Abstract: The present invention relates to an in vitro method for the detection of an anti-drug antibody (ADA) against a therapeutic drug antibody (TDA) in a biological sample. The in vitro method comprises detecting and capturing said ADA using affinity moieties obtained from an intact therapeutic drug antibody, or a Fab fragment thereof, in a certain manner. Avoiding using only intact therapeutic drug antibodies or only Fab fragments thereof as reagents in such a method has been proven as an efficient way of increasing sensitivity, decreasing unspecific binding and the formation of large protein complexes. Such a method has great utility in therapeutic drug development or in the evaluation of a particular treatment of a patient.