Federal inspectors documented unwanted “fibers” on the stoppers of vaccine vials at Merck’s vaccine plant in Montgomery County, Pennsvylvania, The Philadelphia Inquirer reports. They also found instances of contaminated children’s vaccines and complaints that were not always investigated at the West Point plant.

FDA inspectors spent 30 days at the plant between November and January and cited 49 areas of concern, including a failure to follow good management practices, the paper writes. The findings are detailed in an unpublished 21-page FDA report obtained by The Inquirer under the federal Freedom of Information Act. UPDATE: On April 30, the FDA released this nine-page warning letter.

Independent experts who reviewed the report say it documents serious concerns in one of the country’s premier vaccine plants, the Inquirer writes, and they suggested the problems could be a symptom of Merck’s cost cutting in the face of rapid growth of its vaccine business. “I would fault the management for not providing enough resources to do the work that needs to be done,” Scott M. Wheelwright, a biotech manufacturing expert and chief executive officer of the biotech consulting firm Strategic Manufacturing Worldwide, tells the paper.

John McCubbins, who heads Merck’s Global Vaccine Manufacturing operations, disputes the assessment. He maintains the division’s employment has kept pace with vaccine production and stresses that no contamination was found in finished vaccines and that Merck was addressing all the problems. McCubbins adds that Merck’s own technicians - not FDA inspectors - detected and reported most of the problems, which were found in the manufacturing process, not in vaccines themselves. “We are absolutely confident in the quality of the product,” McCubbins tells the paper.

The West Point plant, where Merck makes most of its vaccines, has had issues before, the paper notes. Bulk production of varicella-related vaccine for chicken pox has been down for many months, leading to shortages. The supply of Vaqta for hepatitis A also has been disrupted. In June 2006, Merck paid $20 million in a consent decree after a chemical spill shut down recreation on the Wissahickon Creek and closed water-intake pipes on the Schuylkill. Last December, Merck voluntarily withdrew 1.2 million doses of the childhood vaccines PEDVAXHIB and COMVAX because execs couldn’t guarantee the products’ sterility.

In their report, FDA inspectors criticized Merck for making a manufacturing change involving the withdrawn vaccines in mid-2006 and later reversing course and citing the change as the cause for the withdrawal. McCubbins maintains the recall showed Merck’s quality-control systems were effective. All the recent problems reflect the inherent difficulty of working with living organisms to make vaccines. “The primary driver when we get here is the quality of the products we produce,” McCubbins tells the paper, adding that Merck will resolve the agency’s concerns.

The report cites cases where bulk lots of PEDVAX and ProQuad were contaminated. Unwanted “fibers” were found on the vial stoppers of MMR, the measles mumps and rubella vaccine, among others. They were caused by “lesser quality” supplies from a vendor and, the report noted, defective vials had to be rejected twice to be discarded, and that one internal quality investigation went on for more than a year, the paper writes.

Several experts said no single finding was horrendous but the overall pattern is troubling. “It’s the sum of many small things that puts the whole operation in question,” says Wheelwright. Sammie Young, a retired FDA deputy director, inspected the West Point plant early in his career and for many years oversaw vaccine-plant inspections for the agency. “There are a lot of violations there,” Young tells the paper, after reading the report. “I’m surprised.” Vaccine-makers, he adds, are supposed to investigate vaccine lots if their use was associated with a death or a life-threatening event.

Merck failed to investigate two such cases, the FDA report said. A patient treated with the pneumococcal vaccine Pneumovax developed a half-dollar-size abscess and needed intravenous antibiotics to contain the infection. A pregnant woman who took the HPV vaccine Gardasil lost her baby, the FDA report noted. The Gardasil packaging warns against its use for pregnant women, the paper writes.

“I am concerned about the adverse-event reporting system,” Young tells the paper. “It looks like the people didn’t know when they were supposed to report. I find that hard to believe.”

“I would not judge the plant as being out of control,” Wheelwright wrote in an e-mail to the Inquirer. “There are numerous issues where they failed to comply with their own documentation and (standard operating procedure) requirements. This suggests insufficient staff. There are other instances where the validation was insufficient. This also looks to me like overwork of the available crew. Sometimes in a plant where everyone feels overburdened…they give up trying to do everything and just try to keep their heads above water.”

McCubbins disputed the criticism, saying the staff follows its procedures and investigates complaints, the paper writes. “There’s always a level of interpretation,” he tells the paper, adding that he fears the FDA report could create unwarranted “panic” about the firm’s vaccines. The plant would make changes, he continued, “where we believe that the agency may have a point and often they do. Nobody’s perfect.”

Source: The Philadelphia Inquirer