MORGANTOWN, W.Va. -- Late this spring, Mylan Inc. took the unusual step of halting production at its sprawling generic drug manufacturing plant in Morgantown for an emergency meeting. Hundreds of employees, gathered in the cafeteria, were about to hear a bombshell.
Days earlier, Mylan learned two production workers had violated government-mandated quality control procedures intended to ensure the safety and effectiveness of prescription drugs. The company was launching a probe.
Publicly, Mylan officials have refused to discuss or even acknowledge the matter.
But according to a confidential internal report obtained by the Pittsburgh Post-Gazette, the company discovered that workers were routinely overriding computer-generated warnings about potential problems with the medications they were producing.
The violations of standard operating procedure at the world's third largest generic drug company, uncovered May 11, were "very serious," the report stated, involving "falsifying information" and "altering product."
The report said the practice was "pervasive," occurring on all three shifts at the plant, which makes roughly 19 billion doses of medication annually. The drugs are used to treat diabetes, high blood pressure, depression, cancer, epilepsy and other conditions.
The report did not say how long the unauthorized practice had been going on at the plant, which employs about 2,000. One worker interviewed by company investigators indicated it had been happening for at least two years.
Former Food and Drug Administration inspectors and industry consultants say the widespread breach of protocol raises troubling questions about the integrity and oversight of the plant's quality control operations.
"I've never before seen anything like this, that has reached this level of cheating," said James Akers, a longtime pharmaceutical industry consultant in Kansas City, Mo., who reviewed the document for the newspaper. "It certainly indicates a significant problem within their company."
Mylan's report offered conflicting and sometimes changing versions of what happened. When questioned by company investigators, most workers said they did not remember who showed them how to get around alerts designed to ensure drugs are properly made.
Although supervisors told the company they were unaware of what production workers were doing, some workers said supervisors were aware of the practice. At least one worker said supervisors directed her to break protocol.
Roughly a week after the breach was discovered, Mylan's quality assurance team had concluded that no medications were compromised, the report said. It did not say how the company made that determination.
In response to the breach, the report said, two union workers were suspended for 15 days and Mylan's quality team was to provide additional training and "evaluate the possibility" of revisions to the computerized quality control data management system used on the production line.
Company officials did not respond to requests for interviews for this story and did not respond to a series of questions faxed and e-mailed to Mylan's corporate offices in Cecil.
Last month, when Mylan officials learned that the newspaper had contacted several employees about the matter, CEO Robert Coury issued a memo reminding employees of the company's policy prohibiting unauthorized employees from talking with the news media.
The problem outlined in the report involved computer alarms known as "red screens." These alerts, triggered during the making of tablets and capsules, warn production workers that the medications may fail to meet specifications for weight, thickness or hardness, according to interviews with current and former Mylan employees. If the drug deviates from specifications, patients may not receive the proper dosage.
When a red screen occurs, workers are required to stop production and summon a quality control supervisor who launches an investigation to determine what triggered the alert and whether any drugs must be discarded, according to the report and interviews with employees. In some cases, the red screen turns out to be a false alarm of sorts. For example, it could be set off by a scale that needs to be recalibrated rather than an actual problem with the amount of active ingredient in the pills, and production resumes.
In any case, regulations require a written record of the investigation be compiled as part of the medication's batch record.
According to the internal report, workers admitted to ignoring protocol by clearing red screens on their own, deleting the record and keeping production rolling. When confronted by company investigators, these workers claimed they only did so after determining that the red screens weren't serious.
Two workers who said that the red screens they deleted weren't serious lied about other issues during the company's investigation, according to the report.
The report did not say how often red screens typically occur or exactly how often they were handled improperly. One production worker apparently deleted "five or six" red screens in a single shift, according to the report.
"Those judgments are not to be made by the people who are making [the tablets and capsules]," said Dr. Akers, the industry consultant who specializes in regulatory compliance. Overriding a red screen once is a serious problem and, according to the report, Mylan workers did it many times, he said.
The actions described in the report "certainly would not indicate a strong quality system or attention to detail regarding regulatory compliance" at the plant, Dr. Akers said.
FDA regulations require companies to develop and adhere to good manufacturing practices. Those practices involve a wide range of operational issues including personnel, training, facilities and equipment, quality and record keeping. For example, the regulations require drug companies to maintain a written statement of production and quality control procedures, document that the procedures are being followed and justify any deviation in writing. They require that changes in production and other records be made only by authorized personnel.
The agency also mandates that a company's quality control unit review production records to make sure that errors that occurred during production have been fully investigated and conclusions and follow-up actions were documented.
Martha Bennett, an industry consultant in Arizona and former investigator and senior compliance officer at the FDA, said Mylan's report described multiple serious FDA violations, including the falsification of batch production records. Batch records are important because they are used as the basis for an investigation if any drugs in the marketplace are suspected of causing problems, she said. Regulations also require computer systems be designed "so that operators can't do a go-around and delete information," Ms. Bennett said.
"The batch record is there to tell the story, the good, bad and ugly," said Robert Lewis, a regulatory consultant in Georgia and former FDA investigator who also reviewed Mylan's report. "Whenever there is a problem [during production] it should be noted and discussed and evaluated."
Experts said there was not enough information in the report to judge whether any drugs going out the door had been compromised.
The report described "serious [FDA] violations, no question about that," Ms. Bennett said. "To cheat, if you will, with an electronic record and say it is pervasive on all three shifts ... is very, very serious.
"But I can't determine from this report whether it's catastrophically serious," she said, meaning whether the breaches resulted in tainted medications.
Although workers were deleting red screens, the company likely would be able to perform a computer audit to access a permanent record showing when every red screen occurred, experts said. Indeed, Mylan's report indicates there was such a record.
To do the kind of thorough investigation that the FDA would want to see, experts said, the company should have identified all red screens that employees overrode improperly and determined what potential problem the quality control system was flagging. They said Mylan also should have tested samples from those drug lots -- samples the FDA requires drug makers to retain -- to ensure the medications met specifications.
The report did not state whether those steps were taken.
"I would have expected [Mylan] to have done that," Dr. Akers said.
The company's review should have extended back "to a point in time that could be set with a high-level of assurance that this is when [the unauthorized practice] started," Dr. Akers said. "You would want to go back to when this started and review all possible [drug] lots that were implicated," he said.
The report did not say how far back in time the company investigated. Portions of the report referred to specific red-screen incidents in April of this year.
According to the report, Mylan began interviewing about two dozen employees about the matter on May 13, two days after the breach was discovered, and concluded the questioning on May 20. The investigation was closed two days later, according to the report, at which time quality assurance had "concluded that the quality of the product is not affected."
Ms. Bennett said she had "no idea" whether that would have been sufficient time to make that determination.
"They could have put everyone in the lab on this [investigation] 24 hours a day," she said.
Mr. Lewis said it was unlikely the company could conclude medications weren't tainted within two days of finishing interviews with employees.
"Interviews are usually the first step" in an investigation, he said. "Once you have an idea how pervasive [the problem] is, you begin to set up some type of investigation."
The report did not address why employees violated quality control regulations.
At least one worker broke protocol "to save time," the report stated. Later, the report concluded that "the root cause of this is unknown at this point."
Current and former employees told the newspaper the plant has been under intense pressure to boost productivity amid an internal debate about possibly moving production from Morgantown to India to cut costs. Mylan has a drug plant in the state of Maharashtra, about 115 miles northeast of the port city of Mumbai.
One worker told company investigators that when it came to clearing red screens without following proper procedures, the environment at the plant "was conducive." The report stated that she told investigators "this was OK to do."
A quality control supervisor told the company she felt the practice started by accident and became "something that they did daily in their job duties," the report stated.
Workers "had to know what they were doing was not right," the supervisor told the company.
One worker who denied deleting red screens told the company he was "aware that this is altering product and is very serious," the report said.
According to the report, a tablet press operator said he first learned about the practice in May when he was approached by a co-worker who told him: "If you have a red screen appear, I know how to get that to go away and [quality assurance] downstairs don't even know that is taking place."
