The nonclinical safety assessment for marketing approval of a pharmaceutical product usually includes pharmacology studies, general toxicity studies, toxicokinetic and nonclinical pharmacokinetic studies, reproduction toxicity studies, genotoxicity studies. For drugs that have special cause for concern or are intended for a long duration of use, an assessment of carcinogenic potential is also required. Other nonclinical studies to assess phototoxicity, immunotoxicity, juvenile animal toxicity and abuse liability are conducted on a case-by-case basis. For biotechnology- derived products, appropriate nonclinical safety studies should also be conducted on case-by-case basis. Nonclinical safety studies and human clinical trials should be planned and designed to represent an approach that is scientifically and ethically appropriate.

The development of a pharmaceutical product is a stepwise process involving an evaluation of both animal and human efficacy and safety information. The goals of the nonclinical safety evaluation generally include a characterization of toxic effects with respect to target organs, dose dependence, relationship to exposure, and, when appropriate, potential reversibility. This information is used to estimate an initial safe starting dose and dose range for the human trials and to identify parameters for clinical monitoring for potential adverse effects. Serious adverse events determined in toxicology studies can influence the continuation of drug development. Those involved in drug development should be aware of what are the toxicology requirements for marketing approval. This will allow non-toxicologists to learn the jargon and be able to effectively communicate with colleagues. In addition, the webinar will describe the basics of toxicology to allow non-specialists to understand the content of a toxicology report.

In toxicology, it should be possible to distinguish expected pharmacology (related to the mechanism of action of the drug) from unexpected or abnormal pharmacology. Toxicity should also allow to rank molecules based on their intrinsic toxic potential and to identify potential adverse effects. These effects should be correlated in toxicology with the exposure, to assess the presence of a dose-response. Overall toxicology studies should allow to extrapolate from non-clinical data the human situation. This will allow the inclusion of suitable assessments during clinical development to ensure that safety of the enrolled subjects (either healthy volunteers or patients) is maintained. In addition, toxicology studies should allow the identification of patients at higher risk of an adverse event that should be excluded for the initial phases of drug development if this is deemed necessary.

This masterclass will cover these aspects that are relevant for non-toxicologists involved in drug development.