Safety Guidelines
S10
Last Updated: March 3, 2025PHOTOSAFETY EVALUATION OF PHARMACEUTICALS 1. INTRODUCTION 1.1. Objectives of the Guideline The purpose of this document is to recommend international standards for photosafety assessment, and to harmonise such assessments supporting human clinical trials and marketing authorizations for pharmaceuticals. It includes factors for initiation of and triggers for additional photosafety assessment and should be read in conjunction with ICH M3(R2), Section 14 on Photosafety Testing (Ref. 1). This guideline should reduce the likelihood that substantial differences in recommendations for photosafety assessment will exist among regions. This guideline is divided into several sections. Section 2 discusses factors to consider in any evaluation of photosafety. Section 3 describes existing...
S11
Last Updated: March 3, 20251. INTRODUCTION 1.1 Objectives of the Guideline The purpose of this document is to recommend international standards for, and promote harmonisation of, the nonclinical safety assessments to support the development of pharmaceuticals intended for paediatric use. Harmonisation of the guidance for nonclinical safety studies will define the current recommendations and reduce the likelihood that substantial differences will exist among regions. It should facilitate the timely conduct of paediatric clinical trials and reduce the use of animals in accordance with the 3R (replace/reduce/refine) principles....
S12
Last Updated: March 3, 20251. INTRODUCTION 1.1. Objectives of the ICH S12 Guideline The objective of this guideline is to provide harmonised recommendations for the conduct of nonclinical biodistribution (BD) studies in the development of gene therapy (GT) products. This document provides recommendations for the overall design of nonclinical BD assessments. Considerations for interpretation and application of the BD data to support a nonclinical development programme and the design of clinical trials are also provided. The recommendations in this guideline endeavour to facilitate the development of GT products while avoiding unnecessary use of animals, in accordance with the 3Rs (reduce/refine/replace) principles. 1.2. Background An understanding of the BD profile of...
S9
Last Updated: March 3, 2025NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS 1. INTRODUCTION 1.1 Objectives of the Guideline The purpose of this guidance is to provide information to assist in the design of an appropriate program of nonclinical studies for the development of anticancer pharmaceuticals. The guidance provides recommendations for nonclinical evaluations to support the development of anticancer pharmaceuticals in clinical trials for the treatment of patients with advanced disease and limited therapeutic options. This guideline aims to facilitate and accelerate the development of anticancer pharmaceuticals and...
S8
Last Updated: March 3, 2025IMMUNOTOXICITY STUDIES FOR HUMAN PHARMACEUTICALS 1. INTRODUCTION 1.1 Objectives of the Guideline The objectives of this guideline are to provide (1) recommendations on nonclinical testing approaches to identify compounds which have the potential to be immunotoxic, and (2) guidance on a weight-of-evidence decision making approach for immunotoxicity testing. Immunotoxicity is, for the purpose of this guideline, defined as unintended immunosuppression or enhancement. Drug-induced hypersensitivity and autoimmunity are excluded. 1.2 Background Evaluation of potential adverse effects of human pharmaceuticals on the immune system should be incorporated into standard drug development. Toxicity to the immune system encompasses a variety of adverse effects. These include suppression or enhancement of...
S7B
Last Updated: March 3, 2025THE NON–CLINICAL EVALUATION OF THE POTENTIAL FOR DELAYED VENTRICULAR REPOLARIZATION (QT INTERVAL PROLONGATION) BY HUMAN PHARMACEUTICALS 1. INTRODUCTION The assessment of the effects of pharmaceuticals on ventricular repolarization and proarrhythmic risk is the subject of active investigation. When additional data (non- clinical and clinical) are accumulated in the future, they will be evaluated and this guideline might be revised. 1.1 Objective of the Guideline This guideline describes a non-clinical testing strategy for assessing the potential of a test substance to delay ventricular repolarization. This guideline includes information concerning non-clinical assays and...
S7A
Last Updated: March 3, 2025SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS 1. INTRODUCTION 1.1 Objectives of the Guideline This guideline was developed to help protect clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals, while avoiding unnecessary use of animals and other resources. This guideline provides a definition, general principles and recommendations for safety pharmacology studies. 1.2 Background...
S6(R1)
Last Updated: March 3, 2025PART I: PRECLINICAL SAFETY EVALUATION OF BIOTECHNOLOGY-DERIVED PHARMACEUTICALS ICH Harmonised Tripartite Guideline Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 16 July 1997, this Guideline is recommended for adoption to the three regulatory parties to ICH 1. INTRODUCTION 1.1 Background Biotechnology-derived pharmaceuticals (biopharmaceuticals) were initially developed in the early 1980s. The first marketing authorisations were granted later in the decade. Several...
S5(R3)
Last Updated: March 3, 2025DETECTION OF REPRODUCTIVE AND DEVELOPMENTAL TOXICITY FOR HUMAN PHARMACEUTICALS S5(R3) ICH Consensus Guideline TABLE OF CONTENTS TABLE OF CONTENTS LIST OF ABBREVIATIONS 6 1. INTRODUCTION & GENERAL PRINCIPLES 7 1.1. AIM OF STUDIES ...
S4
Last Updated: March 3, 2025DURATION OF CHRONIC TOXICITY TESTING IN ANIMALS (RODENT AND NON RODENT TOXICITY TESTING) ICH Harmonised Tripartite Guideline Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 2 September 1998, this guideline is recommended for adoption to the three...
S3B
Last Updated: March 3, 2025PHARMACOKINETICS: GUIDANCE FOR REPEATED DOSE TISSUE DISTRIBUTION STUDIES ICH Harmonised Tripartite Guideline Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 27 October 1994, this guideline is recommended for adoption to the three regulatory parties to ICH Introduction A comprehensive knowledge of the absorption,...
S3A
Last Updated: March 3, 2025NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT OF SYSTEMIC EXPOSURE IN TOXICITY STUDIES 1. Introduction This Note for Guidance concerns toxicokinetics only with respect to the development of pharmaceutical products intended for use in human subjects. In this context, toxicokinetics is defined as the generation of pharmacokinetic data, either as an integral component in the conduct of non-clinical toxicity studies or in specially designed supportive studies, in order to assess systemic exposure. These data may be...
S2(R1)
Last Updated: March 3, 2025GUIDANCE ON GENOTOXICITY TESTING AND DATA INTERPRETATION FOR PHARMACEUTICALS INTENDED FOR HUMAN USE 1. INTRODUCTION 1.1 Objectives of the Guideline This guidance replaces and combines the ICH S2A and S2B Guidelines. The purpose of the revision is to optimize the standard genetic toxicology battery for prediction of potential human risks, and to provide guidance on interpretation of results, with the ultimate goal of improving risk characterization for carcinogenic effects that have their basis...
S1C(R2)
Last Updated: March 3, 2025DOSE SELECTION FOR CARCINOGENICITY STUDIES OF PHARMACEUTICALS 1. INTRODUCTION Traditionally, carcinogenicity studies for chemical agents have relied upon the maximally tolerated dose (MTD) as the standard method for high dose selection (Note 1). The MTD is generally chosen based on data derived from toxicity studies of 3 months’ duration. In the past, the criteria for high dose selection for carcinogenicity studies of human pharmaceuticals have not been uniform among international regulatory agencies. In Europe and Japan, dose selection based on toxicity endpoints or attaining high multiples of the maximum recommended human daily dose (>100x on a mg/kg basis) has been accepted. However, in the United States, dose selection based on the MTD has traditionally been considered the only appropriate practice. All regions have used a maximum feasible dose as an appropriate endpoint. For pharmaceuticals with low rodent...
S1B(R1)
Last Updated: March 3, 20251. OBJECTIVE This document provides guidance on approaches for evaluating the carcinogenic potential of pharmaceuticals. 2. BACKGROUND Historically, the regulatory requirements for the assessment of the carcinogenic potential of pharmaceuticals in the three regions (E.U., Japan, U.S.) provided for the conduct of long-term carcinogenicity studies in two rodent species, usually the rat and the mouse. Given the cost of these studies and their extensive use of animals, it is in keeping with the mission of ICH to examine whether this practice requiring long...
S1A
Last Updated: March 3, 2025GUIDELINE ON THE NEED FOR CARCINOGENICITY STUDIES OF PHARMACEUTICALS 1. INTRODUCTION The objectives of carcinogenicity studies are to identify a tumorigenic potential in animals and to assess the relevant risk...