It was a scandal the Indian government was least prepared for. Just two months ago, a controversy erupted involving the death of 66 children in the Gambia allegedly after taking cough syrup imported from India. Last month, a similar case came to light in Uzbekistan. In a press release at the end of December 2022, Uzbekistan’s Ministry of Health stated that 18 of 21 children with acute respiratory diseases died after ingesting Dok-1 Max syrup manufactured by Marion Biotech Pvt Ltd, a company based in Noida, Uttar Pradesh.
The firm Quaramax Medical LLC had imported the syrup. Marion Biotech had a licence from the Food Safety and Drug Administration department in Uttar Pradesh to manufacture the cough syrup and tablets for export.
The Central government has been quick to deny any causal connection between the medicine and the deaths in the Gambian case, and results of the investigations in the Uzbek case are pending. All manufacturing activities in the two pharmaceutical companies have been stopped until further notice. Frontline’s email to Marion Biotech got no response until the magazine went to print.
The Uzbek incident
According to the Uzbekistan Health Ministry’s press note, a special working group it constituted began an inspection after children in Samarkhand who had consumed the syrup reported side effects. The main substance in the drug is paracetamol, and parents used it as an anti-cold remedy on their own or on the recommendation of pharmacists.
The working group concluded that the dosage—2.5-5 millilitres three to four times a day for up to seven days—was a “little above the norm for a child”. However, there were other problems too. Preliminary laboratory tests of a series of cough syrup samples detected ethylene glycol in them.
Ethylene glycol, the press note said, was poisonous, and 1.2 ml/kg of a 95 per cent solution could cause serious changes in a patient’s health, including vomiting, fainting, seizures, cardiovascular problems and acute kidney failure.
The working group dismissed seven officials for neglecting their duties, failing to analyse the deaths on time, and for not taking necessary precautions. Disciplinary action was taken against specialists too. Dok-1 tablets and medicines have been withdrawn from all pharmacies in Uzbekistan. Other issues, such as the question of accountability of medical personnel, are to be taken up at a board meeting of the Ministry, the press note said.
Indian response
India’s Health Ministry, responding to the Uzbek incident, stated on December 29 that the Central Drugs Standard Control Organisation (CDSCO) and the FSDA of UP had “immediately on receipt of the information” conducted a joint inspection of the Marion Biotech facility. Samples were sent to the Regional Drug Testing Laboratory in Chandigarh.
The results are awaited. The FSDA of UP told Frontline that the testing was in progress but they were unsure when it would be completed.
On December 27, Union Health Minister Mansukh Mandaviya ordered CDSCO and State Drug Control authorities to conduct joint inspections of some drug manufacturing units. Which these units were or on what basis they were identified were not stated. Two joint drug controllers were appointed to monitor the inspection process and ensure compliance with the Drugs and Cosmetics Act, 1940, and its Rules.
Deaths in the Gambia
In the earlier case, reported from the Gambia in West Africa in October 2022, the children had died allegedly after consuming cough syrup exported by Maiden Pharmaceuticals, based in Sonipat district of Haryana. The deaths were attributed to the company’s four brands, Promethazine Oral Solution BP, Kofexmalin Baby Cough Syrup, MaKoff Baby Cough Syrup, and Magrip N Cold Syrup.
The matter came to light after the World Health Organisation informed the Drugs Controller General of India (DCGI) that the use of medicines contaminated with diethylene glycol (DEG) or ethylene glycol (EG) was a contributing factor to the death of some children. The WHO issued a public alert in the first week of October (Medical Product Alert N 6/2022) about substandard paediatric medicines identified in Africa and named Maiden Pharmaceuticals as the company in question.
According to WHO’s analysis of samples, each of the four products contained “unacceptable amounts of diethylene glycol and ethylene glycol as contaminants”. All batches of these products should be considered unsafe, it said, until further analysis by national regulatory authorities.
India’s Health Ministry explained that Maiden Pharmaceuticals had obtained an export licence from the Haryana Drug Controller for the four products. The only country to which the company exports was the Gambia. Its products are not licensed for sale in India. Samples were collected and sent to the Chandigarh laboratory.
Uzbekistan’s Ministry of Health stated that 18 of 21 children with acute respiratory diseases had died after taking Dok-1 Max syrup manufactured by Marion Biotech Pvt Ltd, based in Noida, Uttar Pradesh. | Photo Credit: ANUSHREE FADNAVIS/Reuters
The CDSCO asked WHO to share details of the causal connection between the medical products and the deaths. According to WHO’s tentative results, India’s Health Ministry said, only four of the 23 samples were found to contain DEG or EG. The Health Ministry also said it was the usual practice for an importing country to test products for quality before allowing their use.
On December 13, in a letter addressed to Rogerio Gaspar, Director, Regulation and Prequalification at WHO, V.G. Somani, the DCGI, said that the technical team constituted by the government had sought details on causality on more than one occasion but had not yet received a reply. He said the Indian government had acted promptly by issuing a show-cause notice to Maiden for violation of Good Manufacturing Practices and by stopping the firm’s manufacturing activities on the basis of an independent inspection. The samples sent for testing by the DCGI were found to be compliant with specifications and neither DEG nor EG was found in any of them.
According to the DCGI, WHO had deduced the cause of death prematurely without waiting for an independent verification. It also stated that WHO’s statement in October 2022 was “unfortunately amplified by the global media which led to a narrative being built internationally targeting the quality of Indian pharmaceutical products”.
This had adversely impacted the image of Indian pharmaceutical products globally, and caused “irreparable damage” to the supply chain of pharmaceutical products and the “repute of the national regulatory framework”.
