U.S. FDA warns of problems with EpiPen manufacturing plant

The U.S. Food and Drug Administration told EpiPen's maker, Pfizer Inc., this week that it failed to properly investigate reports of malfunctioning auto-injectors, including incidents associated with patient deaths and severe illnesses.

The FDA's Sept. 5 warning letter to Pfizer's Meridian Medical Technologies unit includesnew details surrounding a global recall of EpiPen and EpiPenJr. in March.

Tens of thousands ofEpiPens, sold byMylanNV, wererecalled worldwide in March after two reports of thelife-saving shot failing to work in emergencies.

"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 U.S. regulator wrote.

The letter outlines the FDA's inspection of Meridian'smanufacturing facility inBrentwood,Mo.

Christina Antoniou, senior managerof corporate affairs forPfizer Canada, said the manufacturing facility supplies all EpiPens.

The FDA letter says the company failed to investigate problems with the devices, recall batches and act on problems, including expanding its internal investigation after two customer complaints of EpiPenfailures were traced to a deformed component.

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Pfizer makes EpiPens for Mylan, which has come under firefor hiking the price of the device in the U.S.

"Between 2015 and now, we have shipped more than 30 millionEpiPen Auto-Injectors globally. It's not unusual to receiveproduct complaints, especially when the product is frequentlyadministered by non-medically trained individuals," Pfizer saidin an emailed statement.

"We currently have no information toindicate that there was any causal connection between theseproduct complaints and any patient deaths."

In an interview with CBC News,Antoniousaid all necessary actions were taken to remediate the component, which she called a "low-level defect."

There is currently no recall.

Carry 1 pen minimum

Antoniou said the complaints were from outside Canada and the U.S.

The Institute for Safe Medication Practices Canada,an independent, not-for-profit organization committed to medicationsafety, said it hasn't received any reports ofmalfunctioning devices.

Since such reports to the institute andregulators such as Health Canada are voluntary,it's impossible to say what percentage of incidents relate to failed activations, said Dr.Michael Hamilton, physician lead at ISMP Canada.

"Ifyou particularly rely on this medication and it doesn't work, that can certainly lead to catastrophe. We'd encourage users of these devices to maybe be aware of the potential for a failed deployment or failed activation," said Hamilton, a family physician who has treated anaphylaxis in the emergency room.

Hamilton said a backup plan can include calling 911 as the injector is applied and alerting a caregiver.

Anaphylaxis is a cascade of events that can involve everything from skin rashesto vomiting to gastrointestinal problems, with trouble swallowing,speaking or breathingand even a reduced level of consciousness, said Dr. Elana Lavine,apediatric allergist and clinical immunologist at Humber River Hospital in Toronto.

Administeringepinephrine as quickly as possible can avert and reduce the severity of the reaction.

"At a minimum we want everyone to carry one unexpired pen that contains the appropriate dose of epinephrine for their weight,"Lavine said.

No specific details

Anaphylaxis may cause deaths even with the best treatment available, Lavine noted.

"The language [in the letter] is so opaque, in terms of it doesn't mention any specific details, it doesn't mention a time frame, I think it would be tragic if it made people less likely to carry the No.1, meaning first-line treatment in the form of ephinephrine auto-injector."

In an emailed statement, Mylan said: "Pfizer's recallseveral months ago of certain lots of EpiPen Auto-Injector wastaken as a proactive and precautionary measure with FDA inrelation to these issues."

Both Mylan and Pfizer said they are confident in the safetyand efficacy of EpiPen products being produced at the site.

Mylan said it does not currently anticipate any supplyissues as a result of the warning letter.

In an email to CBC News, the FDA said it will "work to ensure that the company's corrections are adequate."

The FDA has given Pfizer 15 working days to detailwhat it's done to correct and to prevent further violations.

The EpiPen is used to treat allergic reactions to certain foods and stings from bees, wasps and hornets.