SMITHKLINE'S FAILURE TO FORWARD SELACRYN REPORTS TO FDA FROM FRENCH DRUG DEVELOPER ANPHAR IS BASIS OF JUSTICE DEPT.'s 34 CHARGES AGAINST THE FIRM

SmithKline's failure to pass on Selacryn adverse reaction reports to FDA from the drug's developer, the French firm Anphar, is the basis of seven of 34 charges against the firm in a Justice Dept. criminal information filed in Philadelphia Federal Court on June 12. According to the Justice Dept. filing, SmithKline did not report either Anphar's adverse reaction summary covering the drug's use in France over the three years prior to U.S. marketing, or two updates of the summary that allegedly established a link between the antihypertensive and liver problems suffered by patients on the drug. Both reports were sent by Anphar to SmithKline in the two months following Selacryn's U.S. approval on May 2, 1979. One of the Anphar reports to SmithKline in late June-early July 1979, Justice asserts, contained an updated summary of adverse reactions as well as "analyses and clinical details of individual hepatic adverse reactions, including hepatic positive rechallenges with ticrynafen." Justice is arguing that SmithKline and three physician employees violated reporting requirements by not providing FDA with the Anphar findings in either three-month post-marketing adverse reaction reports or in "unexpected" adverse reaction reports required 15 days after notice of such an event. In addition, Justice alleges that SmithKline was aware of at least five Selacryn-related adverse liver reactions in the U.S. that were not passed on to FDA. Selacryn Labeling "False And Misleading," Did Not Note Abnormal Liver Function Tests -- Justice SmithKline marketed Selacryn for the treatment of hypertension from May 1979 to January 1980 when the firm withdrew the drug from the market due to liver toxicity reports. FDA referred the findings of its own investigation into SmithKline adverse reaction reporting to the Justice Dept. in June 1981 following a "Section 305" hearing with company reps the previous fall. Approved in France in 1976, ticrynafen continues to be marketed in that country by Anphar. Overall, the Justice Dept. criminal information includes 14 counts against SmithKline and employees Philip Tannenbaum, MD, Ralph Myerson, MD, and Theodore Selby, MD, for failing to make the required adverse reaction reports to FDA. SmithKline, the three physicians, and Thomas Davis, MD, are also named in 20 counts of "misbranded" drug labeling for each mfr. shipment of Selacryn made between Sept. 24, 1979 and Jan. 9, 1980. Justice is maintaining that Selacryn was misbranded since SmithKline's approved labeling for the drug was "false and misleading." The labeling did not reflect adverse reactions reported to the firm, Justice asserts. In the information filing, Justice argues that the labeling was "false and misleading" because: "(a) Selacryn had been shown to cause and to be capable of causing abnormal liver function tests and jaundice and (b) such labeling failed to reveal material facts, namely, that hepatic positive rechallenges had been reported with Selacryn and Selacryn had been reported as the probable cause of abnormal liver function tests and jaundice." SmithKline's approved labeling for Selacryn had stated: "Abnormal liver function tests and jaundice have been reported in a few patients treated with Selacryn (brand of ticrynafen); however, no causal relationship has been established." In a June 12 statement to employees and shareholders, SmithKline said that the Justice Dept. "charges are technical in nature and related to the timeliness of reporting of side effects to the U.S. FDA and the description of side effects in the prescribing information for the drug. There are no charges that the company or its employees acted intentionally or for a commercial motive. In this regard, the exhaustive investigation by the Department of Justice confirmed our internal findings." SmithKline continued: "The experience has been a profoundly said one for all of us. SmithKline Beckman continues to maintain that the judgments about the side effects were made in good faith, involved complex medical considerations, and should not be the subject of Justice Dept. action." The case against SmithKline will be prosecuted by Assistant U.S. Attorney Peter Smith, Justice Dept. attorney Lawrence McDade, and FDA Assistant Chief Counsel for Enforcement Eric Blumberg. The next step for the Justice Dept. proceeding is for the defendants to appear at an arraignment in Philadelphia federal court some time in the next few weeks. "The is the first time the criminal provisions of the Federal Food & Drug Act have been used in connection with violations of FDA reporting requirements for new drugs," Justice stated in a June 12 press release. "The offenses are misdemeanors, carrying maximum penalties of one year imprisonment and a $1,000 fine for each violation," the release adds. The last major Justice Dept. suit against a health care firm was the Abbott I.V. contamination trial in 1975. Justice is currently considering whether to take action against Lilly for its adverse reaction reporting for Oraflex. However, Justice's case against Lilly would be very different from the SmithKline suit. Whereas the Justice Dept.'s action against SmithKline is concerned with adverse reaction reporting after market approval, a case against Lilly would more likely focus on whether the firm was required by law to report foreign clinical or commercial adverse effects while the drug was under review at FDA. Chart omitted.