The manufacturing practices of Indian drug makers have once again come under the scanner after the US Food and Drug Administration (USFDA) recently issued 11 observations to Intas Pharmaceuticals Limited over questionable practices at its manufacturing facility in Pharmez Special Economic Zone (SEZ) near Ahmedabad.
Three USFDA regulators inspected the facility for nine days between November 22 and December 2, 2022, and highlighted glaring lapses in areas such as data integrity, standard documentation practices, accuracy, sensitivity, specificity and reproducibility of test methods on products, and the procedures designed to prevent microbiological contamination of drug products, among others.
Intas, part of the 24-member Indian Pharmaceutical Alliance (IPA), exports its products to the US, European Union, and emerging markets. According to the company’s last quoted 2019 data, US revenues contribute about 18 per cent to its total revenues of $1,884 million, while EU contributes 42 per cent, and emerging markets 9 per cent. India revenues account for 31 per cent.
Intas makes solid oral products, injectibles and liquid oral products at the Pharmez unit.
Documents in scrap area
In its Form 483 observations, the USFDA noted, “There is a cascade of failure in your quality unit’s lack of oversight on the control and management of GMP documents that are critical in ensuring the drug products manufactured and tested at your site are safe and effective.” It noted that the employees destroyed good manufacturing practices (GMP) documents pertaining to original records and raw data, and disposed of them inside the quality control laboratory and general scrap areas, which according to the USFDA regulators, supported the manufacturing and testing activities for the drug products sold in the US market.
An emailed query to the company remained unanswered.
The regulators also “found a truck full of transparent plastic bags containing shredded documents and black plastic bags mostly containing documents torn randomly into pieces by hand and mixed with other scrap materials. This truck was found about 150 metrers away from the facility, waiting for the clearance to remove the scrap material”.
“Your firms’ quality unit lacked adequate oversight on documents being lost from the system,” the investigators noted in their Form 483 observations.
Missing test data
The inspection also found that laboratory records did not include complete data derived from all tests, examinations and assay needed to assure compliance with established specifications and standards. There were instances of differing or inadequate time stamps on documents, inadequate action taken by the senior manager of the quality control lab against employees who allegedly destroyed data, lack of justification for missing destroyed data, and poor documentation practices.
Earlier, the USFDA had found data integrity issues at leading Indian players such as Cadila Pharmaceuticals, Sun Pharmaceuticals, Wockhardt and the formerly Ranbaxy Laboratories, among others.