Safety of human recombinant proteins

Recombinant human proteins play an important role in therapy, especially in stimulating the hematopoiesis after chemotherapy, e.g., erythropoietin and colony stimulating factors, while several promising candidates such as IL-6, IL-12, thrombopoietin and others are in clinical development. Since the recombinant proteins are copies of endogenous proteins, it was assumed that they would be well tolerated. While this assumption is correct for some, other proteins proved to be less well tolerated. Therefore, preclinical safety assessment of these proteins is necessary. Based on the experience with several proteins, some guidance for the safety assessment can be given. Furthermore, data are presented demonstrating that preclinical toxicity studies may have a predictive value for man. Limitations of the classical approach of safety tests and new concepts are discussed.