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Addendum to E2C : Periodic Safety Update Reports for Marketed DrugsBased on the comments made by the members of the Expert Working Group on CIOMS V recommendations and the PhRMA-EFPIA working document, this guideline has been finalised and reached Step 4 in February 2003. This Addendum should always be used in conjunction with the E2C Guideline.

The Addendum intends to provide further clarification and guidance in the preparation of PSURs as specified in E2C. Additionally, the document addresses some new concepts not in E2C but reflecting current pharmacovigilance practice needs, including Proprietary Information (Confidentiality), Executive Summary, Summary Bridging Report, Addendum Reports, Risk Management Program and Benefit-Risk Analysis.
Efficacy TopicsDownload0.03 MB
E1- The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening ConditionsThe tripartite harmonised ICH guideline was finalised (Step 4) in October 1994. This document gives recommendations on the numbers of patients and duration of exposure for the safety evaluation of drugs intended for the long-term treatment of non-life-threatening conditions.Efficacy TopicsDownload0.10 MB
E10: Choice of Control Group and Related Issues in Clinical Trials The harmonised tripartite guideline was finalised, having reached Step 4 in July 2000 .
This document addresses the choice of control groups in clinical trials considering the ethical and inferential properties and limitations of different kinds of control groups. It points out the assay sensitivity problem in active control equivalence / non-inferiority trials that limits the usefulness of trial design in many circumstances.
Efficacy TopicsDownload0.30 MB
E11: Clinical Investigation of Medicinal Products in the Pediatric PopulationThe harmonised tripartite guideline was finalised, having reached Step 4 in July 2000. This document addresses the conduct of clinical trials of medicines in pediatric populations. This document will facilitate the development of safe and effective use of medicinal product in pediatrics.Efficacy TopicsDownload0.17 MB
E12: Principles for Clinical Evaluation of New Antihypertensive Drugs Consensus Draft Principle This therapeutic area guideline considers the Clinical Evaluation of New Antihypertensive Drugs. It provides a set of "Principles" on which there is general agreement among all three ICH regions covering endpoints and trial designs. Since there are a few differences in the requirements of the three regions that have not been harmonised, this document should be considered an "ICH Principle Document" rather than an "ICH Guideline". It will not be subject to the usual procedures leading to a fully harmonized document.Efficacy TopicsDownload0.13 MB
E14: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugshe harmonised tripartite guideline was finalised, having reached Step 4 on 12 May 2005 .

This document provides recommendations to sponsors concerning the design, conduct, analysis, and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarization.
This assessment should include testing the effects of new agents on the QT/QTc interval as well as the collection of cardiovascular adverse events. The investigational approach used for a particular drug should be individualized, depending on the pharmacodynamic, pharmacokinetic, and safety characteristics of the product, as well as on its proposed clinical use.
The assessment of the effects of drugs on cardiac repolarization is the subject of active investigation. When additional data (non-clinical and clinical) are accumulated in the future, this document may be reevaluated and revised.
Efficacy TopicsDownload0.20 MB
E14: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs Questions & AnswersSince reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E14 guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.Efficacy TopicsDownload0.07 MB
E15: Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding CategoriesThe harmonised tripartite guideline was finalised, having reached Step 4 on 1 November 2007.
This guideline contains definitions of key terms in the discipline of pharmacogenomics and pharmacogenetics, namely genomic biomarkers, pharmacogenomics, pharmacogenetics and genomic data and sample coding categories. The validation and qualification processes for genomic biomarkers, evidence for their intended use and acceptance criteria across ICH regions are outside of the scope of this guideline. As new scientific knowledge in the discipline of pharmacogenomics and pharmacogenetics emerges, the current guidance will be reviewed and expanded if appropriate.
Efficacy TopicsDownload0.14 MB
E16: Genomic Biomarkers Related to Drug Response: Context, Structure and Format of Qualification SubmissionsThis guideline has been released for consultation under Step 2 of the ICH process on 10 June 2009.
The guideline describes recommendations regarding context, structure, and format of regulatory submissions for qualification of genomic biomarkers, as defined in ICH E15.
Efficacy TopicsDownload0.09 MB
E2A: Clinical Safety Data Management : Definitions and Standards for Expedited ReportingThe tripartite harmonised ICH guideline was finalised (Step 4) in October 1994. This document gives standard definitions and terminology for key aspects of clinical safety reporting. It also gives guidance on mechanisms for handling expedited (rapid) reporting of adverse drug reactions in the investigational phase of drug development.Efficacy TopicsDownload0.14 MB
E2B Q&As (R5): Questions and AnswersSince reaching Step 4 and publication within the ICH regions as E2B(R1) in November 2000, experiences by all parties with the implementation of the First Revision of the E2B Guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.

Please note that the Implementation Working Group has been discontinued in November 2004. Therefore, all technical questions should now be addressed to the regional Regulatory Authorities.
Efficacy TopicsDownload0.12 MB
E2B(R3): Revision of the E2B(R2) ICH Guideline (previously coded E2B(M)) on Clinical Safety Data Management Data Elements for Transmission of Individual Case Safety Reports This guideline has now been updated based upon feedback received during Step 3 public consultation in 2005, as well as additional considerations following its submission to ISO for development as an International Standard. Key parts of this updated guideline will be incorporated into the Implementation Guide for Electronic Transmission of Individual Case Safety Reports Message Specification (see http://estri.ich.org/new-icsr/index.htm) which is currently available for public awareness. Efficacy TopicsDownload0.00 MB
E2C(R1): Clinical Safety Data Management : Periodic Safety Update Reports for Marketed DrugsThe tripartite core harmonised ICH guideline was finalised (Step 4) in November 1996. This document gives guidance on the format and content of safety updates, which need to be provided at intervals to regulatory authorities after products have been marketed. The guideline is intended to ensure that the worldwide safety experience is provided to authorities at defined times after marketing with maximum efficiency and avoiding duplication of effort.
E2C Final Concept Paper, October 1994
Efficacy TopicsDownload0.25 MB
E2D: Post-Approval Safety Data Management: Definitions and Standards for Expedited ReportingThe Guideline was finalised, under Step 4 of the ICH process, on November 12, 2003. This document provides a standardized procedure for post-approval safety data management including expedited reporting to relevant authority. The definitions of the terms and concept specific to post-approval phase are also provided. E2A definitions in clinical safety data management was maintained in this document as post-approval safety data management, such as seriousness definition. The practices of the data management were standardized in such cases obtained from consumers, literatures, internets which are all specific to post-approval data management. Good case management practice was focused and recommended for expedited reporting with clear definitions.Efficacy TopicsDownload0.20 MB
E2E: Pharmacovigilance PlanningThe tripartite harmonised ICH guideline was finalised (Step 4) in November 2004. This guideline is intended to aid in planning pharmacovigilance activities, especially in preparation for the early postmarketing period of a new drug (in this guideline, the term "drug" denotes chemical entities, biotechnology-derived products, and vaccines). The main focus of this guideline is on a Safety Specification and Pharmacovigilance Plan that might be submitted at the time of licence application.Efficacy TopicsDownload0.21 MB
E2F: Development Safety Update ReportThis guideline has been released for consultation under Step 2 of the ICH process on 5 June 2008.
The main focus of the DSUR is data from interventional clinical trials (referred to in this document as "clinical trials") of investigational drugs including biologicals, with or without a marketing approval, whether conducted by commercial or non-commercial sponsors.
Efficacy TopicsDownload0.25 MB
E3: Structure and Content of Clinical Study ReportsThe tripartite harmonised ICH guideline was finalised (Step 4) in November 1995. This document describes the format and content of a study report that will be acceptable in all three ICH regions. It consists of a core report suitable for all submissions and appendices that need to be available but will not be submitted in all cases.Efficacy TopicsDownload0.46 MB
E4: Dose-Response Information to Support Drug RegistrationThe tripartite harmonised ICH guideline was finalised (Step 4) in March 1994. This document gives recommendations on the design and conduct of studies to assess the relationship between doses, blood levels and clinical response throughout the clinical development of a new drug.Efficacy TopicsDownload0.14 MB
E5(R1): Ethnic Factors in the Acceptability of Foreign Clinical DataThe tripartite harmonised ICH guideline was finalised (Step 4) in February 1998. This document addresses the intrinsic characteristics of the drug recipient and extrinsic characteristics associated with environment and culture that could affect the results of clinical studies carried out in regions and describes the concept of the "bridging study" that a new region may request to determine whether data from another region are applicable to its population.Efficacy TopicsDownload0.18 MB
E5: Ethnic Factors in the Acceptability of Foreign Clinical Data Questions & Answers (R1)Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E5 guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.Efficacy TopicsDownload0.06 MB
E6(R1): Good Clinical Practice : Consolidated GuidelineThe tripartite harmonised ICH guideline was finalised (Step 4) in May 1996. This Good Clinical Practices document describes the responsibilities and expectations of all participants in the conduct of clinical trials, including investigators, monitors, sponsors and IRBs. GCPs cover aspects of monitoring, reporting and archiving of clinical trials and incorporating addenda on the Essential Documents and on the Investigator's Brochure which had been agreed earlier through the ICH process.Efficacy TopicsDownload0.37 MB
E7: Studies in Support of Special Populations : GeriatricsThe tripartite harmonised ICH guideline was finalised (Step 4) in June 1993. This document provides recommendations on the special considerations which apply in the design and conduct of clinical trials of medicines that are likely to have significant use in the elderly.Efficacy TopicsDownload0.11 MB
E7: Studies in Support of Special Populations : Geriatrics Questions & AnswersSince reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E7 guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.Efficacy TopicsDownload0.04 MB
E8: General Considerations for Clinical TrialsThe tripartite harmonised ICH guideline was finalised (Step 4) in July 1997. This document sets out the general scientific principles for the conduct, performance and control of clinical trials. The guideline addresses a wide range of subjects in the design and execution of clinical trials.Efficacy TopicsDownload0.18 MB
E9: Statistical Principles for Clinical Trials The harmonised tripartite guideline was adopted in February 1998. This biostatistical guideline describes essential considerations on the design and analysis of clinical trials, especially the "confirmatory" (hypothesis-testing) trials that are the basis for demonstrating effectiveness.Efficacy TopicsDownload0.28 MB
M2: (ESTRI)-Electronic Standards for the Transfer of Regulatory InformationThe lack of internationally harmonized standards related to core sets of medicinal product information and medicinal product terminology is hindering the scientific evaluation and comparison of product data as well as healthcare. This applies in particular to the area of pharmacovigilance, where the exchange and management of medicinal product information in expedited and periodic adverse reaction reports at the international level is a key aspect of ensuring drug safety.

