Issues with biotechnology products in toxicologic pathology.

The emergence of the biotechnology industry and introduction of drugs derived from recombinant DNA technology has generated many new issues in approaches to preclinical safety evaluation and extrapolation of results to risk assessment in humans. Products or therapeutic approaches for consideration include hormones, growth factors, cytokines, monoclonal antibodies, vaccines, blood products, antisense, and gene therapy. In many instances the application of standard safety tests conventionally used for small molecules are of limited value or are inappropriate. Studies should be designed to answer specific scientific questions rather than simply to fulfill regulatory requirements. Special consideration must be given to study design and species selection in terms of biological activity and species specificity, implications of immunological responses in the animal studies, and effects of systemic administration of molecules at clinically relevant doses. A full understanding of the clinical relevance of toxicological and pathologic findings associated with administration of these molecules to laboratory animals requires definition of the pathogenic mechanism of lesion induction.