title: Pre-clinical methods for detecting the hypersensitivity potential of pharmaceuticals: regulatory considerations.
abstract: Immune-based systemic hypersensitivities account for a significant number of adverse drug reactions. There appear to be no adequate nonclinical models to predict systemic hypersensitivity to small molecular weight drugs. Although there are very good methods for detecting drugs that can induce contact sensitization, these have not been successfully adapted for prediction of systemic hypersensitivity. Several factors have made the development of adequate models difficult. The term systemic hypersensitivity encompases many discrete immunopathologies. Each type of immunopathology presumably is the result of a specific cluster of immunologic and biochemical phenomena. Certainly other factors, such as genetic predisposition, metabolic idiosyncrasies, and concomitant diseases, further complicate the problem. Therefore, it may be difficult to find common mechanisms upon which to construct adequate models to predict specific types of systemic hypersensitivity reactions. There is some reason to hope, however, that adequate methods could be developed for at least identifying drugs that have the potential to produce signs indicative of a general hazard for immune-based reactions.
authors.affiliation: Division of Special Pathogen and Immunologic Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, USA. hastingsk@cder.fda.gov
authors.forename: K L
authors.initials: KL
authors.lastname: Hastings
mesh_terms: D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology; D004335:Drug and Narcotic Control; D015507:Drugs, Investigational / Q000633:toxicity*; D007107:Immune System / Q000187:drug effects*; D023441:Local Lymph Node Assay; D051379:Mice; D023421:Models, Animal; D051381:Rats
chemical_list: D015507:Drugs, Investigational