Warning letter delineates brandholder/CMO roles

Despite having developed new procedures for product approval processes and promising to review its validation program with contract manufacturers, complete vendor audits and conduct annual product reviews, River's Edge Pharmaceuticals in Suwanee, GA, has still come up lacking by FDA standards.

The regulator says in Warning Letter 10-ALT-15 that it acknowledges these efforts. "However, we are concerned about your firm's fundamental understanding of what is required by your [quality control unit] and the regulatory expectations for a firm that enters into agreements with contract manufacturers."

River's Edge is an "own-label distributor" that has hired contractors to manufacturer all of its products. Among the GMP violations cited are inadequate investigation of red speckles in Reme-Tussin DM cough syrup. The company has promised to re-open the investigation to determine a root cause. But the FDA notes the lack of a timeline for the investigation, and a little guidance: "Please ensure that your investigation includes a root cause determination and a corrective action plan. Also, for lots that have been distributed, please provide an evaluation of product impact."

The warning also notes a lack of scientifically sound and appropriate specifications, standards, sampling plans and test procedures to ensure drug efficacy and safety. For example, the company had released and distributed two lots of a product that had failed stability testing. In another case, the quality unit did not reject a product lot that failed the assay specification during accelerated stability testing.

The company also failed to review products' certificate of analysis prior to release and distribution. The existing process calls for a check to make sure a certificate is in place prior to accepting shipment. But there's no mandate for the certificate to actually be reviewed. "Your warehouse supervisor responded ‘no' when asked if the receiving employee is required to review the certificate for conformance of specifications prior to accepting the shipment," the letter states.

In addressing the relationship between River's Edge and its CMOs, the FDA leaves little room for misinterpretation: "You are ultimately responsible for the quality of your products. Regardless of who manufactures your products or the agreements in place, you are required to ensure that these products meet predefined specifications prior to distribution."

- see Warning Letter 10-ATL-15