Ich – guidelines
- 1. GUIDELINES OF ICH Presented By :- SK JAFAR FAROOQUE M.Pharm 1st Sem (Pharmaceutics) SCHOOL OF PHARMACEUTICAL EDUCATION AND RESEARCH JAMIA HAMDARD, NEW DELHI Guieded By :- PROF. SANJULA BABOOTA MA’AM
- 2. • Introdution • Mission • History • Members • Observers • Organisation • Process • Guidelines • Quality Guidelines • Safety Guidelines • Efficacy Guidelines • Multidisiplinary Guidelines Contents :-
- 3. INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE (ICH) Introduction :- • The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is unique in bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of pharmaceuticals and develop ICH guidelines. • ICH's mission is to achieve greater harmonisation worldwide to ensure that safe, effective and high quality medicines are developed, and registered and maintained in the most resource efficient manner whilst meeting high standards. • The Secretariat is located in Geneva, Switzerland. • The ICH Assembly meets on a biannual basis & the location of each meeting rotates between the ICH Member countries/regions.
- 4. Mission:- With ICH’s establishment as an international non-profit Association under Swiss law on October 23, 2015, ICH’s mission has been embodied in its Articles of Association as follows: • To make recommendations towards achieving greater harmonisation in the interpretation and application of technical guidelines and requirements for pharmaceutical product registration and the maintenance of such registrations; • To maintain a forum for a constructive dialogue on scientific issues between regulatory authorities and the pharmaceutical industry on the harmonisation of the technical requirements for pharmaceutical products; • To contribute to the protection of public health in the interest of patients from an international perspective; • To monitor and update harmonised technical requirements leading to a greater mutual acceptance of research and development data; • To facilitate the adoption of new or improved technical research and development approaches which update or replace current practices
- 5. History :- • The International Council for Harmonisation (ICH), formerly known as International Conference on Harmonisation (ICH). • It was pioneered by the EC, Europe, in the 1980. • There were discussions between Europe, Japan and the US on possibilities for harmonization • It was, however, at the WHO Conference of Drug Regulatory Authorities (ICDRA), in Paris, in 1989, that specific plans for action began to materialise. • The birth of ICH took place at a meeting in April 1990, hosted by EFPIA in Brussels. Representatives of the regulatory agencies and industry associations of Europe, Japan and the US. • Topics selected for harmonisation would be divided into Safety, Quality and Efficacy. • Since its inception in 1990, ICH has gradually evolved, to respond to increasingly global developments in the pharmaceutical sector and these ICH guidelines are applied by a growing number of regulatory authorities. • Since its announcement of organisational changes in October 2015, ICH has grown as an organisation and now includes 17 Members and 32 Observers.
- 6. Founding Regulatory Members • EC, Europe • FDA, United States • MHLW/PMDA, Japan Founding Industry Members • EFPIA • JPMA • PhRMA Standing Regulatory Members • Health Canada, Canada • Swissmedic, Switzerland Industry Members • BIO • Global Self-Care Federation • IGBA Regulatory Members • ANVISA, Brazil • HSA, Singapore • MFDS, Republic of Korea • NMPA, China • TITCK, Turkey • TFDA, Chinese Taipei Members :-ICH Members are voting Member of the Assembly and actively support the compliance with ICH Guidelines, appoint experts in Working Groups, and support the aims of the ICH Association.
- 7. Standing Observers • IFPMA • WHO Legislative or Administrative Authorities • ANMAT, Argentina • CDSCO, India • CECMED, Cuba • COFEPRIS, Mexico • CPED, Israel • INVIMA, Colombia • JFDA, Jordan • MMDA, Moldova • MOPH, Lebanon • National Center, Kazakhstan • NPRA, Malaysia • NRA, Iran • Roszdravnadzor, Russi a • SAHPRA, South Africa • SCDMTE, Armenia • SFDA, Saudi Arabia • TGA, Australia Regional Harmonisation Initiatives (RHIs) • APEC • ASEAN • EAC • GHC • PANDRH • SADC Observers :-Attendees of ICH Assembly meetings who may provide input on ICH harmonisation activities but who do not have voting rights.
- 8. International Pharmaceutical Industry Organisation • APIC International Organisation regulated or affected by ICH Guideline(s) • Bill & Melinda Gates Foundation • CIOMS • EDQM • IPEC • PIC/S • USP Conti….
