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.
Understand the principles of practical toxicology
Gain a deeper insight into the role of toxicology in the different phases of drug development
Understand the principles of regulatory toxicology
Dive deep into the definition and role of “toxicokinetics”
Describe the significance of dose-response relationships
Discuss the effects of toxic substances on organ systems
Understand the future trends and newer technologies used in toxicology
Discuss toxicology regulatory requirements to ensure compliance
Dr. Stefano Persiani is currently Director of Translational Sciences and Pharmacokinetics at Rottapharm Biotech, Italy. He graduated in Pharmacy at the University of Milan, Italy and completed a post-doctoral fellowship in the Department of Pathology of the University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA, and later as a Research Associate in the Department of Pharmaceutics of the University of Southern California, School of Pharmacy in Los Angeles, California, USA. After these academic positions, he entered the pharmaceutical industry at Farmitalia Carlo Erba, Pharmacia, Upjohn, and Zambon Group and in the CRO sector with different managerial roles in drug R&D. Dr. Persiani is currently applying translational approaches from drug discovery to development and registration in several therapeutic areas. He is a member of various international scientific societies and serves on the review board of numerous professional journals. Dr. Persiani acts as an external expert evaluator for the European Commission on the 7th Framework Program, Maria Sklodowska-Curie Individual Fellowships, HORIZON 2020, and Innovative Medicine Initiative, and for several other government organizations where he evaluates and provides recommendations on applications requesting funding. Dr. Persiani has many years of teaching and training experience in several fields of Translational Sciences.