The US Food and Drug Administration (FDA) has issued two warning letters to Indian pharmaceutical manufacturers Apotex and Micro Labs, accusing both of potentially falsifying the data used to show their drugs were made to federal quality standards.
The letters are similar in nature to nearly a dozen others sent to Indian pharmaceutical manufacturers since May 2013. To date, FDA has sent 15 letters to Indian companies accusing them of violating standards on ensuring data integrity.
Read more about FDA's crackdown on Indian data integrity problems here.
The problem, as FDA has explained in the past, is that if companies are selectively choosing which drug test results they accept and which results they discard, it will make their drugs appear to be safer than they actually are.
The testing is meant to ensure the drugs contain the proper amount of active ingredient, the presence of impurities and other data.
Some companies have been accused of unofficially testing drugs prior to their official tests, allowing them to only test the drug products they know will pass tests. Other companies have been accused of lacking controls to ensure data about failed test results can't be deleted from their systems, while others have been found by FDA to be throwing test results out in the trash.
Two New Warning Letters
FDA's Warning Letters to Apotex and Micro Labs follow similar trends.
In the case of Apotex, a May 2014 inspection by FDA officials discovered that the company had reportedly conducted unofficial testing, apparently in the hopes of improving official test results.
"During the inspection, your management admitted that employees in both of your Quality Control (QC) laboratories had frequently conducted unauthorized “trial” High Performance Liquid Chromatography (HPLC) injections prior to additional injections that were used in the reported test results," FDA wrote in its letter. "Although your management stated that this practice ended in February 2014, FDA investigators discovered evidence that this practice continues."
The results from "trial" tests were not reviewed for the purposes of determining whether a batch of drugs could be released, FDA noted.
In addition, FDA said the company had failed to "exercise appropriate controls" over its computer systems, which are meant to prevent employees from retroactively changing control records or test results. The company's computer systems were apparently configured such that data could be over-written.
FDA also chided the company for submitting Field Alert Reports (FARs)—used by FDA to assess reports of quality defects—weeks late. FARs are supposed to be submitted within three days of receipt under 21 CFR 314.81(b)(1)(i). Apotex submitted at least one of these reports in 29 days, FDA said.
Micro Labs: In Deep, Digging Deeper
FDA's Warning Letter to Micro Labs raised similar arguments, and noted the company's alleged use of "trial" testing of drug samples and "reporting only those results" which were favorable to the company.
"Our inspection identified numerous examples of ‘trial’ injections for various drug products (U.S. and non-U.S. markets), which suggests that this is a common practice," FDA wrote. FDA's Warning Letter observes that Micro Labs attempted to justify its practice of resampling. The company argued, for example, that fluctuations in electricity and pressure had caused its chromatography testing to fail. However, FDA disregarded this argument.
"The fact that you did not observe the peak in commercial and exhibit batches does not justify disregarding the test run or failing to follow up with appropriate corrective actions and preventive actions," it told Micro Labs.
The company's response to FDA may have actually put it in worse standing with FDA. The regulator said Micro Labs told it that a laboratory supervisor was "aware of the repeated testing of … stability samples, and that he allowed the analyst to repeat the analysis without conducting further investigation."
"This explanation does not resolve the Agency’s concerns, but instead raises further issues," FDA wrote.
The company also failed to have adequate controls on its computerized systems, FDA added.
Warning Letter to Apotex
Warning Letter to Micro Labs