Paulette saw it happen at the playground from several feet away, the panic-inducing moment in 2014 when her 3-year-old son Charlie, who has a life-threatening allergy to milk, grabbed a playmate's sippy cup and took a gulp.
Thankfully, Paulette had the anaphylaxis-stopping EpiPen and was able to quickly use the auto-injector on her son. But when she pulled the needle from his thigh, it was sticking out of the device at an angle instead of being under an orange cover, leaving her unsure whether the lifesaving medicine had been administered.
Not wanting to take a chance, Paulette (who requested anonymity to protect her son's identity) called 911, and Charlie was rushed to a hospital where he remained for several hours until doctors were sure he was all right.
"He was OK, but it was nerve-racking to say the least, not knowing if the EpiPen had worked or not," she said.
Not everyone has been as lucky as Charlie.
EpiPens, which contain the hormone epinephrine (also known as adrenaline), are used to stave off allergic reactions that can in some cases kill. Failure of EpiPens to deploy correctly have been cited in seven deaths this year through mid-September, according to reports by patients and physicians made to the Food and Drug Administration and obtained by Bloomberg News. The FDA received a total of 228 reports of EpiPen or EpiPen Jr. failures during the same time period, according to documents made available as a result of a Freedom of Information Act request. In addition to the deaths, 35 people were hospitalized, according to the reports.
Until now, the medical device has been the subject of controversy for a different reason. EpiPen is sold by Mylan NV, a drugmaker legally based in the Netherlands but run from Pennsylvania, that was under fire last year for significantly raising the price of the allergy shot, from about $50 for a single pen to more than $600 for a two-pack. Congress held hearings, government agencies began inquiries, and rival Sanofi sued. The Paris-based competitor claimed Mylan sought "to preserve the monopoly position of their $1 billion crown jewel" by engaging in anti-competitive conduct. Mylan has denied any wrongdoing.
EpiPen and EpiPen Jr. failures, meanwhile, resulted in a recall of some units in March by the company that makes the device for Mylan, Pfizer's Meridian Medical Technologies. Mylan, which sells the drug-device combo using Meridian's "pens," called the defect "extremely rare."
Reports submitted by users to the FDA, however, show broadening accounts of malfunctions dating as far back as 2014.
In 2012 there were four reports of EpiPen and EpiPen Jr. failures to the FDA, followed by 12 in 2013, according to an agency database. In 2014, those reports jumped more than 400 percent, to 67, according to the reports obtained by Bloomberg.
It's important to note that so-called adverse event complaints don't confirm that a product caused the incident. At the same time, such reports typically don't depict the full extent of a problem, given that most people aren't aware they can submit them in the first place.
Pfizer has previously said consumer complaints aren't unusual when a product "is frequently administered by non-medically trained individuals." In an emailed statement Tuesday, the company said it's "confident in the quality, safety and efficacy of EpiPens manufactured by" its Meridian subsidiary. Pfizer noted, however, that "in the case of EpiPen, adverse events can also be due to epinephrine itself, for a variety of reasons as reflected in the product label."
For its part, Mylan said it was "confident in the safety" of the EpiPen product "being produced at Pfizer's manufacturing site. Testing and analysis across lots impacted by the recall have not identified any units with a defect."
Although the reports provided by the FDA don't explain how the EpiPens failed, FDA investigators who inspected Meridian's Missouri plant earlier this year said in a warning letter sent in September that epinephrine had in some cases leaked out of the pens. In other cases, the injectors didn't work properly, the regulator said.
"We are not aware of defective EpiPens currently on the market and recommend that consumers use their prescribed epinephrine auto injector," the FDA said in an emailed statement Tuesday. "We have seen circumstances in which adverse events reports increase once a safety issue is publicized, like a recall. We continue to monitor and investigate the adverse event reports we receive."
The company had "failed to thoroughly investigate multiple serious component and product failures"
The auto-injecting pen was first developed at a company called Survival Technology, which through a series of deals ended up becoming Meridian. The device was originally used to administer the drug lidocaine for people with irregular heartbeats. Around the same time, the U.S. military approached Survival about using the device to administer treatments for chemical warfare, and NASA astronauts reportedly used a similar approach for nutrition delivery.
Mylan bought the right to sell and market EpiPen in 2007 from Merck KGaA. Meridian has made the auto-injector for Mylan the entire time and has primary manufacturing responsibilities, Mylan spokeswoman Julie Knell said in an email.
The EpiPen's design has changed in recent years, including tweaks to the orange cap where the needle in Paulette's device should have been after she injected her son. Mylan said the advancements are crucial to the pen's safety and functionality, but the changes also protect it from competition by generic device makers until 2025.
In its warning letter, the FDA noted that Meridian staff had said the company initiated a recall of some EpiPens only after government prodding. The agency said inspectors found the device maker had "failed to thoroughly investigate multiple serious component and product failures" for EpiPen products, "including failures associated with patient deaths and severe illness." The FDA at the time didn't specify how many were hurt or had died.
"This is a lifesaving product. If it fails 105 times, that's significant"
But even before the recall, which often boosts reports as word spreads, the FDA received 105 complaints of EpiPen failures in 2016.
"This is a lifesaving product," Diana Zuckerman, president of the National Center for Health Research, said in an interview. "If it fails 105 times, that's significant."
From 2014 to 2017, Meridian received 171 product samples that were the subject of complaints, but didn't disassemble the "vast majority" of them or offer FDA investigators a reason why, according to the agency's letter.
Mylan controls about 70 percent of the market for emergency allergy treatments, according to data compiled by Bloomberg in the first quarter of this year. Impax Laboratories Inc.'s lower-cost version, Adrenaclick, accounted for about 18 percent of the market, followed by Auvi-Q with about 12 percent.
Almost 4 million prescriptions were dispensed last year for EpiPens, according to data compiled by Bloomberg. Mylan doesn't break out EpiPen revenue, but its respiratory and allergy sales totaled $1.8 billion in 2016. By comparison, only about 318,000 prescriptions were dispensed for competitor Auvi-Q in 2015, the same year manufacturer Sanofi recalled the product because of a risk of inaccurate dosage. Auvi-Q is now sold by Kaleo Inc.