Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 55; no. 5; pp. 878 - 888
• Main Authors: Gupta, Shalini, Devanarayan, Viswanath, Finco, Deborah, Gunn, George R., Kirshner, Susan, Richards, Susan, Rup, Bonita, Song, An, Subramanyam, Meena
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.07.2011; Elsevier
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibody Formation; Biological and medical sciences; Biological Assay - methods; Biological Products - immunology; Blood Proteins - chemistry; Cell-based assay; Chemistry, Pharmaceutical - methods; Chemistry, Pharmaceutical - standards; Fundamental and applied biological sciences. Psychology; General pharmacology; Humans; Immune response; Immune System; Immunogenicity assay; Medical sciences; NAb assay; NAb assay validation; neutralization; Neutralization Tests; neutralizing antibodies; Neutralizing antibody bioassay; Pharmaceutical Preparations; Pharmacology. Drug treatments; Reproducibility of Results; Sensitivity and Specificity; Serum-based bioassay; Software; therapeutics; LIMS; FDA; Neutralizing antibody bioassay; EMEA; Immunogenicity assay; NAb assay validation; NAb; ICH; SD; Serum-based bioassay; PC; ANOVA; NAb assay; HPC; Cell-based assay; DOE; ADA; LPC; Validation; Biological fluid; Bioassay; Immune response; In vitro; Neutralizing antibody; Recommendation; Treatment; Immunogenicity; Detection
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2011.03.038

The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases, ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 [1]. This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors.