Bausch & Lomb permanently removed its ReNu with MoistureLoc from worldwide markets after company investigations suggested that the contact lens care solution’s formulation can increase the risk of a rare fungal infection under certain circumstances.
The company announced the move on May 15, after meeting with officials from the Food and Drug Administration the previous week.
In the recall announcement, B&L’s chairman and chief executive officer, Ronald L. Zarrella, said the company’s “top priority is the safety of our customers, and we want them to have complete confidence in our products.”
The recall was the company’s latest move in response to investigations showing that its ReNu with MoistureLoc contact lens solution was “disproportionately associated” with recently reported cases of Fusarium keratitis in soft contact lens wearers, according to B&L statements. Other ReNu contact lens care solutions, including ReNu MultiPlus, do not have a higher than expected association with Fusarium infections, according to the FDA, and remain on the market.
“After an extensive investigation involving thousands of tests, millions of dollars and collaboration with government agencies, health authorities and independent experts, there is no evidence of product contamination, tampering, counterfeiting or sterility failure,” Mr. Zarrella said in the announcement on May 15.
The following day, the FDA released a report that backed up Mr. Zarrella’s statement, but also drew attention to some “deviations from good manufacturing practices” at Bausch & Lomb’s plant in Greenville, S.C., the facility where ReNu with MoistureLoc was made for the U.S. and some Asian markets.
The FDA report, which announced preliminary findings of its inspection of the plant, conducted in cooperation with the federal Centers for Disease Control and Prevention, said investigators had not found evidence that environmental factors, raw materials or manufacturing processes had contributed to Fusarium contamination.
B&L’s investigation concluded that it is a combination of factors that come together in rare circumstances with the formulation of its ReNu with MoistureLoc solution, not any defect in manufacturing, that is the root cause of the increased relative risk of Fusarium infection.
“The observations from the FDA inspection … do not necessarily support a connection between the formulation of the ReNu with MoistureLoc product and the Fusarium infections,” a statement from the FDA said, noting that the report is preliminary. “It is premature to conclude that some of the observations cited in the report are associated with the cases of Fusarium keratitis.”
The federal investigation
The FDA’s preliminary report, accessed by OSN on the FDA Web site, states that the B&L plant in South Carolina deviated from federal regulations in its manufacturing process. The report also noted that B&L officials failed to notify the FDA in writing about 35 serious Fusarium keratitis cases in Singapore.
According to the report, B&L also failed to report five cases of keratitis that were reported to the company in July 2005 and neglected to report its decision to remove the ReNu with MoistureLoc from the Singapore and Hong Kong markets in February.
In a response dated May 17, B&L noted that reports in the lay press “erroneously suggest that Bausch & Lomb withheld from FDA information the company received about Fusarium infections in Singapore.”
When read closely, the FDA report notes that Bausch & Lomb did not provide the agency of these events with reports “in writing” or in the proper document format.
The B&L statement said that “within days of receiving a report of an unusual spike of Fusarium keratitis in contact lens wearers in Singapore” the company “discussed those initial case reports” with FDA officials, and the company continued to provide updates to the FDA as details were gathered. On April 5, company representatives met in person with the FDA to provide a full briefing on the situation, according to the B&L statement.
B&L also stated that the keratitis complaints from July 2005 cited in the FDA’s report were noninfectious and not related to Fusarium infection. As those incidents did not require medical treatment, the company was not required to report them to the FDA, the company stated.
At press time for this issue of Ocular Surgery News, the latest report on the fungal keratitis outbreak from the CDC, issued on May 12, states that the CDC has received reports of 122 cases of Fusarium keratitis, 15 possible cases and 60 cases that are still under investigation. The reports come from 33 U.S. states and territories.
The May 12 statement from CDC contained no breakout of numbers of infections associated with different lens care solutions, but an earlier CDC report on May 9 did.
In the May 9 report, the CDC said it had confirmed 98 cases of Fusarium keratitis. Of those, five (5%) did not wear contact lenses.
Of the 93 cases (95%) confirmed in patients who wore contact lenses, 59 (63%) reported using any B&L ReNu MoistureLoc; 19 (20%) reported using any B&L ReNu MultiPlus; nine (10%) reported using any unspecified B&L ReNu product; three (3%) reported using any Advanced Medical Optics product; and four (4%) reported using any Alcon product. Some patients reported using more than one type of solution.
