GlaxoSmithKline: Manufacturing processes being addressed to correct drug defects

06/01/2005

BY STEVE SMITH

ROCKVILLE, Md.-British pharmaceutical manufacturer GlaxoSmithKline (GSK; Brentford, U.K.; www.gsk.com) says it has identified and is addressing unspecified manufacturing processes at its Cidra, Puerto Rico, facility that led to a March raid by the Food and Drug Administration (FDA; www.fda.gov), during which batches of defective medications were seized.

Declining to specify which steps in the manufacturing process are involved, due to proprietary concerns, Gail Renegar of GlaxoSmithKline’s corporate communications U.S. media relations office did acknowledge that “it was not a contamination issue.” While an official company statement says GSK “believes it has identified the source of the manufacturing issues,” Renegar emphasized that GSK has “a high degree of confidence” that it has specifically targeted the problem areas.

The Agency found that certain lots of the Paxil CR tablets could split apart, resulting in patients receiving a portion of a tablet that either lacks an active ingredient or has the active ingredient but not the intended controlled-release effect. FDA inspectors also found that some Avandamet tablets did not have an accurate dose of the active ingredient rosiglitazone.

“We believe we’ve identified the problem and are addressing it,” Renegar says of the Paxil malfunction. As for the Avandamet situation, Renegar says GSK has “reassessed that manufacturing process and is implementing remedial measures.”

In late April, GlaxoSmithKline, through its U.S. subsidiaries SB Pharmco Puerto Rico Inc., GlaxoSmithKline Puerto Rico Inc., and SmithKline Beecham Corp., signed a consent decree with the FDA to correct the manufacturing deficiencies, whereby the pharmaceutical manufacturer agreed to post a bond of $650,000,000 contingent upon it either successfully reconditioning drugs seized in March or destroying them and paying costs to the government.

No financial penalties were issued, although the decree calls for potential penalties of up to $10 million a year if GlaxoSmithKline fails to meet the terms of the agreement.

The company can resume manufacture of Paxil CR and Avandamet under the condition that it takes measures to ensure that the Cidra facility and its manufacturing processes comply with cGMP requirements. The decree also requires that all corrections and cGMP compliance be certified by a third-party expert. In addition, the FDA will continue to monitor these activities through future inspections.

"We are moving forward with third-party validation of these new processes, and expect to resume manufacturing mid-year,” says Renegar. III