In~vitro testing of drug-induced systemic hypersensitivity: Just a burden or an opportunity?

Hypersensitivity drug reactions (HDRs) are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated (‘allergic’) and non immune-mediated (‘pseudo allergic’) reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of-understanding of the adverse phenomenon. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs.