API firm remains open after signing GMP consent decree pursuant to court-ordered injunction
From FDA Enforcement Manual, Thompson Publishing Group
Table of Contents
Multiple warnings
Decree terms
Companies that choose to go to court rather than settling enforcement actions with the FDA may get better results even if the judge finds that the firm has violated good manufacturing practices (GMPs). That is what a June 14 consent decree of injunction signed by active pharmaceutical ingredient (API) manufacturer Particle Size Technology Inc. (PST) indicates.
PST and the FDA initially tried to settle the GMP enforcement action without going to court, but negotiations broke down when the Pennsylvania-based company refused to sign an FDA-proposed decree that closely mirrored the terms of the agency's standard decree. Under the terms of that decree, the company would have had to cease operations immediately and only could resume manufacture after the FDA determined that it had made necessary corrections and come into compliance with GMPs.
After negotiations broke down, the FDA filed a complaint for permanent injunction December 13, 1999, in the U.S. District Court for the Eastern District of Pennsylvania, again seeking its standard injunction terms. Although the court on March 20 ruled in favor of the FDA and permanently enjoined PST and two of its executives from manufacturing, holding or distributing adulterated drugs, the court found that PST had "taken steps to improve and substantial changes [in its operations had] been made." Consequently, the court requested that the FDA and PST negotiate a decree that would enable the company to remain in operation, under specified conditions.
In an interview, Paul Logan, PST's attorney, noted that the firm decided to contest the FDA's enforcement action in court because it already had taken corrective action to address the agency's concerns and was therefore in substantial compliance with GMPs by the time settlement negotiations broke down. Accordingly, the company was unwilling to sign a decree that would have required it to shut down operations, he said.
The firm eventually chose to sign a less burdensome decree because complying with that decree was cheaper than continuing to litigate, Logan explained, noting that PST already had satisfied many of the provisions of the June 14 decree before its signing.
Nevertheless, according to former FDA Deputy Director of Enforcement Arvin Shroff, the decree still vests the agency with sufficient enforcement powers to ensure that PST maintains compliance. The decree puts the FDA "in the driver's seat," Shroff said, noting that the agency can shut down the firm without returning to court if it determines that PST has violated the decree.
Multiple warnings
The enforcement action stems from four inspections the FDA conducted at PST's plant between 1997 and 1999, during which investigators uncovered similar alleged GMP deviations, according to the agency's complaint. After each inspection the FDA issued PST a list of inspectional observations (FDA Form 483). The agency also issued a Warning Letter to PST in January 1998.
In response to the Warning Letter and each 483, PST promised to take corrective action, the FDA's complaint states. Nevertheless, in the agency's opinion, PST repeatedly failed to bring its operations into compliance with GMPs.
In the FDA's most recent inspection, conducted in November 1999, the agency uncovered alleged deviations regarding: airborne dust; cleaning and processing procedures; cleaning validation; cross-contamination; equipment calibration; record keeping; and standard operating procedures.
According to Logan, PST acknowledged to the agency that its most recent 483 observations were accurate and pledged to correct the alleged deviations immediately. The firm then hired an outside consultant who helped it come into GMP compliance, he said, adding that PST forwarded copies of the consultant's reports to the FDA.
Decree terms
Although PST never shut down operations, the decree permanently enjoined the firm—and its president and chairman of the board—from manufacturing, holding or distributing any APIs until the firm's methods, facilities and controls were in conformity with GMPs. The decree also reiterated the terms of the court's March 20 order of permanent injunction.
Under the decree, PST had to retain an independent expert to examine all APIs in the firm's possession and submit a report to the FDA regarding the products' GMP status. For any API that the FDA determined could not be brought into compliance, PST had to notify the product's purchasers of the FDA's findings. The independent expert also had to inspect PST's plant and certify to the agency that the firm was in compliance with GMPs.
Unlike most FDA consent decrees, PST did not need the agency's permission to continue operations. Instead, the decree provides that the FDA may order PST to stop operations if the agency determines that the company is not in compliance with the decree or applicable regulations. If the agency issues such an order, PST may not resume production until it receives written permission from the agency. In addition, the FDA may order PST to notify its purchasers if the agency determines that the company has manufactured violative APIs.
According to Logan, the FDA inspected PST after the signing of the decree and determined that the firm was in compliance with GMPs, making only one minor recommendation regarding a company forklift. The agency did not issue a 483 at the end of the inspection and currently considers PST to be in compliance with GMPs, he said, noting that the plant remains fully operational.
The decree states that an independent expert must inspect PST at least twice a year and submit a report to the FDA detailing whether the company is in compliance with GMPs. The agency may inspect PST throughout the life of the decree to confirm its compliance status. PST has agreed to pay for the inspections and other FDA costs associated with administering the decree.
Although the decree is permanent, the FDA has pledged not to object if PST petitions the court to dissolve the decree after three years, provided the company has complied fully with its terms.
It is Logan's position—based in part on the outcome of this case—that it pays to confront the FDA in court in an injunction action if a firm believes that it already has made corrections and come into compliance with GMPs. He noted that PST and the agency have a good relationship, despite the litigation, because PST pledged to come into compliance with GMPs and then met its commitments.
According to Shroff, the PST decree also demonstrates that drug manufacturers should be aware of the compliance status of an API supplier, before agreeing to outsource production.
For more information on this or other Thompson publications, contact: Don Montuori, Thompson Publishing Group, 1725 K. Street NW, Washington, DC 20006. Tel: 202-872-4000. Fax: 202-296-1091.
This article is ©Thompson Publishing Group. Visit Thompson's storefront on Pharmaceutical Online.