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 re sults to risk assessment in humans. Products or therapeutic approaches for consideration include hormones, growth factors, cytokines, monocl onal antibodies, vaccines, blood products, antisense, and gene therapy . In many instances the application of standard safety tests conventio nally used for small molecules are of limited value or are inappropria te. Studies should be designed to answer specific scientific questions rather than simply to fulfill regulatory requirements. Special consid eration must be given to study design and species selection in terms o f biological activity and species specificity, implications of immunol ogical responses in the animal studies, and effects of systemic admini stration of molecules at clinically relevant doses. A full understandi ng of the clinical relevance of toxicological and pathologic findings associated with administration of these molecules to laboratory animal s requires definition of the pathogenic mechanism of lesion induction.