Indian pharmaceutical company Lupin Limited has been sent a warning letter by the US FDA for its inadequate actions to address the manufacturing practices violations at the facility in Tarapur, Maharashtra. Lupin Limited is a transnational company with plants throughout the US, Mexico, Brazil, and India. They specialize in producing generic medicines, branded medicines, APIs, and biosimilars.
The Food and Drug Administration only issues warnings to manufacturers that violate the guidelines described by the agency. It can pertain to anything from poor manufacturing practices, incorrect directions to use, or problems in claims of what the product can do. When a manufacturer is issued a warning, they are also given a window of time to correct the problem. The warning letter only follows Form 483, which is disseminated after an inspection of the manufacturer’s plant and premises are inspected by a regulator and aberrations are found.
What tipped off the FDA?
For Lupin Limited, the warning letter describes that active pharmaceutical ingredients or APIs used in making drugs were found to be adulterated and in violation of the FDA’s Current Good Manufacturing Practice (CGMP). At the Tarapur plant where the alleged allegations have occurred, the company produces fermentation-based and synthetic APIs.
The warning letter received details three different concerns regarding the manufacturing plant. To begin with, genotoxic impurities were traced in the drugs and APIs. Genotoxic impurities are substances that alter the human DNA in the cell and may cause cancer. The facility also had ‘deviations’ from the regulations that FDA has mandated. These ‘deviations’ are not specified in the letter, but investigation and determination of the causes behind such violations are warranted. Finally, the cleanliness of the facility has been brought to question. The equipment used to produce the drugs needs better cleaning procedures so that cross-contamination is avoided.
The spokesperson for the drugmaker claims that initially, corrective procedures were undertaken but did not satisfy the authorities. FDA states that the company has looked away from the unfavorable data about its cleanliness practices and disregarded the research relevant to the matter as ‘lacking in scientific justification.’
‘Prompt’ actions in progress
At the time of receipt of Form 483 in April, Lupin Limited was confident in its ability to take corrective procedures as required. However, the regulatory body was not satisfied with the reformations made by the company and issued a warning in September. The warning letter issued on September 27, 2022, asked the company to respond within 15 days – or before October 11. If corrective actions cannot be completed within 15 working days, the reasons for the delay and the schedule for completion of the project have to be relayed to the FDA.
Until the necessary changes are seen, FDA may withhold the approval of any new application or supplement that lists the company as the manufacturer. Despite the need for ‘prompt’ actions, no other notification has been made by the company so far. Lupin Limited’s Pune facility is also under the radar of the FDA.
