New Jersey Firm Gets FDA Warning Letter

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FDA sent a warning letter to Tris Pharma Inc. after investigators found the company had failed to properly investigate batch failures and establish quality control procedures.

FDA sent a warning letter, dated March 26, 2018, to Tris Pharma Inc. after investigators inspected the company’s Monmouth Junction, NJ facility and found deviations in current good manufacturing practices (CGMP). During the inspection, which was conducted Feb. 14 to March 20, 2017, inspectors found that the company had failed to properly investigate batch failures and establish quality control procedures.

Specifically, inspectors found that the company did not thoroughly investigate product failures, dissolution testing failures, and defect complaints. Root cause investigation and corrective actions and preventive actions (CAPA) were not “prompt and effective.” According to FDA, previous inspections conducted in 2011, 2012, and 2014 found similar problems.

“Your firm and Pfizer conducted a review of all changes to the manufacturing process and process controls initiated since NDA 202100 approval. You also performed an analysis of process capability. Your review found that one or more steps in the manufacturing process may contribute excessive variation that could cause the dissolution failures. A further assessment of process controls is also being conducted using Failure Mode and Effect Analysis. You expect to complete your process assessment work and perform new process validation studies by (b)(4),” the agency stated. “Your response is inadequate because you did not promptly and thoroughly investigate variables in the manufacturing process that may be responsible for inconsistent product quality (e.g., dissolution performance). You also did not fully address the quality of all in-date Quillivant XR lots on hold or released for distribution in the United States.”

The agency requested the company provide an update on the retrospective review of dissolution and assay failures, a risk assessment of the quality of distributed batches, and an update on the company’s CAPA plans.


An update on the company’s CAPA and risk assessment regarding complaints of leaking or under-filled bottles was also requested by FDA. “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. Defective product remained on the market for an additional eight months before you completed a thorough investigation and initiated a recall in July 2017,” the agency stated in the letter.

The agency also stressed the responsibility of the contract facility in ensuring the quality of drug products: “You and your customer, Pfizer, have a quality agreement regarding the manufacture of drug products. You are responsible for the quality of drugs you produce as a contract facility, regardless of agreements in place with application sponsors. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity … You are responsible for ensuring that your firm complies with all applicable requirements, including the CGMP regulations. You should immediately notify the drug application sponsor of changes to the manufacturing or testing of the drug product, and any relevant drug master file updates, so they can file an appropriate submission to the application (supplement or report in annual report). A major change should not be implemented until a prior approval supplement is approved by FDA.”

Source: FDA