European Regulatory Roundup: EMA in Argument With Ombudsman Over AbbVie Data (13 November 2014)

Welcome to our European Regulatory Roundup, a new feature exclusively for RAPS members. Each week our roundup will provide you with the latest, most important regulatory news affecting the EU and the companies operating therein.

Ombudsman Pressures EMA to Explain Redactions to Humira Clinical Study Reports

European Union Ombudsman Emily O’Reilly is pressuring regulators to explain why certain details were redacted from clinical study reports (CSRs) relating to AbbVie’s Humira. Having reviewed both the redacted and original CSRs, O’Reilly is concerned about the legality of some of the changes.

O’Reilly opened an investigation into the case in April 2014 and sent a letter to the European Medicines Agency (EMA) asking for clarifications late last month. The ombudsman published the letter this week, prompting a reply from EMA within hours. The regulator explained that while there is clear guidance on what personal details should be redacted, the procedure for commercially confidential information is more vague.

This vagueness is at the heart of the exchange between O’Reilly and EMA. In her letter, O’Reilly accepts some of the redactions as being valid, either because they remove personal details or legitimately commercially confidential information such as the software AbbVie used and the companies with which it worked. However, there are 16 different sets of redactions with which O’Reilly takes issue and on which she wants EMA to explain its reasoning.

The 16 redactions cover everything from lot numbers to whole sections describing the protocol of the trial. O’Reilly notes five pieces of redacted information that may have clinical value and a similar number of removed details for which she is unclear on how they could undermine AbbVie’s legitimate commercial interests. EMA has until 31 January 2015 to reply to the letter. In a statement, EMA said it would send a detailed response in due course.

EMA’s response has implications for the transparency agenda in Europe. The CSRs at the center of the debate were due to be released with limited redactions, only for the settlement of a court case to result in more extensive amendments to the documents. EMA, by its own admission, is still searching for the right balance on redactions and the Humira CSRs are an important test case for exactly what information is regarded as commercially confidential.

Ombudsman Letter I EMA Statement

Off-Patent Drugs Bill Fails to win Support of UK Government

Proposed legislation that would give the UK's National Institute for Health and Care Excellence (NICE) the power to license off-patent drugs in new indications has failed to win the support of the UK government. The politicians in power agree with the aims of the bill, but think it is unnecessary and the wrong way to encourage greater off-label use of drugs.

George Freeman, minister for life sciences, explained the government's position in a parliamentary session to debate the bill. “The lack of a license is not the restraining factor. In this landscape, the restraining factor is the lack of information for clinicians about off-label use,” Freeman said. Physicians are already free to prescribe drugs off-label, and NICE has recommended unlicensed use of tamoxifen and raloxifene.

The bill has nonetheless managed to win the support of a clutch of leading nonprofits, including the Association of Medical Research Charities, the Breast Cancer Campaign, Leukaemia and Lymphoma Research and the Alzheimer’s Society. There is also still a possibility that the bill will advance. Fewer than 40 politicians attended this week’s debate, The Pharmaceutical Journal reports, meaning it must be discussed again at a later date.

Parliamentary Debate I The Pharmaceutical Journal

PRAC Recommends Steps to cut the Risk Posed by Amgen and Servier’s Heart Drug

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended taking steps to cut the risk posed by Amgen and Servier’s heart drug, ivabradine. PRAC based the decision on clinical trial data that link ivabradine to increased incidence of heart attacks and unusually low heart rates.

To cut the risk of people taking the drug suffering from these adverse events, PRAC recommends physicians check each patient’s resting heart rate before prescribing ivabradine. Physicians should also monitor patients who take the drug for signs of an irregular and unusually fast heartbeat, known as atrial fibrillation.

The Committee for Medicinal Products for Human Use (CHMP) will now review the recommendations, after which the European Commission will make the final decision. EMA approved ivabradine in 2005, but the drug is yet to go on sale in the United States. European regulators began a review of the drug in May amid mounting concerns about its side effect profile.

PRAC Recommendations I Reuters

EMA Creates Bulk Edit Tool to Help Industry hit Data Maintenance Deadline

EMA has created a tool to help companies keep information on authorized medicines up to date. The industry has until the end of December to update information on its approved drugs, a deadline EMA is trying to ensure companies meet by providing a tool for editing important data fields.

Companies can use the tool to make bulk edits to the eXtended EudraVigilance Medicinal Product Dictionary (XEVMPD), potentially eliminating some of the more repetitive maintenance tasks. EMA asked companies to update the information in January and again in June as part of its new reporting requirements and data-submission format.

The changes mean new pieces of data are needed for authorized medicines and make it particularly important to keep information up to date. EMA is relying on the database to enact aspects of the 2010 pharmacovigilance legislation, notably by simplifying adverse event reporting and cutting the risk of fee miscalculations.

EMA Notice

Other News:

The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has told suppliers of drugs to the maritime sector they have until 1 December to apply for a dealer’s license. MHRA issued the notice after few maritime drug distributors responded to the initial message it sent in November 2013. Suppliers who fail to get licensed by the deadline must stop their operation. MHRA Notice

NICE has ruled that while the ReCell Spray-On Skin system and Parafricta Bootees and Undergarments have the potential to improve outcomes for patients, more research into both technologies is needed. The agency wants to see data on the time to 95% healing for the ReCell system and comparative research against standard care for the Parafricta products. ReCell I Parafricta

The Committee for Medicinal Products for Veterinary Use (CVMP) has upgraded the authorization for Coxevac. Previously, Coxevac was only authorized for use in exceptional circumstances. CVMP also ruled to maintain the exceptional circumstances provision for Bluevac BTV8, agreed to set maximum residue limits for propyl 4-hydroxybenzoate and reviewed pharmacovigilance programs. CVMP Report 

NICE has issued another defense of its position on statin use. In a statement aimed at the Health Select Committee, NICE Chair Professor David Haslam said statins have a notable effect on the likelihood of a cardiovascular event when the risk is more than 10% over a 10-year period. Some doctors are opposed to NICE’s stance on the use of statins. OnMedicaI NICE Statement

European authorities have awarded CE Marks to Augmenix and ViewRay. Augmenix received the status for two products used as markers in radiology imaging, while ViewBay got clearance for a system to deliver MRI-directed radiation therapy. Augmenix I ViewRay

MHRA has named Baxter Healthcare, Covidien, GE Medical Systems and Illumina on its weekly list of medical device field safety notices. The companies are among the 15 medical device manufacturers to post notices about problems with their products recently. Field Safety Notices