“Since the first report on this outbreak in the April 10, 2006, Morbidity and Mortality Weekly Report, CDC has noted that patients have reported using multiple products, including those manufactured by Bausch & Lomb, Alcon and Advanced Medical Optics,” the May 9 CDC report stated. “At this point, it is too early in the investigation to say whether a particular product or solution may be responsible for the outbreak.”
The report noted that, throughout the CDC’s investigation, “the proportion of patients who reported using Bausch & Lomb’s ReNu with MoistureLoc has remained relatively consistent, at around 50% to 60% of confirmed cases.”
The CDC report said its investigations are ongoing.
Increasing infection rate
When extensive investigations by Bausch & Lomb began to rule out contamination, product tampering or counterfeiting as possible causes of the Fusarium keratitis cases linked to its ReNu with MoistureLoc lens care solution, the company directed its attention to the product formulation, according to a company official.
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Culture positive Fusarium corneal ulcer in a contact lens wearer showing characteristic hazy white flocculent appearance with fuzzy margins.
Image: University of Iowa
“We knew MoistureLoc worked really well under standard conditions, so we asked the question, ‘What is going wrong with the formulation under stressful or noncompliant situations, which could result in an increased risk of infection in very rare circumstances?’” said Brian Levy, OD, MSc, vice president and chief medical officer for Bausch & Lomb, in an interview with Ocular Surgery News.
According to Dr. Levy, David M. Geiser, PhD, a geneticist and Fusarium expert in University Park, Pa., concluded that the strains of Fusarium causing the infections were genetically diverse, not out of the ordinary, and common in sinks and drains.
Dr. Levy said B&L’s investigators have theorized that a “perfect-storm scenario” must take place in order to increase the risk of a Fusarium infection with use of its ReNu with MoistureLoc solution. The scenario includes the presence of Fusarium in the environment, patient wear and care practice, evaporation of the solution in open lens cases, lack of cleaning of cases, and the susceptibility of the individual patient.
When combined, these factors may increase the risk for Fusarium keratitis in contact lens wearers, Dr. Levy said. The rare fungal infection, most common in tropical regions and generally associated with corneal trauma by vegetation, had not previously been commonly linked to contact lens wearers, he said.
With proper use, Dr. Levy said, the MoistureLoc formulation works effectively, so B&L explored the behavior of the solution under stressed conditions emulating common noncompliant practices.
“We know noncompliance occurs, but it’s nothing new, so our investigation focused on why it should be different with MoistureLoc,” he said.
Researchers first examined the results of a fairly common behavior called “topping off.”
Dr. Levy said that, in topping off, the contact lens wearer does not fully replace the lens care solution in the wells of the contact lens storage case, but rather continues to place the lens in the case after wear without discarding the used solution or cleaning out the case.
“They simply throw the lens in the case at night and add more solution as needed. As we simulated that situation, we found that after three or more cycles the solution showed reduced efficacy,” Dr. Levy said.
“We did this with control solutions too, and we did find this is a risky practice, no matter which solution is being used,” he added.
Although topping off proved to reduce efficacy of the solution, it still did not explain why Fusarium, of all possible pathogens, was surviving the disinfection process, Dr. Levy said.
Further study by Bausch & Lomb addressed evaporation of the solution.
“What you are typically doing with topping off is reducing the available solution and adding more of the fresh solution,” Dr. Levy said. “The MoistureLoc has a relatively high concentration of surfactants, or polymers, which we used as a comfort component in the solution. If the solution is allowed to evaporate in an open case, these polymers can form a film. We produced concentrations of MoistureLoc to emulate evaporative conditions that would concentrate the polymers in the formula and compared it to our MultiPlus product, which does not have the surfactant package in it that MoistureLoc does.
“When we challenged the concentrated solutions with Fusarium and Staph, we found the efficacy against both Staph and Fusarium fell off pretty sharply for MoistureLoc, but remained highly effective for MultiPlus,” Dr. Levy continued. “This told us that the MoistureLoc formulation, with this polymer package, was more sensitive to evaporation than a solution like MultiPlus.”
Taking a step further, investigators tested a polymer film similar to what would remain in a lens storage case after the MoistureLoc solution evaporated.
“We asked the question, can such a film support the Fusarium?” Dr. Levy said.
Dr. Levy said investigators added an isolate of Fusarium to test this possibility.
“We challenged the combination of the polymer film and Fusarium with varying strengths of MoistureLoc, once we had combined the two together, and found that viable Fusarium survived a challenge of MoistureLoc. The results indicated that Fusarium could survive such a challenge, even full-strength MoistureLoc,” he said. “This indicated that the polymer film in this formulation, under rare circumstances, could be contributing to these low rates of infections that have been reported around the world.”
