FDA posted 10 warning letters this week:

  • Several for misbranded drugs
  • 2 in the drug area:
    • 1 for a finished drug manufacturer
    • 1 for a compounding pharmacy

Note the FDA ‘requests’ that the firm must respond to. These always provide a roadmap for the type of activities expected of manufacturers who might find themselves with similar challenges. Free learning.


  • Tris Pharma Inc (Monmouth Junction, NJ) received a warning letter on March 26th 2018 based on the outcome of an inspection ending March 20th 2017. The firm is identified as a contract manufacturer for Pfizer and likely others. FDA reminds the firm that the firm must operate in compliance with CGMPs. FDA also stresses the importance of communicating changes to the product sponsor. And, finally, FDA suggests the firm employ qualified GMP consultants to assist in coming in compliance with CGMPs.
    • The firm did not adequately investigate OOS events. FDA indicates that in the 2011, 2012, and 2014 inspections, failure to conduct adequate investigations was also identified. The firm modified the analytical method to address the OOS events in dissolution. The modification differed from the method submitted in the NDA. 5 lots failed dissolution testing between May and November 2016. The firm also identified that one or more steps in manufacturing may also have a negative impact on dissolution results. In response to the warning letter, FDA requests:
      • “An update on the retrospective review of all dissolution and assay failures for lots within expiry, and a risk assessment that evaluates the quality of all distributed batches;
      • An update on investigations and CAPA plans initiated to address dissolution method and manufacturing process variability related to Quillivant XR;
      • An update on corrective actions implemented regarding communication with sponsors to enable changes to be promptly submitted to drug applications (e.g., dissolution test method).”
    • The firm also failed to address at least 24 complaints for three lots of > 1,000 leaking bottles of an oral solution product. The firm commits to conduct a “holistic” investigation. They are also to provide the following to FDA:
      • “A summary of the steps you have taken to ensure timely root cause evaluations and effective corrective action and preventive action (CAPA) for all drug products;
      • An assessment to determine whether all containers, closures, and components are assigned appropriate expiration or retest dates, and incoming material controls are adequate to prevent use of unsuitable containers, closures, and components.”
    • The firm made a change to the filling line that was not adequately assessed and resulted in super-potent product. The firm destroyed a group of super-potent products, but FDA expressed concern that not all super-potent products may have been identified. Once again, the FDA requests the firm to provide the following:
      • “A review of changes implemented since March 2015 to determine potential effect on product quality;
      • An update on your improvements in risk management and include the relevant procedure(s);
      • A risk assessment of the lots released to the market with possible OOS units and an explanation for why potentially defective lots remained in distribution;
      • An independent evaluation of your change management system. This review should include but not be limited to review of your procedure(s) to ensure changes are sufficiently justified and adequately reviewed and approved by your quality unit. The change management program should also include specific provisions for determining change effectiveness;
      • A comprehensive, independent assessment of your overall system for investigations and deviations, atypical events, complaints, OOS results, and failures. The CAPA should include but not be limited to improvements in investigation competencies, root cause analysis, written procedures, and quality unit oversight of investigations;
      • An independent assessment of your sampling operations to improve detection of upstream process variation with special focus on process steps that can introduce significant variation
      • A CAPA plan to improve upstream controls and sampling plans;
      • Documentation to support the destruction of all rejected shipper cases of codeine polistirex and chlorpheniramine polistirex extended-release oral suspension.”


  • Preferred Homecare (Phoenix, AZ) received a warning letter on March 1st 2018 based on the outcome of an inspection ending July 11th 2017. 5 GMP deficiencies in the manufacturing of sterile drug products are identified.