Preliminary report suggests lapse in manufacturing process at Maiden Pharma

The firm has been in news for supplying contaminated cough syrups to Gambia, which is linked to the deaths of 66 children due to the presence of contaminants

Delhi-based Maiden Pharmaceuticals may be in trouble as a preliminary report by the Haryana state drug authorities and the Central Drugs Standards Control Organisation (CDSCO) has shown violations of good manufacturing practices (GMP) by the firm.

The government sources confirmed that a preliminary report has been submitted to the Union Health Ministry based on the visits made by the regulatory authorities to the company’s factory premises in Sonepat, Haryana.

The laboratory test results of the samples collected from the facility are, however, awaited. The samples have been sent to Central Drugs Laboratory, Kolkata. The government officials from CDSCO visited their facilities on October 1, October 3, October 6 and October 7 and samples were taken by the CDSCO along with all relevant documents in the presence of company directors.

“Most of the lapses in good manufacturing practices were related to record-keeping – for example, batch numbers, records for quality testing, sourcing of materials like solvents etc,” said an official on grounds of anonymity.

The firm has been in news for supplying contaminated cough syrups to the West African country of Gambia that is linked to the deaths of 66 children due to the presence of contaminants such as Diethylene Glycol (DEG) or Ethylene Glycol (EG).

Leena Menghaney, lawyer and India Head and Global IP Advisor Medecins Sans Frontieres – Access Campaign, says that India’s fragmented regulatory system is a major challenge for procurers and quality assurance. She adds, "CDSCO has a dossier approach for each drug when it approves a new drug at the central level. However, when a drug becomes older by more than four years or so, then any manufacturer can seek a license to manufacture it from the state regulator. In this case, no dossier approach is followed,” Menghaney claims. 

She adds that the manufacturers change the source of the active pharmaceutical ingredients (APIs) or even excipients, and these important changes are not necessarily reported to the state regulator. 

"Testing samples, the finished formulation, which is the quality control approach, is important, but not enough to address concerns. A more robust quality assurance approach is needed. Looking at systems and processes for how the drug is assessed by drug regulatory authority is crucial for quality assurance on which medicine procurers can rely. This is what we do for Indian antiretrovirals that HIV programmes procure worldwide. This quality assurance approach has saved millions of lives of people living with HIV. Why can’t we do this for all essential medicines? she says.

On September 29, the WHO informed the DCGI about the deaths in Gambia and suspected links with Maiden Pharma.

“The CDSCO took up the matter immediately with the Haryana State Regulatory Authority, under whose jurisdiction the drug manufacturing unit of Maiden Pharmaceutical, Sonepat, is located,” the Union Health Ministry said on Thursday.

As the controversy grew, the Pharmaceutical Exports Promotion Council (Pharmexcil) suspended the membership of the firm. Going forward, the import-export code (IEC) of the company may also be withdrawn by the Directorate General of Foreign Trade (DGFT), officials said.

India, meanwhile, is also waiting for the causality assessment report from the WHO that it had sought on Gambian deaths.

Violations by Maiden Pharma detected during inspection by regulators

• A team comprising Rakesh Dahiya, senior drugs control officer, Sonipat, Sandeep Kumar, and Devender Pratap Singh, drug inspectors from CDSCO zonal office in Ghaziabad inspected the facilities of Maiden Pharma on October 1 and 3.
• A show-cause notice was issued on October 7 under Rule 85 (2) of Drug Rules, 1945 by the State Drugs Controller-cum-Licensing Authority based in Panchkula, Haryana asking the firm why its manufacturing license may not be suspended/cancelled
• During inspection the authorities found that batch numbers, expiry and manufacturing dates, name of manufacturer were missing from the invoices of propylene glycol, an ingredient used in cough syrups.
• Drug authorities noted Maiden Pharma has not performed the quality testing of propylene glycol for diethylene glycol and ethylene glycol
• The firm failed to produce the log books of equipment and instruments regarding manufacturing and testing for the drugs in question
• Firm  had not performed process validation and analytical method validation for the drug products of these four cough syrups
• Issues with stability study of the four cough syrups. Inspecting team did not find the cough syrups charged/monitored in stability chambers
• However, the firm had submitted accelerated stability study data when seeking marketing authorization (indication of data being fudged).