ICH Guidelines with details of ICH Q3 Guidelines
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The document provides an overview of the International Conference on Harmonisation (ICH) guidelines, focusing on harmonization of technical requirements for global pharmaceutical registration. It outlines the purpose, structure, and key parties involved in ICH, aiming to enhance the quality, safety, and efficacy of pharmaceuticals while facilitating international regulatory collaboration. Additionally, it details various guideline series related to quality, safety, and efficacy assessments for drug substances and products.
![First recommended for adoption on 30 March 1995, the Guideline was revised on 7 October 1999
and finalised on 7 February 2002 [Q3A(R1)]. It includes:
5.1.1 PREAMBLE : This document is intended to provide guidance for registration applications on
the content and qualification of impurities in new drug substances produced by chemical syntheses
and not previously registered in a region or member state.
The following types of drug substances are not covered in this guideline:
Biological/biotechnological, peptide, oligonucleotide, radiopharmaceutical, fermentation product
and semi-synthetic products derived from, herbal products, and crude products of animal or plant
origin.
ICH guidelines with regard to impurities in API (Q3A)](https://image.slidesharecdn.com/507-3-240518171626-07f3ca41/85/ICH-Guidelines-with-details-of-ICH-Q3-Guidelines-11-320.jpg)
ICH Guidelines with details of ICH Q3 Guidelines
- 1. GURU GOBIND SINGH COLLEGE OF PHARMACY Presented To: Dr. Anjali Sharma Presented By: Prabhjot Kaur (M-507) ICH Guidelines
- 2. INTRODUCTION 1 2 3 4 CONTENTS 5 PURPOSE ICH PARTIES ICH ORGANISATION BREIF OVWEVIEW OF QSEM GUIDLINES
- 3. 1. INTRODUCTION • Harmonisation : It is the act of making something consistent. • The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use is a joint initiative established in 1990 involving both regulatory agencies and research - based industry representatives of the European Union, Japan, and the United States. • ICH operates through the ICH Steering Committee with administrative support from the ICH Secretariat and ICH Coordinators. • The ICH Steering Committee meets at least twice a year. During these meetings, new topics will be considered for adoption, reports are received on the progress of existing topics, and maintenance and implementation of the guidelines are discussed. The topics identified for harmonisation by the ICH Steering Committee are elected from Safety, Quality, Efficacy, and Multidisciplinary matters of a pharmaceutical drug product
- 4. 2. PURPOSE • Maintaining safeguards on quality, safety, efficacy, and regulatory obligations to protect public health. • More economical use of human, animal and material resources. • Eliminate unnecessary delay in the global development and availability of new medicines. • Develop policy for the ICH Medical Dictionary for Regulatory Activities Terminology (MedRA) which facilitates the sharing of regulatory information internationally for medicinal products used by humans. • To encourage implementation and integration of common standards through communication of information and coordination of training on harmonised guidelines and their use. • To monitor and update technical requirements leading to a greater acceptance of research and data
- 5. 3. ICH PARTIES • The six parties to ICH represent the regulatory bodies and research based industry in the three regions - Europe, Japan, and USA, where the vast majority of new medicines are currently developed. 1. European Commission – European Union (EU) 2. European Federation of Pharmaceutical Industries and Associations (EFPIA) 3. Ministry of Health, Labour, and Welfare, Japan (MHLW) 4. Japan Pharmaceutical Manufacturers Association (JPMA) 5. US Food and Drug Administration (FDA) 6. Pharmaceutical Research and Manufacturers of America (PHRMA)
- 6. 4. ICH ORGANISATION STEERING COMMITTEE The body that governs the ICH, determines the policies and procedures for ICH, selects topics for harmonisation and monitors the progress of harmonisation initiatives. Each of the six parties has two seats on the ICH steering committee ICH Secretariat - Primarily concerned with preparations and documentation of meetings of the Steering Committee as well as coordination of preparations for Working Groups and discussion group meetings. - Information on ICH Guidelines and the ICH process can be obtained from the ICH Secretariat. ICH Coordinators -These are fundamental to the smooth running of the ICH and are nominated by each of the six parties. An ICH Coordinator acts as the main contact point with the ICH Secretariat. ICH Working Group Depending on the type of harmonization activity needed, the Steering Committee will endorse the establishment of one of 3 types of working group - Expert working group (EWG) - Implementation working group (IWG) - Informal working group (InWG).
- 7. 5. BREIF OVWEVIEW OF QSEM GUIDLINES Quality Guidelines -Topics related to chemical and pharmaceutical quality assurance. -Includes Stability Testing, Photostability Testing of New Drug Substances and Products, Validation of Analytical Procedures, Impurities in New Drug Substances Efficacy Guidelines -Concerned with the design, conduct, safety and reporting of clinical trials (dose response studies, good clinical studies etc). -Also covers novel types of medicines derived from biotechnological processes and the use of pharmacogenetics to produce better targeted medicines. Safety Guidelines -To uncover the potential risks in the in vitro and in vivo pre-clinical studies including Carcinogenecity Studies, Genotoxicity and Pharmacokinetic Studies and Reproductive Toxicity Studies. Multidisciplinary Guidelines -Include, the ICH medical terminology, common technical document and development of electronic standards for the transfer of regulatory information.
