Fit-for-Purpose Validation and Establishment of Assay Acceptance and Reporting Criteria of Dendritic Cell Activation Assay Contributing to the Assessment of Immunogenicity Risk.
AAPS J
; 22(5): 114, 2020 08 24.
Article
en En
| MEDLINE
| ID: mdl-32839919
ABSTRACT
Validation of key analytical and functional performance characteristics of in vitro immunogenicity risk assessment assays increases our confidence in utilizing them for screening biotherapeutics. Herein, we present a fit-for-purpose (FFP) validation of a dendritic cell (DC) activation assay designed to assess the immunogenicity liability of protein biotherapeutics. Characterization of key assay parameters was achieved using monocyte-derived DCs (MoDCs) treated with cell culture medium only (i.e., background control (BC)), keyhole limpet hemocyanin (KLH) as system positive control (SPC), and 2 therapeutic monoclonal antibodies (mAbs) with known clinical immunogenicity profiles (bococizumab and TAM163) as therapeutic controls (TCs). In the absence of established validation guidelines for primary cell-based assays, the present DC activation assay was validated using a novel FFP approach which allows more flexibility in selection of validation parameters and designing of experiments based on the intended use of the assay. The present FFP validation allowed us to understand the impact of experimental variables on assay precision, develop a clear concise readout for DC activation results, establish a reliable response threshold to define a result as a positive DC activation response, and define in-study donor acceptance criteria and cohort size. FFP validation of this DC activation assay indicated that the assay is sufficient to support its context of use, a preclinical immunogenicity risk management tool.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Productos Biológicos
/
Células Dendríticas
/
Evaluación de Medicamentos
/
Inmunogenética
Tipo de estudio:
Etiology_studies
/
Guideline
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
AAPS J
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos