- The Food and Drug Administration has issued a warning letter to Tris Pharma Inc. for not adequately investigating product failures at its Monmouth Junction, New Jersey, facility.
- During an early 2017 inspection, regulators found that five lots of Quillivant XR, a Pfizer Inc. drug for attention deficit hyperactivity disorder, had failed dissolution testing at the facility between March and November 2016. Rather than determine the root cause of the failures, Tris dismissed out-of-specification results and simply tweaked the testing method "several times."
- Those tweaks meant Tris was "deviating from the method deemed acceptable" for Quillivant XR detailed in the drug's approval application, the FDA argued. What's more, Tris didn't appear to address the problem — the agency noted one lot of drug product still failed under the revised testing method.
The FDA's letter, dated March 26, extends a lengthy past of production problems at the Monmouth Junction plant. Three prior inspections identified similar issues with Tris' investigations. Meanwhile, drug product that failed dissolution testing was passing through to market.
The letter also creates a fuller picture of the supply troubles Pfizer has experienced with Quillivant XR. The big pharma recalled multiple lots of the product last year because they didn't meet dissolution specifications.
By November, it was telling healthcare professionals that a manufacturing issue had caused a shortage of both Quillivant XR (methylphenidate HCl) oral suspension and QuilliChew ER (methylphenidate HCl) chewable tablets.
Pfizer more recently said it would release 11 lots of Quillivant XR to address the supply shortage, but cautioned that each of the lots might not meet dissolution test specifications either.
Aside from the Quillivant XR debacle, inspectors determined that in the last six months of 2016, Tris received at least two dozen complaints concerning roughly 1,000 bottles of morphine sulfate oral solution seen leaking or under-filled.
Tris blamed shipping for the damaged bottles, and concluded its investigation even though more complaints were rolling in, according to the FDA.
"Your response stated you would conduct a 'holistic' investigation to identify a root cause for the leaking bottles. After this investigation, you attributed the leaks to a specific lot of caps that had cracks in their liners and remained in inventory for an extended time without retesting. Your response is inadequate," the FDA wrote, adding that it took eight months before Tris recalled the defective product from the market.
In typical fashion for repeat violations, the FDA advised Tris to hire a current good manufacturing practice consultant and communicate better with drug application sponsors.