ABBOTT ERYTHROMYCIN I.V. SAMPLING BY CONTRACT SALES GROUP LIFETIME LEARNING VIOLATES DIVERSION ACT, FDA SAYS; ABBOTT GMP VIOLATIONS QUESTIONED BY REP. DINGELL

Abbott and a contract sales firm, Lifetime Learning, received the first reg letters FDA has sent out for a violation of the Prescription Drug Marketing Act. The agency sent reg letters to the two firms on March 8 for illegal distribution of erythromycin I.V. samples at focus sales meetings conducted by Lifetime Learning in support of Abbott's Add-Vantage System. The reg letters follow an inspection conducted by FDA in late October/early November. According to Abbott, the illegal sampling involved an isolated incident of a nurse picking up a sample of the company's erythromycin I.V. during one of the sales demonstrations. * FDA's reg letter, however, implies that the product was distributed to more than one person. "Lifetime Learning Inc., distributed the Abbott erythromycin lactobionate product to persons other than licensed practitioners and such distribution was done without benefit of signed sample request forms," containing the practitioner's name, address, and professional designation, the identity of the drug sample requested, the quantity of drug sample requested, the name of the manufacturer or distributor of the drug sample, the date of the request and signature of the practitioner making the request," FDA said. In its response to the reg letter, Abbott said it told FDA that from now on the company will provide labels for all demonstration products that state that the products are for demonstration purposes only, and not for use. Abbott also said it promised to remind its contract sales groups to account for all products used in sales demonstrations. FDA also issued Abbott a March 14 reg letter on good manufacturing practice deficiencies observed during a July-November 1989 inspection of its North Chicago, Illinois sterile processing plant. The reg letter asserts that Abbott's response to the Nov. 3 FD-483 that issued from the inspection ("The Pink Sheet" Dec. 11, p. 13) was "insufficient" and that the firm should address the deficiencies "with a more global perspective." FDA said that Abbott's plan to address the FD-483 focused "only on correction of the incident-specific" observations and "fails to provide adequate assurance that the same general type of violations observed during the investigation will not recur in the future." "By focusing only on correction of the incident-specific FD-483 observations, your action plan fails to provide adequate assurance that the same general type of violations observed during the investigation will not recur in the future," FDA said. For example, the agency said that Abbott's procedures "for documentation, recordkeeping, assuring that personnel consistently carry out responsibilities properly over time, and investigation of deviations are some general functions needing plant-wide scrutiny for adequate identification and correction of [the] underlying causes" of the company's GMP violations. Among deficiencies cited in the 41-page FD-483 were manufacturing problems that involved the potential for particulate contamination. The agency had cited the company for the release of seven products with high environmental particulate counts and for problems with validation and operation of the lyophylizer and autoclaves. The follow up reg letter includes a number of deficiencies related to contamination and sterility, as well as recordkeeping and employee oversight problems. For example, FDA cited the firm for: * failing "to assure that employees remain familiar with their assigned functions"; * not adequately assuring "that pyrogenic properties are removed from your containers"; * failing "to establish and follow adequate procedures to prevent microbiological contamination of your aseptically processed drug products purported to be sterile"; * failing "to determine the sterility of each batch of drug product purporting to be sterile by appropriate laboratory testing"; * and not including complete information on batch production records. The reg letter threatens that "if corrective actions are not implemented promptly, FDA is prepared to invoke regulatory sanctions...[including] seizure and/or injunction." FDA said that until it can "confirm through reinspection that adequate corrective action has been taken," the agency "will not approve NDAs, ANDAs or requests for procurement by federal agencies involving products affected by these violations." Abbott says its response to the FD-483 was intended to be "global," and that it will inform the agency of that intent in an official response to the reg letter. Rep. Dingell (D-Mich.) considers the Abbott violations further evidence of problems in the pharmaceutical industry that were uncovered in inspections at Lilly and in the generic drug industry. In a March 22 letter to Abbott Chairman and CEO Duane Burnham, the House Energy & Commerce/Oversight Subcommittee chairman said information about the plant "from several sources...has led the subcommittee to expand its inquiry to determine whether your firm has manufacturing or other problems similar to those already uncovered in the generic drug industry and at Eli Lilly and Company." The investigation into serious regulatory violations by the pharmaceutical industry began in 1988, when the Oversight Subcommittee launched its inquiry into FDA's generic drug review process. Dingell said his subcommittee wants to examine records of Abbott's perspective of FDA inspections and to learn about company officers who managed the North Chicago, Ill. plant that received the FD-483. The congressman told Burnham that adverse observations during the July-November 1989 inspection "confirm that very serious manufacturing problems were common" in the plant. The regulatory letter, he continued, "says that these problems persist." The subcommittee is requesting all Abbott records since Jan. 1, 1985 that document company "evaluations...or analyses of" inspections by FDA "or by any other person or entity of [the firm's U.S. drug] manufacturing or research facilities." Dingell also asked Abbott to provide a list of its "management personnel for the North Chicago small volume parenteral manufacturing facility, with a brief description of duties and reporting responsibilities." The congressman set an April 4 deadline for Abbott's submission of the records requested in the letter. He asked Burnham to notify the subcommittee by March 30 if "you require a subpoena to produce all or part of the requested material." * The subcommittee is also reviewing FDA's perspective of the company's responses to the regulatory actions. In a March 22 letter to FDA Acting Commissioner Benson, Dingell asked FDA to provide his subcommittee with copies of Abbott's action plan, all related documents and "any future documents relating to Abbott's efforts to resolve widespread problems at its North Chicago plant." The congressman added that he wants to review the records on all FDA inspections of Abbott dating from Jan. 1, 1988. Dingell told Benson that the regulatory letter indicates there are "serious and continued deviations from current GMPs" at the North Chicago plant. He additionally inferred that the agency believes "Abbott's action plan does not adequately address resolving GMP problems with regard to whole manufacturing systems."