This document provides guidance on the harmonized standards that are being proposed by the ICH M5 EWG to facilitate the exchange and practical use of medicinal product data by regulators and pharmaceutical industry.
Multidisciplinary TopicsDownload0.32 MB
M3(R2): Guidance on Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for PharmaceuticalsThe recommendations of this revised guidance further harmonise the nonclinical safety studies to support the various stages of clinical development among the regions of European Union (EU), Japan, and the United States. The present guidance represents the consensus that exists regarding the type and duration of nonclinical safety studies and their timing to support the conduct of human clinical trials and marketing authorization for pharmaceuticals.Multidisciplinary TopicsDownload0.23 MB
Maintenance of the Clinical Safety Data Management including Data Elements for Transmission of Individual Case Safety Reports The tripartite harmonised ICH guideline was finalised as E2B (Step 4) in July 1997 and amended for Maintenance as E2B(R1) on 10 November 2000.
Post Step 4 editorial corrections were given on 5 February 2001 (second revision) and the guideline renamed E2B(R2).
Efficacy TopicsDownload0.28 MB
Q10: Pharmaceutical Quality SystemThe tripartite harmonised ICH guideline was finalised (Step 4) in June 2008
This guideline applies to pharmaceutical drug substances and drug products, including biotechnology and biological products, throughout the product lifecycle.
The elements of Q10 should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognizing the differences among, and the different goals of each stage.
Quality TopicsDownload0.42 MB
Q1A(R2): Stability Testing of New Drug Substances and Products (Second Revision)This guideline has been revised a second time in order to accommodate for the consequences of Q1F and has reached Step 4 of the ICH process on 6 February 2003.

This guideline provides recommendations on stability testing protocols including temperature, humidity and trial duration. Furthermore, the revised document takes into account the requirements for stability testing in Climatic Zones III and IV in order to minimize the different storage conditions for submission of a global dossier.
Quality TopicsDownload0.21 MB
Q1B: Photostability Testing of New Drug Substances and ProductsThe tripartite harmonised ICH guideline was finalised (Step 4) in November 1996. This forms an annex to the main stability guideline, and give guidance on the basic testing protocol required to evaluate the light sensitivity and stability of new drugs and products.Quality TopicsDownload0.20 MB
Q1C: Stability Testing for New Dosage FormsThe tripartite harmonised ICH guideline was finalised (Step 4) in November 1996. It extends the main stability guideline for new formulations of already approved medicines and defines the circumstances under which reduced stability data can be accepted.Quality TopicsDownload0.09 MB
Q1D: Bracketing and Matrixing Designs for Stability Testing of Drug Substances and Drug ProductsThe tripartite harmonised ICH guideline was finalised (Step 4) in February 2002. This document describes general principles for reduced stability testing and provides examples of bracketing and matrixing designs.Quality TopicsDownload0.19 MB
Q1E: Evaluation of Stability Data The tripartite harmonised ICH guideline was finalised (Step 4) in February 2003. This document extends the main guideline by explaining possible situations where extrapolation of retest periods/shelf-lives beyond the real-time data may be appropriate. Furthermore, it provides examples of statistical approaches to stability data analysis.Quality TopicsDownload0.20 MB
Q1F: Stability Data Package for Registration Applications in Climatic Zones III and IV Guideline withdrawn on June 8, 2006. The ICH Steering Committee endorsed the withdrawal of the Q1F guideline at its meeting in Yokohama, June 2006 and decided to leave definition of storage conditions in Climatic Zones III and IV to the respective regions and WHO. Quality TopicsDownload0.01 MB
Q2(R1): Validation of Analytical Procedures: Text and MethodologyThe core tripartite harmonised ICH text (previously coded Q2A) was finalised (Step 4) in October 1994. This identifies the validation parameters needed for a variety of analytical methods. It also discusses the characteristics that must be considered during the validation of the analytical procedures which are included as part of registration applications.

The addendum tripartite harmonised ICH text (previously coded Q2B) was finalised (Step 4) in November 1996. It extends the guideline Q2A to include the actual experimental data required, along with the statistical interpretation, for the validation of analytical procedures.

The addendum has been incorporated into the core guideline in November 2005.
Quality TopicsDownload0.18 MB
Q3A(R2): Impurities in New Drug Substances (Revised Guideline)First Recommended for Adoption at Step 4 of the ICH Process on 30 March 1995, the guideline was revised under Step 2 of the ICH Process on 7 October 1999 and Recommended for Adoption under Step 4 on 7 February 2002 by the ICH Steering Committee.

The guideline addresses the chemistry and safety aspects of impurities, including the listing of impurities in specifications and defines the thresholds for reporting, identification and qualification. The revision of the guideline has allowed clarifying some inconsistencies, to revise the decision tree, to harmonize with Q3B and to address some editorial issues.

