- The EpiPen is a treatment for severe allergic reactions. People who carry EpiPens rely on them to work in emergency, life-or-death situations.
- US Food and Drug Administration inspectors raised concerns about how the product was being manufactured over the last few years, including in 2017 around the time of a large EpiPen voluntary recall.
- FDA inspectors had also been telling the EpiPen's manufacturer, a unit of drug giant Pfizer called Meridian Medical Technologies, for years that it should be taking complaints from customers about malfunctioning EpiPens more seriously, Business Insider recently reported for the first time.
- Meridian has said that it is challenging to test EpiPens before they get into patients' hands because the one-time devices are destroyed in the process.
- Pfizer told Business Insider that it is "very confident" in its EpiPens and that the manufacturing process has many steps of "stringent controls."
People who carry an EpiPen hope they'll never have to use it.
That's because the EpiPen is an emergency medication, used when someone has a severe allergic reaction to foods like peanuts, or stings from insects like bees. Patients rely on the device in life-or-death scenarios, so it has to be dependable.
US Food and Drug Administration inspectors have warned for years about problems at EpiPen manufacturing facilities, Business Insider recently reported for the first time.
The situation came to a head in 2017, when the device's manufacturer, Pfizer's Meridian Medical Technologies unit, voluntarily recalled a number of EpiPens because of concerns about a faulty part. Meridian failed to thoroughly investigate product failures or take appropriate corrective action, the FDA told the company in a September 2017 warning letter. A subsequent, nearly year-long shortage of the products continues to this day, in part because of the manufacturing issues.
But testing EpiPens to ensure that they work before they're sent to pharmacies across the country is particularly challenging, according to two high-up employees who work for the device's manufacturer. The details are revealed in internal Meridian documents, which were obtained by Business Insider in a public records request.
EpiPens are a "one-shot" device, and can't be used again once they're tested, the documents state. In other words, "a successful test results in the destruction of the device," two employees at Pfizer's Meridian Medical Technologies unit wrote in an April 2017 correspondence with the FDA.
So the company tests a certain number of individual EpiPens from each manufacturing batch to make sure they're up to par. Then, it uses a statistical method to make a more sweeping prediction about whether all the devices are reliable.
That means balancing two different factors: the risk that the EpiPen won't work, and the need to make enough EpiPens available to people with severe allergies, according to the documents obtained by Business Insider.
Pfizer said in a statement to Business Insider that it is "very confident" in the safety of its EpiPens and how well they work.
"The manufacturing process of EpiPen includes numerous steps of stringent controls to verify the quality and reproducibility of the product," the company said, including "chemical, microbiological and functional tests - from the manufacture of vendor components through processing to the shipment of the finished medicine."
EpiPen concerns
The EpiPen is a relatively simple device, consisting of the rescue medication epinephrine and a device, an auto-injector, which delivers the drug into the user's outer thigh.
But the correspondence between Meridian and the FDA also shows just how much it has to be able to do in a scary scenario.
When an individual is having a severe allergic reaction, an EpiPen must quickly deliver the right amount of epinephrine under their skin or into the thigh muscle, without accidentally sticking people with a needle or injuring someone if used before intended.
EpiPens must be highly reliable, but just a small minority of them are actually used. Meridian estimates that just 5% of the millions sold each year are deployed, a figure that's based on scientific literature and real-world databases, according to the documents obtained by Business Insider. Pfizer's Meridian has shipped more than 30 million EpiPens globally between 2015 and the present, the company told Business Insider in a statement.
But the FDA was concerned about the EpiPen and how it was being manufactured - so much so that it had sent Meridian a "Form 483," which the regulator uses to tell companies about "objectionable conditions" at its factories, in March of 2017.
The same month, Meridian announced a voluntary recall of an estimated 260,000 EpiPens because of a defective part.
FDA inspectors had also been telling the firm for years prior that it should be taking complaints from customers about malfunctioning EpiPens more seriously.
Read more: The strange history of the EpiPen, the device developed by the military that turned into a billion-dollar business and now faces generic competition between Mylan and Teva
In the Meridian leaders' mid-April response to the FDA, though, they insisted that Meridian's system to ensure EpiPen quality and reliability was good enough.
Meridian also has other systems in place to ensure safety and efficacy besides testing, including robust product and process development, and rigorous manufacturing and quality management processes and procedures, according to Pfizer.
Still, because of FDA feedback, the firm would do a risk assessment to look at reliability at a system-wide level, the two employees said.
The FDA uses a strategy similar to Meridian's when its inspectors visit companies' manufacturing facilities, testing random samples rather than a number of products in a row, Diana Zuckerman, president of the National Center for Health Research, a think tank that conducts research on behalf of consumers, told Business Insider.
"Obviously, the EpiPen is a little different because it truly is life-saving," she said. "How many things can you absolutely say that lives truly depend on it?"
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