A quality assurance manager on the midnight shift blew the whistle on the practice May 11, according to the report, when he ran "a report" and "saw there was a red screen and there was not an investigation created."
Mylan's investigation did not address a common question the experts had: Why didn't the company discover the breaches sooner?
"Why this report was suddenly being looked at [by the quality assurance manager], I don't know," Mr. Lewis said.
Said Dr. Akers: "If I were involved in the management of Mylan, I would be very concerned as to how this happened and why it was not caught sooner. ... Quality systems are designed to prevent this kind of thing from happening."
Roughly a week after the quality assurance manager reported the practice, an anonymous caller to Mylan's ethics and compliance line alleged that the same manager plus six other managers and supervisors had given their passwords to production workers, making the unauthorized clearing of red screens possible, according to a written report on the call obtained by the Post-Gazette.
The caller stated that "employees had the passwords and cleared the red screen(s) and continued to run the product ... and did not fix the problems," according to that report.
Three days after that anonymous call, Mylan concluded that "employees were not given passwords from supervisors." Instead, they were able to clear red screens on their own by using the "right click" function of their computer mouse, the report said.
"Supervisors are unaware of this function," the report stated. "This process is being done on all three shifts."
Mr. Lewis said he was surprised that more people weren't held accountable considering the breaches were widespread.
"It seems like there would be more disciplinary action," he said.
"Any time that you may have a situation where employees manipulate the data or delete data or make a record look different than it should look ... it's extremely serious," he said.
Dr. Akers said he didn't understand why the two workers disciplined were not fired.
Wayne Mazanec, a former FDA investigator and assistant regional director who spent 33 years with the agency, said the actions of Mylan employees could be considered criminal.
"The repeated acts are each fraudulent in nature and are each subject to felonious considerations," he said in an e-mail to the newspaper after reviewing Mylan's report.
Federal court records show that since 2004, Mylan attempted to fire two union workers who admitted to violating quality control procedures at the Morgantown plant unrelated to the current problem. One case involved a female worker who placed three pieces of gum into an empty medicine bottle to send to co-workers down the packaging line. The other involved a worker who manipulated and falsified records when raw materials failed to meet specifications.
In each case, the employee was discharged and the union filed a grievance. When an arbitrator overturned the dismissals, Mylan appealed to federal court but lost and the employees were reinstated. In the lawsuit filed over the gum incident, Mylan maintained it had to fire the woman to protect the public from an "adulterated" product.
A product is considered adulterated when good manufacturing practices are violated, Mylan said in the suit. The company's complaint outlined the potential consequences of allowing such a product on the market.
"This clear violation of ... FDA's regulations could result in severe civil penalties for the drug manufacturer, including seizures, recalls, injunctions/consent decrees and warnings letters," Mylan stated.
Moreover, the FDA could reject or withdraw Mylan's permits to make drugs, consumers could file lawsuits and the company and its officials could face criminal prosecution, Mylan said in the suit.
In the current matter, Mylan's report did not say whether the company notified the FDA about the problems. The name of the agency was not mentioned in the report. An FDA spokesman said last week that the agency could only comment publicly about a breach in quality control if and when the agency had taken action against a company or an action was imminent.
Both Dr. Akers and Ms. Bennett said it would be their recommendation that Mylan contact regulators.
"It would be my advice to clients ... to volunteer the information to the agency rather than take the chance the FDA finds out on inspection," Ms. Bennett said. The agency typically inspects U.S. pharmaceutical plants once every two years, more often if there are consumer complaints or if the company has repeated infractions.
While Ms. Bennett said it was not clear whether the company would be required to report this event, "most good companies do because they would rather work with the agency rather than start out in a defensive mode."
Employees who provided information about the breaches to the newspaper did so on the condition that they remain anonymous. They said they feared losing their jobs at Mylan, one of the Morgantown region's largest and best-paying employers.
Some of them are bracing for more fallout.
"There's an overwhelming feeling this is not over," said a source close to the situation. "It's like a slow boil. Everyone is waiting to see what happens."
First Published: July 26, 2009, 8:00 a.m.
