India’s drug regulatory authorities have ordered Maiden Pharmaceuticals, the Haryana-based firm that had exported paediatric syrups allegedly linked to child deaths in The Gambia, to stop all manufacturing, citing process violations that could impact the quality and safety of products.

An inspection of the firm’s plant and documents has revealed that the company is not meeting drug production rules “across its manufacturing and testing activities”, the Central Drugs Standard Control Organisation (CDSCO) and Haryana drug regulators said, ordering the shutdown.

“In view of the seriousness of the contraventions and potential risk to the quality, safety and efficacy of drugs being produced, all manufacturing activities of the firm (are) being stopped with immediate effect,” an order signed by the CDSCO and Haryana regulators said.

The CDSCO, the country’s apex drug regulatory authority, had ordered the inspection last week after the World Health Organisation issued a global alert linking the deaths of 66 children in The Gambia to four syrups supplied by Maiden.

The WHO said analysis on samples of each of the four products had found unacceptable amounts of diethylene glycol and ethylene glycol as contaminants whose toxic effects include acute kidney injury that may lead to death.

The Haryana FDA inspection report has said the firm did not perform quality testing on propylene glycol for diethylene glycol and ethylene glycol. Propylene glycol was a key substance used during the manufacture of the drugs.

The firm also did not perform process validation and analytical method validation for the drugs in question and failed to produce in-process testing reports for the products, the report said. The two validations and in-process testing results are designed to help maintain production integrity.

The batch numbers, the manufacturer’s identity, and manufacturing and expiry dates of the chemical excipients — including propylene glycol — used in the drugs were not found on the purchase invoices, the inspection report said, putting a question mark on the source of the raw materials.

“The findings reflect a failure of the drug regulatory system, both at the central and state level,” Mahesh Zagade, former commissioner with Maharashtra’s food and drug administration department, who was not associated with the inspection, told The Telegraph.

Zagade and others say the inspection’s findings reinforce concerns about how central and state regulators had permitted the company to export even after several state regulators and Vietnam’s national regulator had flagged quality concerns about its products over the past decade.

Kerala state regulators have since December 2021 declared two batches of metformin — a drug used to treat diabetes, one batch each of aspirin, and a combination of calcium carbonate and vitamin D — from Maiden as substandard.

Between 2011 and 2013, Maiden was among over 40 Indian companies accused by Vietnam regulators of supplying poor quality medicines.

The Union health ministry, announcing the CDSCO probe of Maiden last week, had said the company had produced the four paediatric syrups only for export and supplied them only to The Gambia. The four products are Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup and Magrip N Cold Syrup.

The probe has also detected discrepancies relating to the manufacturing dates printed on the products, the actual batch manufacturing dates and production approvals. For instance, Kofexmalin has a printed manufacturing date of December 2021, but batch manufacturing record shows production started on February 26, 2022, and was completed on March 1, 2022. The firm received permission for the production on February 24, 2022.

The Union health ministry on Wednesday announced a four-member expert panel that will examine and analyse reports received from the WHO on the investigations into the deaths in The Gambia of children who had received paediatric syrups from Maiden.

The panel led by Y.K. Gupta, a senior pharmacologist and chair of the national standing committee on vaccines, will examine reports of the adverse events and the tests conducted on the samples of medicines, and evidence, if any, for a causal relationship between the drug and adverse effects.