For the second time in less than a year, the US Food and Drug Administration (FDA) has issued a warning letter to Indian active pharmaceutical ingredient (API) maker Pan Drugs over data integrity and sanitation violations at one of its facilities.
Due to the extent and repeat nature of the violations, FDA says Pan must carry out a comprehensive plan to investigate and address the issues.
Data Integrity and Quality Control
The warning letter, dated 25 August 2016, comes as a result of a four-day inspection of Pan's Makarpura facility in Gujarat, India late last year. In September 2015, FDA warned Pan for similar issues at its Nandesari facility, also in Gujarat. Both inspections resulted in the company's products being banned from import into the US.
During the inspection, FDA says it found evidence that Pan used APIs manufactured at its Nandesari facility to produce batches of drugs that were shipped to the US, after the facility had been placed on import alert.
According to FDA, its investigators also observed a pattern of data integrity issues at the company that went unnoticed by its quality unit.
"Your quality unit failed to identify data integrity issues in 11 batch production records reviewed by our investigator. Your production manager admitted that he falsified the signatures of other employees in the 'Prepared By,' 'Reviewed By,' 'Approved By,' and 'Authorized By' sections," FDA writes.
On the first day of the inspection, FDA says it observed a warehouse supervisor "tearing out pages from [Pan's] annual report and placing the pages into his pocket" before eventually handing them over to FDA investigators.
FDA also cites the company for failing to have appropriate controls over computer systems to ensure than only authorized employees could make changes to master records.
"For example, the computer in [Pan's] quality unit area did not have controls to restrict access and prevent unauthorized changes to data files and folders," FDA writes.
In light of these issues, FDA says that Pan's quality system "does not adequately ensure the accuracy and integrity of data" for its products and operations. As such, FDA says the company must complete the following:
- "a comprehensive investigation into the extent of the inaccuracies in data records and reporting"
- a current risk assessment of the potential effects of the observed failures on the quality of your drugs [that] should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity, and risks posed by ongoing operations"
- "a management strategy that includes the details of global corrective action and preventative action plan."
Cleaning and Sanitation
The warning letter also cites Pan for failing to keep its facilities and equipment clean, noting the presence of mold, rodent feces and a lizard in the company's processing area, as well as rust and dirt on some of its manufacturing equipment.
"Our investigators also observed gaps and holes in the walls of your facility around piping and air ducts ... During the inspection, we observed a lizard exiting one of the holes, and evidence of other pest activity. For example, our investigators observed what appeared to be rodent droppings within three feet of [Redacted] bags purported to hold [Redacted] drug product," FDA writes.
FDA said it also found lubricant leaks and "black particles" in some of the equipment used at the site, commenting that some of the equipment was also in "poor operating condition."
According to FDA, a Pan representative told investigators the company "had no cleaning procedure for the equipment or facility."
FDA Warning Letter