FDA Warns Indian Drugmaker Over Major Data Integrity Violations at Three Plants

Posted 09 February 2016 By Zachary Brennan

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The US Food and Drug Administration (FDA) on Tuesday released a warning letter to India-based Ipca Laboratories after inspections at three of its manufacturing facilities revealed data integrity violations. All three of the plants are already banned from sending products to the US.

The warning letter, dated 29 January, reveals how inspectors found “systemic data manipulation” at Ipca’s Ratlam facility in Madhya Pradesh, “including actions taken by multiple analysts, on multiple pieces of testing equipment, and for multiple drugs.”

Investigators even spoke with an Ipca analyst at the site who reported that: “…if we find a failure, we set back the date/time setting and re-integrate to achieve passing results…” The analyst also explained that deleting, overwriting, changing integration parameters, and altering computer date and time settings were done for raw materials, in-process testing and finished active pharmaceutical ingredients (APIs).

The inspection of the site’s microbiology laboratory uncovered “multiple examples” of the company’s practice of back-dating and falsifying laboratory data, which should be a major issue for the countries that receive exports from the firm. In October, Ipca reported almost $60 million in exports income in Q2.

The company also ran an internal investigation that concluded that some chromatograms were manipulated at the Ratlam site, though the company failed to identify the scope or extent of that manipulation. The company also “lacked sufficient rigor to demonstrate that other laboratory data were not compromised, including data supporting drug applications or stability,” FDA said.

At the company’s Pithampur site, FDA said the firm has “no way to ensure that the tests you use to evaluate the quality of incoming raw materials are accurate or reliable.”

And at the Piparia Silvassa manufacturing facility, FDA said Ipca lacks an evaluation of the acceptability of its media supplier, the adequacy of laboratory controls and a determination of whether laboratory personnel (including supervisors) are appropriately qualified to detect and correct these deviations.

Response

Following the uncovering of systemic data manipulation and other good manufacturing practice violations at the three sites, FDA is now seeking the following:

  • A comprehensive investigation and evaluation of operations, including conclusions about the extent of data integrity deficiencies and their root causes; 
  • A risk assessment of how the observed deficiencies may affect the reliability and completeness of quality information available for Ipca’s drugs;
  • A management strategy that includes a detailed global corrective action and preventive action plan. “Describe the actions you will take, such as contacting your customers, recalling drugs, conducting additional testing and/or adding lots to your stability programs, or other steps to assure the quality of your drugs manufactured under the deficient conditions discussed above,” FDA said.

A previous FDA Form 483 cited Ipca after an FDA inspector found a quality affairs officer had partially shredded training validation forms for multiple manufacturing operators.

Warning Letter

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Categories: Active pharmaceutical ingredients, Drugs, Audit, Crisis management, Manufacturing, News, US, India, FDA

Tags: Ipca Laboratories, data integrity violations, GMP warning letters

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