A major challenge for biologics reviews is assessing potential immunogenicity, which is desirable in vaccine strategies but is not wanted in single or chronic dosing of a biologic. Potential immunogenicity can alter the pharmacokinetics of the therapeutic and cause allergic reactions. So, if a firm is developing an endogenous therapeutic protein and the patient mounts an immune response to that therapeutic protein which crosses to the endogenous therapeutic protein, this outcome creates cross-reactivity to a normal, essential protein; such an event can have a profound safety impact.
There are limitations of non-clinical studies for biologics, if they are species-specific to the biologic. If a firm develops a human protein then does non-clinical studies in primates or rodents, the primate or rodent will mount an immune response against that human protein; this step limits the applicability of non-clinical studies.
