FDA warns Schering and Berlex about late adverse reaction reports

Company delayed reporting by as much as two years

German pharmaceutical firm Schering AG and its U.S. subsidiary, Berlex Laboratories, last month received warning letters from the Food and Drug Administration related to the companies' reporting of several incidents in which patients experienced allergic reactions to their products. The letters charged that Schering did not report the adverse drug reaction incidents to Berlex in a timely manner, resulting in late reporting to the FDA, and that some of the reactions were classified or dated incorrectly.

The incidents involve Schering's Magnevist MRI agent, Ultravist x-ray contrast agent, and its chronic lymphocytic leukemia treatment, Fludara. In one Ultravist case, the patient stopped breathing, while in a Magnevist case, the patient died, according to the FDA letter.

The agency objected to the way the company reported the incidents, claiming that Schering delayed notifying Berlex of the adverse reactions, which resulted in Berlex's failure to submit reports within the 15-day reporting period required by law. In one case, Schering did not notify Berlex until almost two years after the incident occurred. Some reports were late because they were classified incorrectly, according to the letters. In addition to chronicling Schering's incorrect and delayed reports, the FDA charged Berlex with inaccurately dating adverse drug reaction filings so that there were discrepancies between the date the company actually received the report and the date noted in its response to the FDA.

The FDA discovered the reporting delays and discrepancies in August and September of 1998, during inspections of Schering and Berlex facilities in Berlin and in Wayne, NJ. The inspections were conducted to determine compliance with the Postmarketing Adverse Drug Experience (PADE) reporting requirements mandated by federal law. After the inspections, the FDA issued a report outlining its concerns, and Schering and Berlex responded in September and October 1998,
detailing the corrective actions taken, according to Wendy Neininger, Berlex spokesperson.

The FDA's February warning letters cite the same concerns as the earlier report, Neininger said. Both Berlex and Schering have responded to the warning letters and are waiting for the agency's response.

"We have taken appropriate corrective action, and have responded to the FDA with a full outline of those corrective steps," Neininger said.