When drugmaker Alkem gets a regulatory rap in Europe over the reliability of data from some of its clinical studies, there is a sense of déjà vu.

Not just because data integrity has in the past tripped up many domestic drug companies in foreign markets. But the specifics in the Alkem case are also disconcertingly reminiscent of the GVK Biosciences episode, in terms of data concerns linked to electrocardiograms (ECGs).

Alkem may have stemmed the immediate slide of its stock price on the local bourses by committing to the European Medicines Agency (EMA) that it would take remedial action within a timeframe.

But the German regulator, the Federal Institute of Drugs and Medical Devices’ observation of “intentional misrepresentation of study data” after it visited Alkem’s Taloja site reveals a tardy approach that the domestic company and drug industry can ill afford. The German regulator’s report followed a joint inspection of the site with Dutch authorities.

The regulatory observations reflect poorly on the integrity of the people involved with these studies and the sponsor (the company in this case), says Shoibal Mukherjee, a seasoned industry-hand. But the occurrence reflects even more poorly on the Indian regulator who should have caught these discrepancies before a foreign regulator did, he says, adding that Indian regulations need to be more stringently implemented.

ECG transgression

Three of Alkem’s bio-equivalence trials, two in 2013 and one in 2014, were inspected by the foreign regulators. (Bio-equivalence helps establish that the generic version of a drug is similar to the innovator medicine in terms of how it is absorbed by the body etc.)

The discrepancies highlighted include: an ECG printout being the source data for two different subjects. “As the subject’s identifier and date of birth must have been actively changed, this is considered by the inspection team as intentional misrepresentation of study data,” the regulator said.

Referring to more transgressions around ECG data, the regulator adds, “In response to the inspection report, the inspected site acknowledged that there were severe errors with the ECGs which were recorded by contractual technicians and acknowledged carelessness and non compliance of the quality system by these users.“

This affects the trustworthiness of the data generated by the site (clinical and bioanalytical) in the time period from the beginning of the first study in March 2013 until the inspection took place in March 2015, the regulator says. Naturally, marketing authorisations for products from this site were refused.

Not too long ago, Indo-European trade talks were strained over GVK Biosciences being hauled up by the European authorities over its clinical data. This had affected the EU marketing approvals of 700 generic drugs belonging to different drug companies, including those not from India.

Industry experts explain that the safety profile of an innovator drug is clinically established and ECG tests by generic companies are to prove that they are similar in action to the innovator’s medicine. Since the active ingredient in the generic is the same, ECG data discrepancies do not usually affect the safety of the generic drug. But it does send out a message of slip-shod work and that hurts the image of the Indian industry, say industry veterans.

The latest action comes at a time when Indian drugmakers are already dealing with regulatory action from the United States Food and Drug Administration. As the Indian drug industry grows in foreign markets, companies need to get their act together and ensure that quality systems are not just put in place, but also followed, rigorously.


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