- 10. PROCESS FOR ICH GUIDELINE DEVELOPMENT CONSISTS OF 5 STEPS: • to prepare a consensus draft of the Technical Document based on the objectives set out in the Concept Paper. Step 1: Consensus Building • the MC will provide a recommendation to the Assembly on the decision to endorse the final Technical. Step 2a: Confirmation of Member Consensus of the Technical Document, • Adoption of Draft Guideline by Regulatory Members, Step 2b: Adoption of Draft Guideline • It divided into three phases including i) regional consultation, ii) discussion of regional comments, and iii) Step 3 Experts Sign-Off by the regulatory experts. Step 3: Regulatory Consultation and Discussion, • Regulatory Members of the Assembly adopt a harmonised Guideline in consultation with the MC Step 4: Adoption of an ICH Harmonised Guideline, • implemented by each of the Regulatory Members in their respective regions Step 5: Implementation.
- 11. ICH GUIDELINES :- The ICH topics are divided into four categories and ICH topic codes are assigned according to these categories: QUALITY (Q) • i.e., those relating to chemical and pharmaceutical Quality Assurance (Stability Testing, Impurity Testing, etc.) SAFETY (S) • i.e., those relating to in-vitro and in-vivo preclinical studies ((Carcinogenicity Testing, Genotoxicity Testing, etc.) EFFICACY (E) • i.e., those relating to clinical studies in human subject (Dose Response Studies, Good Clinical Practices, etc.) MULTIDISIPLINARY (M) • i.e., cross cutting Topics which do not fit uniquely into one of the above categories (MedDRA, ESTRI, M3, CTD M5)
- 12. Quality Guidelines Q9:- Quality Risk Management Q10:- Pharmaceutical Quality System Q11:- Development & Manufacture of Drug Substances Q12:- Lifecycle Management Q13:- Continuous Manufacturing of Drug Substances and Drug Products Q14:- Analytical Procedure Development Q1A-Q1F:- Stability Q2:- Analytical Validation Q3A-Q3E:- Impurities Q4A-Q4B:- Pharmacopoeias Q5A-Q5E:- Quality of Biotechnological Products Q6A-Q6B:- Specifications Q7:- Good Manufacturing Practice Q8:- Pharmaceutical Development
- 13. Q1A – Q1F Stability • Q1A(R2) :-Stability Testing of New Drug Substances and Product:- Provides recommendations on stability testing to minimise the different storage conditions • Q1B :- Stability Testing : Photostability Testing of New Drug Substances and Products:-This Guideline gives guidance on the basic testing protocol required to evaluate the light sensitivity and stability of new drugs and products. • Q1C :-Stability Testing for New Dosage Forms:- Guideline for new formulations of already approved medicines • Q1D :-Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products:- It is for stability testing of product using Bracketing and Matrixing in accordance with principles outlined in the main stability Guideline. • Q1E :- Evaluation of Stability Data:- This section has the method of evaluation of data found after analysis of drug products for stability testing. • Q1F :- Stability Data Package for Registration Applications in Climatic Zones III and IV:- Withdrawn
- 14. Q2 Analytical Validation • Q2(R1) :- Validation of Analytical Procedures: Text and Methodolog:- This identifies the validation parameters needed for a variety of analytical methods. • Q2(R2)/Q14 EWG :- Analytical Procedure Development and Revision of Q2 (R1) Analytical Validation:- Potentially combine both documents into one, for simplification and clarity. Q3A - Q3E Impurities • Q3A(R2) - Impurities in New Drug Substances:- It has information about chemistry and safety aspects of impurities in active pharmaceutical ingredients. • Q3B(R2) - Impurities in New Drug Products:- It has information about impurities in products containing new, chemically synthesized drug substances. • Q3C(R6) - Maintenance of the Guideline for Residual Solvents:- 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. • Q3C(R8) Maintenance EWG - Maintenance of the Guideline for Residual Solvents:- EWG working on the PDE levels for solvents 2-methyltetrahydrofuran, cyclopentylmethylether and tert-butanol
- 15. • Q3D(R1) - Guideline for Elemental Impurities:- This is a quality guideline for the control of elemental impurities in new drug products (medicinal products), and it establishes Permitted Daily Exposures (PDEs) for 24 Elemental Impurities (EIs) for drug products administered by the oral, parenteral and inhalation routes of administration. • Q3D(R2) Maintenance EWG - Revision of Q3D(RI) for cutaneous and transdermal products:- It is currently undertaking a maintenance of the Guideline to develop PDE levels for cutaneous and transdermal products. • Q3D training - Implementation of Guideline for Elemental Impurities:- A training programme developed for Implementation of Guideline for Elemental Impurities • Q3E EWG - Impurity: Assessment and Control of Extractables and Leachables for Pharmaceuticals and Biologics:-