The Attachment 2 of this guideline has been revised under Step 4 without further public consultation on 25 October 2006.
Quality TopicsDownload0.19 MB
Q3B(R2): Impurities in New Drug Products (Revised Guideline)This guideline has been revised and finalised under Step 4 in February 2003. It complements the guideline on impurities in new drug substances and provides advice in regard to impurities in products containing new, chemically synthesized drug substances. The guideline specifically deals with those impurities which might arise as degradation products of the drug substance or arising from interactions between drug substance and excipients or components of primary packaging materials. The guideline sets out a rationale for the reporting, identification and qualification of such impurities based on a scientific appraisal of likely and actual impurities observed, and of the safety implications, following the principles elaborated in the parent guideline. Threshold values for reporting and control of impurities are proposed, based on the maximum daily dose of the drug substance administered in the product.

The Attachment 2 of this guideline has been revised under Step 4 without further public consultation on 2 June 2006.
Quality TopicsDownload0.18 MB
Q3C(R4): Impurities: Guideline for Residual Solvents The tripartite harmonised ICH guideline was finalised (Step 4) in July 1997. This recommends the use of less toxic solvents in the manufacture of drug substances and dosage forms, and sets pharmaceutical limits for residual solvents (organic volatile impurities) in drug products.

Impurities: Guideline for Residual Solvents (Maintenance)

A Maintenance process has been done to revise PDEs, as new toxicological data for solvents becomes available.

The two documents have reached Step 4 of the process in September 2002.

Limit values for two residual solvents in drug products were revised on basis of the newly recognized toxicity data; lower PDE (permissible daily exposure) for N-Methylpyrrolidone being kept in Class 2 (limited by health-basis) and for Tetrahydrofuran being placed into Class 2 from Class 3 (no health-based).
Quality TopicsDownload0.23 MB
Q4B Annex 10: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Polyacrylamide Gel Electrophoresis General ChapterThis guideline has been released for consultation under Step 2 of the ICH process on 11 June 2009.
This annex is the result of the Q4B process for Polyacrylamide Gel Electrophoresis.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.10 MB
Q4B Annex 1: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Residue on Ignition/Sulphated Ash General ChapterThe tripartite harmonised ICH guideline was finalised (Step 4) on 1 November 2007.
This annex is the result of the Q4B process for Residue on Ignition/Sulphated Ash.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.00 MB
Q4B Annex 2: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Test for Extractable Volume of Parenteral Preparations General ChapterThe tripartite harmonised ICH guideline was finalised (Step 4) on 5 June 2008.
This annex is the result of the Q4B process for the Test for Extractable Volume of Parenteral Preparations General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.10 MB
Q4B Annex 3: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Test for Particulate Contamination: Sub-Visible Particles General ChapterThe tripartite harmonised ICH guideline was finalised (Step 4) on 5 June 2008.
This annex is the result of the Q4B process for Test for Particulate Contamination: Sub-Visible Particles.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.45 MB
Q4B Annex 4A: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests General ChapterThe tripartite harmonised ICH guideline was finalised (Step 4) on 13 November 2008.
This annex is the result of the Q4B process for Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.12 MB
Q4B Annex 4B: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms General ChapterwwwThe tripartite harmonised ICH guideline was finalised (Step 4) on 13 November 2008.
This annex is the result of the Q4B process for Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.12 MB
Q4B Annex 5: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Disintegration Test General ChapterThe tripartite harmonised ICH guideline was finalised (Step 4) on 10 June 2009.
This annex is the result of the Q4B process for Disintegration Test.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.21 MB
Q4B Annex 7: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Dissolution Test General ChapterThis guideline has been released for consultation under Step 2 of the ICH process on 13 November 2008.
This annex is the result of the Q4B process for Dissolution Test General Chapter.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.34 MB
Q4B Annex 8: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Sterility Test General ChapterThe tripartite harmonised ICH guideline was finalised (Step 4) on 11 June 2009.
This annex is the result of the Q4B process for Sterility Test.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.15 MB
Q4B Annex 9: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Tablet Friability General ChapterThis guideline has been released for consultation under Step 2 of the ICH process on 11 June 2009.
This annex is the result of the Q4B process for Tablet Friability.
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).
Quality TopicsDownload0.11 MB
Q4B: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH RegionsThe tripartite harmonised ICH guideline was finalised (Step 4) on 1 November 2007.
This document describes a process for the evaluation and recommendation by the Q4B Expert Working Group (EWG) of selected pharmacopoeial texts to facilitate their recognition by regulatory authorities for use as interchangeable in the ICH regions. Following favourable evaluations, ICH will issue topic-specific annexes with information about these texts and their implementation (the Q4B Outcomes). Implementation of the Q4B annexes is intended to avoid redundant testing by industry.
Quality TopicsDownload0.15 MB
Q5A(R1): Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal OriginThe tripartite harmonised ICH guideline was finalised (Step 4) in March 1997. This is concerned with testing and evaluation of the viral safety of biotechnology products derived from characterised cell lines of human or animal origin. The purpose is to provide a general framework for virus testing experiments for the evaluation of virus clearance and the design of viral tests and clearance evaluation studies.Quality TopicsDownload0.28 MB
Q5B: Quality of Biotechnological Products : Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein ProductsThe tripartite harmonised ICH guideline was finalised (Step 4) in November 1995. It advises on the types of information that are considered valuable in assessing the structure of the expression construct used to produce recombinant DNA derived proteins.Quality TopicsDownload0.11 MB
Q5C: Quality of Biotechnological Products : Stability Testing of Biotechnological/Biological ProductsThe tripartite harmonised ICH guideline was finalised (Step 4) in November 1995. This document augments the stability guideline (Q1A above) and deals with the particular aspects of stability test procedures needed to take account of the special characteristics of products in which the active components are typically proteins and/or polypeptides.Quality TopicsDownload0.12 MB
Q5D: Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological ProductsThe tripartite harmonised ICH guideline was finalised (Step 4) in July 1997. This document provides broad guidance on appropriate standards for the derivation of human and animal cell lines and microbes used to prepare biotechnological/biological products and for the preparation and characterisation of cell banks to be used for production.Quality TopicsDownload0.16 MB
Q5E: Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing ProcessThe tripartite harmonised ICH guideline was finalised (Step 4) in November 2004. The objective of this document is to provide principles for assessing the comparability of biotechnological/biological products before and after changes are made in the manufacturing process for the drug substance or drug product. Therefore, this guideline is intended to assist in the collection of relevant technical information which serves as evidence that the manufacturing process changes will not have an adverse impact on the quality, safety and efficacy of the drug product. The document does not prescribe any particular analytical, nonclinical or clinical strategy. The main emphasis of the document is on quality aspects.Quality TopicsDownload0.18 MB
Q6A: Specifications : Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products : Chemical SubstancesThe tripartite harmonised ICH guideline was finalised (Step 4) in October 1999. This addresses the process of selecting tests and methods and setting specifications for the testing of drug substances and dosage forms. Account has been taken of the considerable guidance and background information which are present in existing regional documents.Quality TopicsDownload0.21 MB
Q6B: Specifications : Test Procedures and Acceptance Criteria for Biotechnological/Biological ProductsThe tripartite harmonised ICH guideline was finalised (Step 4) in March 1999. This document provides guidance on justifying and setting specifications for proteins and polypeptides which are derived from recombinant or non-recombinant cell cultures. The scope of this part is initially limited to well-characterised biotechnological products, although the concepts may be applicable to other biologicals as appropriate. In view of the nature of the products, the topic of specifications include in-process controls, bulk drug, final product and stability specifications and give guidance for a harmonised approach to determining appropriate specifications based on safety, process consistency, purity, analytical methodology, product administration and clinical data considerations.Quality TopicsDownload0.20 MB
Q7: Good Manufacturing Practice Guide for Active Pharmaceutical IngredientsEarly in the ICH Process it was agreed that there was adequate international agreement on the technical aspects of Good Manufacturing Practices (GMP) for Pharmaceutical Products and that further harmonisation action through ICH was not needed. Recently, however, attention has focused on the need to formalise GMP requirements for the components of pharmaceutical products - both active and inactive. In February 1998, the ICH Steering Committee agreed that GMP for Active Pharmaceutical Ingredients (APIs) should be adopted as an ICH Topic.

When this topic was adopted, the Steering Committee took steps to ensure that due account was taken of the work already in progress by PIC/S, FDA and other parties. In view of the unusually wide implications of this Topic, a much extended EWG has been established which includes, in addition to the six ICH parties and the Observers, experts representing IGPA (generics industry), WSMI (self medication industry) and PIC/S. With respect to the latter representatives from China, India and Australia have been invited to participate.
Quality TopicsDownload0.34 MB
Q8(R2): Pharmaceutical DevelopmentThe core tripartite harmonised ICH guideline was finalised (Step 4) in November 2005.
This guideline is intended to provide guidance on the contents of Section 3.2.P.2 (Pharmaceutical Development) for drug products as defined in the scope of Module 3 of the Common Technical Document (ICH topic M4). The guideline does not apply to contents of submissions for drug products during the clinical research stages of drug development. However the principles in this guideline are important to consider during these stages. This guideline might also be appropriate for other types of products. To determine the applicability of this guideline for a particular type of product, applicants should consult with the appropriate regulatory authorities.
Q8 Final Concept Paper, September 2003

The annex tripartite harmonised ICH text (previously named Annex to Q8) was finalised (Step 4) in November 2008.
The annex provides further clarification of key concepts outlined in the core guideline. In addition, this annex describes the principles of quality by design (QbD). The annex is not intended to establish new standards: however, it shows how concepts and tools (e.g., design space) outlined in the parent Q8 document could be put into practice by the applicant for all dosage forms. Where a company chooses to apply quality by design and quality risk management (Q9: Quality Risk Management), linked to an appropriate pharmaceutical quality system, then opportunities arise to enhance science- and risk-based regulatory approaches (see Q10: Pharmaceutical Quality System).

The annex has been incorporated into the core guideline in November 2008.
Quality TopicsDownload0.15 MB
Q8, Q9, Q10: Quality Implementation Working Group Questions & AnswersSince reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the Q8, Q9 and Q10 guidelines have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues. The Questions & Answers document was finalised (Step 4) in April 2009. In October 2009, a third set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document. Quality TopicsDownload0.14 MB
Q9: Quality Risk ManagementThe tripartite harmonised ICH guideline was finalised (Step 4) in November 2005.
This guideline provides principles and examples of tools of quality risk management that can be applied to all aspects of pharmaceutical quality including development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances and drug (medicinal) products, biological and biotechnological products, including the use of raw materials, solvents, excipients, packaging and labeling materials.
Quality TopicsDownload0.20 MB
S1A: Guideline on the Need for Carcinogenicity Studies of PharmaceuticalsThe tripartite harmonised ICH guideline was finalised (Step 4) in November 1995. 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.Safety TopicsDownload0.12 MB
S1B: Testing for Carcinogenicity of PharmaceuticalsThe tripartite harmonised ICH guideline was finalised (Step 4) in July 1997. This document provides 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.Safety TopicsDownload0.15 MB
S1C(R2): Dose Selection for Carcinogenicity Studies of PharmaceuticalsThis second revision has been approved by the ICH Steering Committee directly under Step 4 without further public consultation in March 2008.

Note 2 of the parent guideline has been deleted, and the text referring to the Notes has been revised. The title has been changed by deleting "& Limit Dose".
The Addendum has been integrated in the text.

This document 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.

In this revision, the pharmacokinetic endpoint of 25 is declared to be applicable also for pharmaceuticals with positive genotoxicity signals. This change has implications on "Refinement" (one of the 3R's) in enhancing the welfare, i.e., reducing the pain or discomfort of the animals at the MTD.
Safety TopicsDownload0.13 MB
S2(R1): Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human UseThis guideline has been released for consultation under Step 2 of the ICH process on 6 March 2008.
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 in changes in the genetic material. The revised guidance describes internationally agreed upon standards for follow-up testing and interpretation of positive results in vitro and in vivo in the standard genetic toxicology battery, including assessment of non-relevant findings.
Safety TopicsDownload0.25 MB
S2A: Guidance on Specific Aspects of Regulatory Genotoxicity Tests for PharmaceuticalsThe tripartite harmonised ICH guideline was finalised (Step 4) in July 1995. This document provides 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.Safety TopicsDownload0.16 MB
S2B: Genotoxicity: A Standard Battery for Genotoxicity Testing for PharmaceuticalsThe tripartite harmonised ICH guideline was finalised (Step 4) in July 1997. This document addresses two fundamental areas of genotoxicity testing: 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.Safety TopicsDownload0.14 MB
S3A: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity StudiesThe tripartite harmonised ICH guideline was finalised (Step 4) in October 1994. This document 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.Safety TopicsDownload0.16 MB
S3B: Pharmacokinetics: Guidance for Repeated Dose Tissue Distribution StudiesThe tripartite harmonised ICH guideline was finalised (Step 4) in October 1994. This document gives guidance on circumstances when repeated dose tissue distribution studies should be considered (i.e., when appropriate data cannot be derived from other sources). It also gives recommendations on the conduct of such studies.Safety TopicsDownload0.09 MB
S4: Duration of Chronic Toxicity Testing in Animals (Rodent and Non-Rodent Toxicity Testing)A tripartite, harmonised ICH guideline was finalised (Step 4) in September 1998. The recommendations are unchanged from those in the consultation draft issued in July 1997. The text incorporates the guidance for repeat-dose toxicity tests that was agreed at the time of ICH 1, in 1991 (reduction of the duration of repeat dose toxicity studies in the rat from 12 to 6 months).Safety TopicsDownload0.09 MB
S5(R2): Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility
S5(R2): Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility

The core tripartite harmonised ICH guideline was finalised (Step 4) in June 1993. 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.

The addendum to the core ICH guideline above with respect to male fertility studies was finalised (Step 4) in November 1995. The guideline has been amended on November 9, 2000, under the Maintenance Process.

The amendments provide a better description of the testing concept and recommendations, especially those addressing flexibility, pre-mating treatment duration, and observations.
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S6: Preclinical Safety Evaluation of Biotechnology-Derived PharmaceuticalsThe tripartite harmonised ICH guideline was finalised (Step 4) in July 1997. This document covers the pre-clinical safety testing requirements for biotechnological products. 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.Safety TopicsDownload0.15 MB
S7A: Safety Pharmacology Studies for Human PharmaceuticalsThe ICH guideline reached Step 4 of the ICH process in November 2000. This document addresses the definition, objectives and scope of safety pharmacology studies. It also addresses which studies are needed before initiation of Phase 1 clinical studies as well as information needed for marketing.Safety TopicsDownload0.17 MB
S8 : Immunotoxicity Studies for Human Pharmaceuticalshe Guideline reached Step 4 of the ICH process on 15 September 2005.

This guideline addresses the recommendations on nonclinical testing for immunosuppression induced by low molecular weight drugs (non-biologicals). 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. In addition, the guideline might also apply to drugs in which clinical signs of immunosuppression are observed during clinical trials and following approval to market. The term immunotoxicity in this guideline will primarily refer to immunosuppression, i.e. a state of increased susceptibility to infections or the development of tumors.
It is beyond the scope of this guideline to provide specific guidance on how each immunotoxicity study should be performed.
General guidance is provided in Appendix 1.
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S9: Nonclinical Evaluation for Anticancer PharmaceuticalsThis guideline has been released for consultation under Step 2 of the ICH process on 13 November 2008.
This guideline 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.
Safety TopicsDownload0.12 MB