Validation and life-cycle management of a quantitative ligand-binding assay for the measurement of Nulojix®, a CTLA-4–Fc fusion protein, in renal and liver transplant patients. (May 2012)

• Record Type: Journal Article
• Authors: Myler, Heather A; Phillips, Kelli R; Dong, Huijin; Tabler, Edward; Shaikh, Mehmooda; Coats, Valarie; Hay, Laura; Tacey, Richard; Stouffer, Bruce
• Is Part Of: Bioanalysis. Volume 4:Number 10(2012)
• Page Start: 1215
• Page End: 1226
• Publication Date: 2012-05
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.12.79
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: Nulojix ® is a fusion protein composed of the Fc portion of a human IgG1 linked to the extracellular modified domain of CTLA-4. Nulojix differs from another Bristol Myers Squibb product, Orencia ® by two amino acids and was approved by the FDA on 15 June 2011 for the prophylaxis of organ rejection in adult patients receiving kidney transplant.Results: A sandwich ELISA utilizing two monoclonal antibodies against CTLA-4 was employed for Nulojix quantification and pharmacokinetic analysis. At least 17 analysts have qualified on the assay and contributed to reportable results over the last 7 years. In-study accuracy and precision demonstrate suitable performance: %bias within -4 to 4%, %CV ≤13% and total error within 6–15%. Incurred sample reanalysis was completed in applicable disease-state populations. The assay was automated and validated in additional clinical matrices (ascites and urine) and Nulojix quantification was validated in the presence of clinically relevant co-administered compounds. In 2011, the biotinylation procedure was modified meriting a regression change (quadratic to 4-parameter logistic) and associated partial validation.Conclusion: This long-term pharmacokinetic program provides a good example of the dynamic clinical environment and adaptation requirements of ligand-binding assays.