World Health Organization : Year 2004 ; The Special Programme for Research and Training in Tropical Diseases Prd Nct, No. 04.1: Non-Clinical Safety Testing

By World Health Organization

Book Id: WPLBN0000168641
Format Type: PDF eBook
File Size: 0.4 MB
Reproduction Date: 2005

Title:	World Health Organization : Year 2004 ; The Special Programme for Research and Training in Tropical Diseases Prd Nct, No. 04.1: Non-Clinical Safety Testing
Author:	World Health Organization
Volume:
Language:	English
Subject:	Health., Public health, Wellness programs
Collections:	Medical Library Collection, World Health Collection
Historic Publication Date:
Publisher:	World Health Organization


Citation APA MLA Chicago Organization, W. H. (n.d.). World Health Organization : Year 2004 ; The Special Programme for Research and Training in Tropical Diseases Prd Nct, No. 04.1. Retrieved from http://gutenberg.cc/

Description
Medical Reference Publication

Excerpt
1. INTRODUCTION 1.1 GENERAL REMARKS A number of diseases place heavy burdens in terms of morbidity and mortality, and economic losses, onto the populations and health systems of disease endemic countries (DECs). Fighting these diseases (malaria, tuberculosis, filariasis, trypanosomiasis, etc.) is thus of great importance for DECs; however, only a limited number of affordable drugs are available for their treatment. Furthermore, the available drugs are mainly “old” and of partially limited efficacy, while problems of resistance have emerged and are of major concern. Development of new drugs being rather slow, due to the limited interest of multinational pharmaceutical companies in developing drugs for diseases which offer only a small chance of sufficient returns, this situation has created a need for DECs to engage in developing new treatment options from existing sources and knowledge.

Table of Contents
TABLE OF CONTENTS FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1.1 General Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1.2 Scope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 1.3 Objectives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2. CONSIDERATIONS IN THE NON-CLINICAL DEVELOPMENT OF PHARMACEUTICALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.1 Regulatory Aspects of Pharmaceutical Development and Submissions. . . . . . . . 11 2.2 Methodological Aspects of Safety Testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2.2.1 Selection of test system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2.2.2 Conditions for test systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 2.2.3 Size of the experiment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 2.2.4 Selection of doses and concentrations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 2.2.5 Monitoring of exposure and reversibility of effects . . . . . . . . . . . . . . . . . . . . . . . . . . 21 2.2.6 Test item characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.2.7 Good Laboratory Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.3 Legal Aspects in Pharmaceutical Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3. NON-CLINICAL SAFETY TESTING STRATEGY . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.1 General Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.2 The General Design of Non-clinical Safety (Toxicity) Testing Programmes for Pharmaceuticals in International Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.2.1 Single dose acute toxicity studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 3.2.2 Repeated dose toxicity studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 3.2.3 Reproductive toxicity studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3.2.4 Genotoxicity studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29