Considerations in Assessing the Immunotoxic Potential of Investigational Drugs *

Abstract

Determination of the potential for an investigational drug to adversely affect the immune system is a standard component of nonclinical toxicology studies. Potential adverse immune effects include drug-induced hypersensitivity, immunosuppression, autoimmunity, immunostimulation, and drug antigenicity. Although immunotoxicology studies are rarely incorporated under a single heading in submissions, sponsors frequently conduct specialized assays to determine immunotoxic effects. Skin and respiratory sensitization studies are usually conducted if a drug is to be administered topically or by the inhalation route, respectively. These studies are designed to model clinical effects rather than to determine sensitization potential based on underlying immune mechanisms. Passive and active anaphylaxis assays are used to demonstrate biological effects indicative of drug antigenicity. Studies designed to determine immunosuppressive or immunostimulatory potential are often conducted when these effects are related to pharmacodynamic properties of the drug. Nonclinical studies designed to detect potential to induce autoimmune reactions are rarely conducted, primarily due to a lack of adequately characterized assays. In addition, newer assays designed to determine sensitization and autoimmunity-inducing potential are being evaluated.