CDC links India-made eye drops to outbreak of rare strain in US

The outbreak strain — VIM-GES-CRPA, a rare strain of the extensively drug-resistant Pseudomonas aeruginosa bacterium, and never been reported before in the US  — has been detected in 68 cases from 16 states, according to the CDC. Of these, 37 patients were linked to four healthcare facility clusters. Three people have died and there have been 8 reports of vision loss and 4 reports of enucleation (surgical removal of eyeball).

The CDC conclusion is based on its investigations at healthcare centres from where the cases were reported and testing of opened bottles of the eye drops.

In February this year, the company had initiated a voluntary recall of the eye drops.

The CDC tested open bottles of the eye drops and found contamination in multiple lots.

Asked if the contamination could have happened during transportation or storage, the CDC, in an email response to The Indian Express, said this was unlikely.

“If the product was not sealed completely, contamination could occur during transportation or storage. However, the widespread nature of the outbreak strain suggests a point source and not contamination at multiple points along storage and distribution pathways,” the CDC said.

At the healthcare facilities, the CDC conducted a case-control study using patient records. According to the study, individuals with the infection were five times more likely to have used an artificial tear drop. The CDC clearly states that this establishes an association between the two, but not necessarily a causal link.

“Based on the findings of the investigation, the organism appears to have spread via a contaminated point source (eye drops) with possible secondary transmission among contacts in some healthcare settings,” the CDC stated in its email.

Could the contamination in the opened bottles have been introduced during use? “If the outbreak strain is identified from unopened bottles, then there is a suggestion of contamination before use,” the CDC stated in its reply.

Sealed bottles of the eye drops were sent for testing to the US Food and Drug Administration. On being asked about its findings, the FDA, in an email, said: “The U.S. FDA takes its responsibility seriously to ensure the medical products the American public relies on meet our rigorous standards for quality, safety and effectiveness. The FDA continues to investigate this issue and the agency generally does not publicly discuss ongoing compliance matters.”

The Indian drug regulator, which had collected control samples from the manufacturing plant near Chennai, found no contaminants in the eye drops, according to sources. Control samples are samples from the batches exported and maintained by the company as part of quality control processes.

Sources in the Union Health Ministry said similar samples were collected by the US FDA in India and were tested at an approved laboratory in Bengaluru.

These samples also did not have contaminants, a Health Ministry official said.

An inspection conducted by the US FDA of the manufacturing site in India found several deficiencies: the manufacturer released the active pharmaceutical ingredients based on certificate of analysis from the supplier without verifying it for identity, purity, or strength; bottles, caps, other packaging materials were released without testing for sterility; batches were released to the market, including the US market, without review from quality control unit; systems for cleaning and disinfecting aseptic areas were found to be deficient; and systems for monitoring the environment of aseptic areas were also found to be deficient.

Phone calls and emails by The Indian Express to the company for comments did not elicit a response.

A joint investigation by India’s apex drug regulator and state drug controller in February had found that the company carried out “media fill validation” biannually for which the records were verified.

The media fill validation test is used to check for microbial contamination of manufacturing surfaces by exposing growth medium to the areas. The record verification also found that the company had undertaken yearly stability studies, where the products are placed in controlled environments to check whether they meet the stipulated specifications.