December 2008




FDA takes a stand ... unapproved ophthalmic irrigating solutions

by Maxine Lipner Senior EyeWorld Contributing Editor


New regulations mandate changes for some balanced salt solution users

November 24, 2008, began a new chapter for ophthalmic irrigating solutions. That was the day by which the Food and Drug Administration (FDA) determined that manufactures needed to stop producing unapproved balanced salt solution. FDA concerns for ophthalmic safety with the unapproved solutions were peaked by an outbreak of toxic anterior segment syndrome (TASS), according to Henry F. Edelhauser, Ph.D., professor of ophthalmology and director of ophthalmic research, Emory School of Medicine, Atlanta. A study reported in the April 2008 issue of the Journal of Cataract and Refractive Surgery, highlighted the outbreak of TASS syndrome that occurred at seven centers from July 19, 2005, through November 28, 2005. Investigators here determined that of the 112 cases identified, 100 had undergone surgery with a balanced salt solution manufactured by Cytosol Laboratories (Lenoir, N.C.). They found that endotoxin limits were exceeded in 35% of the balanced salt solution lots. Once these products were withdrawn, investigators noted that the outbreak terminated.

In the recent ruling, the FDA urged users of irrigating solutions to switch to the approved versions of balanced salt solution such as those manufactured by Alcon (Fort Worth, Texas) and Akorn (Lake Forest, Ill.). These approved versions include BSS and BSS Plus surgical solution (Alcon) and Balanced Salt Solution (Akorn).

The FDA action was taken with patient’s safety in mind, according to Michael Pfleger, vice president, regulatory affairs, Alcon. “The FDA’s September 23, 2008 federal register notice stated that the FDA had received reports of serious safety concerns from users of ophthalmic balanced salt solution products and that in some instances adverse effects could be the result of improperly manufactured products,” Mr. Pfleger said. “Specifically they cited the 2006 example of contamination with endotoxins of an unapproved balanced salt solution associated with several hundred reports of adverse events including toxic anterior segment syndrome.”

Solution basics

Balanced salt solution is a key component of cataract and refractive surgery, according to Joe Vonderhaar, marketing manager, surgical solutions, Alcon. “It maintains the shape of the eye, giving the surgeon space to perform the delicate procedures of cataract removal and vitrectomy,” he said. “It also provides key nutrients for the tissues during the surgery.”

The solution is made up of some core ingredients. “Basically it consists of five salts and a buffer,” Dr. Edelhauser said. Alcon’s BSS Plus has a couple of extra ingredients as well. “The difference between BSS and BSS Plus is that BSS Plus has bicarbonate, which is the natural buffer in the anterior chamber,” Dr. Edelhauser said. “It also has glutathione which acts as an antioxidant and it has some glucose in it which provides an energy source.”

The use of balanced salt solutions began simply enough. “The whole basis of irrigating solutions started with doing extra-cap cataract surgery because up until that time when they did intra-cap there was only 15 ml’s needed in a little squeeze bottle,” Dr. Edelhauser said. “Then once they started doing phaco and vitreoretinal surgery there was the need to make a better intraocular irrigating solution that was compatible with the intraocular tissues.” Alcon was an early manufacturer of such solutions and moved to take it to the next level as surgery evolved. “Alcon was marketing the 15 ml and of course they had to do a number of studies to gear up to take that to the 500 ml,” Dr. Edelhauser said. The approval process for BSS Plus involved a lengthy series of studies. “It took Alcon seven years to get the BSS Plus through the FDA,” Dr. Edelhauser said. “The reason was that glutathione was considered a drug.” Meanwhile, off-label solutions were grandfathered in under an FDA clause, according to Becky Kirkwood, director, cataract marketing for the Americas, Advanced Medical Optics (AMO, Santa Ana, Calif.). “AMO’s two balanced salt solution suppliers, B. Braun and Baxter, have been manufacturing and selling balanced salt solution under the Grandfather Clause of the Food, Drug and Cosmetic Act as amended in 1962 because it was generally recognized as safe and effective,” she said. “Balanced salt solution distributed by AMO is in compliance with section 510 of the Food Drug and Cosmetic Act as the product is listed with an NDC number and copies of labeling are submitted to the FDA by our suppliers per regulation.”

Current impact

In the modern world, balanced salt solutions have become an integral part of ophthalmic surgery. “None of the (phaco) machines run without an irrigating solution,” Dr. Edelhauser said. “Then when you finish your cataract surgery what you leave in the anterior chamber after you reform the anterior chamber stays there for longer than four hours.” As a result, practitioners need to be very sure that what goes into the eye isn’t harmful, he believes.

In Dr. Edelhauser’s view the FDA ruling is helpful to practitioners. “There’s no doubt that it’s safer,” he said. “Also, I think that it gives more support to surgery that you’re using FDA approved products.”

Likewise, Francis S. Mah, M.D., co-medical director, Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh School of Medicine, Pittsburgh, sees the ruling as a good one, but is unsure of its impact. “I think it’s a good move—obviously the FDA is supposed to be watching out for patients,” he said. “I would say that probably the majority of surgeons in the United States were using only approved balanced salt solution, so I would say probably a minority of U.S. surgeons were impacted.”

Overall, Dr. Mah thinks that the ruling underscores the importance of using products that have been properly reviewed. “I think that it reinforces the idea that number one the FDA is doing their job,” he said. “Number two, it shows that we should be very cognizant of everything that goes inside of the eye during intraocular surgery.”

Editors’ note: Drs. Edelhauser and Mah have financial interests with Alcon (Fort Worth, Texas).

Contact information:

Edelhauser: 404-778-5853,
Mah: 412-647-2211,
Pfleger: 817-293-0450, michael.pfleger@alconlabs
Vonderhaar: 817-293-0450,

FDA takes a stand ... unapproved ophthalmic irrigating solutions FDA takes a stand ... unapproved ophthalmic irrigating solutions
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