Firm linked to Gambia deaths failed to meet standards for other drugs four times in India this year

A day after the World Health Organisation on Wednesday issued an alert that four types of cough and cold syrups exported by an Indian pharmaceutical firm could be linked to the deaths of 66 children in Gambia, the Haryana Food and Drug Administration said it was preparing to test samples of these medicines.

The unit of Maiden Pharmaceuticals that manufactured the syrups is located in Haryana’s Sonipat. The medicines in question are Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup and Magrip N Cold Syrup.

Manmohan Taneja, the senior drug controller officer in Haryana, said these syrups had been manufactured exclusively for export and have not been sold in India. “We have consulted with the Drug Controller General of India and samples of cough syrups are being taken for testing,” Taneja said.

Following this alert, several state drug controllers also issued directions to their drug inspectors to test other locally manufactured cough syrups.

Naresh Kumar Goel, director of Maiden Pharmaceuticals, could not be reached for comment. This article will be updated if he responds.

This is not the first time Maiden’s medicine has failed drug tests. Over the last seven years, six medicines manufactured by the company have been found substandard, data published by the Food and Drug Administration in India shows. Of these, four drugs were tested this year alone.

Substandard medicines

At least two batches of Metomin, which is used to lower high blood sugar, failed the dissolution test in Kerala this year and a third batch failed last year, information on the Food and Drug Administration website shows. A dissolution test checks the average time an active pharmaceutical ingredient in a drug takes to dissolve or get released into the body.

This test is important for the safety and efficacy of a medicine. It explains its performance, how quickly or slowly the drug is released and whether it is accomplishing the purpose for which it is made.

The Metomin tablet, also referred as Metformin, is manufactured in the Maiden’s Sonipat unit.

In March, a batch collected from the Taluk Headquarters Hospital in Pattambi failed a dissolution test in a laboratory in Thiruvananthapuram, Food and Drug Administration data shows. Another batch collected from a primary health centre in Eranakulam in September failed the dissolution test in a laboratory in that city, data shows.

In March, Maiden’s Maical-D tablets, used to treat calcium and Vitamin-D deficiency, were found substandard during a test in a Thiruvananthapuram laboratory, Food and Drug Administration data shows. The tablets were also manufactured in Sonipat.

In June, another Maiden Pharmaceutical drug, Easiprin 75 mg, an aspirin for blood thinner to reduce risk of blood clots, was found substandard in a laboratory test in Thiruvananthapuram. The drug failed the Salicylic test, Food and Drug Administration data shows. Salicylate poisoning can lead to inflammation in the brain, seizures, fast breathing rate and abdominal pain.

In December 2021, Maiden Pharmaceutical’s Metomin tablets, used to lower high blood pressure, were tested in a Thiruvananthapuram laboratory and failed the dissolution test. The tablets had been collected for testing from a primary health centre in Edakkadu.

The primary health centre’s medical officer Lekshmi Dileep told Scroll.in that the drug was collected as part of a routine exercise, “We gave the drug to some patients but froze its use immediately after the laboratory report was communicated to us,” she said. “After that I have not seen that particular medicine in our PHC pharmacy.”

Kerala drug controller PM Jayan told Scroll.in that following the tests, the use of these drugs was halted in Kerala. All these reports were submitted to the Haryana drug controller and the Central Drugs Standard Control Organisation. “We are yet to hear back from them,” he said.

Jayan said ideally, Haryana drug controller should suspend or cancel the manufacturer’s licence for repeated offences. “We have no communication if they did that,” Jayan said. “I am issuing an order today to stop procurement and use of all Maiden products in our state.”

Gujarat case

In December 2015, the food and drug laboratory in Vadodara, Gujarat, submitted a report stating Maiden’s Macipro 250 tablet, used to fight bacterial infection, had failed a dissolution test.

The report prepared by Vadodara laboratory was sent to Bharuch drug inspector and stated that Macipro 250 failed standard drug quality as per the Indian Pharmacopoeia 2010 and Drugs and Cosmetics Act, 1940. The tablet is made of ciprofloxacin, which is an antibiotic used to treat bacterial infections. It is manufactured in Maiden Pharmaceutical’s Haroli unit in Himachal Pradesh.

Safikul Alam, owner of Zeal Pharma store in Piraman village in Bharuch, from where the tablet was collected by a drug inspector, said he later received a call from the Food and Drug Administration about the test reports. “I stopped selling that medicine after that call,” he told Scroll.in, adding that he does not remember how long the Food and Drug Administration took to test and report the sample. “It was several years ago.”

Whose problem?

Hemant Koshia, Gujarat Food and Drug Administration commissioner, said since the manufacturing unit for that drug was in Himachal Pradesh, Gujarat officials would have communicated the findings to them. “We usually refer to the concerned drug controller of the manufacturing state,” Koshia said. “That state has to investigate the case then, not us.”

However, he said he did not have specific information about Macipro 250 tablet test reports and would have to check.

Abhay Pande, president of All Food and Drug License Holders Foundation, an association of drug manufacturers, said when a drug fails repeated tests, the drug controller must withdraw it from the market and blacklist the manufacturer. “Despite failing tests again and again, it is clear there was no strict action against the manufacturer,” Pande said. “This has led to the death of so many children in Gambia.”

Taneja, the drug controller in Haryana where Metomin, Easiprin, Maical-D and the cough syrups are manufactured by Maiden, said the current focus of the authorities is testing and investigating the company’s cough syrups. “Right now we are not concerned with past cases,” he said.

Gambian deaths

The Gambian government reported the cough syrups to the WHO in September. “To date, the stated manufacturer has not provided guarantees to the WHO on the safety and quality of these products,” WHO stated in its alert on Wednesday.

All these syrups had high levels of diethylene glycol and ethylene glycol, the WHO said on Wednesday. Diethylene glycol and ethylene glycol are common impurities in cough syrups.

Excessive levels of these substances are associated with acute kidney injuries, altered mental states and, in some cases, death. WHO chief Dr Tedros Adhanom Ghebreyesus said in a statement on Wednesday that the global body “is conducting further investigation with the company and regulatory authorities in India”.

According to DR Gahane, joint commissioner in the Food and Drug Administration, Maharashtra, two standards of glycerol, glycerine or glycol are used for manufacturing purposes – industrial grade and Indian Pharmacopoeia grade, which meets the standards laid down by the Indian Pharmacopoeia Commission.

“For cough syrups, Indian Pharmacopoeia grade glycerol must be used,” Gahane said. “Levels of diethylene glycol and ethylene glycol are within permissible limits in it. Industrial-grade glycerine has high levels of diethylene glycol and ethylene glycol. which means the impurities are far higher than what is permitted.”

Pande, from the All Food and Drug Licence Holders Foundation, said the Indian Pharmacopoeia-grade glycol is more expensive than the industrial grade. “This encourages some manufacturers to opt for cheaper substitutes,” he said.

The WHO has advised countries to immediately notify it if cough syrup from the same manufacturer is found substandard.

Daara Patel, president of Indian Drug Manufacturers’ Association, said the Indian drug controller has to test and approve the medicine before its export. “At the same time, the importing country tests the product before use,” he said. He said it is surprising that checks were missed. Gahane, however, said it is the manufacturer’s responsibility to conduct those tests, not the regulator’s.

The Haryana drug controller said it is trying to contact vendors who supplied syrups manufactured by Maidens to other countries.