The European Medicines Agency on Friday recommended suspending the sale of dozens of generic medicines — many of which are sold by Novartis and Teva Pharmaceuticals — over concerns about “flawed” studies that were conducted by an Indian clinical research organization.
The move comes three months after the US Food and Drug Administration alerted an untold number of drug makers of problems at the Semler Research Center, which is located in Bangalore. An inspection last fall found “significant instances of misconduct and violations of federal regulations, including the substitution and manipulation of study subject samples.”
Two weeks earlier, the World Health Organization had issued a notice to Semler for the same reasons. As we wrote previously, the global health agency had examined company computer servers and found a spreadsheet file containing detailed instructions for manipulating drug samples that were used in clinical trials for its clients. The WHO inspections were conducted early and late last year.
“The findings from (the) FDA and WHO inspections call into question the quality management system in place at Semler, and, thus, on the reliability of the data of all bioequivalence studies, including those used to support marketing authorization applications in the European Union,” the EMA wrote in a statement explaining its decision. Bioequivalence studies are usually the basis for approving generic drugs.
Semler could not be reached for comment.
These moves are yet another knock on the Indian pharmaceutical industry, which has been under a microscope in recent years over a raft of quality-control concerns. Numerous drug makers and ingredients suppliers have been issued warnings for various manufacturing gaffes and, in some cases, the FDA has banned shipments into the United States.
Last year, for instance, the European Union suspended hundreds of drugs that were authorized for use based on what European regulators called “flawed” studies conducted by GVK Biosciences, a clinical research organization based in Hyderabad. The episode triggered protests from drug makers and caused a brief diplomatic row between the Indian government and the EU.
The implications for the generic drug makers affected may be substantial.
The EMA will recommend lifting suspensions if drug makers provide alternative data demonstrating bioequivalence. The FDA is requiring the same thing. And so, these companies must decide whether it will be worth the expense of conducting new studies for pending or approved applications. They will also have to review drugs in their pipelines where studies were run by Semler and find a new CRO, which could result in delayed filings.
As we indicated in an earlier post, this is the second time in the past year that the WHO issued a so-called notice of concern to an Indian CRO. In July 2015, the global health agency cited problems at Quest Life Sciences involving a clinical study of different AIDS drugs and recommended rejecting the study, according to the notice.
Meanwhile, regulators in each EU country will have to determine the extent to which specific medicines that were tested by Semler are critically needed before proceeding with suspensions. The EMA noted there is no evidence, to date, that any patients were harmed or that any of the drugs were not effective.