- 16. Q4A - Q4B Pharmacopoeias • Q4A Pharmacopoeial Harmonisation:- Details about the harmonization of pharmacopeias like USP, JP and EP • Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions:- It is to facilitate their recognition by regulatory authorities for use as interchangeable in the ICH regions. ICH decided to issue topic-specific annexes with information about these texts and their implementation (intended to avoid redundant testing by industry). Q4B Annex 1(R1) Residue on Ignition/Sulphated Ash General Chapter Q4B Annex 2(R1) Test for Extractable Volume of Parenteral Preparations General Chapter Q4B Annex 3(R1) Test for Particulate Contamination: Sub-Visible Particles General Chapter Q4B Annex 4A(R1) Microbiol ical Examination of Non-Sterile Products: Microbial Enumeration Tests General Chapter Q4B Annex 4B(R1) Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-Organisms General Chapter
- 17. Q4B Annex 4C(R1) - Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use General Chapter Q4B Annex 5(R1) - Disintegration Test General Chapter Q4B Annex 6 - Uniformity of Dosage Units General Chapter Q4B Annex 7(R2) - Dissolution Test General Chapter Q4B Annex 8(R1) - Sterility Test General Chapter Q4B Annex 9(R1) - Tablet Friability General Chapter Q4B Annex 10(R1) - Polyacrylamide Gel Electrophoresis General Chapter Q4B Annex11 - Capillary Electrophoresis General Chapter Q4B Annex 12 - Analytical Sieving General Chapter Q4B Annex 13 - Bulk Density and Tapped Density of Powders General Ch. Q4B Annex 14 - Bacterial Endotoxins Test General Chapter Q4B FAQs - Frequently Asked Question
- 18. Q5A - Q5E Quality of Biotechnological Products • Q5A(R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin :- It provide a general framework for virus testing, experiments for the assessment of viral clearance and a recommended approach for the design of viral tests and viral clearance studies. • Q5A(R2) EWG - Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin :- EWG is working with a view to reflecting new biotechnology product types, advances in manufacturing technology, analytical methods for virus testing. • Q5B Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products :- It describe the types of information that are considered valuable in assessing the structure of the expression construct used to produce recombinant DNA derived proteins. • Q5C Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products :- 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.
- 19. • Q5D Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products :-provides broad guidance on appropriate standards for the derivation of human and animal cell lines and microbial cells used to prepare biotechnological/biological products, and for the preparation and characterisation of cell banks to be used for production • Q5E Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process :-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. Q6A- Q6B Specifications • Q6A Specifications : Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances This document provides guidance on the setting and justification of acceptance criteria and the selection of test procedures for new drug substances of synthetic chemical origin, and new drug products produced from them, which have not been registered previously in the ICH regions.
- 20. • Q6BSpecifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products This document provides general principles on the setting and justification of a uniform set of international specifications for proteins and polypeptides which are produced from recombinant or non-recombinant cell-culture expression systems. Q7 Good Manufacturing Practice • Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients provide guidance regarding Good Manufacturing Practice (GMP) for the manufacturing of Active Pharmaceutical Ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the requirements for quality and purity that they purport or are represented to possess. Q8 Pharmaceutical Development • Q8(R2) Pharmaceutical Development 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).
- 21. Q9 Quality Risk Management • Q9 Quality Risk Management This Guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality • Q9(RI) EWG Quality Risk Management It is focusing on the following harmonisation activities: • Make limited and specific adjustments to specific chapters and annexes of the current ICH Q9 Guideline on Quality Risk Management (QRM); • Develop specific training materials (with examples) to supplement the existing ICH briefing pack on ICH Q9, as well as to explain and facilitate the implementation and application of the proposed revisions. Q10 Pharmaceutical Quality System • Q10 Pharmaceutical Quality System This Guideline applies to the systems supporting the development and manufacture of pharmaceutical drug substances and drug products throughout the product lifecycle.
- 22. Q11 Development and Manufacture of Drug Substances • Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities) This Guideline describes approaches to developing and understanding the manufacturing process of the drug substance. It addresses aspects of development and manufacture that pertain to drug substance, including the presence of steps designed to reduce impurities. Q12 Lifecycle Management • Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management This new Guideline is proposed to provide a framework to facilitate the management of post-approval Chemistry, Manufacturing and Controls (CMC) changes in a more predictable and efficient manner across the product lifecycle • Q12 IWG Training on Regulatory and Technical Considerations for Pharmaceutical Product Lifecycle Management It was established to prepare a comprehensive training programme and a harmonized implementation of ICH Q12 in ICH and non-ICH regions.
- 23. Q13 Continuous Manufacturing of Drug Substances and Drug Products • Q13 EWG Continuous Manufacturing of Drug Substances and Drug Products Provide guidance to industry and regulatory agencies regarding regulatory expectations on the development, implementation, and assessment of CM technologies used in the manufacture of drug substances and drug products Q14 Analytical Procedure Development • Q2(R2)/Q14 EWG Analytical Proc Development and Revision of Q2 (RI) Analytical ValidationThis guideline is proposed to harmonise the scientific approaches of Analytical Procedure Development, and to provide the principles relating to the description of Analytical Procedure Development process
- 24. SAFETY GUIDELINES :- S1A – S1C :-Carcinogenicity Studies S2 :- Genotoxicity Studies S3A – S3B :- Toxicokinetics & Pharmacokinetics S4 :- Toxicity Testing S5 :- Reproductive Toxicology S6 :- Biotechnological Products S7A – S7B :- Pharmacology Studies S8 :- Immunotoxicology Studies S9 :- Nonclinical Evaluation for Anticancer Pharmaceuticals S10 :- Photosafety Evaluation S11 :- Nonclinical Paediatric Safety S12 Non-clinical Biodistribution Studies for Gene Therapy Products ICH has produced a comprehensive set of safety Guidelines to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity.
- 25. S1A - S1C Carcinogenicity Studies • S1A 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. • S1B Testing for Carcinogenicity of PharmaceuticalsThis document provides guidance on approaches for evaluating the carcinogenic potential of pharmaceuticals and 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) Dose Selection for Carcinogenicity Studies of Pharmaceuticals 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
- 26. • S1(R1) EWG Rodent Carcinogenicity Studies for Human PharmaceuticalsGuidelines on rodent carcinogenicity testing is proposed to introduce a more comprehensive and integrated approach to addressing the risk of human carcinogenicity of pharmaceuticals, clarify and update, without compromising safety, the criteria for deciding whether the conduct of a two-year rodent carcinogenicity study of a given pharmaceutical would add value to this risk assessment S2 Genotoxicity Studies • S2(R1) Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human. It is a combination of ICH S2A and S2B Guidelines. • The S2A Guideline on Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals This document provided specific guidance and recommendations for in vitro and in vivo tests and on the evaluation of test results for genotoxicity • A Standard Battery for Genotoxicity Testing for Pharmaceuticals This document addressed 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
- 27. S3A - S3B Toxicokinetics and Pharmacokinetics • S3A Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studieshis document gives guidance on developing test strategies in toxicokinetics and highlights 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 Pharmacokinetics: Guidance for Repeated Dose Tissue Distribution StudiesThis document gives guidance on circumstances when repeated dose tissue distribution studies should be considered (e.g., when appropriate data cannot be derived from other sources). It also gives recommendations on the conduct of such studies. S4 Toxicity Testing • S4 Duration of Chronic Toxicity Testing in Animals (Rodent and Non Rodent Toxicity Testing) The objective of this guidance is to set out the considerations that apply to chronic toxicity testing in rodents and non rodents as part of the safety evaluation of a medicinal product. In Rodents (a study of 6 months duration) & in Non-rodents (a study of nine months duration.
