- The Food and Drug Administration has issued a warning letter to a manufacturer of Mylan N.V.'s EpiPen, underscoring safety concerns related to the life-saving drug's production that began earlier this year.
- Dated Sept. 5, the letter to Pfizer Inc. subsidiary Meridian Medical Technologies Inc. harshly criticized the manufacturer for, among other things, its quality controls, classification and handling of product complaints, and investigations into defective autoinjectors.
- "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 agency said in the letter.
The FDA's warning looks to be the culmination of several voluntary recalls Mylan enacted in the spring for EpiPen product coming from St. Louis-based Meridian.
The first such recall happened in March after two devices in a batch of about 80,000 were found to have defective parts. While that number may seem insignificant to the casual observer, EpiPen is often used to treat serious allergic reactions — meaning that even small deviations in the amount of drug administered or in the autoinjector's functionality could be life-threatening.
Those, however, were the exact problems regulators identified at the Meridian facility. In fact, the FDA has taken issue with the Pfizer subsidiary since a previous inspection that stretched between October abd November 2014. From that year until 2017, Meridian records indicate the company has received more than 170 complaints about autoinjectors that didn't work properly, according to the agency's warning letter.
Pfizer, however, said it's confident in the quality of EpiPen produced by Meridian.
"Between 2015 and now, we have shipped more than 30 million EpiPen Auto-Injectors globally," Pfizer wrote in an emailed statement to BioPharma Dive. "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 show that there was any causal connection between these product complaints and any patient deaths."
In the FDA's recent inspection, which took place between Feb. 20 and March 24, it found glaring quality control and current good manufacturing practice (cGMP) violations at Meridian.
For instance, the company found in February 2016 there was a faulty unit in an incoming lot of autoinjector components responsible for firing the drug into patients.
Meridian rejected that lot and another associated lot and called on its supplier to investigate the causes for the defective parts. And yet it still used different lots of the same component to make autoinjectors for market, all the while neglecting to expand its own product and quality reviews, the FDA found. Meridian received another complaint on April 28, 2016 about an device that didn't activate properly, and ultimately determined it was because of the same defective parts. The component supplier didn't finish its investigation until six months after the April complaint.
The FDA also speared Meridian for the ways it classifies product complaints — based on the speed at which they should be dealt with: either "expedite," "high," or "normal." In particular, the agency questioned why Meridian grouped complaints about autoinjectors that didn't activate as "expedite" while complaints about autoinjectors that dispensed epinephrine before it was actually used were billed as "normal."
"Both problems result in the patient not receiving the needed drug in a life-threatening situation," the FDA wrote.
While the list of cGMP violations was long, the FDA generally asked for Meridian to provide the reasoning behind its current protocols and initial response to the agency's most recent inspection, as well as detail actions that would fix the problems.
"Pfizer is continuing to work with FDA to resolve the points raised in the letter regarding Pfizer’s manufacturing of EpiPen Auto-Injector and Mylan will do whatever it can to support this process," Mylan said in an emailed statement to BioPharma Dive.
"We note that Pfizer’s recall several months ago of certain lots of EpiPen Auto-Injector was taken as a proactive and precautionary measure with FDA in relation to these issues," the company added. "Mylan has an unwavering commitment to quality and patient safety and we are confident in the safety and efficacy of EpiPen products being produced at the site. Further, we do not currently anticipate any supply issues as a result of the warning letter."