The World Health Organization (WHO) reported in an “information exchange system alert” issued in late January that cough syrup manufactured in India using an incorrect raw material has resulted in the deaths of at least 60 people in Pakistan and India.
The incidents occurred in November and December and were linked to cough syrup produced by two different local firms that used an active pharmaceutical ingredient (API) dextromethorphan produced by Konduskar Laboratories located in Kolhapur, Maharashtra, India.
The Indian government suspended the production and supply of both medicines and recalled large quantities of the products as well as unused API. It is unclear whether any of the API was exported outside of India and Pakistan.
Investigations conducted with the manufacturers confirmed that they had both recently changed the source of their dextromethorphan to Konduskar Laboratories and that the adverse reactions commenced immediately after distribution of medicine produced with API from that source.
Lab analysis revealed that both the API and the cough syrups were contaminated with varying levels of levomethorphan, the enantiomer of dextromethorphan, which is a potent opioid analgesic and controlled substance.
WHO reports that all of the victims of both incidents had a history of drug abuse. Interviews with the survivors “confirmed that they had been taking large quantities of the syrup exceeding therapeutic doses in conjunction with other narcotics for many years with no unexpected serious adverse reactions.”
India Reviews EU API Rules; Issues Draft GDPs
The contamination outbreak occurred as India was beginning to review how to address the EU requirements for API export into Europe stipulated in the Falsified Medicines Directive.
In early February, the Pharmaceuticals Export Promotion Council of India (Pharmexcil) released procedures from the country’s Central Drug Standards Control Organization (CDSCO) for how Indian active pharmaceutical ingredient (API) manufacturers can obtain a written confirmation of quality that will be needed to ship their products to the EU (IPQ “Updates in Brief” February 18, 2013).
India’s CDSCO also published a draft guideline on “good distribution practices for pharmaceutical products” in early January with a three-week comment period.
The draft covers only finished products, with an objective to “ensure the quality and identity of pharmaceutical products during all aspects of the distribution process.” These aspects “include, but are not limited to, procurement, purchasing, storage, distribution, transportation, documentation and record-keeping practices.” It does not address the upstream part of the supply chain such as APIs or raw materials.
A detailed summary of the 28-page, 20-section document is available from the supply chain consortium Rx-360.