GlaxoSmithKline (GSK) has received a warning letter from the FDA, citing what it said were quality control problems at the Canadian plant where the pharma giant produces its FluLaval influenza vaccines.
The warning letter followed an inspection by the FDA of GSK’s Ste-Foy manufacturing facility in Quebec from March 31 to April 9. The agency faulted GSK for failing to assure that it established and followed written procedures to prevent microbiological contamination of drug products purporting to be sterile; for inadequately investigating past manufacturing and quality control problems; and for what the agency called inadequately controlling against bioburden and endotoxin for both the purified water system and manufacturing processes.
Two examples cited by FDA: 20 lots of flu vaccine manufactured this year (21%) were rejected after showing bacterial growth and endotoxin excursions. And in April 2013, contamination was identified as the root cause for the 80% mortality rate of eggs used in the vaccine.
Five times last year, FDA wrote, it alerted GSK to water system problems that explain the presence of organisms such as Ralstonia pickettii and Achromobacter xylosoxidans:
“Achromobacter xylosoxidans and other water borne gram negative bacteria have been implicated in product contamination issues at your facility as far back as 2011,” according to the warning letter, written by Mary A. Malarkey, director of the Office of Compliance and Biologics Quality at FDA’s Center for Biologics Evaluation and Research.
“The deficiencies described in the Form FDA 483 issued at the close of the inspection referenced above and this letter are an indication of your quality control unit not fulfilling its responsibility to assure the identity, strength, quality, and purity of your licensed biological drug product and intermediates,” Malarkey added.
While acknowledging GSK’s three responses earlier this year to issues raised by this year’s inspection, as well as what the company said was its commitment to resolving them, the FDA added: “You provided insufficient detail in your response.”
Addressing John Glavas, site director, Quebec operations for GSK Biologicals, North America, FDA’s warning letter requested a meeting with him and other senior managers to further discuss the issues and how the company planned to address them.
“Given the potential contributions of Flulaval to the public health, we encourage frequent interaction between your management and technical staff with FDA to help ID Biomedical and GSK move forward with corrective actions as rapidly as possible,” the letter stated.
GSK responded with a statement insisting that it is making progress addressing the FDA’s concerns.
“We are committed to working with the agency to fully resolve all outstanding issues,” GSK stated. “Patient safety is our first priority, and we are confident in the safety of the influenza vaccines we have provided to patients.”
GSK insisted that the plant issues have not resulted in contaminated vaccines being distributed to patients, because it discards issues that fail safety reviews, and would not affect its ability to produce FluLaval this winter:
“Pending FDA approvals, GSK anticipates providing between 28 million and 33 million doses of influenza vaccine to the U.S. for the 2014–15 flu season," the company stated.
FluLaval and Fluarix generated £251 million ($426.5 million) in 2013 sales, according to GSK—up 25% at constant exchange rates over 2012, driven by the launch of four-strain quadrivalent versions of the flu vaccines in the U.S.