FDA 483 - ImClone Systems, LLC - November 26, 2019

The FDA Form 483 documents significant deficiencies in computer and laboratory system controls at a facility manufacturing biological drug substances like Cetuximab, Ramucirumab, Necitumumab, and Galcanezumab, which are used in drug products distributed in the U.S. market.

A primary observation is the lack of appropriate controls over electronic data from manufacturing process equipment. Specifically, electronic files identified as "Calibration Study," "Qualification Study," and "Verification Study" were deleted from (b)(4) units used for equipment qualifications involving (b)(4) processes. These deletions and related audit trails were not reviewed by the quality unit. Furthermore, audit trails from (b)(4) units (Serial No. (b)(4), (b)(4), and (b)(4)) showed users logging in for "AuditTrail" operations followed by adjusting the system clock, with one instance showing a clock adjustment from 11:03:47 to 10:49:00 on September 28, 2018. Operators were assigned administrative privileges, and the firm lacked sufficient controls to prevent deletion of electronic data, which was not periodically backed up.

Additionally, test runs were aborted from (b)(4) Test Instruments (ID: (b)(4)) without being logged, documented, or reviewed. These instruments are critical for (b)(4) and (b)(4) testing of (b)(4) used in manufacturing