Regulatory Focus™ > News Articles > New Warning Letters to Indian Manufacturers Again Find CGMP Violations, Falsified Test Results

New Warning Letters to Indian Manufacturers Again Find CGMP Violations, Falsified Test Results

Posted 20 August 2013 | By Alexander Gaffney, RAC 

Another batch of Warning Letters made public by the US Food and Drug Administration (FDA) has brought still more negative attention toward Indian pharmaceutical manufacturers, with issues that mirror recent letters and include falsification of records and failure to assure product sterility.

Background

Indian manufacturers have been the focus of intense scrutiny in recent months following a major court case involving Indian manufacturer Ranbaxy, in which it pleaded guilty to falsifying regulatory documents to mislead investigators.

In the wake of that settlement and a widely-read investigation in Fortune, a sister publication of CNN,that detailed the alarming extent of the abuse, FDA has seemingly begun to focus additional energies on Indian companies.

For example, a Warning Letter to Wockhardt regarding its Waluj, India facility discovered standing urine in bathrooms, products contaminated with glass and unknown "black particles," staff who repeatedly lied to FDA on multiple occasions, manufacturing lines that were kept hidden from investigators, and repeated instances where the company had falsified its testing practices or actively sought to hide requested evidence from FDA inspectors.

A second Warning Letter to Fresenius illustrated disturbingly similar trends, with investigators discovering that some samples were repeatedly tested outside of established quality systems, allowing it to discard unfavorable test results. Other quality violations included a quality testing system that permitted changes to be made despite a lack of management authorization, employees of the facility reportedly lying to FDA investigators, and one instance where an employee literally tried to (unsuccessfully) hide records from FDA in his pocket.

New Letters, Old Story

But if regulators had any hopes that these observations were anomalies and that other companies would quickly clean up their acts in the meantime, those hopes appear to be ill-founded, if two recent Warning Letters are any indication.

The first, to Posh Chemicals, made public on 20 August 2013, references a March 2013 inspection of the company's Hyderabad, India facility. There, FDA investigators said they found "significant deviations" from current good manufacturing practices, resulting in the active pharmaceutical ingredients (APIs) manufactured by the company being found to be adulterated under the Federal Food, Drug and Cosmetic Act (FD&C Act).

That finding was caused by many of the same issues found at the Fresenius and Wockhardt facilities, including laboratory data that could reportedly be accessed or changed by nearly anyone, employees of the facility that had admitted to recording "false visual examination data" at the urging of senior colleagues, and the use of non-validated assays.

The falsified test result in particular, FDA said, was "concerning," and it called on the company to provide it with a full accounting on the extent of the "data falsification."

Investigators also noted a bizarre trend in impurity test results for the API, noting that many of the most recent tests showed a "drop in the total impurities result regardless [of when the test was conducted]," implying the results are being routinely falsified.

The company is now subject to refused admission into the US, the Warning Letter adds.

Sterility Problems

The second Warning Letter to Promed Exports of Himachal Pradesh, India, also notes extensive CGMP deviations related to the company's ability to ensure sterile manufacturing conditions.

FDA's March 2013 inspection illustrated a number of problems, including inadequate monitoring of aseptic processing areas, air samples taken at inadequate times, uninvestigated batch failures and components, and failure to properly clean manufacturing areas.

As a result, that company is also subject to import restrictions, including refusal.


Warning Letter to Promed

Warning Letter to Posh Chemicals


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