FDA EIR - QPS, LLC - January 16, 2019

QPS, LLC underwent a directed, comprehensive FDA inspection from January 7-16, 2019, at its Newark, DE facility. The inspection, conducted under Compliance Program Guidance Manual 7348.004 for In Vivo Bioavailability/Bioequivalence Studies (Analytical), evaluated the contract research organization's adherence to regulatory standards. While no Form FDA 483 (Inspectional Observations) was issued, five significant discussion items were presented to management during the exit meeting, indicating areas requiring improvement.

Key concerns focused on the validation and performance of both Anti-Drug Antibody (ADA) and Pharmacokinetic (PK) assays. Issues included the use of endpoint titers instead of representative positive controls for monitoring assay performance, leading to an unclear picture of assay precision and stability. The FDA also noted the firm's previous practice of using different ADA assays for different drug products, which raised concerns about unblinding samples and data comparability. Furthermore, significant variability in sample reproducibility, potential false negatives, and the use of a 5% false positive rate for confirmatory cut-point calculations were highlighted for ADA assays.

For PK assays, the absence of long-term stability assessments for certain US-products was a point of emphasis. The FDA also identified instances where data from "incomplete" runs were included in stability assessments without proper evaluation. Crucially, the selection process for Incurred Sample Reanalysis (ISR) was found to be inadequate, as samples were not consistently chosen to represent Tmax and elimination phases, impacting data reliability. QPS, LLC acknowledged these concerns and indicated updates to their practices, such as investigating significant drops in signal and utilizing single assays for all subjects. Future studies were advised to adopt a 1% false positive rate for cut-point determination and ensure comprehensive ISR selection.