The probe comes after UK regulators identified deficiencies in reporting adverse events after conducting recently review procedures and was actually part of a coordinate European program to inspect safety reporting systems in the pharmaceutical industry, according to the EMA.

At the time of the inspection, Roche identified some 80,000 reports for medicines marketed in the US that had been collected through its patient support program, the EMA states, but these had not been evaluated to determine whether they should have been reported as suspected adverse reactions to EU authorities. There were also questions about 23,000 adverse events related to evaluating and reporting to national regulators and 600 pertaining to clinical trials.

For now, it remains unclear whether the deaths were due to natural disease progression or a causal link to a drug. More recent information from Roche indicates a smaller number of reports, but this information needs to be verified by the authorities. It is also uncertain whether any of the reports have already been submitted to EU authorities through other channels, for example by the healthcare providers.

For now, the EMA says there is no evidence of a negative effect on patients or any need for patients or healthcare providers to take any action. But the EMA is looking at whether the deficiencies in reporting adverse events are having an impact on the overall benefit-risk profile for any of the drugs involved. The agency’s Committee for Medicinal Products for Human Use, CHMP Pharmacovigilance Working Party and the Coordination Group for Mutual Recognition and Decentralised Procedures discussed the problems at meetings in May and June.

In any event, the EMA is telling Roche to ensure that all known, reportable adverse events are immediately reported to the appropriate EU authorities as required by law and the drugmaker must confirm to the agency that this has been done, both for products in clinical trials and for marketed products. Roche must also to submit a revised, comprehensive action plan by June 27 for evaluating and reporting all outstanding cases and plans for corrective measures to ensure advere events are reported correctly in the future. This includes evaluation of each of the 80,000-plus reports received by the patient support program in the US.

We asked Roche for comment and will update you accordingly (here is the EMA statement).

[UPDATE: A Roche spokeswoman wrote this: "In January and February 2012, the UK Medicines and Healthcare products Regulatory Agency (MHRA) conducted a routine inspection of Roche’s global pharmacovigilance processes at Roche’s site in Welwyn, UK. The inspection found deficiencies related to Roche's global pharmacovigilance processes. In addition, Genentech identified potential adverse events from our Patient Reimbursement Program in the US, which were not sent to the safety department for full evaluation, hence were not reported to the health authorities according to the applicable regulation. We have provided initial estimates of potentially unassessed AEs to health authorities and are in the process of confirming the final number.

Roche and Genentech acknowledge we did not fully comply with regulations and appreciate the concerns that may be caused by this issue for people using our products. We are committed to actively pursuing corrective and preventative actions to address this matter expeditiously. Patient safety is of paramount importance to us and we are fully committed to being in compliance with all pharmacovigilance/safety reporting regulations and to ensuring that effective quality systems and procedures are in place for recognizing and reporting adverse events appropriately.

Based on our assessments to date, no impact on the safety profile of any of its products has been found. Our products have a well-characterised benefit-risk profile based on all available safety information, such as the clinical trials on which their approval by health authorities was based on, extensive programs of post-approval clinical studies, scientific publications, pre-clinical data and epidemiologic publications. This information is complemented throughout the life-cycle of the product with spontaneous safety reports coming from doctors and patients.]

By Ed Silverman