(W0930-10-59) Matrix Comparability Assessment between 3.2% Sodium Citrate and 3.8% Sodium Citrate Human Plasma in PK and ADA Assays

Purpose: Clinical sample processing can impact the results of bioanalytical assays. For a large molecule therapeutic candidate, pharmacokinetic (PK) and anti-drug antibody (ADA) assay validation were conducted with spiked samples prepared in 3.8% sodium citrate human plasma while Phase 1 study samples and Phase 2 study samples were collected in 3.2% sodium citrate. The primary objective of this evaluation was to determine if there was equivalency between 3.8% and 3.2% sodium citrate human plasma in PK and ADA assays for this therapeutic candidate.

Methods: To assess PK assay equivalency, three accuracy and precision runs were conducted using at least three determinations of frozen quality control samples prepared in both 3.2% and 3.8% sodium citrate human plasma pools. Each consisted of one set of frozen qualified standards and a blank matrix. For ADA assay equivalency, the sensitivity of the assay was confirmed using positive and negative controls prepared in 3.2% sodium citrate plasma and results were compared to the sensitivity observed in 3.8% sodium citrate plasma. The precision of controls prepared in 3.2% and 3.8% plasma in screening and confirmatory assays were also compared.

Results: The validation data for the PK assay demonstrated equivalency between 3.8% and 3.2% sodium citrate human plasma: QCs prepared in 3.2% sodium citrate plasma showed acceptable recovery from a standard curve prepared in 3.8% sodium citrate plasma and vice-versa. Validation data for the ADA assay also showed equivalency between the two matrixes: PCs (Positive control) and NCs (Negative control) prepared in 3.2% sodium citrate and 3.8% sodium citrate demonstrated similar assay sensitivity between two matrixes.

Conclusion: Overall, this study provides evidence supporting the use of 3.2% sodium citrate as a viable alternative to 3.8% sodium citrate in PK and ADA assays.