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World Health Organization (WHO) issued an alert on October 5, 2022, advising the Drug Regulatory Authorities and the public to stop consumption of four medical products made by an Indian pharmaceutical company, Maiden Pharmaceuticals. The WHO claimed that the four cold and cough drug products contaminated with diethylene glycol and ethylene glycol has caused death of 66 children in Gambia, a West African country. The death number has gone up to 70. The preliminary inquiry by Central Drugs Standard Control Organization (CDSCO), country’s apex drug regulatory authority, revealed that the manufacturer is licensed by the Haryana State Drugs Controller. The licence is to manufacture Promethazine oral solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup and Magrip N Cold Syrup for export purpose only. These products are not marketed in India and there is no direct impact on India’s population. Though the regulatory authorities started taking actions, India is awaiting report establishing causal relationship to death and medical products. The WHO reports that the laboratory analysis of the cough syrup confirmed the presence of ‘unacceptable’ amount of diethylene glycol and ethylene glycol. Both are toxic and can lead to acute kidney injury. Joint inspection of CDSCO and Haryana State Drugs Control Authority found several lapses by the company: batch number was not given, manufacturer’s name, manufacturing date and quality details of propylene glycol was missing. Even expiry date of the ingredient was missing on the label.
For the first time the issue of diethylene glycol surfaced in USA in 1937. The incidence is known as Sulfanilamide Elixir disaster. Sulfanilamide was the wonder drug of the period. It was used to treat streptococcal infection. It was available as tablet and powder form. There was a demand for liquid product. In June 1937, the company experimented and found that the Sulfanilamide was soluble in diethylene glycol. The company’s quality control tested the product for flavour and appearance and found it satisfactory. The company has shipped its product to all over the country. The new product had not been tested for toxicity.
Elixir of Sulfanilamide containing the poisonous diethylene glycol killed more than 100 persons and many of them were children. The incidence made the congress to realize the need to establish drug safety before marketing and to enact the pending food and drug law. The Federal Food, Drug and Cosmetics Act of 1938 was passed by the congress. The new Act required the new drugs to be shown safe before marketing. Thus began a new system of drug regulation. The Act 1938 prohibits the distribution and use of any drug or drug product without filing New Drug Application (NDA) and approval of FDA. It becomes the responsibility of FDA to either grant or deny permission. The Act of 1938 required manufactured pharmaceutical product to be safe for human use. It did not require them to be efficacious. The need of drugs to be effective was introduced much later.
The first Indian incidence of diethylene glycol poisoning was reported in 1986 where administration contaminated glycerol caused 14 deaths at government run JJ Hospital in Mumbai (then it was known as Bombay), during 21 January and 7 February. Glycerine was the routine medicine for the treatment of oedema. It was used to combat swelling. This led to the inquiry by Justice Lentin though nothing happened and no action was initiated either to prevent such occurrences. In 1998, another case of diethylene glycol contamination was reported. The cough syrup contaminated with 17.5% DEG has been implicated in 33 deaths among 36 children aged less than 6 years were hospitalised with acute renal failure between April and June 1998. However, how DEG came to the cough syrup was not known.
It reminds us of a three-year-old incidence occurred in Jammu and Kashmir which caused death of 14 infants after consuming spurious cough syrup manufactured by Digital Vision Pharmaceutical Company. This happened during December 2019 and January 2020. The presence of diethylene glycol (DEG) was detected in the sample of propylene glycol used in the syrup. Though almost three years on no charge sheet has been filed. The DEG contamination case was first reported by the Post Graduate Institute Medical Education and Research (PGIMR), Chandigarh. It was not just the issue of one product or one company.
Following the episode of DEG poisoning there are many initiatives by different agencies including government. Haryana government formed a committee for detailed investigation. The Haryana has given licence for manufacturing. This licence is for export only and thus India is saved from this episode. The committee will investigate as to what level supervision has been lacking and who is responsible for this lapse which has caused this tragedy. It is a big blow to India’s image as ‘Pharmacy of the World’ that supplies medicine to all other countries. The Central government has stopped the export of company’s syrup. The export of syrup of this company to other major countries is also stopped. The Pharmaceutical Export Promotion Council has suspended its certificate of approval for export. Maharashtra government has ordered the recall of all oral liquid products made by this company.
The tragedy has taken about 70 lives. The parents who have lost their children are deeply distressed. No amount actions can compensate the loss of the parents. But most important is to take steps to prevent such occurrences. Even after repeated occurrence of such incidents, it is continuing. First happened in India in 1986, still our manufacturing process is not full proof. There could be some or other reasons, but truth is we have failed to prevent the avoidable incidence. It is unfortunate this has happened even after 36 years of first happening. No compete strategy? How the syrup error was not caught?
It reminds the sensitization of our teachers emphasizing the importance of pharmacists. If a surgeon commits a mistake, one person may die on the operation table, if a pharmacist makes a mistake in manufacturing several persons consuming that medicine are likely to die. Though it is yet to be investigated to know the person responsible to cause the incident, mostly it is ignorance of hazards of the person responsible in manufacturing products. There are several incidences of using diethylene glycol as solvent. It is used mistakenly in several countries including India. Do the teachers tell or discuss such incidences of drug tragedy or disaster in the class. They are not in the syllabus or curriculum. Can they be made part of the curriculum? Mostly, thalidomide incident is discussed by the teachers. Thalidomide incident was the issue of drug. But the problems of formulation are rarely given importance in teaching. The present article narrated few examples which can be used as tool to educate and sensitize the pharmacy students to be vigilant that such harmful substances are not included in the formulation.
Education is the most powerful tool to make a change. Not only it catalyses change, it makes them sustainable too. The teachers have the tremendous opportunity to use this type of incidents as an example while teaching formulation. It is not the drug alone but the whole drug product should be considered. The people use medicines to safeguard their health or promote health, but improperly formulated and manufactured medicinal products can harm greatly. The sensitized students who would be the future professionals would not be ignorant and would avoid the occurrence of such incidences. This is an example of problem-based learning. We can make the medical products safer!
(Authors are professors, C. L. Baid Metha College of Pharmacy, Thoraipakkam, Chennai 600 097)
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