U.S. regulator warns Canadian drug maker Apotex about quality control
U.S. regulators are threatening to block imports of some drugs produced by Canada's largest maker of generics after investigators raised questions about quality control at two of its Toronto-area manufacturing facilities.
In a February warning obtained by The Globe and Mail, the U.S. Food and Drug Administration said its inspectors have found "repeated deficiencies" in quality-control systems at Apotex Inc.'s facilities.
Foreign inspectors at the facilities found that Apotex released drugs into the U.S. market, despite defects discovered in part of the same batch. They also found that the drug maker did not adequately control or detect microbial growth, which could compromise drug safety.
The warning did not cite specific drugs and did not say what health risks the lapses created for the public. But the findings shed light on a regulatory disparity after the U.S. raised a flag and Canada didn't.
Apotex, which declined several requests for interviews, said in a statement that it is working with the FDA to address its concerns.
Health Canada said it is not concerned by the U.S. warnings, although Canadian inspectors have not inspected the facilities in question since 2011.
FDA investigators conducted the inspections last August and October at Apotex plants in Richmond Hill and Toronto. The investigators gave the plants a failing grade and told Apotex it had to address the issues. But in a warning letter sent to the company in February, 2013, the FDA said Apotex has not addressed the violations and that an import ban may be put on products coming out of those two plants.
This is the second time Apotex has been warned by U.S. regulators in recent years. In 2009, the FDA imposed a two-year import ban on Apotex after inspectors found major deficiencies in good manufacturing practices, notably failure to investigate how drugs that were rejected for public use became contaminated.
Apotex and Health Canada have been under pressure for their handling of a massive birth-control recall, which was triggered this month after a customer discovered an extra week of sugar pills in a package of Alysena. The dosage problem – which could dramatically increase the likelihood of pregnancy – was identified on April 3, but an urgent public warning was not issued by Health Canada until April 8. Spanish firm Laboratorios Leon Farma manufactured the pills, which were distributed in Canada by Apotex.
Federal Health Minister Leona Aglukkaq has ordered Health Canada to investigate the time lag and what factors led to the delayed warning.
Apotex has submitted its responses to the FDA, the company's statement said, and is "very confident that they will be resolved successfully in a short period of time."
An FDA spokesman said the agency is reviewing Apotex's response.
The problems identified at Apotex's manufacturing facilities should have Canadians questioning the safety of the drug supply, said Joel Lexchin, a health-policy professor at York University and one of Canada's leading experts on drug safety. He also questioned whether Health Canada is doing enough to hold companies to account.
"We should not have to go to the Americans to find out what's going on at plants here in Canada," Prof. Lexchin said.
In an e-mailed statement, Health Canada spokeswoman Blossom Leung said the department found "no evidence of impacts on health products destined for the Canadian market."
Ms. Leung said the violations identified by the FDA relate to drugs that never made it to market, which means there is no cause for alarm. In its warning, the FDA criticized Apotex for failing to discover the source of contamination in numerous drug batches that were rejected for public use.
She added that Health Canada is overseeing the corrective actions being put in place and "continues to have oversight" on the company's progress.
The department is scheduled to inspect both plants in May and October of this year.
In the letter dated Feb. 21, 2013, the FDA said Apotex kept a batch of drugs on the market despite the fact a separate batch manufactured on the same filling line failed a sterility test. The inspection also cited instances where Apotex released questionable drugs onto the market. In one case, an Apotex employee identified a "critical defect" with drug tablets and held them back. But the rest of the batch was released.
"Please explain the basis for your conclusion that the only affected part of the batch was the rejected portion," the FDA warning letter said. "Your firm's practice of rejecting portions of drug product batches is an indication that your firm does not have well-controlled manufacturing processes."