- 28. S5 Reproductive Toxicology • S5(R3) Revision of S5 Guideline on Detection of Toxicity to Reproduction for Human Pharmaceuticals Guideline incorporates experience gained with the testing of pharmaceuticals using the current and novel testing paradigms as well as the advances of scientific, technological and regulatory knowledge over the past years and provides human safety assurance at least equivalent to that provided by current testing paradigms. • S5(R4) Maintenance EWG Revision of S5 Guideline on Detection of Toxicity to Reproduction for Human Pharmaceuticals It has maintenance procedure for the S5 Guideline on on Detection of Toxicity to Reproductions for Human Pharmaceuticals. S6 Biotechnological Products • S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived PharmaceuticalsThis document covers the preclinical 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.
- 29. S7A - S7B Pharmacology Studies • S7A Safety Pharmacology Studies for Human Pharmaceuticals This document provides a definition, general principles and recommendations for safety pharmacology studies. • S7B The Non-Clinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human PharmaceuticalsThis 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 integrated risk assessments. S8 Immunotoxicology Studies • S8 Immunotoxicity Studies for Human PharmaceuticalsThis Guideline provides recommendations on nonclinical testing approaches to identify compounds which have the potential to be immunotoxic, and decision- making approach for immunotoxicity testing. S9 Nonclinical Evaluation for Anticancer Pharmaceuticals • S9 Nonclinical Evaluation for Anticancer Pharmaceuticals This Guideline provides information for pharmaceuticals that are intended to treat cancer
- 30. S10 Photosafety Evaluation • S10 Photosafety Evaluation of PharmaceuticalsThis Guideline provides international standards for photosafety assessment and harmonises such assessments supporting human clinical trials and marketing authorizations for pharmaceuticals. S11 Nonclinical Paediatric Safety • S11 Nonclinical Safety Testing in Support of Development of Paediatric Medicines Guideline provides direction on the nonclinical safety studies important to support a paediatric development programme. S12 Non-clinical Biodistribution Studies for Gene Therapy Products • S12 EWG Non-clinical Biodistribution Studies for Gene Therapy Products Recommends on the elements of nonclinical studies performed that include Biodistribution assessment, and will contribute to the streamlined development of the Gene.
- 31. • The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials. It also covers novel types of medicines derived from biotechnological processes and the use of pharmacogenetics/genomics techniques to produce better targeted medicines. EFFICACY GUIDELINES :-
- 32. EFFICACY GUIDELINES E1 :- Clinical Safety for Drugs used in Long-Term Treatment E2A- E2F :- Pharmacovigilance E3 :- Clinical Study Reports E4 :- Dose-Response Studies E5 :- Ethnic Factors E6 :- Good Clinical Practice E7 :- Cllinical trials in Geriatic Population E8 :- General Considerations for Clinical Trials E9 :- Statistical Principles for Clinical Trials E10 :- Choice of Control Group in Clinical Trials E11 – E11A :- Clinical Trials in Pediatric Population E12 :- Clinical Evaluation by Therapeutic Category E13 E14 :- Clinical Evaluation of QT E15 :- Definitions of Pharmacogenitics / Pharmacogenomics E16 :- Qualification of Genomic Biomarkers E17 :- Multi-Regional Clinical Trials E18 :- Genomic Sampling E19 :- Safety Data Collection E20 :- Adaptive Clinical Trials
- 33. E1 Clinical Safety for Drugs used in Long-Term Treatment • E1 The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life Threatening Conditions 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.
- 34. E2A - E2F Pharmacovigilance • E2A Clinical Safety Data Management: Denitions and Standards for Expedited ReportingThis 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. • E2B(R3) Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports (ICSRs) • E2B(R3) Q&As Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports • E2B(R3) EWG/IWG Electronic Transmission of Individual Case Safety Reports (ICSRs)
- 35. • E2C(R2) Periodic Benet-Risk Evaluation Reportgives guidance on the format and content of safety updates, which need to be provided at intervals to regulatory authorities after products have been marketed. • E2C(R2) Q&As Questions & Answers: Periodic Benet-Risk Evaluation Report • E2D Post-Approval Safety Data Management: Denitions and Standards for Expedited Reportingprovides a standardised procedure for post- approval safety data management and the guidance for gathering and reporting information. • E2D(R1) EWG Post Approval Safety Data Management: Denition and Standards for Expedited Reporting • E2E Pharmacovigilance Planning The main focus of this Guideline is on a Safety Specification and Pharmacovigilance Plan that might be submitted at the time of licence application. • E2F Development Safety Update Report intended to be a common standard for periodic reporting on drugs under development among the ICH regions.