Somani claimed, citing media reports, that the Gambia had informed India that there was no causal relation between the use of cough syrup and the deaths, and that some of the children who had died had not taken the syrup.
The Gambian version
A Gambian parliamentary inquiry report released on December 20 says otherwise. Frontline has a copy of the report.
On October 26, the National Assembly of the Gambia appointed a Select Committee to conduct a full-scale parliamentary inquiry into the acute kidney infection (AKI) and other related deaths. The Medical Control Agency (MCA) of the country’s Health Ministry told the committee that quality control testing of samples in Switzerland showed unacceptable levels of DEG and EG and these contaminants were linked to the AKI that reportedly killed more than 66 children.
Atlantic Pharmaceuticals, the importer, was licensed by the MCA. This was its first import from Maiden Pharmaceuticals. The imported products were inspected and everything was found satisfactory; all the products had come with the required certificate of analysis from the manufacturer, indicating that the products were of good quality and fit for use.
Between June 4 and November 6, 2022, eight suspected cases, two probable cases, 82 confirmed cases, and 70 deaths (case fatality rate of 85 per cent) because of AKI were recorded in the country. The majority of cases were male and children below three years of age.
A 46-month-old boy who was admitted to the Emergency Pediatric Unit (EPU) in Banjul, the capital, on July 7 with vomiting and fever was the first case of AKI. His mother noticed that he was not “making urine”. By July end, the EPU had attended to 21 patients with a similar problem. Of 66 children who were admitted with AKI, 63 died, two survived, and one was discharged against medical advice. The two survivors had taken only one dose of one of the four drugs in question.
Most of the blood samples showed high levels of paracetamol. Additional samples were sent to Ghana, Switzerland, and France for investigation. The preliminary toxicology report from Ghana showed that of nine drug samples tested, eight (89 per cent) had propylene glycol, two had EG, and one DEG. The Swiss laboratory analysis showed “proper quantities of these compounds which turned out to be unacceptably high”.
The MCA then demanded that both those products and all other products of Maiden be suspended. The Ministry also banned paracetamol syrup which resulted in the “crashing down of number of AKI patients presenting at the hospitals”.
The Ministry issued another ban on September 16 to include Promethazine syrup, after which the number of children with AKI was further reduced. On September 29, all banned drugs were recalled from pharmacies. A consultant nephrologist told the committee that as soon as the drugs were taken out of the community and pharmacy shelves, the cases stopped coming.
The West African Postgraduate College of Pharmacists conducted an investigation at the request of the Select Committee and came to the conclusion that Maiden had failed to provide adequate quality assurance. At the Gambian end, the damage could have been minimised if there had been a robust pharmacovigilance unit at the MCA, it said.
Of 14 pharmaceutical importers and drug stores inspected by the Select Committee, only one, Pharma Star Pharmacy, had bought its products from Atlantic Pharmaceuticals. Pharma Star said as soon as it learned about the deaths due to the drugs, it recalled all the medicines.
Atlantic Pharmaceuticals was established in 2019 and imported mainly from two Indian manufacturers, Maiden Pharmaceuticals and Lexine Technology. The first imports from Maiden arrived in April 2022 and the second in June 2022, with the contaminated drugs. Of 10 syrups the Ministry collected, four were found to be contaminated. The four were Maiden’s products.
“All cases of AKI were linked to the consumption of contaminated medical products imported by Atlantic Pharmaceuticals and manufactured by Maiden Pharmaceuticals Ltd India,” concluded the Select Committee. “The Select Committee is convinced that Maiden Pharmaceuticals Ltd is culpable and should be held accountable for exporting the contaminated medicines that were linked to the deaths of at least 70 children in the Gambia.”
While opposition parties in India raised the issue of the drugs causing deaths, government spokespersons downplayed the issue of contamination and pointed out that causality had not been established.
DEG deaths in India
Deaths due to DEG contamination are not new to India. As documented by Dinesh Thakur and Prashant Reddy in their book The Truth Pill, there have been at least half a dozen cases of DEG poisoning in India.
In 2019, 12 children died in Ramnagar, Jammu district, after being given a cough syrup manufactured by a company in Himachal Pradesh. All the children were diagnosed with AKI. Samples of the syrup tested positive for DEG, which is known as an industrial solvent used in the manufacture of brake fluids, cosmetics, and lubricants.
Given the Gambian and Uzbekistan cases now, as well as earlier domestic DEG poisoning cases, it is crucial that pharma companies are monitored more rigorously and held to account.
The Crux
- Uzbekistan’s Ministry of Health has stated that 18 of 21 children with acute respiratory diseases died after ingesting Dok-1 Max syrup manufactured by Marion Biotech Pvt Ltd, a company based in Noida, Uttar Pradesh.
- India’s Health Ministry stated on December 29 that the Central Drugs Standard Control Organisation (CDSCO) and the FSDA of UP had “immediately on receipt of the information” conducted a joint inspection of the Marion Biotech facility. Samples were sent to the Regional Drug Testing Laboratory in Chandigarh. The results are awaited.
- In an earlier case, reported from the Gambia in West Africa in October 2022, the children had died allegedly after consuming cough syrup exported by Maiden Pharmaceuticals, based in Sonipat district of Haryana.
- The Central government denied any causal connection between the medicine and the deaths.
- A Gambian parliamentary inquiry report released on December 20 says that Maiden Pharmaceuticals Ltd should be held accountable for exporting the contaminated medicines that were linked to the deaths of at least 70 children in the Gambia.
