The US Food and Drug Administration (FDA) has posted a Warning Letter to GlaxoSmithKline for deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (APIs) at the company’s manufacturing facility in Worthing, UK. The Warning Letter relates to an inspection made from July 2–10, 2015.

Among the deviations noted by the agency were issues related to cross-contamination from dedicated penicillin manufacturing area to non-dedicated areas. The agency noted that it documented findings of penicillin in non-penicillin manufacturing areas approximately 69 times in 2012, 72 times in 2013, 30 times in 2014, and 16 times through July 7, 2015. The FDA said that the company’s facility and controls to prevent contamination of non-penicillin drugs with penicillin were “wholly inadequate.”

The FDA also noted that the firm recalled various lots of Bactroban (mupirocin calcium) products because of potential contamination with penicillin and foreign substances, such as glass, paint fragments, and fibers. The agency noted that that company said it was committed to revalidating its penicillin decontamination method but that the FDA said the response “is inadequate because it lacks a comprehensive reassessment of the extent of contamination throughout your facility, a gap analysis of previous decontamination efforts, and a copy of your new decontamination plan.”

The agency also noted issues with the validation of the company’s penicillin-detection method validation and penicillin-cleaning method validation.

The agency provided the company with two options for the building in which it manufacturers penicillin: (1) dedicate the facility to penicillin-only production and if the company decides on this option to provide a timeline for implementation as well indicate the controls its has implemented to prevent any non-penicillin drugs previously manufactured at this facility from entering the US supply chain or (2) fully decontaminate the facility. The agency noted that it is “profoundly difficult to completely decontaminate a facility of beta-lactam residues,” but if the company intends to attempt decontamination to be able to resume solely non-penicillin API production for the US market, it must provide a comprehensive decontamination plan, update its methods for detection of penicillin, and address all potential sources of cross-contamination of penicillin into non-penicillin drugs. The FDA said until it determines that the proposed decontamination plan, methods, and procedures are adequate, comprehensively implemented, and verified via an FDA inspection, the company should not introduce any non-penicillin drugs into the US supply chain from the facility.

The FDA also cited the firm for microbial contamination in water systems, citing at least 25 breaches of the alert level from April 20, 2014, to February 17, 2015. It also cited the firm for API batches with out-of-specification bioburden and foreign particles in certain batches, noting green fibers consistent with scouring pads, red flakes consistent with paint in the manufacturing plant, and black particulates consistent with glass .

Source: FDA