MP cough syrup deaths linked to toxic DEG: why it has been long under the scanner

What is DEG and how does it end up in syrups?

Diethylene glycol — and sometimes ethylene glycol — can be present in certain syrups as contaminants. These are toxic to human beings and can result in abdominal pain, vomitting, diarrhoea, inability to pass urine, headache and altered mental state. More importantly, it can lead to acute kidney injury that may be fatal in children.

Many syrups, especially the ones that contain paracetamol, much like Coldrif, use propylene glycol as a solvent. This compound also has industrial uses as an antifreeze, heat transfer fluid and emulsifier among others. Hence, there are two different grades of this raw material available — an industrial grade that may contain higher levels of DEG and a pharmaceutical grade where the contaminant level has to be strictly below the permissible limits. DEG, or even ethylene glycol, can enter syrups when either industrial grade propylene glycol is used for the manufacturing of the medicines or the companies fail to properly test the raw materials for contaminants before use.

A history of DEG poisoning in India

At least 14 children from Madhya Pradesh have died due to kidney failure and another nine continue to receive treatment in various hospitals in Nagpur. This cluster of cases was first picked up by the surveillance teams in Nagpur.

An alert was raised by the World Health Organisation (WHO) in 2022 after reports of 70 children dying in The Gambia and another 18 dying in Uzbekistan after consuming syrups manufactured by a Haryana-based and an Uttar Pradesh-based company. This prompted the government to mandate a testing of all batches of syrups meant for export at Central or State drug-testing laboratories. One of the experts quoted later, said: “Why should only the syrup meant for export be tested? Why is the regulation different for our own people?”

At least 17 children had died in Jammu and Kashmir’s Ramnagar in 2020 after consuming a cough syrup manufactured by a Himachal Pradesh based company. The syrup was later found to contain 34.97 per cent DEG. Another 33 children had died in Gurugram in 1998 after consuming a syrup manufactured by a company based in the same district. The syrup was later found to contain 17.5 per cent DEG. Around 150 children were brought with acute kidney failure to Delhi’s Kalawati Saran Children’s Hospital, which rang the alarm bells.

What are the regulatory gaps that have led to repeated incidents?

Experts on drug regulation, on condition of anonymity, said that there are several regulatory gaps with easy fixes that can be put in place to avoid such incidents in the future.

One, testing of propylene glycol at the ports. One of the experts said that there are only two sources of propylene glycol in the country — Manali Petrochemicals Limited that has manufacturing units in Manali and Chennai and products imported from China. A simple fix would be to test the raw materials coming into the country at the port itself rather than asking the companies to individually test them at their manufacturing units.

Two, disallowing manufacturing of these syrups by companies that do not have gas chromatography. A 2001 paper by the World Health Organisation (WHO), following the 1998 DEG poisoning incident, said that thin layer chromatography alone may not identify DEG contamination and gas chromatography may be needed. The expert said that while the bigger manufacturing units in the country do have facilities to conduct gas chromatography testing, many small companies do not. They said, the drug regulators, therefore should not allow these companies to manufacture the syrups at all. “The companies are supposed to test the raw materials and finished products. They are supposed to maintain records of these tests for inspection when needed, so companies may not conduct the appropriate tests at all,” the expert said.

Three, complete ban or restriction on syrups. The expert said that propylene glycol as solvent is only needed for the manufacturing of syrups, which are usually sweeter in taste and more appealing to children. Suspensions of medicines such as paracetamol can be equally as effective and do not require the use of propylene glycol at all.

Four, restriction on over the counter sale of the syrups. Another expert on drug regulation said that there should be a restriction on the over the counter sale of these syrups as parents can easily get the medicine for their children without a doctor’s recommendation. These cough syrups are ideally not supposed to be prescribed to children under the age of four years, they said.

What are the actions that have been taken?

After the incident came to light, the Tamil Nadu government initiated action against the company Sresan Pharmaceutical. Madhya Pradesh suspended three officials from its state Food and Drug Administration. And, several states have banned the use of the syrup Coldrif.

Six states have also initiated a risk-based inspection of 19 manufacturing units. These inspections are undertaken based on whether the company in the past has produced not of standard quality drugs or has had other violations.

The country’s apex drug regulator has urged drug manufacturers to comply strictly with the new Schedule M — a list of good manufacturing practices at par with what is followed globally. While around 2,000 of the country’s biggest pharmaceutical manufacturing units were already compliant with the WHO Good Manufacturing Practices, the government asked even the smaller 8,500 units to comply with the requirements. The smaller companies have time till December this year to implement the new norms.