More than a year after initiating an investigation into "serious" pharmacovigilance shortcomings at Roche, EU regulators say they have found new evidence of unreported adverse events associated with the company's products, but that none will be withdrawn from the market.

Background

In October 2013, UK regulators conducting an inspection of Roche said they found "Serious shortcomings" with respect to the company's pharmacovigilance practices and processes that resulted in nearly 80,000 adverse events going unreported to regulators.

Those findings were the result of a May 2012 inspection by the UK's Medicines and Healthcare products Regulatory Agency (MHRA), which was conducting a routine inspection of the company's UK facility. Among the tens of thousands of adverse event reports were more than 15,000 reports of patient deaths, 23,000 suspected adverse reactions and 600 clinical trial-related adverse events. Those numbers have, according to Roche, been revised substantially downward since the initial reports.

Regulators cautioned that the reports did not imply causation, and were not necessarily even associated with the drug product being taken by consumers. Regulators were nevertheless furious, and immediately launched an investigation into whether any laws were broken and just as importantly if any medicines had previously unknown risks that might require them to be removed from the market.

Conclusion of Investigation

The European Medicines Agency (EMA) has now released the results of its investigation, saying it has conducted a "thorough review" of the 19 medicines affected by Roche's lack of reporting.

Regulators said that while some new adverse events had been discovered that "had not previous been provided by Roche," those new effects did not substantially impact the benefit-risk assessment of any drugs to the point of requiring their withdrawal from the market.

The drugs included many of Roche's most popular products, such as Avastin, Herceptin, Pegasys, Tamiflu, Zelboraf, MabThera and Boniva.

Fortunately for Roche, EMA's Pharmacovigilance Risk Assessment Committee (PRAC) concluded that for all drugs, "There is no new advice regarding their use."

"However, as Roche continues to provide additional data as part of their obligatory follow-up, they are required to ensure that these data are included and considered in their routine pharmacovigilance activities, including the periodic cumulative reviews of the benefits and risks of these medicines," EMA wrote.

Unresolved Legal Issues

Roche, though, is still not in the clear. Under the terms of the infringement procedure launched against the company at the time of the launch of the investigation, it could be subject to massive fines.

Article 16.2 of EC No 658/2007 allows for the EC to impose a penalty of up to 5% of a company's revenue for the preceding year. Continued non-compliance can lead to an ongoing, periodic fine of 2.5% of the company's daily revenues until compliance is assured.

EMA said the conclusion of its investigation was "without prejudice to the infringement procedure."

EMA Statement