Overview

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.

Why Should You Attend

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 course will describe the basics of toxicology to allow non-specialists to understand the content of a toxicology report. This will be also accomplished with dedicated case studies during the course to optimize learning.

Key Learning Objectives

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

The course will cover the following topics:

  • Principles of practical toxicology
  • Role of toxicology in the different phases of drug development
  • Principles of regulatory toxicology
  • Toxicology terminology
  • Main toxicology studies and related disciplines
  • Definition and role of “toxicokinetics”
  • Description the concept of “safety margins”
  • Practical case studies

Agenda

The role of toxicology in drug development

  • What is toxicology and how is it valuated?
  • Why do we perform toxicology studies?
  • The importance of toxicology throughout phases of drug development and the increasing importance of toxicology in go/no go decisions
  • Toxicology and the regulatory authorities
  • Toxicology as a strategy tool -establishing what is needed and interpreting results
  • Interdisciplinary interaction in the pharmaceutical industry - let’s all speak the same language

How drugs cause toxicity - what do we measure and how do we measure it?

  • How do we measure toxicity? Risk vs hazard assessment
  • Establishing why and what we are studying 
  • Explaining basic terminology
  • Introducing the range of toxicology study types from single dose to lifetime exposure
  • What toxicological endpoints are measured?
  • Assessing appropriate dose and safety margins for first into man studies 
  • Selecting the appropriate species for toxicological evaluation

The place of toxicology studies in the regulatory world

  • Regulatory guidelines
  • Impact of ICH on toxicology studies
  • Toxicology data required for clinical trials and submission dossiers
  • How toxicology testing is constantly evolving

Toxicological disciplines - what are they & how do they differ?

  • Safety pharmacology
  • General toxicology
  • Genetic toxicology
  • Reproductive toxicology
  • Carcinogenicity
  • Local tolerance

Group Discussion and Case Studies

  • As a toxicologist in your company, you need to design an appropriate package of safety pharmacology and toxicology studies to support initial clinical trial work. Proposed studies and the rationale for their inclusion will be discussed.

The role of toxicokinetics in toxicology

  • Basics of toxicokinetic testing
  • Toxicokinetic measurement in toxicology studies
  • Establishing safety margins for clinical investigations
  • Extrapolation to man: What is the relationship between pre-clinical and clinical toxicology?

Q&A Session

Who Will Benefit

Clinical research associates, medicinal chemists, pharmacologists, toxicologists, project managers, business development managers, medical writers.

FDA Faculty Dr. Stefano Persiani

Faculty Dr. Stefano Persiani 

Internal & External Innovation, Director Translational Sciences and Pharmacokinetics at Rottapharm Biotech

Italy

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 as Scientific Director for Clinical Pharmacology

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