The use of animal models for the detection of adventitious agents has been a feature of biologic testing packages for many decades. However, as alternative methods such as PCR and NGS have emerged these in vivo tests have stubbornly remained a central part of testing. Here we examine the current in vivo methods and explore alternatives which can be employed today. We also propose that while the industry may be some years away from removing in vivo testing completely, a case could be made for removing animal use from very well-characterized production systems such as CHO.