Indian API Makers in Hot Water With FDA Yet Again
The FDA hit another Indian active pharmaceutical ingredients maker with a warning letter after an inspection revealed data integrity issues and significant cGMP violations.
During the March 18 to 21, 2014, inspection, FDA investigators observed that Unimark Remedies had no unique usernames, passwords or user access levels to prevent raw data from being deleted or altered.
For example, all employees had full privileges to the computer systems, with the ability to alter a wide array of data, and there were no audit trail functions to record data changes.
The investigators also noted that analytical testing data were poorly maintained and reviewed. For instance, there were raw data on undocumented stability samples, but no indication of where they came from and why they were tested, the warning letter says.
The FDA also dinged the Mumbai-based company for not including start or stop times in batch records and for having incomplete water testing records. In its response to a Form 483, the company blamed its manufacturing staff for the poor documentation practices, and said the chemist and microbiologist each had neglected their work, the letter says.
Investigators also saw evidence of pests in the facility, including a lizard, a bird’s nest and bird feces in the general raw material warehouse.
The FDA asked Unimark — which counts Teva, Mylan and Actavis as clients — to provide an evaluation of the extent of inaccuracies in its reported data, a risk assessment of potential effects of these deviations on data submitted in drug applications and a management strategy, including details of its corrective and preventive action plan. The agency also recommended hiring an outside cGMP consultant.
The warning letter is the first issued to an API maker in the new federal fiscal year, which began Oct. 1. In FY 2015, the FDA issued eight warning letters to API makers — all to foreign firms and all citing data integrity issues.
Unimark did not return a request for comment by press time.
Megafine Import Ban
Meanwhile, the FDA placed another Indian API maker on its import alert list, adding one of Megafine Pharma sites to 46 other India-based finished drug and API sites whose products are banned from entering the U.S.
Since September 2009, 30 companies’ sites have been placed on import alert, creating a major black eye for India’s pharma industry and its reputation as a global supplier of generic drugs.
Megafine’s Nashik, Maharashtra, India, site produces 24 APIs for the U.S. market, including ambrisentan for hypertension, the anticoagulant apixaban, vildagliptin for diabetes and drugs for Alzheimer’s disease, depression, schizophrenia, multiple sclerosis and overactive bladder.
The FDA did not specify what issues resulted in the import alert. Megafine’s site in Vape, India, is not listed on the import alert list.
The company also exports its APIs to the EU, Canada, Mexico, Australia, Brazil and South America, according to its website.
This is the fifth Indian drugmaker placed on import alert since July. In October, the FDA added Mumbai, India-based Polydrug Laboratories to the list, citing GMP violations at its Ambernath, India, plant.
In August, Akorn India’s Himachal Pradesh site and Sri Krishna Pharmaceuticals’ Andhra Pradesh plant were listed. In July, Emcure Pharmaceuticals’ Hinjewadi, Maharashtra, India, plant was banned.
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