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FDA Consumer magazine
September-October 1999
by Tamar Nordenberg
In the first-ever criminal prosecution of a drug company for violating FDA's rules against promoting a drug for unapproved uses, a San Francisco-based drug maker has paid $50 million to settle charges that it illegally promoted a growth hormone. This is one of the biggest penalties ever paid by a drug company.
The company, Genentech Inc., is among the world's largest biotechnology corporations. As part of its plea agreement, approved May 7 in the U.S. District Court for the District of Northern California, Genentech admitted that it aggressively marketed the drug Protropin (somatrem for injection) for uses other than the one approved by FDA. Specifically, it illegally marketed Protropin for treating children who were short for reasons other than the lack of adequate growth hormone, children with a rare form of juvenile obesity, and a small number of burn patients. FDA had approved the drug only for a rare condition in which children don't grow normally because their bodies lack the ability to make enough growth hormone.
While FDA knows of no injuries connected with the unapproved uses of Protropin, it is generally illegal for a drug company to market a drug for unapproved, or "off-label," uses.
"It's a public health issue," says Jud Bohrer, special agent in charge of the Los Angeles field office of FDA's Office of Criminal Investigations. "It's one thing for a physician with medical training to make decisions about the conditions for which they will use a particular drug. But it's quite another matter when a manufacturer actively promotes its drug to treat conditions for which it hasn't been proven safe and effective."
FDA estimated that from 1985, when the drug was approved, until 1994, Genentech got about $158 million in total Medicaid reimbursement for Protropin prescriptions and more than $5 million from CHAMPUS, a federal military insurance program. Genentech's financial gain from sales of Protropin for unapproved uses was about $20 million, according to FDA's calculations.
FDA began looking into Genentech's marketing of Protropin following the June 1991 New York Times article "How Short Is Too Short?" FDA inspected the company in 1992 and, in September 1994, asked the company to turn over all its documents relating to the drug's promotional campaign. Then, starting in 1995 and continuing into this year, FDA and the FBI interviewed people connected with Protropin's marketing.
"We interviewed hundreds of people," Bohrer says, "including Genentech sales reps, employees of the company's distributor [Caremark Inc.], and others. We asked them the hard questions: 'Who told you to do what to promote the drug? Whom did you contact? What did you tell them?'"
FDA and the FBI also interviewed doctors who received financial incentives for prescribing Protropin in the name of studying the drug's effectiveness. These interviews were aimed at determining whether Genentech used "grant programs" as vehicles to pay prohibited kickbacks to doctors who prescribed Protropin. This aspect of the investigation was later dropped in favor of focusing on the charges related to Genentech's off-label promotion of the drug.
Based on Genentech's documents and the follow-up interviews, FDA determined that the company started actively promoting Protropin for off-label uses not long after the drug's approval. By the end of 1985, Genentech had "gone beyond the bounds of FDA-approved activity," according to the sentencing memorandum submitted to the court, "and begun marketing Protropin for use in the treatment of medical conditions for which it did not have FDA approval."
As part of its guilty plea, Genentech admitted that from 1985 until 1994, it aggressively marketed Protropin to doctors, hospitals and others for treating conditions that FDA had not approved. For its part, the government agreed that this criminal behavior stopped in 1994. In 1995, Genentech came under new management, which FDA concluded took additional steps to prevent violations of the law, including educating its sales force on proper drug promotion.
The $50 million settlement that Genentech agreed to pay is made up of a $30 million criminal fine plus a $20 million civil penalty to reimburse Medicaid and CHAMPUS, which FDA determined were the main victims of the illegal promotions.
The unprecedented prosecution and fine, said FDA Commissioner Jane Henney, M.D., after the settlement was announced, "sends a clear and strong signal that FDA takes very seriously promotions using illegal means."
Tamar Nordenberg is a staff writer for FDA Consumer.
by John Henkel
Two U.S. animal drug companies agreed to stop importing and selling certain injectable drugs after FDA determined that dangerous bacteria had contaminated the products. The bacteria, which may have caused illness in several herds of cows, also could have harmed humans who ate food from infected animals.
Veterinary Pharmaceuticals Inc. (VPI), importer and distributor of the drugs, and Sierra Pharmaceutical Inc., which manufactured the drugs in its Mexico plant, signed a consent decree March 9 that barred the companies from distributing injectable animal drugs until processing improvements were made. Both companies are based in Hanford, Calif.
The drugs--which included hypertonic saline solution, lactated ringer's solution, calcium gluconate 23 percent solution, dextrose solution 50 percent, and electrolyte solution with dextrose--are commonly used to treat dehydration in cows. VPI sold the drugs to customers in California, Missouri, and several other states.
FDA's laboratory analyses found samples of the drugs contained Bacillus cereus and three other related bacterial types. In cows, these bacteria can cause blood poisoning, respiratory infections, and mastitis (inflammation of the udder), and can produce toxins that remain in animal tissue. In humans consuming infected meat, the toxins can cause nausea, vomiting and diarrhea.
FDA has received no reports of human sickness tied to the drugs. But during the investigation, agency officials met with a California veterinarian, who reported that several cows in certain dairy herds he had treated had suffered illnesses that he attributed to Sierra-brand drugs he had prescribed.
FDA learned of the contamination in late 1997 after Kamaljit Kaura, then president of Sierra, informed the agency that the company had discovered bacterial contamination in some of its drug products and, along with VPI, planned to recall these products. Kaura attributed the contamination to the reuse of lab coats and said the company was taking corrective actions to ensure that these coats were sterile in the future. Kaura, however, was removed as president shortly after he contacted FDA with this information, according to FDA officials, and the company's new management conducted a recall of only one lot of the contaminated drugs, hypertonic saline.
In response to Kaura's report, in October 1997, FDA investigators collected samples of 45 lots of Sierra's injectable veterinary drugs for analysis by agency laboratories in San Francisco and Seattle.
Though the drugs were labeled "sterile," FDA labs found that nine lots were contaminated with Bacillus cereus, B. licheniformis, B. sphaericus, and B. subtilis. Analysis also showed that most samples contained alcohol as a preservative, though labels stated that they were "preservative free."
During an FDA inspection of VPI in November 1997, company officials turned over to investigators results of independent analytical tests that showed Bacillus contamination in three Sierra brand drugs the company had sold.
On Jan. 9, 1998, FDA sent VPI a letter asking the company to begin a recall of all Sierra-made drugs identified as contaminated. Two weeks later, the company began recalling all the products, and on June 5, 1998, VPI destroyed 23,700 vials of drugs, valued at $29,700.
FDA again inspected VPI in June and July 1998 and found that, despite promises to the contrary, the company had imported and sold drugs from Sierra's Mexican plant on two occasions between January and July. On July 15, the state of California placed an embargo on all remaining lots of Sierra animal drugs that had not been distributed. Two weeks later, FDA recommended that VPI and Sierra be enjoined from importing and distributing Sierra drugs.
VPI and Sierra, along with Harold Des Jardins, VPI's president and majority owner of Sierra, and James Mann, Sierra's president, entered into the consent decree of permanent injunction in March 1999 in the U.S. District Court for the Eastern District of California. The decree bars VPI from importing any drugs into the United States until FDA has inspected Sierra's Mexican facilities and approved its controls and procedures. Also, before VPI can again import drugs, it must:
On May 19, under FDA supervision, VPI destroyed 27,060 vials of Sierra brand drugs that California officials had embargoed the previous year.
John Henkel is a staff writer for FDA Consumer.
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