The 2023 eye drop recalls

Between May 2022 and April 2023, laboratories found a strain of Pseudomonas aeruginosa in 81 patients across 18 states that had never before been reported in the United States. Fourteen patients lost vision, four had an eye surgically removed, and four died within 30 days of a positive culture, according to the Centers for Disease Control and Prevention's final outbreak update¹, dated May 15, 2023.

What linked them was a bottle of over-the-counter artificial tears. The product was imported, preservative-free and sold in multidose bottles, and bacteria matching the outbreak strain turned up in opened bottles and in sealed ones. CDC investigators later called it the first time in the US that a manufactured medical product had carried this kind of drug-resistant organism to patients, in a report in Clinical Infectious Diseases².

That outbreak opened a year in which FDA warned the public about several groups of eye products and, in October, about 26 OTC eye drops sold under retail store labels. This history lays out what CDC and FDA found, what the recall records show and what changed in FDA's expectations for eye products. In keeping with GxRadar policy, it does not name manufacturers or brands.

How the outbreak was traced

Investigators were dealing with a carbapenem-resistant P. aeruginosa strain carrying two resistance enzymes, a combination CDC abbreviated as VIM-GES-CRPA. Isolates tested at public health laboratories resisted nearly every standard antibiotic class, the CDC page¹ says, though small subsets were susceptible to one newer drug, cefiderocol.

Patients were first identified from many specimen types. Of the 81, 21 were found from eye-related sites such as the cornea, 14 from respiratory samples, 13 from urine and 26 from rectal swabs collected for surveillance. Several clusters were in health care facilities, and CDC warned that these bacteria "have the potential to spread rapidly in healthcare settings," which helps explain infections outside the eye.

Evidence for the product link came from several directions. Patients reported more than 10 different brands of artificial tears, but one brand was the most commonly reported and was the only artificial tears product common to all four health care facility clusters. In a matched case-control study at the post-acute care facility with the most cases, patients who got the outbreak strain had five times the odds of having received artificial tears (crude matched odds ratio 5.0), the published investigation² found. Of 56 case-patients with brand information, 43 reported the same imported product, and bacteria from opened and unopened bottles were genetically related to patient isolates.

FDA's first warning

On Feb. 2, 2023, FDA warned consumers and clinicians to stop using two artificial tears products made by a manufacturer in India, and the company recalled all unexpired lots. FDA's warning³ said it recommended the recall because of violations of current good manufacturing practice rules, "including lack of appropriate microbial testing, formulation issues (the company manufactures and distributes ophthalmic drugs in multi-use bottles, without an adequate preservative), and lack of proper controls concerning tamper-evident packaging." The agency also placed the manufacturer on import alert, which allows FDA to stop its products at the border, after what it called "an inadequate response to a records request."

At the time, CDC counted 55 patients in 12 states. On Feb. 21, FDA extended the warning to an eye ointment from the same plant, and the company agreed to recall it the next day. The case count kept rising after the recall because confirming the strain took time; of 13 patients added in CDC's final update, six had specimens collected before the recall date.

A second warning, a different plant

October's warning had a different trigger. No outbreak was involved. FDA said on Oct. 27, 2023, that it was warning consumers not to buy, and to stop using, 26 OTC eye drop products sold under several retail and private labels, because of "the potential risk of eye infections that could result in partial vision loss or blindness," according to its notice⁴. The agency had recommended on Oct. 25 that the manufacturer recall all lots "after agency investigators found insanitary conditions in the manufacturing facility and positive bacterial test results from environmental sampling of critical drug production areas."

FDA said it had received no adverse event reports of eye infection linked to those products. It added one more product on Oct. 30 and updated the list again on Nov. 3 as distributors launched their own recalls. The agency's reasoning is in one line of the notice: "Ophthalmic drug products pose a potential heightened risk of harm to users because drugs applied to the eyes bypass some of the body's natural defenses." For more on how investigators document conditions like these, see our explainer on inspections, Form 483s and warning letters.

What the recall records show

GxRadar searched FDA's openFDA enforcement database⁸ for products described as ophthalmic, eye drops, artificial tears or lubricant eye drops. Records in FDA's 2023 weekly enforcement reports numbered 96, from 22 recall events. (Eye and ear products as a group are compared with other dosage forms in our piece on which kinds of products get recalled most.) Seven of the 96 were Class I, FDA's most serious tier, up from none in 2022 under the same search.

Not every 2023 eye recall was about contamination. Some were for products that ran low on their active ingredient, a label mix-up, or a maker that went out of business and could not finish stability studies. A sterility thread still runs through the list. Besides the outbreak recall and the October recalls, it includes a glaucoma drop whose caps had cracked, a line of homeopathic eye drops recalled for lack of sterility assurance, and a pharmacy-made eye solution after an FDA inspection found insanitary conditions.

Classification lagged the warnings. The outbreak recall was initiated at the end of January 2023, but its records were classified Class I only on July 14, 2023. The October recalls reached FDA's weekly enforcement report as Class I on Nov. 29, 2023. GxRadar's analysis of Class I records and our guide to how recalls work explain why the classification often trails the public warning.

What changed afterward

On Oct. 13, 2023, FDA published a draft guidance, "Quality Considerations for Topical Ophthalmic Drug Products," that applies to applications for brand and generic eye products and, according to the Federal Register notice⁵, to over-the-counter monograph drugs. On Dec. 28, 2023, the agency issued a revised draft that, per its notice⁶, addresses "microbiological considerations related to product sterility for all ophthalmic drug products" subject to manufacturing quality rules, including products not marketed under an application. FDA staff presented the guidance to generic makers in April 2024; the slides⁷ list topics from microbiology and visible particles to container design and stability.

CDC's published investigation drew a broader lesson about imports, concluding that the outbreak showed the need for "improved requirements for US OTC product importers," in the authors²' words. Many OTC eye products are sold without an individual FDA approval under the monograph system, which is why plant inspections and import screening carry so much weight. GxRadar's piece on store-brand OTC medicines covers how the same product can appear under many labels, and our recalls page tracks new eye product recalls as FDA classifies them. Questions about a specific bottle are best taken to a pharmacist, and our guide to checking whether a medicine was recalled shows where lot numbers are listed.