Roche may be fined up to five percent of its European Union turnover of over $13 billion, which could amount to $685 million.
The infringement is against Roche Registration Ltd, after a request from the European Commission to investigate allegations that the company did not provide details on the side effects of 19 centrally authorized medications, including Herceptin and Tamiflu.
This is the first time EMA, which is based in London, has initiated such proceedings since new laws came into force five years ago.
In an online communiqué issued today, EMA informed:
"The start of this procedure means that the Agency will further investigate the allegations against Roche within the legal framework of Regulation (EC) No 658/2007. It does not prejudge the outcome of the investigation.
The Agency will report the outcome of its investigation to the European Commission who may impose fines or periodic penalty payments under the Regulation mentioned above if it finds that Roche has committed an infringement of its obligations.
The issue of the alleged failure to properly report drug safety started after a pharmacovigilance inspection in 2012 by the MHRA (Medicines and Healthcare products Regulatory Agency) of the United Kingdom. The MHRA identified "serious shortcomings of Roche's pharmacovigilance processes". Apparently, Roche had not completely assessed up to 80,000 cases of potential drug side effects.
Among the reports, there were details of 15,161 deaths. It is unknown how many of them were due to natural causes or linked to medications.
Roche, which stressed that none of its medications' safety profiles has been affected, says it is cooperating fully with health authorities. The company added that reports on possible safety issues did not come from clinical trials, but from a support scheme for patients in the USA who could not afford medications. The reports had not been processed within a Roche database, and as such were not passed on to EU regulatory authorities. However, possible side effects could have been submitted through other channels.
EMA said that despite data on potential adverse events, the company's drugs remained authorized, without any alterations to the treatment advice for doctors or patients, because there was no evidence of a "negative impact" of the medications.
EMA says it has informed the European Commission, the regulatory authorities of relevant nations, as well as Roche itself that it has started an infringement procedure in this case.
EMA says it has to make a recommendation to the EU Commission by April 2014.
Below are some questions and answers EMA issued today.
Why is the assessment being carried out?The assessment comes after a routine inspection by the MHRA, which found a number of deficiencies in the safety reporting systems at Roche Registration Ltd.
According to the MHRA inspection, case reports for medications marketed by Roche gathered from a US PSP (Patient Support Program) had not been evaluated to find out whether or not they were suspected side effects which should have been reported to European regulatory authorities.
EMA added "Other deficiencies identified related to the evaluation and reporting to national medicines agencies of suspected adverse reactions from their reporting systems and clinical trials."
What has happened so far?After the inspection, the MHRA asked Roche to take corrective actions to make sure the proper processing of reports of suspected adverse drug reactions was completed. Also, Roche was requested to report any missing cases of suspected side effects to the relevant EU authorities in accordance with the current legislation.
At the moment, PRAC (Pharmacovigilance Risk Assessment Committee), part of EMA, is reviewing data Roche has provided, which include previously missing case reports and corrections to data which had been previously processed.
PRAC is also determining whether these deficiencies might have an impact on the overall risk-benefit balance for any of the medications involved.
What are the recommendations?No indication of a negative impact on the benefit-risk balance of the drugs affected has been found.
For the moment, all medications remain authorized; treatment advice for patients and doctors remains unchanged.
EMA estimates that the review of individual drugs will be completed by March 2013. As appropriate, EMA says it will issue updates.
Written by Christian Nordqvist