Assessing the long-term stability of anti-drug antibodies in method validation: what is the added value?

The stability of analytes in biological matrices is a critical parameter assessed under bioanalytical method validations. Assessing the stability of anti-drug antibodies (ADA) is, however, not evident given the polyclonal antibody response and the practicality of obtaining reference material from human subjects. Moreover, the same argument that different test articles exhibit different stabilities does not translate to polyclonal antibodies, for which there is a body of literature supporting the stability of human antibodies in undiluted human biological matrix for several years. Herein, the current recommendations from industry leaders and health authorities is summarized, and the literature supporting the stability of ADAs is described to provide a consolidated reference for bioanalytical scientists submitting ADA method validations to regulatory agencies.