Autoimmunity and Allergy: Regulatory Implications

Abstract

Although allergies and autoimmunity are among the most serious adverse reactions associated with drug therapy, there are few truly useful nonclinical models for predicting these phenomena. Drug-associated allergies or autoimmune reactions are usually observed either in clinical trials or during postmarketing surveillance. There are no general regulatory requirements in the United States concerning nonclinical evaluation of drugs for sensitizing potential. Drugs intended for topical application are usually evaluated for skin sensitizing potential and assays for this phenomenon are somewhat predictive and useful. If a drug is demonstrated to have skin-sensitizing potential, it is likely that it could produce other types of sensitization as well. Particular classes of drugs should be evaluated based on known mechanisms of sensitization or antigenicity (eg, proteins, highly reactive small molecular weight molecules, photoreactive compounds, β-lactams, etc.). There are no useful models for predicting autoimmune reactions. Development and validation of animal and/or in vitro models for determining the potential of drugs to induce hypersensitivity and/or autoimmune reactions would greatly enhance the power of nonclinical toxicology to predict drug safety.