ICH-S Guidelines: ICH-S Guidelines Safety Guidelines: Safety Guidelines ICH has produced a comprehensive set of safety guidelines to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity. A recent breakthrough has been a non-clinical testing strategy for assessing the QT interval prolongation liability: the single most important cause of drug withdrawals in recent years. S1A (Nov. 1995): S1A (Nov. 1995) Need for Carcinogenicity Studies of Pharmaceuticals This document provides a consistent definition of the circumstances under which it is necessary to undertake carcinogenicity studies on new drugs. These recommendations take into account the known risk factors as well as the intended indications and duration of exposure. Results from genotoxicity studies, toxicokinetics, and mechanistic studies can now be routinely applied in preclinical safety assessment. S1B (July 1997): S1B (July 1997) Testing for Carcinogenicity of Pharmaceuticals Guidance on the need to carry out carcinogenicity studies in both mice and rats, and guidance is also given on alternative testing procedures which may be applied without jeopardizing safety. S1C-R2 (March 2008): S1C-R2 (March 2008) Dose Selection for Carcinogenicity Studies of Pharmaceuticals addresses the criteria for the selection of the high dose to be used in carcinogenicity studies on new therapeutic agents to harmonise current practices and improve the design of studies. the pharmacokinetic endpoint of 25 is declared to be applicable also for pharmaceuticals with positive genotoxicity signals. This change has implications on reducing the pain or discomfort of the animals at the maximally tolerated dose (MTD). S2-R1 (March 2008): S2-R1 (March 2008) Guidance On Genotoxicity Testing And Data Interpretation For Pharmaceuticals Intended For Human Use S2A: Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals :specific guidance and recommendations for in vitro and in vivo tests and on the evaluation of test results. It includes a glossary of terms related to genotoxicity tests to improve consistency in applications. S2B: Genotoxicity: A Standard Battery for Genotoxicity Testing for Pharmaceuticals ; the identification of a standard set of assays to be conducted for registration, and the extent of confirmatory experimentation in any particular genotoxicity assay in the standard battery. S3A (Oct. 1994): S3A (Oct. 1994) Note For Guidance On Toxicokinetics: The Assessment Of Systemic Exposure In Toxicity Studies gives guidance on developing test strategies in toxicokinetics and the need to integrate pharmacokinetics into toxicity testing, in order to aid in the interpretation of the toxicology findings and promote rational study design development. S3B (Oct. 1994): S3B (Oct. 1994) Pharmacokinetics: Guidance For Repeated Dose Tissue Distribution Studies This study is required when appropriate data cannot be derived from other sources A comprehensive knowledge of the absorption, distribution, metabolism and elimination of a compound is important for the interpretation of pharmacology and toxicology studies. useful for designing toxicology and pharmacology studies S4 (Sep. 1998): S4 (Sep. 1998) Duration Of Chronic Toxicity Testing In Animals (Rodent And Non Rodent Toxicity Testing) safety evaluation of a medicinal product for the development of medicinal products with the exception of those already covered by the ICH Guideline on Safety Studies for Biotechnological Products , e.g., Monoclonal antibodies, recombinant DNA proteins. S5-R2 (Nov. 2000): S5-R2 (Nov. 2000) Detection Of Toxicity To Reproduction For Medicinal Products & Toxicity To Male Fertility This document provides guidance on tests for reproductive toxicity. It defines the periods of treatment to be used in animals to better reflect human exposure to medical products and allow more specific identification of stages at risk S6 (Oct. 2009): S6 (Oct. 2009) Addendum To Ich S6: Preclinical Safety Evaluation Of Biotechnology-derived Pharmaceuticals It addresses the use of animal models of disease, determination of when genotoxicity assays and carcinogenicity studies should be performed, and the impact of antibody formation on duration of toxicology studies Clarification on species selection, study design, immunogenicity, reproductive and developmental toxicity and assessment of carcinogenic potential. S7A (Nov. 2000): S7A (Nov. 2000) Safety Pharmacology Studies for Human Pharmaceuticals addresses the definition, objectives and scope of safety pharmacology studies also addresses which studies are needed before initiation of Phase 1 clinical studies as well as information needed for marketing. S7B (May 2005): S7B (May 2005) The Non-clinical Evaluation Of The Potential For Delayed Ventricular Repolarization (Qt Interval Prolongation) By Human Pharmaceuticals This Guideline describes a non-clinical testing strategy for assessing the potential of a test substance to delay ventricular repolarization. Includes non-clinical assays and integrated risk assessments S8 (Sep. 2005): S8 (Sep. 2005) Immunotoxicity Studies for Human Pharmaceuticals addresses the recommendations on nonclinical testing for immunosuppression induced by low molecular weight drugs (non-biologicals and how each immunotoxicity study should be performed It applies to new pharmaceuticals intended for use in humans, as well as to marketed drug products proposed for different indications or other variations on the current product label in which the change could result in unaddressed and relevant toxicologic issues Also applicable during CT and following approval to market. S9 (Oct. 2009): S9 (Oct. 2009) Nonclinical Evaluation for Anticancer Pharmaceuticals provides information for pharmaceuticals that are only intended to treat cancer in patients with late stage or advanced disease regardless of the route of administration, including both small molecule and biotechnology-derived pharmaceuticals. It describes the type and timing of nonclinical studies in relation to the development of anticancer pharmaceuticals and references other guidance as appropriate. S10 (June 2010): S10 (June 2010) Photosafety Evaluation of Pharmaceuticals This new Guideline on photosafety testing will be a valuable adjunct to the guidance provided in the M3(R2) Guideline. Thank you…..: Thank you…..