FDA Raises Tablet Contractor Validation, Aseptic Processing Concerns at Gilead

Tablet contractor process revalidation and aseptic processing of injectible AmBisome were areas of concern addressed in a warning letter from FDA’s Los Angeles District office to San Dimas, CA-based Gilead Sciences in late September.

The focus in the letter on Gilead’s oversight of its tablet manufacturer lines up with the affirmation by FDA compliance officials in recent public forums that the sponsor/contractor relationships will be getting closer investigator scrutiny (IPQ “In the News” June 18 and October 6).

The Gilead warning letter provides insight into the types of concerns FDA will have in evaluating these relationships.

At issue in Gilead’s case was a process revalidation study its tablet contractor performed following a change in an ingredient supplier and placing a new tablet press into service in August 2008.  The problem was that the lots manufactured during the revalidation study by the contractor “exhibited excessive amounts of defective tablets” and did not meet the predetermined acceptance criteria, according to the 483 issued after the late January/early February inspection.

Gilead’s investigation of the revalidation concluded that neither the supplier nor the tablet press change had an “adverse impact” on the manufacturing process.  In the letter FDA disagreed with the assessment, stating that it did not consider the process to be validated.  The agency pointed out that the “investigation report conclusion was based on finished product results alone and did not consider in-process testing and analyses.”

[More on the Gilead warning letter and FDA expectations for sponsor/contractor relationships is provided for subscribers here.  To subscribe to IPQ, click here.]