The letter, dated March 26 and published by the US Food and Drug Administration (FDA) today, is the result of an inspection carried out in March 2017 at Tris Pharma’s facility in Monmouth Junction, New Jersey.
The FDA highlighted significant violations of current good manufacturing practice (cGMP) regulations for finished pharmaceuticals, including the firm not investigating product failures and significant defect complaints adequately.
“You lacked thorough investigations into root causes, and failed to implement prompt and effective corrective actions and preventive actions (CAPA).”
In the letter, the Agency says five lots of Quillivant XR (methylphenidate HCl) for extended-release oral suspension failed dissolution testing between May and November 2016.
“Three lots failed during release testing, and two lots failed when tested for stability. Your investigations typically invalidated out-of-specification (OOS) results and attributed the cause to the dissolution test method rather than manufacturing. However, you failed to adequately investigate the sources of variation in your manufacturing operation that may have caused your dissolution problems.”
The product is a once-daily liquid methylphenidate for the treatment of attention deficit hyperactivity disorder (ADHD) in children ages six years and above, marketed by Pfizer which is –unusually – named by the FDA in the letter.
“You and your customer, Pfizer, have a quality agreement regarding the manufacture of drug products,” the Agency said. “You are responsible for the quality of drugs you produce as a contract facility, regardless of agreements in place with application sponsors.”
Last year, Pfizer initiated a recall of Quillivant XR because product from a number of lots did not meet the specification for dissolution.
Leaking Morphine Sulfate Oral Solution bottles
Tris Pharma was also pulled up on at least 24 complaints concerning approximately 1000 leaking or under-filled bottles of morphine sulfate oral solution.
“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,” the letter said. “Defective product remained on the market for an additional eight months before you completed a thorough investigation and initiated a recall in July 2017.”
Pfizer does market a morphine sulfate product under the brand Avinza, but the FDA did not state this was the product Tris recalled.