European drug regulator suspends medicines tested at Semler Research

The European Medicines Agency (EMA) has recommended suspension of many approved medicines for which bioequivalence studies were conducted at Bangalore-based contract research organisation (CRO) Semler Research Centre Pvt Ltd. The agency has also recommended that medicines currently being evaluated for authorisation and which rely only on bioequivalence studies from Semler site should not be authorised until bioequivalence is demonstrated using alternative data. Bioequivalence studies usually form the basis for approval of generic medicines.

“A number of medicines for use in the EU rely on studies carried out at the Semler site in India. The studies, called ‘bioequivalence’ studies, are usually the basis for approving generic medicines. The bioequivalence studies performed at the Semler site have been found to be flawed, so they cannot be relied on. As a result, several medicines approved in the EU are being suspended. Medicines to be suspended can have their suspension lifted if the companies provide alternative data demonstrating bioequivalence,” said EMA in a press statement on July 22, 2016.

The list of medicines recommended by EMA for suspension pertains to large generic manufacturers such as Sandoz, Teva, Mylan, Zydus France, Micro Labs, Lupin Europe Ltd, Glenmark Arzneimittel, etc.

EMA’s review followed an FDA inspection1 that identified several issues at Semler’s bioanalytical site, including the substitution and manipulation of subjects’ clinical samples. The World Health Organization (WHO) also raised serious concerns regarding data integrity and manipulation of study samples following its own inspections of Semler’s bioanalytical and clinical sites.

The findings from 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 authorisation applications in the EU. EMA’s Committee for Medicinal Products for Human Use (CHMP) has concluded that the studies conducted at Semler cannot be accepted in marketing authorisation applications in the EU. Thus, no medicines can be approved on the basis of these studies.

During the evaluation, alternative studies were provided for some of these medicines, for example abacavir/lamivudine (used to treat HIV). These studies show bioequivalence, and therefore, the CHMP has recommended that these medicines can remain on the market.  

“Some of the medicines which have been recommended for suspension may be of critical importance (eg due to lack of available alternatives) in a given EU member state. Therefore national authorities can temporarily postpone the suspension in the interest of patients. Member states should also decide whether recalls of the affected medicines are needed in their territories,” added EMA.

The CHMP’s recommendation concerning these medicines will now be sent to the European Commission for a legally binding decision valid throughout the EU.