German firm fined under FD&C Act – Hoechst AG, federal Food, Drug, and Cosmetic Act
A large German pharmaceutical and chemical company that does business in the United States and one of its former research directors have become the first foreign entities to be successfully prosecuted under the Federal Food, Drug, and Cosmetic Act for conduct that occurred overseas.
Hoechst Aktiengesellschaft, or Hoechst AG, of Frankfurt, Germany, and Rainer Zapf, M.D., a former director of the company’s clinical research division, were sentenced last April in the U.S. District Court for the District of New Jersey for failing to report in a timely manner the deaths of two foreign patients associated with the use of the company’s antidepressant nomifensine maleate.
FDA regulations require drug manufacturers to report to FDA serious and unexpected adverse drug reactions both before and after the drug is approved for marketing in the United States. During clinical testing before approval), such adverse drug reactions must be reported within three days. After approval, significant adverse drug reactions must be reported within 15 days after the manufacturer has received the information.
These reports are required whether the adverse reactions occurred in the United States or elsewhere. Until now, FDA has charged only U.S. drug manufacturers with failing to file such reports.
In the Hoechst AG case, FDA determined that the deaths of an Italian woman, age unknown, in 1980 and a 57-year-old French woman in 1984-before die drug was approved in the United States – were associated with the use of nomifensine and that Hoechst AG had known of the deaths but failed to report them until 1986, months after the drug had been withdrawn from the market.
The drug was approved by FDA in 1984 and marketed in this country as a prescription drug under the trade name Merital between 1985 and 1986 by the company’s subsidiary, Hoechst-Roussel Pharmaceuticals Inc., of Somerville, N.J.
Hoechst AG, which had marketed the drug in almost 80 countries, voluntarily stopped selling it in January 1986 because of a rising incidence of hemolytic anemia associated with its use. Hemolytic anemia is a potentially fatal condition in which the oxygen-carrying red blood cells break down faster than the body can replace them.
Nine other deaths involving hemolytic anemia – including three deaths in the United States – were reported in people who used the drug. (Most of these were promptly reported to FDA.) However, the agency was able to confirm only the deaths of the two European women as definitely associated with nomifensine.
In August 1986, shortly after Hoechst AG halted sales of nomifensine, FDA began an investigation of the company’s U.S. subsidiary, Hoechst-Roussel. The investigation stemmed from a congressional hearing on Merital earlier in the year.
The investigation, which lasted a year and a half, was lengthy because officials of the U.S. company refused to allow personnel who had been directly involved in analyzing and reporting adverse drug reactions to speak to FDA investigators. In addition, months often passed before they provided written answers to investigators’ questions.
Despite the obstacles, investigators pieced together evidence showing Hoechst AG and Zapf had been aware of the deaths of the two European women shortly after they had occurred but had failed to report them to FDA as required. FDA found no evidence that Hoechst-Roussel had withheld such information from FDA.
In April 1989, FDA forwarded its evidence to the Department of Justice. On Dec. 12, 1990, the U.S. attorney for the District of New Jersey charged Hoechst AG with failing to report the deaths of the two European women, first while Merital was being tested and then again after it was approved. Zapf was charged with pre-approval violations. No charges were filed against Hoechst-Roussel.
On April 26, 1991, Hoechst AG and Zapf pleaded guilty to the charges. The company was fined $202,000, and Zapf, $2,200. Both fines were the maximum allowed under then existing law.
I. Michael Bruckheimer, the lead investigator, received FDA’s 1991 Patrick J. Pouzar Investigator of the Year Award for his work on this case.
Paula Kurtzweil is a member of FDA’s public affairs staff.
COPYRIGHT 1991 U.S. Government Printing Office
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