Integra gets FDA warning letter after recalling 5 years' worth of devices made at Boston facility

Despite taking the dramatic step earlier this year of voluntarily recalling a broad swath of its regenerative tissue technologies and pausing further production at its Boston-based manufacturing facility while it sorts out issues raised in an FDA inspection, Integra LifeSciences is still in hot water with the regulator.

The FDA has issued a warning letter to the company. Dated July 17 and published online for public viewing this week, the letter acknowledged Integra’s attempts so far to rectify the original issues, but still found fault with them, concluding in a four-point list that many of the company’s moves are “not adequate.”

Many of the issues raised in the warning letter revolve around Integra’s existing methods of dealing with faulty products.

In one case, according to the FDA, the company had released one lot of its Durepair collagen matrix “without an investigation or product risk assessment” despite testing that revealed the product lot included high levels of a bacterial endotoxin. Though Integra claimed that the abnormal test results were caused by a transcription error, the FDA still took issue with the processes the company has in place to prevent the release of other non-conforming products.

The FDA also said that Integra has yet to submit a comprehensive list of the corrective actions it’s taken to mitigate previously identified endotoxin concerns and other quality issues, nor the processes it’s put in place to prevent further issues.

“We understand that you have taken a series of corrective actions, including a recall and production hold, however your response does not indicate how you will prevent such errors from recurring when you resume operations,” the agency wrote.

Elsewhere in the letter, the regulator took issue with the validation—or the lack thereof—of Integra’s bacterial endotoxin testing methods, as well as with the company’s device storage procedures at the facility.

The FDA warned that a failure to correct any of the outlined issues could result in further regulatory actions, including “seizure, injunction and civil money penalties.” It also noted that the letter didn’t represent an all-inclusive list of issues with Integra’s manufacturing processes.

In fact, the FDA wrote, the listed violations “may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.”

The issues behind the warning letter arose during an FDA inspection of the Boston plant that spanned from March 1 through May 17 of this year. After the probe, the agency concluded that Integra’s collagen-based medical devices were “adulterated,” it wrote in the letter, meaning that their production didn’t match up to the FDA’s current requirements for good manufacturing.

A week after the inspection wrapped up, Integra put all manufacturing at the facility on hold and began a voluntary recall of all SurgiMend, PriMatrix, Revize and TissueMend products that had been made there and sold between March 2018 and May 22 of this year.

In a filing (PDF) with the U.S. Securities and Exchange Commission at the time, Integra said that it had decided to begin the recall after consulting with the FDA and following an internal investigation of the Boston site that found that some of the products manufactured there may contain higher-than-permitted levels of endotoxins—though the company noted that it hadn’t received any customer complaints related to high endotoxin levels.

Integra said in the filing that the recall and production hold would result in an impairment charge of $22 million on its second-quarter earnings. It also estimated that if the hold continued through the end of the year, it would cut about $60 million from the company’s expected full-year earnings.