For a contact lens wearer to be infected with Fusarium, there must be an inoculation of some form, Dr. Levy said.
Investigators found that in some cases Fusarium could be cultured from the tips and caps of bottles, as well as storage cases and lenses used by patients who reported infections, he said, indicating that the fungus had made the next step, the leap from the environment to the lens care system.
“This data aided our attempts to find out more about the relationship between this polymer film and the Fusarium organism in the clinical situation,” Dr. Levy said.
Once the tip of the bottle and the lens storage case become contaminated through the formation of the polymer film, the lens itself can become contaminated. This would then lend itself to inoculating the cornea with placement of the lens continuously over time, he said.
Independent risk factors for fungal corneal infection include overnight contact lens wear, steroid use and trauma, Dr. Levy said.
“We believe that a combination of the contamination, inoculation and ultimately specific patient susceptibility, when MoistureLoc was used in specific noncompliant ways, potentially led to an elevated risk of infection,” he said. “The absolute rate of infection is low based on the fact that this appears to be a perfect storm scenario creating an environment for an infection.”
It appears that a rare combination of factors coming together simultaneously may explain the disproportionate association of MoistureLoc with the Fusarium infections, Dr. Levy said.
Bausch & Lomb is continuing its investigation of the situation, he said.
It is challenging to keep up with the science of the Fusarium investigation, let alone its legal repercussions, noted Thomas L. Steinemann, MD, a spokesman for the American Academy of Ophthalmology.
The spate of infections in the United States has prompted legal actions including class action suits.
The Associated Press reported in April that attorneys in Miami and New York were seeking class action status for a lawsuit blaming ReNu with MoistureLoc for the fungal keratitis outbreaks. The Miami lawsuit represented six plaintiffs who are each seeking $75,000 in personal damages, according to the AP.
Regarding the liability issue, Mr. Zarrella said. “We have third party insurance we think is adequate for the size and nature of our business,” in a conference call with investors held May 15.
“I cannot really comment beyond that because we have to look at every case on its merits,” he said.
Restoring consumer confidence
The company announced May 15 that it planned to shift production from ReNu with MoistureLoc to its ReNu MultiPlus and ReNu Multi-Purpose solutions, which company officials state have long-standing safety records.
“We ask you to continue recommending these products to your patients,” Robert J. Moore, B&L’s general manager for U.S. Vision Care, stated in a letter to practitioners dated May 3.
Dr. Steinemann said the AAO is encouraging its members to reinforce proper lens care techniques with their patients.
“Even though lenses often say they can use no-rub solutions, we want patients to rub all solutions and disinfect their lenses properly, change their solutions, clean their cases and not sleep in their lenses,” Dr. Steinemann said. “These are all things in terms of patient advocacy we stress.”
Bausch & Lomb is still quantifying the financial impact of the decision to recall the MoistureLoc solution from the worldwide market, Mr. Zarrella said in the May 15 conference call.
“There are three buckets of costs that we will incur as a result of the Fusarium outbreak,” Mr. Zarrella said. The three elements are the cost of the recall, the lost sales of ReNu with MoistureLoc and the need for brand-building for the company’s other solutions, he said.
Costs associated with the voluntary recall could run between $50 million and $70 million, Mr. Zarrella said.
For more information:
- Brian Levy, OD, vice president and chief medical officer for Bausch & Lomb, can be reached at 1400 N. Goodman St., Rochester, NY 14609; 585-338-5212; fax: 585-338-0898.
- Thomas L. Steinemann, MD, can be reached at MetroHealth Medical Center/Ophthalmology, 2500 MetroHealth, 3rd Floor, Cleveland, OH 44109; 216-778-4253; fax: 216-778-7863; e-mail: firstname.lastname@example.org.
- Ronald L. Zarrella, chairman and chief executive officer of Bausch & Lomb, can be reached at Bausch & Lomb World Headquarters, One Bausch & Lomb Place, Rochester, NY 14604-2701; 585-338-6000; fax: 585-338-6007.
- Bausch & Lomb, maker of ReNu with MoistureLoc, can be reached at 1400 N. Goodman St., P.O. Box 450, Rochester, NY 14603-0450; customer service: 800-828-9030: Web site: www.bausch.com.
- Daniele Cruz is an OSN Staff Writer who covers all aspects of ophthalmology.
- Michelle Dalton, Managing Editor of OSNSuperSite.com, contributed to this article.