FDA EIR - ICON Laboratory Services, Inc. - November 22, 2019

An FDA Biosimilar User Fee inspection was conducted at ICON Laboratory Services, Inc. in Whitesboro, NY, from November 18-22, 2019. The inspection focused on bioanalytical data supporting two study protocols for drug applications, adhering to FDA procedures for in vivo bioavailability/bioequivalence studies. During the inspection, no formal Form FDA 483 (Inspectional Observations) was issued. However, one key discussion item was raised with management: ICON failed to establish sufficient freeze-thaw stability for immunoassays used to determine certain antibodies. Specifically, samples in two audited studies underwent more freeze-thaw cycles than the validated stability limits. For Study (b)(4), some positive samples exceeded established stability. Similarly, for Study (b)(4), certain antibody positive samples were subjected to excessive freeze-thaw cycles, potentially compromising sample integrity. ICON management acknowledged this finding and committed to evaluating the impact of these additional freeze-thaw cycles on the integrity of study samples. The inspection also reviewed corrective actions from a previous 2017 bioanalytical inspection, which had noted issues with method validation for selectivity, specificity, and relevant concentration selection. While specific Standard Operating Procedures (SOPs) for those previous issues had not been formally revised as promised, ICON stated they were following an alternative analysis plan for industry best practices.