In a $313 million settlement with the Department of Justice, Forest Pharmaceuticals pled guilty to a series of charges, including marketing the hyperthyroidism treatment Levothroid (levothyroxine) without FDA approval and submitting inaccurate information to FDA as part of a new drug approval application.

The company pled guilty one criminal misdemeanor count of distributing an approved drug with regard to Levothroid and to one criminal felony count of obstructing an FDA inspection. The agreement states that Forest expressly and unequivocally admits that it committed the latter offense and "acted knowingly and corruptly."

Forest also pled guilty to promoting the antidepressant Celexa (citalopram) off-label for pediatric uses, specifically a criminal misdemeanor count of distributing a misbranded drug.

In addition, as part of a civil settlement, Forest agreed to resolve allegations that it marketed Lexapro (escitalopram) for unapproved uses, used kickbacks to induce physicians to prescribe Lexapro and Celexa and caused false claims to be submitted to federal health care programs for all three drugs.

Forest also signed a five-year corporate integrity agreement with the HHS Office of Inspector General that requires the company's Board of Directors or a committee of the Board to annually review and certify the company's compliance program, for senior executives to annually certify their departments are compliant and for the company to post payments to physicians on its website, among other things.

The DoJ and Forest announced the agreement Sept. 15. In a side letter agreement, the DoJ said the government would not pursue criminal prosecution of Forest Laboratories or any of its subsidiaries other than Forest Pharmaceuticals as long as Forest Pharmaceuticals fulfills the terms of the plea agreement.

The agreement also resolves three qui tam suits (suits brought by private individuals who share in recovery of government funds).

The $313 million total includes a $150 million criminal fine, $14 million in forfeited assets and $149 million to resolve False Claims Act allegations. Under the civil settlement, states will receive more than $60 million and the federal government more than $88 million.

"We are pleased to bring closure to this long-running investigation," Forest Chairman and CEO Howard Solomon said in a statement. "We have continued to enhance our compliance program since the events at issue in this investigation which occurred a number of years ago."

Complaint Cites Deception in Levothroid Inspection

The most serious charges against the company are outlined in the government's criminal complaint regarding Levothroid.

Levothyroxine drugs were first marketed in the 1950s to treat thyroid hormone deficiency at which time they were not considered to be "new drugs" under the Food, Drug, and Cosmetic Act. In 1997, FDA issued a notice that they were new drugs, that new information showed there were significant stability and potency problems with them and that very small differences in potency could make the difference between a therapeutic dosage and a potentially suboptimal or toxic dosage.

The agency gave manufacturers four years to submit NDAs for the products and in 2001 issued a guidance for phase-down that required them to have an NDA pending or approved by Aug. 14, 2001 to continue distribution.

The complaint states that Forest discovered that the Levothroid it was distributing commercially failed stability testing under specific, controlled temperature and relative humidity conditions and as a result stopped subjecting the drug to those conditions during stability testing. The complaint says that Forest personnel at its Cincinnati plant decided to put a portable home humidifier into a room where stability studies were conducted as a temporary fix to improper humidity levels and that management personnel denied use of the humidifier.

The complaint also says Forrest decided not to comply with the FDA guidance for a phase-down and when it received a warning letter from FDA on Aug. 8, 2003 to cease distribution of Levothroid it continued to ship as much of the product as possible. The complaint details that on that day, employees at its St. Louis distribution center placed a priority on filling Levothroid orders, overrode the computer system to place a priority on filling the largest Levothroid orders first and had its trucking carriers pick up extra trailers full of Levothroid shipments.

More than half a dozen other companies complied with FDA's requirements and went through the NDA process to get their levothyroxine products approved.

As for the marketing charges, the complaint says from 1998 through at least September 2002, Forest promoted Celexa for off-label use in treating children and adolescents. It states that sales representatives made sales calls to pediatricians, hired outside speakers to talk to doctors who specialized in treating children and adolescents, and publicized positive results of one study in children while failing to discuss the negative findings of another study.

The civil complaint also alleges that Forest marketed Lexapro off-label for pediatric use prior to its approval for treatment of major depressive disorder in adolescents in March 2009 and that it used kickbacks, such as cash payments disguised as grants or consulting frees, meals and entertainment, to get doctors to prescribe Lexapro and Celexa.

The company had reported last year that it had reached an agreement in principal with the DoJ and the U.S. Attorney's Office for the District of Massachusetts to settle civil claims in two False Claims Act suits ('DoJ's Microscope: Pharma Companies Under Investigation' 'The Pink Sheet,' Nov. 16, 2009).

- Brenda Sandburg (b.sandburg@elsevier.com)

Forest Admits To Knowingly Obstructing FDA Inspection In Guilty Pleas On Levothroid, Celexa Marketing

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