The Haryana government has halted all drug production at the Sonipat factory of Maiden Pharmaceuticals, a week after the World Health Organization (WHO) potentially linked four cough syrups manufactured at the facility to the deaths of 66 children in Gambia.
The state authorities also issued a show-cause notice to the pharma company to explain within a week "many contraventions" found during a recent inspection, or face suspension or cancellation of license even as the Centre on Wednesday formed a four-member panel of experts to examine the details and adverse event reports received from the WHO on the deaths of the children in the West African nation.
Haryana Health Minister Anil Vij said a joint team of the state and the Centre inspected the Sonipat unit during which it found 12 violations or deficiencies.
"Taking cognisance of this, the state government has ordered that all drug production at this unit be stopped with immediate effect," Vij told PTI over phone.
Among the 12 "violations" highlighted by the state drugs regulator was that the batch number of propylene glycol, sorbitol solution and sodium methyl paraben used in the making of the drugs in question was not mentioned in the certificate of analysis report.
According to the show-cause notice issued by the Haryana Drugs Controller following the inspection of the firm's plant, Maiden Pharmaceuticals Limited did not perform quality testing of propylene glycol, the raw material used for making one of the formulations.
"The firm has not performed the quality testing of propylene glycol for diethylene glycol and ethylene glycol," the notice issued on October 7 said.
The inspection of the firm was conducted by a team comprising senior officials from the Central Drugs Standard Control Organisation(CDSCO) and the Haryana Drugs Controller Authority.
"During inspection many contraventions were detected. You are hereby served with the show-cause notice rule 85(2) of drug rules, 1945 as to why your manufacturing license may not be suspended or cancelled," the notice said.
The state authority had asked the firm to respond within seven days, failing which it said ex-parte -- done with respect to or in the interests of one side only or of an interested outside party -- action will be taken against the company as per the drugs act.
The firm has not performed process validation and analytical method validation for the drug products in question, the notice said.
Also, the complete plant was found under renovation and the firm failed to produce the log books of equipment and instruments regarding manufacturing and testing for the drugs in question, it added.
The batch number, manufacturer name and manufacturing date and expiry date were not found maintained on the purchase invoices of excipients including propylene glycol, it said.
Samples of four cough syrups manufactured by the firm were sent to the Central Drugs Laboratory in Kolkata on October 6 for examination, a day after the WHO flagged four "contaminated" and "substandard" cough syrups made by the company, warning they could be linked to the deaths of 66 children in Gambia.
Minister Vij said the report of the cough syrup samples are yet to arrive from the Kolkata Laboratory.
"Depending on what it says, we will take further action."
Official sources said the four-member panel of experts will advise and recommend further course of action to the Drugs Controller General of India (DCGI) after examining and analysing the adverse event reports, causal relationship and all related details shared by or to be shared by the WHO.
The panel is chaired by Dr Y K Gupta, Vice Chairperson, Standing National Committee on Medicines and has Dr Pragya D Yadav, NIV, ICMR, Pune, Dr Arti Bahl, Division of Epidemiology.
NCDC, New Delhi and A K Pradhan, JDC(I), CDSCO as members.
Official sources said the government has taken note of media reports that Atlanta- based Atlantic Pharmaceuticals company Limited had procured the drugs from Maiden Pharmaceuticals for further export to Gambia.
They said the WHO has not yet made available certificate of analysis and has informed that the same will be made available in the near future.
"The exact one to one causal relation of death has not yet been provided by WHO to CDSCO although the latter has requested the WHO twice in this regard," sources said.
Also, it is a usual practice that the importing country tests such imported medicines on quality parameters and satisfies itself as to the quality of the products before the importing country decides to release such products for usage in the country, they said.
"In the present case it is not yet clear whether these medicines were tested in Gambia before release," they added.
According to official sources, the WHO on September 29 had informed the CDSCO that they were providing technical assistance and advice to Gambia, where children have died and where a contributing factor was suspected to be the use of medicines (Promethazine Oral Solution BP, KOFEXNALIN Baby Cough Syrup, MaKOFF Baby Cough Syrup and MaGrip n Cold Syrup).
These medicines are manufactured and exported by Maiden Pharmaceuticals Ltd, and the WHO had informed they may have been contaminated with Diethylene glycol or Ethylene glycol.
The CDSCO took up the matter immediately with the Haryana State Regulatory Authority, under whose jurisdiction the drug manufacturing unit is located, and a detailed investigation was launched by CDSCO in collaboration with the State Drugs Controller.
It has also been indicated by the WHO that as per the tentative results received by the WHO, out of the 23 samples of the products under reference which were tested by WHO, four have been found to contain Diethylene Glycol/ Ethylene Glycol, sources said.
On further follow up done by CDSCO with the WHO, the Certificate of Analysis (COAS) of the sampled products and the summary of the adverse events etc were shared by the WHO on October 11.