Belgium, France, Germany and Luxembourg made the decision to suspend the marketing authorizations of 25 generics after a site inspection by the French regulatory authority (Agence nationale de sécurité du médicament et des produits de santé; ANSM) highlighted abnormalities in the electrocardiograms (ECG) registration procedures made during clinical trials conducted between 2008 and 2014.

ANSM admits that ECGs in themselves, do not serve to demonstrate bioequivalence of the generics, but that they do allow monitoring of subjects included in clinical trials of bioequivalence. The agency states that ‘these abnormalities characterize a lack of compliance with Good Clinical Practices regarding these bioequivalence studies’, raising concerns about the reliability of studies conducted at the site.

GVK Bio admitted that cardiology assessments of the ECGs indicated that the ECGs could belong to multiple volunteers and it was difficult to conclude that ECGs belonged to the same volunteer. However, they added that they had ‘provided evidence that all key activities such as dosing, blood sampling and processing were adequately controlled, supervised and staff were qualified to do the work’.

GVK Bio also stated that it had ‘strengthened its operating procedures around taking ECGs and these were accepted by the authorities’. The CRO was therefore disappointed in the decision to suspend the generics approvals based on ‘the fact that the same employees were involved in other critical activities left an element of doubt on the bioequivalence results’.

Although the announcement from EMA did not mention which generics companies this would affect, the suspended authorizations included generics from US drugmakers Abbott Laboratories and Mylan.

The decision has been taken as a precaution and EMA admits that, to date, there is no evidence of any risk posed to human health by the medicines concerned. However, it is expected that the generics companies concerned will need to repeat studies in the next 12−15 months in order to resubmit data demonstrating bioequivalence.

EMA’s Committee of Human Medicinal Products (CHMP) launched a review in September 2014 of the benefit/risk of all of the drugs for which the marketing authorization dossier included bioequivalence clinical trials conducted by GVK Bio at its Hyderabad site. The review is expected to be completed in early 2015.

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