US FDA warns of serious data integrity violations at DRL

The US Food and Drug Administration has warned DRL over serious data integrity violations, placing all its new applications or supplements under a cloud

The US Food and Drug Administration (US FDA) has warned Dr Reddy’s Laboratories (DRL) over serious data integrity violations, placing all its new applications or supplements under a cloud. Making its letter public, US FDA has strongly worded that there are significant deviations from current good manufacturing practices (CGMP) for the manufacture of active pharmaceutical ingredients (APIs) for finished pharmaceuticals. This is likely to impact the company for new approvals by US FDA and may lead to drug import ban.

“Until you complete all corrections and FDA confirms your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product or API manufacturer,” the FDA letter said. It also noted that if the company fails to correct these violations, under Section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3), FDA may also refuse admission of articles into the US manufactured at CTO Unit VI, Srikakulam, AP, CTO Unit V, Miryalguda in Telangana and Unit VII, Duvvada, VSEZ, Visakhapatnam, Andhra Pradesh.

The US FDA was not satisfied despite DRL sending responses nine times from December 15, 2014, to September 15, 2015. In a letter addressed to Satish Reddy, Chairman, DRL on November 5, 2015, the regulator said several violations are recurrent or represent long-standing failures to adequately resolve significant manufacturing quality problems.

After receiving the warning letter, DRL had said it will respond with a plan to address the observation within the stipulated time. “We take quality and compliance matters seriously and stand by our commitment to fully comply with the cGMP quality standards across all our facilities,” GV Prasad, Chief Executive Officer, DRL had said earlier.

There were serious data integrity violations, including the backdating of records and failing to provide pertinent data to regulators. This was included in the warning letters for three manufacturing facilities for DRL, according the US FDA. The warning letter for DRL — for three sites in Telangana and Andhra Pradesh — notes several violations that are recurrent or represent ‘long-standing failures to adequately resolve significant manufacturing quality problems.’

The company was also cited for failing to control access to some of its computer systems with passwords and failing to explain discrepancies between the release of APIs and deviations that occurred, among other inconsistencies with media-fill records and batch records for drums used to hold intermediates during manufacturing.

Incidentally, one-third of pharmaceutical companies have not conducted reviews to assess potential gaps in data integrity, according to an EY survey, ‘Analysing the state of data integrity compliance in the Indian pharma industry’. Data integrity reviews are conducted to evaluate if data records are accurate, complete, attributable, legible and maintained within their original context in electronic or paper form. Over 30 per cent of the respondents stated that they have received inspectional observations by regulators. This was despite signing off their understanding and compliance with GMP norms.

“Maintaining data integrity is crucial for the pharma sector. Today, companies with existing or anticipated concerns around data integrity should initiate regular proactive data integrity assessments. This will be beneficial even for companies that enjoy a good reputation in the market. These periodic assessments provide assurance to all stakeholders involved – customers, investors, regulators as well as reaffirm the management’s commitment toward highest standards of quality,” adds Rajiv Joshi, Partner, Fraud Investigation & Dispute Services, EY.

“While data integrity issues are not new for the pharmaceutical industry, the seriousness with which the regulators look at these has changed in recent times. Regulators now expect companies to undertake independent audits to address data integrity issues and improve overall compliance. These audits are expected to adopt a detective approach to proactively identify and address potential data integrity issues,” Sandeep Baldava, Partner, Fraud Investigation & Dispute Services, EY added.