The Agency has also recommended that any medicines currently being evaluated for authorization for which the CRO conducted bioequivalence studies not be authorized until alternative data is provided.
Companies including Teva Pharmaceutical Industries Ltd, Novartis AG’s Sandoz, and Mylan Inc., are among those affected. However, according to the EMA, there is currently no evidence that any of the medicines have resulted in "unexpected harm or lack of effectiveness."
A Novartis representative told us, "We are working closely with our licensing partners to repeat the bioequivalence/bioavailability studies at an acceptable alternate study site." Teva and Mylan have not responded to a request for comment.
The recommendation follows a review of an FDA inspection, which identified several issues at the site.
In a letter issued to the CRO in April, the FDA explained, “objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conduced.”
A notice to pharmaceutical companies was also published on April 20, 2016, following the site’s inspection.
The inspection was conducted between September 29, 2015 and October 9, 2015, as part of the administration’s Bioresearch Monitoring (BIMO) Program, which was designed to evaluate the conduct of FDA-regulated research.
According to the letter, the firm failed to demonstrate that the analytical method used in an in vivo bioavailability or bioequivalence study was “accurate and of sufficient sensitivity to measure, with appropriate precision, the actual concentration of the active drug ingredient or therapeutic moiety, or its active metabolite(s), achieved in the body.”
Additionally, the World Health Organization (WHO) also previously raised concerns in a Notice of Concern (NOC) procedure, which the organization applies “when an inspection is performed and serious observations are made that result in concern about the site’s compliance with specified standards,” such as Good Manufacturing Practices (GMP) or Good Clinical Practices (GCP).
The EMA’s Committee for Medicinal Products for Human Use (CHMP) has reviewed the findings of both inspections, and 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.”
The review was initiated on April, 28 2016 at the request of Denmark, Germany, the Netherlands, Spain, and the United Kingdom, under Article 31 of Directive 2001/83/EC – a pharmacovigilance referral.
The European Commission will issue a legally binding decision for all EU Member States regarding the CHMP's decision.
Semler Research could not be reached for comment.