FDA EIR - Covance Laboratories Inc. - February 14, 2020

An FDA inspection of Covance Laboratories Inc. in Madison, WI, took place from February 10-14, 2020. This PDUFA, Premarket Supplement inspection, conducted under Compliance Program 7348.004 for In Vivo Bioavailability/Bioequivalence studies, was led by the Center for Drug Evaluation and Research, Office of Study Integrity and Surveillance (OSIS). While no formal FDA-483 was issued, four significant observations were discussed with management.

Key issues included the firm's use of a reference standard lacking an expiration date for validation and quality control preparation. Inspectors also identified inconsistent integration of interference peaks in blank matrix samples and a failure to adequately assess their impact. A pervasive problem involved Covance's non-adherence to its Standard Operating Procedures (SOPs) for re-assaying study samples or adjusting calibration curves when affected by carryover or interferences across multiple studies. Furthermore, a Lead Scientist involved in study review was found to lack required training on an SOP for "Multiple Analyte Assays-Data Capture, Regression and Reporting," leading to improper data regression for unwanted analytes.

Covance management committed to providing a written response within 15 working days. Proposed actions included initiating SOP deviations, amending reports to reflect these findings, conducting refresher training on data integration, updating SOPs to mandate secondary verification for carryover/interference impact assessments, and a comprehensive investigation into employee training deficiencies.