PAR's GENERIC VERSION OF MAXZIDE RECALLED JULY 24 DUE TO SAMPLE SWITCH DURING FDA INSPECTION; FIRM RECALLS THREE PRODUCTS REPRESENTING 6% OF SALES

Par recalled its generic version of Mylan/Lederle's Maxzide on July 24 after reporting that an executive switched samples during an FDA inspection. The reason for the switch is not yet known. In a same-day statement, Par explained that "certain product samples furnished to an FDA inspector were intentionally drawn from a production batch other than that represented to the inspector." The company informed FDA and the House Commerce/Oversight Subcommittee of the deception on July 21, two days after the company voluntarily ceased shipping its generic version of the hydrochlorothiazide/triamterene product. Par initiated the voluntary recall of the antihypertensive after FDA requested corrective action at a July 21 meeting. Par recalled three products during the week of July 24. In addition to triamterene/hydrochlorothiazide, Par subsequently recalled the muscle relaxants orphengesic and orphengesic forte. The three products represent 6% of fiscal 1989 sales, Par said. The company also announced the formation of "a special review committee" made up from the firm's outside board members. The committee "will engage outside consultants to perform an independent review of Par's research and recordkeeping systems," Par said. Due to the "urgency of the investigations of these matters," the firm postponed indefinitely its annual shareholders meeting, which had been set for July 28. The allegations regarding Par are noteworthy in that they involve several of the firm's highest-ranking officers. In a July 24 statement, Rep. Dingell (D-Mich.) noted "the direct involvement of another founder of Par . . . in subverting the FDA's generic drug approval process." Par cofounder R. K. Patel is reportedly responsible for the sample switch. The company announced that Patel took "a voluntary leave of absence from his positions as senior vice president and director of Par and will, until further notice, be taking no role in the affairs of the company." In addition, Executive VP Jeffrey Levine and VP-Regulatory Affairs Barry Geller "have taken voluntary leaves of absence from their positions on Par's board of directors." The congressman, whose House Commerce/Oversight Subcommittee has been investigating FDA's generic drug review process, reported: "R. K. Patel, one of three founders of Par Pharmaceutical, had been discovered substituting samples of Par's generic Maxzide . . . which FDA had requested to evaluate the validity of the firm's bioequivalence study" that served as the basis for the product's approval. Furthermore, Dingell said that Jeffrey Levine, son of another founder, Perry Levine, was informed of the discovery on July 6 "but neither FDA nor the subcommittee was informed until" July 21. The third cofounder, former Senior VP Ashok Patel, who admitted paying illegal gratuities to FDA chemistry review staff, has resigned from the company ("The Pink Sheet" May 1, T&G-1). Dingell suggested that the revelations ought to facilitate an FDA determination that the agency has discretionary authority to "debar" corrupt firms by freezing pending applications and withdrawing approvals. "The Vitarine episode was bad enough, but now we have a company that has apparently not only made false statements and destroyed evidence, but has also paid off FDA officials," Dingell said. "I would expect that Commissioner Young will finally take action against companies which corrupt the generic drug approval process." Dingell compared the latest Par disclosure to reports that Vitarine submitted fraudulent test drug samples to a contract lab. In the earlier case, the test drug actually contained SmithKline's Dyazide, the reference drug, inside Vitarine capsules. R. K. Patel's deception occurred July 6 and involved substitution of a current production sample for a bioavailability test sample, which an FDA investigator asked to examine. Dingell speculated that the switch was made because Lederle/Mylan's product was disguised as Par's test drug in the bioequivalence tests. "It is likely that we have another Vitarine episode on our hands," he said. However, FDA postulated a different reason in a July 24 statement: the switch "may have been an effort to conceal the fact that the sample was missing an ingredient (sodium bicarbonate)," FDA suggested. The agency added that the switch was "witnessed by another Par official, and the matter was ultimately brought to the attention of the company's board of directors." The congressman only partially blamed FDA for not catching the generic Maxzide deception. "It is unlikely that a routine inspection would have uncovered this latest fraud," he said. However, he noted that Par's "admissions were triggered by a special investigation instigated by Deputy Commissioner James Benson." The subcommittee further noted that "serious questions involving several other drugs were raised in the course of the special FDA inspection." They involved the muscle relaxants orphengesic and orphengesic forte; the antidepressant valproic acid; and two products for which ANDAs are pending, the steroid methylprednisolone and an unidentified antidepressant product. Regarding orphengesic, "an FDA investigator discovered that Par may have falsified the size of the batch sampled for during the approval process," the agency explained. The records of the batch sample submitted to the laboratory indicated that initial test samples were drawn from a batch of 50,000 tablets, but raw material records showed only 25,000 tablets could have been manufactured. FDA said it was told by Par "that the record of the batch may have been falsified to conceal the fact that someone had cut the production run in half." At the agency's request, the firm recalled the product from retail sale. Par ceased production of valproic acid (generic form of Abbott's Depakene). FDA said an inspector "discovered discrepancies in the company's statement of the generic drug's composition, the record of the batch submitted to the lab, and the composition of the gel used to encapsulate the product." Dingell commented that the valproic acid case exemplifies "several of the problems uncovered by the subcommittee to date." He added that it represents "an intolerable situation when neither the company nor the FDA knows the actual contents of a marketed generic drug." Batch records also were falsified for the two unmarketed products. The methylprednisolone batch record "was falsified to indicate the presence of an inactive ingredient that had been omitted from production," the Dingell subcommittee reported, adding: "Par believes that batch was never used in a biostudy." Regarding the unidentified antidepressant, Dingell said R. K. Patel instructed Par employees to "falsify the inventory card" during an inspection "because of a discrepancy with the batch record." The employees refused to do so, the subcommittee noted.