Another FDA Warning Letter for an Indian Drugmaker: More Data Integrity Violations

The US Food and Drug Administration’s (FDA) interest in rooting out data integrity deficiencies among Indian pharmaceutical manufacturers continued this month with a warning letter issued to Hyderabad-based Sri Krishna Pharmaceuticals.

A lack of data audit trails, deleted sample data by a quality control analyst and loose computer controls that allowed analysts to manipulate data were all examples of issues cited by FDA officials from their inspection in December 2014. More than a year later, Sri Krishna received the warning letter, dated 1 April 2016.

The agency also noted repeat violations from an inspection of the manufacturing site in 2007. FDA added the site to its import alert list for good manufacturing practice (GMP) violations in August 2015, meaning all products made at the site are banned from entering the US.

Sri Krishna is one of at least 15 Indian pharmaceutical and active pharmaceutical ingredient manufacturers that have received warning letters because of data integrity concerns. FDA Form 483s issued to other Indian manufacturers also included a number of the same issues outlined in the Sri Krishna letter.

The letter comes as FDA last week released draft guidance on data integrity in GMP manufacturing of pharmaceuticals to help noncompliant companies.

Letter Details

Among the most egregious violations, FDA found Sri Krishna’s laboratory records “did not contain all raw data generated during each test for finished drug products manufactured at your firm. Your quality unit relied on incomplete records to make batch release decisions in support of regulatory submissions to the Agency.”

During the inspection, Sri Krishna’s management also acknowledged that employees in its quality control laboratories conducted trial high-performance liquid chromatography (HPLC) injections prior to the injections submitted as the reported test results. 

“These trial injection data files were stored on separate drives from the reported test result data. In some cases original data files were deleted. The results from these trial injections and other original data were not reported,” FDA said.

As far as how Sri Krishna can come back into compliance with FDA regulations, the agency calls for a comprehensive investigation into the extent of the inaccuracies in data records and reporting; a risk assessment of the potential effects of the observed failures on the quality of the company's drugs, including analyses of the risks to patients; and a new management strategy that includes the details of a global corrective action and preventive action plan.

“Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer,” the agency said.

Warning Letter