Measuring biotherapeutics with endogenous counterparts and pre-existing antibodies: an interferon case study.
BACKGROUND
This article presents case study data demonstrating the importance of having a thorough understanding of matrix-interference in support of global clinical trials.


RESULTS
A ligand-binding assay used in the measurement of interferon lambda in human serum was transferred from the reference laboratory to a US-based comparator laboratory and then to a China-based comparator laboratory. The method was successfully validated at each laboratory, however, during cross-validation, there were notable differences, including 30-60% difference in incurred study sample results. The differences were attributed to matrix factors included in the serum pool used to prepare standards and quality controls. Newly procured serum (n = 75 individuals) was tested for assay interference. 12% contained either pre-existing antibodies (auto-antibodies) or were identified as pharmacokinetic assay outliers.


CONCLUSIONS
Prescreening of serum to exclude reactive individuals resulted in successful cross-validation and the establishment of a high integrity pharmacokinetic assay in support of global clinical trials.
Bristol-Myers Squibb, Route 206 & Province Line Rd, Princeton, NJ 08543, USA.
Heather
H
Myler
Tonya
T
Felix
Jie
J
Zhu
Matt
M
Hruska
Steven P
SP
Piccoli
D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007372:Interferons; D007378:Interleukins / Q000097:blood* / Q000276:immunology; D015203:Reproducibility of Results; D000095022:Interferon Lambda
D000911:Antibodies, Monoclonal; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda