FDA halts manufacture, sale of non-approved balanced salt solution

Key Points

BSS is a sterile, isotonic irrigating solution used during ophthalmic surgery. It was developed during the 1960s as an alternative to saline solution and is intended to provide a temporary replacement for the aqueous humor. In its warning, the FDA noted that approved solutions have been available since 1997.

The warning does not apply to BSS made by Akorn Inc. and Alcon Laboratories, the only two manufacturers whose solutions have been approved by the FDA. An FDA spokeswoman said she is aware of at least three U.S. companies making unapproved BSS: B. Braun, Baxter, and Hospira.

Hospira spokesman Dan Rosenberg told Ophthalmology Times that the company plans to comply but was surprised by this action because it works closely with the FDA.

"We will stop manufacturing it by Nov. 24 and stop shipping it by Dec. 31, and then we'll evaluate what our next steps will be in relation to the product," he said. "Hospira has been working with the FDA to get specific unregistered drugs approved. We just haven't received any communication with them in the past with regard to this drug. Quality assurance is our highest priority, and this product is manufactured with high quality standards . . . at an FDA-inspected facility" in North Carolina.

Susan Olinger, corporate vice president, regulatory affairs, for B. Braun, relayed to Ophthalmology Times in a statement that the company has been manufacturing BSS "in accordance with the Grandfather Clause of the Food, Drug and Cosmetic Act as amended in 1962, because BSS was generally recognized as safe and effective."

B. Braun will comply with the FDA's directive and is investigating alternatives to returning the product to the market, according to Olinger.

Baxter spokeswoman Erin Gardiner told Ophthalmology Times that the company's solution was "an older niche product" that it had decided to discontinue earlier this year.

"We had notified customers in May that we were discontinuing it, so the FDA warning has no impact," she said, adding that the company's irrigating solution was an older product developed "decades" before the FDA started an approval process.

300 reports

Chappelle said that, as of Jan. 31, the FDA had received more than 300 reports of adverse events associated with all BSS, including toxic anterior segment syndrome (TASS), bacterial endophthalmitis, corneal edema, and corneal opacity. In some cases, these events led to permanent loss of visual acuity.

After announcing its intention to crack down on all unapproved drug manufacturing in 2006, the FDA tried to encourage companies to submit their products for approval and even waived many fees associated with the approval process. The agency is working through its risk-based list of such drugs, and the ophthalmic solution was near the top, she said.

"They've known this was coming," Chappelle said of the drug manufacturers, who now could face seizure and injunction if they continue to make and ship the solution. The companies also would face penalties for any other unapproved drugs they manufacture.

BSS made by Cytosol Laboratories, Braintree, MA, was associated in late 2005 with an increased number of TASS cases because the solution was found to have elevated levels of endotoxins, and the FDA subsequently ordered a recall. The recall included 1 million units of the solution distributed between December 2003 and December 2005. Cytosol Laboratories discontinued manufacturing BSS following the recall, according to company spokesman Court Lewis.

TASS can range from a mild to a serious problem for ophthalmic surgeons and their patients, said Nick Mamalis, MD, professor of ophthalmology, John A. Moran Eye Center, University of Utah, Salt Lake City.

"This inflammation can cause difficulty with corneal edema or corneal clouding," said Dr. Mamalis, who is co-chairman of the American Society of Cataract and Refractive Surgery's TASS Task Force. "You can get a large amount of inflammation in the anterior chamber of the eye and the subsequent problems that inflammation can cause, and you can get problems with glaucoma."

Although the task force had worked with the FDA before the 2006 recall, it was not consulted prior to this action.

"Since that time, there's been a large amount of TASS going on," Dr. Mamalis said. "We've looked at it, and we've not found any linked to a particular brand of BSS."

Discontinuing the manufacture and sale of all but two makers' solution will affect many eye surgeons, he said.

"We certainly use BSS in every single cataract and every anterior segment surgery, so it is one of those materials vital to our surgeries," Dr. Mamalis said. "This is going to have a large impact."

http://edocket.access.gpo.gov/2008/E8-22305.htm

www.fda.gov/cder/news/ophthalmic_BSS/qa.htm