21, 2009. After these dates, all topical products containing papain must have FDA approval to be manufactured or shipped in interstate commerce. Companies that continue to market unapproved topical papain products after these dates may be subject to immediate FDA enforcement action, such as seizure and/or injunction against the company.

No topical drug product containing papain has been approved by the FDA.

Companies that do not comply with the designated timelines may face further FDA action, including enforcement action. If FDA takes enforcement action against a company that continues to market an unapproved product after the stated timeframes, the FDA may simultaneously take additional action regarding any other violative products that the company may be marketing, including any other unapproved drugs.

"These unapproved products have put consumers health in jeopardy, from reports of permanent vision loss with unapproved balanced salt solutions to a serious drop in blood pressure and increased heart rate from the topical papain products," said Janet Woodcock, M.D., director for the Center for Drug Evaluation and Research. "Consumers need to be assured that all drug products are manufactured according to the high quality standards required for FDA approval and that they are safe and effective."

About Unapproved Ophthalmic Balanced Salt Solutions (BSS):Ophthalmic balanced salt solutions are used to irrigate the eye during surgery on the eye, including cataract and other ocular procedures. FDA has received reports of serious injuries to the eye from unapproved ophthalmic BSS. Users of these unapproved products have reported to FDA injuries including eye inflammation, cloudy vision, and permanent loss of visual acuity. Inspection of these products revealed contaminants and other product defects. Thus, FDA urges doctors and others who use these products to switch to approved versions of BSS made by Alcon and Akorn. FDA oversight of the manufacturing of ophthalmic BSS products helps to ensure that they are properly made and to reduce the risk of contamination and associated injuries.

About Unapproved Topical Papain Products:Topical drug ointments containing papain are used to remove dead or contaminated tissue in acute and chronic lesions, such as diabetic ulcers, pressure ulcers, varicose ulcers, and traumatic infected wounds.

Trade names for these products include Accuzyme, Allanfil, Allanzyme, Ethezyme, Gladase, Kovia, Panafil, Pap Urea, and Ziox.

Other products are marketed under the names of the active ingredients, for instance, papain-urea ointment.

The FDA is taking action today against these products because it has received reports of serious adverse events in patients using products containing papain. Reports include hypersensitivity (allergic) reactions that lead to hypotension (low blood pressure) and tachycardia (rapid heart rate). In addition, patients who are allergic to latex can also be allergic to papaya, the source of papain. Therefore, patients with latex sensitivity may be at increased risk of suffering an adverse reaction to a topical papain drug product.

FDA urges consumers who are using topical drug products containing papain, and who have questions or concerns, to contact their health care provider about discontinuing treatment with these products. There are a number of FDA-approved topical products that have been found safe and effective as wound healing agents and that do not contain papain.

"Removing unapproved topical drug products containing papain and unapproved ophthalmic balanced salt solutions is yet another step forward for patient safety," said Deborah M. Autor, director, Office of Compliance for CDER, FDA.

These actions are part of FDA’s unapproved drugs initiative. That initiative seeks to ensure that all drug products marketed in the United States are shown, through the drug approval process, to be safe and effective and to meet appropriate standards for manufacturing and labeling. This represents the eighth and ninth actions taken by the agency against a class of unapproved drugs since issuing a compliance policy guide (CPG) on marketed unapproved drugs in June 2006. The
CPG describes FDA’s risk-based enforcement approach to marketed unapproved drugs.

To read FDA’s Compliance Policy Guide (CPG): http://www.fda.gov/cder/Guidance/6911fnl.htm.