- 36. E3 Clinical Study Reports • E3 Structure and Content of Clinical Study Reports This document describes the format and content of a clinical study report that will be acceptable to all regulatory authorities of the ICH regions E4 Dose-Response Studies • E4 Dose-Response Information to Support Drug RegistrationThis document gives recommendations on the design and conduct of studies to assess the relationships among dose, drug- concentration in blood, and clinical response throughout the clinical development of a new drug. E5 Ethnic Factors • E5(R1) Ethnic Factors in the Acceptability of Foreign Clinical Data 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.
- 37. E6 Good Clinical Practice • E6(R2) Good Clinical Practice (GCP) GCP covers aspects of monitoring, reporting and archiving of clinical trials, and incorporates addenda on the Essential Documents and on the Investigator's Brochure. • E6(R3) EWG Good Clinical Practice (GCP) E7 Clinical Trials in Geriatric Population • E7 Studies in Support of Special Populations: Geriatrics 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. E8 General Considerations for Clinical Trials • E8 General Considerations for Clinical Trials This document sets out the general scientific principles for the conduct, performance and control of clinical trials.
- 38. E9 Statistical Principles for Clinical Trials • E9 Statistical Principles for Clinical TrialsThis document sets out the principles of statistical methodology applied to clinical trials for marketing applications submitted in the ICH regions. • E9(R1) EWG Addendum: Statistical Principles for Clinical Trials E10 Choice of Control Group in Clinical Trials • E10 Choice of Control Group and Related Issues in Clinical Trials 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
- 39. E11 - E11A Clinical Trials in Pediatric Population • E11(R1) Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population This Addendum is proposed to address new scientific and technical knowledge advances in pediatric drug development. • E11A EWG Paediatric Extrapolation This new ICH Guideline is proposed for harmonisation of methodologies and strategies to incorporate paediatric extrapolation into overall drug development plans and therefore improve the speed of access to new drugs for paediatric patients while limiting the number of children required for enrolment in clinical trials. E12 Clinical Evaluation by Therapeutic Category • E12 Principles for Clinical Evaluation of New Antihypertensive DrugThis therapeutic area document considers the Clinical Evaluation of New Antihypertensive Drugs. It provides a set of "Principles" on which there is general agreement among all ICH regions covering endpoints and trial designs.
- 40. E14 Clinical Evaluation of QT • E14 The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic DrugsThis 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 repolarisation. • E14 Q&As (R3) Questions & Answers: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs • E14/S7B IWG Questions & Answers: Clinical and Nonclinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential
- 41. E15 Definitions in Pharmacogenetics / Pharmacogenomics • E15 Denitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding CategoriesThis 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. E16 Qualication of Genomic Biomarkers • E16 Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure and Format of Qualication SubmissionsThe Guideline describes recommendations regarding context, structure, and format of regulatory submissions for qualification of genomic biomarkers E17 Multi-Regional Clinical Trials • E17 General principles for planning and design of Multi-Regional Clinical Trials This Guideline provides guidance on general principles on planning/designing Multi-Regional Clinical Trial (MRCT)
- 42. E18 Genomic Sampling • E18 Genomic Sampling and Management of Genomic Data This document provides Harmonised principles of genomic sampling and management of genomic data in clinical studies. E19 Safety Data Collection • E19 EWG Optimisation of Safety Data Collection Guideline is proposed to provide Harmonised guidance on when it would be appropriate to use a targeted approach to safety data collection in some late-stage pre-marketing or post-marketing studies, and how such an approach would be implemented. E20 Adaptive Clinical Trials • E20 EWG Adaptive Clinical Trial Guideline on the design, conduct, analysis, and interpretation of adaptive clinical trials that provides a transparent and harmonized set of principles for the regulatory review of these studies in a global drug development program.
