The Indian government has halted the Maiden Pharmaceuticals plant that produced the cough and cold syrups that WHO says were tainted with toxic chemicals – possibly linked to the recent deaths of some 66 children in The Gambia.

A senior WHO official confirmed that Indian government health authorities had shut down the plant after WHO shared data showing that samples of four syrup formulations, produced by the firm and tested by the global health agency, contained diethylene glycol and/or ethylene glycol, which are toxic to humans.

Speaking at a WHO press briefing on Wednesday, WHO’s Mariangela Simao said that WHO had requested the suspension of production at the Haryana-based facility, following tests at a Swiss and French reference laboratories, which confirmed the contamination in the four syrup formulations.

“WHO did recommend to the drug control controller in India to suspend the manufacturing in the plants that were involved in this incident, and we hear that this has been done and that the production is suspended,” Simao said.

BREAKING: All the manufacturing activities of Maiden Pharmaceuticals is being stopped with immediate effect under section 22(1d) of Drugs and Cosmetics Act 1940, and Rules framed thereunder till further order, in public interest, without prejudice to further action in the matter

— Himani Chandna (@ChandnaHimani) October 12, 2022

India media reported that the government shut down the plant after WHO shared the formal laboratory results (Certificate of Analysis) with Indian authorities. The government has announced the creation of an expert to further analyse the CoAs provided by WHO, and conduct a state investigation into the reported contamination.

WHO first issued alert on 5 October

WHO first issued an alert about the tainted products on 5 October, stating that laboratory analysis of the medicines which were exported to The Gambia “confirms they contain unacceptable amounts of diethylene glycol and ethylene glycol as contaminants.

“To date, these four products have been identified in The Gambia, but may have been distributed, through informal markets, to other countries or regions,” the global health agency reported.

Speaking to reporters a day later, WHO’s Director General Dr Tedros Adhanom Ghebreyesus said the four cold and cough syrups produced by the firm “have been potentially linked with acute kidney injuries and 66 deaths among children.

“The loss of these young lives is beyond heartbreaking for their families,” the WHO director-general added, saying that the agency was investigating further “with the company and regulatory authorities in India.”

WHO tested the tainted medicines for contamination in Swiss and French laboratories

The Gambian Health Ministry has been investigating an unusual cluster of childhood deaths from acute kidney failure since July. In late September, health authorities concluded that tainted paracetamol or promethazine cold or cough syrups were the most probable cause of deaths in at least some of the cases. The ministry had also investigated high E-coli bacteria levels, due to recent flooding and sewage exposures, as another possible cause.

Following the initial laboratory analysis of the medications in The Gambia, which turned up the chemical contamination, WHO obtained samples of the formulations that had been administered to children who were were hospitalized, and sent them for testing in WHO reference laboratories, Simao said at Wednesday’s briefing,

“23 different samples were sent to our reference labs. One of them is in Switzerland in France,” said Simao. “And then we had unfortunate findings of the four pediatric formulations that had contaminations.

Two products are very old formulations

Two products of the products tested are also “very old” cough and cold formulations, which have known contamination risks in the production cycle, Simao also noted.

“They have been involved in other contaminations that led to serious health problems and deaths since 1930,” Simao added. “It’s a very well known history of diethylene glycol we call it DEG, and ethylene glycol we call it EG – they should never be in anything that human beings ingest.”

There is now “a very in-depth investigation of these deaths by the government of The Gambia, by international partners including WHO, who are supporting the investigation,” she said.

But separate from the investigation into the precise cause of the children’s deaths, “once we detect these products [DEG and EG] in a medicine or something that people will ingest… they should be banned from the market.

“WHO has procedures and one of them is the global medical alert that aims to inform national regulatory authorities when we notice problems with a product, and to also inform the public.

“And also we have to raise the alert in terms of [the possibility that] this product may be circulated in other countries. The information we received from the drug controller in India was that dispatches were manufacturer exclusive for the danger but we don’t rule out the possibility that through unregulated markets that it has reached other countries.”

She noted that several other countries in the African region have in turn issued their own alerts “and are proactively doing surveillance, trying to identify if these products are in the market.”

Meanwhile, she said, WHO is “working very closely with the Indian authorities for the full investigation into the manufacturing process itself and the ways this product reached the market.”

Specifics of WHO warning

The four Maiden Pharmaceutical products specifically called out in the WHO alert include:  Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup and Magrip N Cold Syrup.

“To date, the stated manufacturer has not provided guarantees to WHO on the safety and quality of these products,” WHO said adding, “Diethylene glycol and ethylene glycol are toxic to humans when consumed and can prove fatal.

“Toxic effects can include abdominal pain, vomiting, diarrhoea, inability to pass urine, headache, altered mental state, and acute kidney injury which may lead to death. All batches of these products should be considered unsafe until they can be analyzed by the relevant National Regulatory Authorities. The substandard products referenced in this alert are unsafe and their use, especially in children, may result in serious injury or death.”

Substandard medicines a major problem in Africa

Substandard medicines are a widespread problem in Africa and parts of South-East Asia.  According to one recent estimate, in some parts of Africa, up to 70% of medicines may be either fake or substandard.

There are widespread hopes that the pending establishment of the Africa Medicines Agency (AMA) could help counter this longstanding trend by harmonizing drug regulatory review and approvals across the continent – thereby strengthening the capacity of poorly-resourced countries to supervise its medicines markets.

So far, some 33 of the African Union’s 55 member states have either signed and/or ratified the treaty on the African Medicines Agency. Just this week, South Africa’s cabinet announced it would submit the treaty to its parliament for ratification. The Gambia is one of the 22 countries to have neither signed nor ratified the agreement.  See related AMA coverage here,

African Medicines Agency Countdown

Image Credits: WHO, World Health Organization .