New Delhi: The production of all 14 ophthalmic solutions has been stopped at Tamil Nadu-based Global Pharma Healthcare – a firm whose product has been potentially linked with contamination causing blindness and one death in the US. As many as 55 people were reported to be affected.
Global Pharma Healthcare initiated the recall of the product in question, ‘Artificial Tears’, on February 1. The drug is a lubricant ophthalmic solution and an over-the-counter product. Tamil Nadu drugs controller P.V. Vijayalakshmi told The Wire on February 4 that the production of all ophthalmic solutions have been upheld till the investigation is not completed. For other products, she clarified the production will continue.
“We have collected many control samples of the same batches which were sent to the US. The samples of raw materials used in making those batches have also been collected for investigation,” she added. The samples have been sent to a government lab based in Tamil Nadu.
The US’s Centres for Disease Control and Prevention (CDC) issued an alert on February 1 saying it had found the product contaminated with an extensively drug-resistant strain of Pseudomonas aeruginosa bacteria. Global Pharma Healthcare distributed this product through EzriCare, a US-based firm.
Vijayalakshmi said the particular drug was only meant for export. Asked if she could say with certainty that it was not sold under a different brand name in India, she replied, “Yes.” About the company, she said, “It has been in business for a long time.”
She added this was for the first time that an adverse report has been received against the company – no complaint had been received against any product of the company either for being substandard or adulterated. Asked when was the last time the company had been inspected before this event, she replied, “very recently”, without giving the specifics.
“As soon as we got information [about this event], we proceeded to conduct raids at the company’s premises. It started at 7 pm on Friday [February 3] evening and ended at 2 am on Saturday [February 4] morning,” she said.
She said while doing physical inspection of the plant, the inspectors could not find anything which could have given a clue to the possible contamination – no physical lacuna was found. Now the authorities are waiting for the results from the laboratory.
There were some media reports on February 3 evening mentioning that a team of drug control authorities was on its way to conduct raids. Could this have hampered the sanctity of the investigation? She said she was not aware of any reports. She also added that the department is waiting to hear more from the CDC as its investigation is also ongoing – something that the US body also mentioned on its website.
“[The pathogen] recovered from [the] opened bottles could represent either bacterial contamination during use or during the manufacturing process. Testing of unopened bottles of EzriCare Artificial Tears is ongoing to assist in evaluating for whether contamination may have occurred during manufacturing,” the CDC said.
The bacteria recovered from the bottle is resistant to an entire range of antibiotics – the CDC named at least 12. In other words, all the commonly available antibiotics will not be able to treat the infection caused by the bacteria. The CDC found that the bacteria was susceptible to only cefiderocol – an antibiotic that is used to treat complex infections when no other drug works.
The contamination in eye drops is not very uncommon. There are multiple ways that eye drops can become contaminated, one being less-than-adequate handling of eye drops. According to the American Academy of Ophthalmology, “Once the sterile seal of the bottle is broken, there is concern for contamination, especially if the tip of the bottle touches your eye or any other surface.” Most eye drops contain preservatives to impede the growth of any foreign pathogens. And they should be able to prevent contamination at least till the expiration date “regardless of when it was opened.”
But this product in question was preservative-free, according to the CDC. At times, preservatives are not added to prevent irritation. And those eye drops which don’t contain them are more prone to invasion with other pathogens, and therefore, they require much more careful handling.
However, what is significant in this case is the species of a particular pathogen found – Pseudomonas aeruginosa . Many papers, including this and this, suggest that it is not a common source of contamination in eye drops. Also, a Pseudomonas bacterial infection is generally acquired at hospital settings. It is one of the most common bacteria, among all, causing hospital-acquired infections originating in ICUs where patients are severely sick and susceptible to all sorts of infections.
“This bacteria is found in the environment. In ICUs patients are sick and with weakened immune systems they are more prone to acquiring this bacterial infection which may not commonly cause problems in other settings,” said an Indian Council of Medical Research (ICMR) scientist, who is an expert in antimicrobials, wishing anonymity.
On the other hand, the CDC alert did not make any mention about the specimens collected from such high-grade hospital settings. It said that the specimens were collected from the patients, not those who got treated in inpatient departments, the outpatient department or OPD.
What could possibly explain this – could the patients, using this drug outside such high-grade hospital settings, have acquired infection from their respective environments? “This might be true for one or more [patents]. It is difficult to believe that it could be true for so many of them,” the ICMR scientist said.
The scientist added that there might be a possibility that during manufacturing, enough caution was not exercised. “If the environment was not infection-free during manufacturing, then the Pseudomonas might have crept from there also,” the scientist said. “Even during packaging and transportation of eye drops, this bacterial invasion may occur even due to a small slip,” the scientist added.
While only a proper investigation can throw a light on many of these unknown issues, Pseudomonas is known to wreak havoc when it gets a chance to enter the human body through the eye. “When introduced into the cornea, however, as in penetration by a foreign body or in contaminated medicines, it acts with extreme virulence, in many cases causing blindness and even necessitating enucleation [removal of eyes],” W.H. Spencer, a student at the University of California’s School of Medicine wrote this in a paper way back in 1953.
The fact that CDC says in its alert that the bacteria was found in not just corneal samples, but also in sputum, urine, blood and rectal swabs explains how the infection caused by this bacteria had spread. And the patients reported not only two types of eye infections – keratitis, endophthalmitis – but also respiratory infection, urinary tract infection, and sepsis, which is a pointer towards the severity of the infection that the pathogen caused.