- 43. • Those are the cross-cutting topics which do not fit uniquely into one of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology (MedDRA), the Common Technical Document (CTD) and the development of Electronic Standards for the Transfer of Regulatory Information (ESTRI). MULTIDISCIPLINARY GUIDELINES
- 44. MULTIDISCIPLINARY GUIDELINES M1 :- MedDRA Terminology M2 :- Electronic Standards M3 :- Nonclinical Safety Studies M4 :- Common Technical Document M5 :- Data Elements and Standards for Drug Dictionaries M6 :- Gene Therapy M7 :- Mutagenic Impurities M8 :- Electronic Common Technical Document (eCTD) M9 :- Biopharmaceutics Classification System- based Biowaivers M10 :- Bioanalytical Method Validation M11 :- Clinical electronic Structured Harmonised Protocol (CeSHarP) M12 :- Drug Interaction Studies
- 45. M1 MedDRA Terminology • M1 MedDRA - Medical Dictionary for Regulatory Activities MedDRA is a rich and highly specific standardised medical terminology developed by ICH to facilitate sharing of regulatory information internationally for medical products used by humans. • M1 PtC WG MedDRA Points to Consider To support the use of MedDRA, the M1 PtC WG updates with each MedDRA release the two Points to Consider (PtC) documents on MedDRA Term Selection and MedDRA Data Retrieval and Presentation, available in English and Japanese, as well as condensed versions available in all MedDRA languages. M2 Electronic Standards • M2 EWG Electronic Standards for the Transfer of Regulatory Information objective of facilitating international electronic communication by evaluating and recommending, open and non-proprietary - to the extent possible - Electronic Standards for the Transfer of Regulatory Information (ESTRI) that will meet the requirements of the pharmaceutical companies and regulatory authorities.
- 46. M3 Nonclinical Safety Studies • M3(R2) Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals Harmonise the nonclinical safety studies to support the various stages of clinical development among the ICH regions. • M3(R2) Q&As (R2) Questions & Answers: Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals M4 Common Technical Document • CTD: The Common Technical Document The agreement to assemble all the Quality, Safety and Efficacy information in a common format. M5 Data Elements and Standards for Drug Dictionaries • M5 Data Elements and Standards for Drug Dictionaries To develop ICH requirements for the standardisation of medicinal product identifiers and related terminology.
- 47. M6 Gene Therapy • M6 Virus and Gene Therapy Vector Shedding and Transmission Covers the General Principles to Address Virus and Vector Shedding M7 Mutagenic impurities • M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk Gives recommendations on analysis of Structure Activity Relationships (SAR) for genotoxicity. This is to provide useful information regarding the acceptable limits of known mutagenic impurities/carcinogenic and supporting monographs. M8 Electronic Common Technical Document (eCTD) • The Electronic Common Technical Document (eCTD) allows for the electronic submission of the Common Technical Document (CTD) from applicant to regulator. Guides the key aspects of technical review and impact assessment of issues arising from the use of the ICH M4 CTD Guidelines within the context of the eCTD.
- 48. M9 Biopharmaceutics Classication System-based Biowaivers • M9 Biopharmaceutics Classication System-based BiowaiversThis Guideline provides recommendations to support the biopharmaceutics classification of medicinal products and to support the waiver of bioequivalence studies. M10 Bioanalytical Method Validation • M10 EWG Bioanalytical Method Validation Guideline will apply to the validation of bioanalytical methods and study sample analyses in non-clinical and clinical studies. Reliable data derived through validated bioanalytical methods are key for the review of marketing authorisation application. M11 Clinical electronic Structured Harmonised Protocol (CeSHarP) • M11 EWG Clinical electronic Structured Harmonised Protocol (CeSHarP) This new guideline is proposed to provide comprehensive clinical protocol organization with standardised content, with both required and optional components.The guideline will outline two main sets of harmonised approaches: • a template to include identification of headers, common text and a set of data fields and terminologies which will be the basis for efficiencies in data exchange, • a technical specification that uses an open, non-proprietary standard to enable electronic exchange of clinical protocol information.
- 49. M12 Drug Interaction Studies • M12 EWG Drug Interaction Studies This guideline providing a consistent approach in designing, conducting, and interpreting Drug-drug interactions studies during the development of a therapeutic product. M13 Bioequivalence for Immediate-Release Solid Oral Dosage Forms • M13 EWG Bioequivalence for Immediate-Release Solid Oral Dosage Forms
Editor's Notes
- #16: Permitted Daily Exposure (PDE)