The handwriting was on the wall for a GlaxoSmithKline ($GSK) API operation in the U.K. when the drugmaker recalled more than 425,000 Bactroban antibiotic products last fall after an FDA inspection. Now the extent of the problems at the facility have been laid out in a stern agency warning letter that cited it for penicillin cross-contamination, a problem that can lead to fatal drug reactions, as well as microbial contamination.
The letter, posted Tuesday by the FDA, dates back to an inspection conducted a year ago in July 2015 which led the drugmaker to stop production in part of the plant in Worthing. The FDA said it uncovered 187 instances of penicillin in nonpenicillin manufacturing areas in 3 1/2 years, and that GSK has still not updated its cleaning validation plan.
“Contamination of non-beta-lactam drugs with beta-lactam drugs presents great risks to patient safety, including anaphylaxis and death. No safe level of penicillin contamination has been determined to be a tolerable risk,” the FDA warning letter points out.
The FDA laid out two options for GSK, saying it needs to either dedicate the facility to penicillin API production alone so that cross-contamination will not be an issue, or submit a plan for fully decontaminating the API facility, something it warned up front is extremely difficult so will have to meet high expectations from the agency.
In an email today, GSK explained that the Worthing campus has both primary and secondary manufacturing facilities, and only the active pharmaceutical ingredient manufacturing area is in question in the warning letter. The drugmaker said that as soon as the problems were raised by the FDA, it closed that part of the plant and began work to fix the issues.
“GSK is taking the warning letter extremely seriously and it is now being reviewed to determine if further action is necessary,” a GSK spokeswoman said. “Patient safety is our primary concern at GSK.”
In addition to the recall last year of antibiotic creams, the company is now proposing a class II recall for the “small number of Bactroban batches remaining within shelf life,” the email said.
But cross-contamination is not the only issue the FDA uncovered at the plant. The warning letter says that the plant has had ongoing issues with microbial contamination in the water used to make APIs. It said there had been 25 instances of breaches of the alert level in the 9 months between April 20, 2014 and Feb. 17, 2015. The plant rejected three batches of APIs because of out-of-spec testing but never determined the root cause, leaving the issue unresolved, the letter said.
Further, the inspectors said that in one API batch, GSK found green fibers that were probably from scouring pads, red flakes that might have been painted in the manufacturing plant and black particulates that were consistent with glass particles. While the GSK decided they were “acceptable intrinsic” contaminates, the FDA was not satisfied, asking the drugmaker to provide a risk assessment for the API making process and an evaluation of its equipment, its cleaning and maintenance procedures.
- here’s the warning letter
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