Drug's Removal Exposes Holes in Europe's Net

http://www.nytimes.com/2001/08/22/business/22BAYE.html

August 22, 2001

Drug's Removal Exposes Holes in Europe's Net

By EDMUND L. ANDREWS

RANKFURT, Aug. 21 — When Bayer A.G. announced earlier this month that it was withdrawing its fast-selling cholesterol-lowering drug from the market, it pleased officials at the United States Food and Drug Administration, who had become alarmed by a rising number of deaths and severe reactions linked to the drug.

But in Europe, where Bayer is based, the move startled regulators and exposed considerable confusion. As recently as June, regulators from countries in the European Union decided that problems with the drug, sold under the brand names Lipobay and Baycol, could be handled through new warnings to doctors and patients.

Now, as they seek to respond to the problem, they are also trying to sort out who in Europe is responsible for dealing with such issues. Bayer is a German company, but its drug was licensed in Europe by the British authorities with neighboring countries essentially adopting its decision.

But Britain's regulator, the Medicines Control Agency, does not have the main responsibility for monitoring a drug's safety after it has been approved. That is supposed to be shared by each government within the European Union.

German health officials now complain that Bayer failed to give them the troubling data that it turned over to British regulators in June. The British agency, which never sent the report to its counterparts, says that was Bayer's responsibility.

And Europe's umbrella organization for drug regulation, the European Agency for the Evaluation of Medical Products, contends that it has little role to play because it was not involved in the licensing.

"There is a real problem with coordination," said Karl Lauterbach, a professor of health economics at the University of Cologne and an adviser to the German Ministry of Health. "One country like Great Britain can have responsibility for the approval process, but not for safety. The problem currently is who, exactly, is responsible on the European level for safety."

Bayer says that Baycol, also known by the generic name cerivastatin, has been linked to 52 deaths around the world, mostly in cases where patients took it in combination with another cholesterol-lowering drug, gemfibrozil.

The problem is that Baycol, when used in combination with gemfibrozil, occasionally produced a disorder that caused a breakdown of muscle cells, leading to kidney failure.

Regulators in Europe and the United States had become increasingly worried about Bayer's drug, which was approved in 1997. But their reactions differed considerably.

In the United States, Bayer was required to include warnings to doctors and patients against combining Baycol with gemfibrozil as early as 1999. European regulators did not demand a comparable warning until June, after Bayer presented them with data about harmful reactions in Europe.

Michael Diehl, a spokesman for Bayer, said the European warnings came later because fewer Europeans combined different drugs and fewer problems were arising.

But the F.D.A. may also have had access to more complete data. The agency collects reports from across the country, but in Europe, regulators piece together reports from each member country.

Spanish health officials reported in June that three people had died in the previous six months from the muscle-weakening disease, known as rhabdomyolysis.

More recently, German health officials have said that five deaths may be linked to the drug. But those are much smaller numbers than the 31 deaths recorded by the F.D.A., a fact that Dr. Lauterbach said might have impeded European officials from recognizing the severity of the problem.

Poor information-sharing surfaced again when Bayer submitted a study to British regulators on June 15. That study was based on data compiled by an American health maintenance organization and showed that severe reactions were more common among people who combined Baycol with gemfibrozil than among people who combined other cholesterol-lowering drugs.

Last week, amid a growing public uproar and numerous class-action suits against Bayer, Germany's health ministry complained that it had never received the report. Rather than criticizing their British counterparts at the Medicines Control Agency, German officials denounced Bayer for its "unacceptable information policies."

"It isn't the job of the M.C.A. to be postman for the European Union," said Ulrich Hagemann, deputy director for pharmaceutical monitoring at Germany's Federal Institute for Medicine and Medical Products, which is the German counterpart to the F.D.A.

Mr. Diehl of Bayer responded by saying that Bayer had satisfied its reporting obligations.

Mr. Hagemann defended Europe's decentralized system for drug regulation. Drug approvals can essentially be delegated to a single European country, and a drug manufacturer can choose the country in which it will seek approval. In theory, all countries apply the same rules and guidelines for approving products.

But monitoring safety afterward is more complicated because no country wants to be responsible for collecting data from the entire European Union. As a result, each country has the same obligation to monitor and pass on information about results within its boundaries.

Europe does have a centralized regulatory agency, the European Agency for the Evaluation of Medical Products, which licenses drugs produced through genetic engineering. Companies with new drugs produced by conventional technology can seek approval through the agency, which is in London, but Bayer chose to seek approval through what Europeans call the process of mutual recognition.

"We did not intervene because we did not have to intervene," said Noel Walthion, head of the agency's office of post-authorization evaluation. The only pan-European group with a responsibility for discussing such safety issues is a group of experts known as the Pharmacovigilance Working Party. That group met in June, a few days before Bayer turned in its latest and most troubling study. That was when it decided to impose the warnings that had been standard in the United States for two years.

Mr. Diehl of Bayer confirmed that his company decided to withdraw the drug primarily because of reports in the United States. Now European regulators are trying to organize a review of the safety of other cholesterol-lowering drugs, and they are still considering the case of Baycol.

ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.