Mylan last spring recalled tens of thousands of EpiPen injectors that had been manufactured by a Pfizer unit that were potentially faulty. It turns out the recalls came right after an FDA inspection at the Meridian Medical Technologies plant, where the FDA found it had been producing the pens even in the face of mounting evidence many were failing during life and death emergencies.
The FDA on Tuesday issued the Pfizer facility a warning letter in which it slammed the operation near St. Louis, Missouri, for failing to thoroughly investigate hundreds of complaints about faulty EpiPen and EpiPen Jr. products .
“In fact, your own data show that you received hundreds of complaints that your EpiPen products failed to operate during life-threatening emergencies, including some situations in which patients subsequently died,” the FDA letter said.
In an emailed response today, Pfizer said, “Patient safety is of primary importance to Pfizer. We stand behind the quality, safety and efficacy of the products we manufacture. We will continue to work with the FDA to resolve the points raised in the letter.”
Then a short time letter it added, "Between 2015 and now, we have shipped more than 30 million EpiPen Auto-Injectors globally. It’s not unusual to receive product complaints, especially when the product is frequently administered by non-medically trained individuals. We currently have no information to indicate that there was any causal connection between these product complaints and any patient deaths."
In a September 11 note to clients, Bernstein analyst Ronny Gal, pointed out the frustrated tone in the FDA warning letter and suggested the agency might be making a case to approve a generic, or even remove the EpiPen from the market in the future.
"Epipen can’t be removed from the market today given patient need," Gal wrote. "However, when a couple of generics are approved…brand manufacturing better be fixed, otherwise removal comes into the realm of possibilities."
For years, the epinephrine pens have been the most used product for emergency treatment of serious allergic reactions, including anaphylaxis. Its widespread use, in fact, led to a political and public backlash because of constant price hikes Mylan tacked onto the pens.
The FDA had inspected the plant several years ago then returned in late February for what turned out to be a month-long look at the facility’s manufacturing practices. It was then investigators discovered the facility had received 171 complaints about misfiring pens since the FDA's last visit.
In March, Mylan first recalled about 80,000 injectors from around the world then a week later recalled thousands more from the U.S. even as the FDA was still in the midst of the four-week inspection that concluded March 24.
According to the warning letter, inspectors found the company had let complaints pile up without figuring out the source of the problems. Some complaints were for EpiPen activation problems during use, and some for products that spontaneously dispensed epinephrine so that when a provider needed it for an emergency, there was no drug to inject.
The FDA pointed out that Meridian, a year earlier during receipt testing of some incoming components, discovered a defect in one of the critical parts. It rejected a couple of lots of components, then left it to the supplier to investigate the issue—a process that took eight months.
The FDA upbraided Meridian because it didn’t widen its own investigation to other potentially affected products. It didn’t recall EpiPens from the market at that point, and it didn’t even make the connection that the defective part might be the source of the numerous customer complaints, which in fact it “ultimately confirmed.” Instead, the FDA said, it continued to manufacture units with faulty components which Mylan shipped throughout the country and the rest of the world.
It wasn’t until the FDA urged the company to look at the issue more closely, the warning letter says, that the Pfizer operation discovered that its supplier had produced a “deformed” part that was used in multiple lots of EpiPen products, 13 of which had been distributed in the U.S. It was only at that point the Meridian recalled the potentially defective units.
The FDA letter went on to lay out a host of shortcomings it observed in the company’s methods for detecting and analyzing trends in unit defects and why Meridian’s responses and proposed fixes failed to satisfy the agency.
It also points out that some of the problems were repeat violations, and that they were similar to problems inspectors had found during an inspection in 2014. “These repeated failures demonstrate that your facility's oversight and control over the manufacture of these products is inadequate.”
Meridian has run into federal trouble before. In 2013, it had to replace injectors sold to the military that were to be used in case of a sarin gas attack. Pfizer had discovered that about 7 out of 1,000 of its DuoDote autoinjectors containing atropine and pralidoxime didn't contain enough of one or both of the drugs.