A lab technician conducts a trial of substances during a tour of at the U.S. Food and Drug Administration (FDA) headquarters in Silver Spring, Maryland, Nov. 4, 2009.
As foreign drug companies began cutting high-paying jobs in Quebec in recent years, Sandoz International GmbH looked like it was bucking the trend.
After paying $565-million for Quebec generic drug maker Sabex Holdings in 2004, Sandoz, a division of Swiss pharma giant Novartis International AG , was positioned to become a leader in one of the fastest-growing areas in the global pharma business: generic injectable drugs.
It invested close to $100-million between 2007 and 2009 to build new facilities at Sandoz Canada's base in Boucherville, Que. and made the plant, home to 800 workers, a "worldwide centre of excellence for injectable products" within Sandoz.
Today, Sandoz Canada's reputation lies in tatters after chronic problems at its state-of-the-art plant on Montreal's south shore caught the eye of U.S. regulators. Much of its production is halted as it tries to fix the problems, leaving pharmacists and health-care providers alarmed at what could be months of shortages of injectable medications that treat everything from nausea among cancer patients and abnormal heart rhythms to endometrioisis.
Last week, Sandoz told Canadian health-care providers it would discontinue certain products and temporarily suspend production of other injectable products on the heels of a scathing "warning letter" from the U.S. Food and Drug Administration three months ago that criticized the plant's "ineffective quality system."
"As we progress with our remediation activities, all production processes will be affected, significantly reducing output from our Boucherville plant and likely resulting in temporary supply disruptions," Sandoz Canada president Michel Robidoux said in a Feb. 16 letter to pharmacists, obtained by The Globe and Mail. He didn't specify how long the disruption would last, but that Sandoz Canada would focus on "optimizing" supplies of medically necessary drugs to the Canadian market and had halted production of ointments, ophthalmics, suppositories and all non-medically necessary drugs.
The president of the Quebec Order of Pharmacists told the Montreal Gazette newspaper that Canadian pharmacies could run out of many important drugs. "This kind of shortage with Sandoz will involve a lot of medications," Diane Lamarre said.
The FDA's Nov. 18, 2011 letter to Novartis CEO Joseph Jimenez – which came a year after Sandoz began a company-wide quality improvement program – accused the Boucherville plant of sloppy, error-prone or incomplete documentation, validation and investigation practices. In three investigations during 2011, the FDA found Sandoz did not follow proper procedures "to prevent microbiological contamination of drug products purporting to be sterile," nor had it thoroughly investigated "inconsistent and inaccurate" media fill tests, or simulated procedures drug companies carry out to ensure their normal manufacturing conditions are sound.
The FDA alleged Sandoz failed to adequately investigate after crystals appeared in some of its finished injectable liquid treatments released for distribution in the US – and that it "failed to adequately determine the cause of this crystallization problem."
Furthermore, the company repeatedly failed to provide field alert reports that would have alerted the FDA to any contamination or related issues within the required three days. "We remind you that you are responsible for ensuring that your firm's drug manufacturing operations comply with applicable requirements," the FDA said, threatening to withhold approval of any new drug applications.
In a statement to The Globe and Mail, Sandoz Canada said it was intensifying efforts "to ensure high quality standards" and stood behind the safety and efficacy of its products, none of which have been recalled. It said the decision to halt production was voluntary and related to efforts to restore "high quality standards in manufacturing operations" and said it had no plans to close the Boucherville plant. Sandoz didn't respond to questions about how the problems developed or why they weren't dealt with to the FDA's satisfaction after they were first identified.
In total, Sandoz said it had committed a total of over $170-million (U.S.) to improve quality at the Boucherville plant as well as two other plants in Colorado and North Carolina that were also cited in the FDA letter. Sandoz said those "remediation" efforts were already under way when it received the FDA letter.
Sean Silcoff