- 8. 5.1 QUALITY SERIES Q1A-Q1F: STABILITY Q1A (Stability testing of new drug substance and products) Q1B (Photo stability testing of new drug substance or product) Q1C (Stability testing of new dosage forms) Q1D (Bracketing and Matrixing designs for stability testing of new drug substances or products) Q1E (Evaluation of Stability Data) Q1F (Stability data package for registration applications in climatic zones III and IV) Q2: ANALYTICAL VALIDATION Q2(R1)- Validation of analytical procedures- Text and Methodology Q2(R2)- Analytical Procedure Development and Revision of Q2(R1) Validation of analytical procedures- Text and Methodology Q3A-Q3C: IMPURITIES Q3A- Impurities in a New Drug Substances Q3B- Impurities in a New Drug Products Q3C- Impurities in Residual Solvents
- 9. Q4(A)-Q4(B): PHARMACOPOEIA Q4(A) Pharmacopoeial Harmonisation Q4(B) Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions. Q5(A)-Q5(E): QUALITY OF BIOTECHNOLOGICAL PRODUCTS Q5(A)(R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin Q5A Q5(B) Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products Q5(C) Stability Testing of Biotechnological/Biological Products Q5(D) Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/ Biological Products Q5(E) Comparability of Biotechnological/ Biological Products subject to Changes in their Manufacturing Process
- 10. Q6A-Q6B: SPECIFICATIONS Q6(A) Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Q6(B) Specifications: Test Procedures and Acceptance Criteria for Biotechnological/ Biological Products QQ(7): GOOD MANUFACTURING PRACTICES Q(8): PHARMACEUTICAL DEVELOPMENT Q(9): QUALITY RISK MANAGEMENT QQ(10): PHARMACEUTICAL QUALITY SYSTEM Q(11): DEVELOPMENT AND MANUFACTURE OF DRUG SUBSTANCES Q(12): LIFECYCLE MANAGEMENT Q(13): CONTINOUS MANUFACTURING OF DRUG SUBSTANCE AND DRUG PRODUCTS Q(14): ANALYTICAL PROCEDURE DEVELOPMENT
- 11. First recommended for adoption on 30 March 1995, the Guideline was revised on 7 October 1999 and finalised on 7 February 2002 [Q3A(R1)]. It includes: 5.1.1 PREAMBLE : This document is intended to provide guidance for registration applications on the content and qualification of impurities in new drug substances produced by chemical syntheses and not previously registered in a region or member state. The following types of drug substances are not covered in this guideline: Biological/biotechnological, peptide, oligonucleotide, radiopharmaceutical, fermentation product and semi-synthetic products derived from, herbal products, and crude products of animal or plant origin. ICH guidelines with regard to impurities in API (Q3A)
- 12. 5.1.2 CLASSIFICATION OF IMPURITIES : Impurities can be classified into the following categories Organic impurities (process- and drug-related) Inorganic impurities Residual solvents - Can arise during the manufacturing process and/or storage of the new drug substance. -They can be identified or unidentified, volatile or non- volatile, and include: • Starting materials • By-products • Intermediates • Degradation products • Reagents, ligands and catalysts - Can result from the manufacturing process. They are normally known and identified and include: • Reagents, ligands and catalysts • Heavy metals or other residual metals • Inorganic salts • Other materials (e.g., filter aids, charcoal) - Residual solvents in pharmaceuticals are defined here as organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. - The solvents are not completely removed by practical manufacturing techniques.
- 13. 5.1.3 RATIONALE FOR THE REPORTING AND CONTROL OF IMPURITIES: a) Organic Impurities: The applicant should summarise the actual and potential impurities most likely to arise during the synthesis, purification, and storage of the new drug substance. In addition, the applicant should summarise the laboratory studies conducted to detect impurities in the new drug substance. b) Inorganic Impurities: Inorganic impurities are normally detected and quantified using pharmacopoeial or other appropriate procedures. Carry-over of catalysts to the new drug substance should be evaluated during development. c) Solvents: The control of residues of the solvents used in the manufacturing process for the new drug substance should be discussed and presented according to the ICH Q3C Guideline for Residual Solvents. 5.1.4 ANALYTICAL PROCEDURES : The registration application should include documented evidence that the analytical procedures are validated and suitable for the detection and quantification of impurities (ICH Q2A and Q2B Guidelines for Analytical Validation).
- 14. 5.1.5 REPORTING IMPURITY CONTENT OF BATCHES 5.1.6 LISTING OF IMPURITIES IN SPECIFICATIONS 5.1.7 QUALIFICATION OF IMPURITIES: The applicant should provide a rationale for establishing impurity acceptance criteria that includes safety considerations. The level of any impurity present in a new drug substance that has been adequately tested in safety and/or clinical studies would be considered qualified. 5.1.8 GLOSSARY 5.1.9 ATTACHMENTS 1 to 3
- 15. - This Guideline has been first revised and finalised 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. ICH guidelines with regard to impurities in New Drug Product (Q3B)
- 17. S1(A): Guideline on the need for carcinogenicity studies of pharmaceuticals • S1(B): Testing for carcinogenicity of pharmaceuticals • S1(C)(R2): Dose selection for carcinogenicity studies of pharmaceuticals S2(R1):Guidance on genotoxicity testing and data interpretation for pharmaceuticals intended for human use S3(A): Note for guidance on toxicokinetics: the assessment of systemic exposure in toxicity studies S3(B): Pharmacokinetics:guidance for repeated dose tissue distribution studies S(4): Duration of chronic toxicity testing in animals (rodent and non rodent toxicity testing) S5(R2): Detection of toxicity to reproduction for medicinal products & toxicity to male fertility S6(R1): Addendum to ICH S(6): preclinical safety evaluation of biotechnology-derived pharmaceuticals S7(A): Safety pharmacology studies for human pharmaceuticals • S7(B): The non-clinical evaluation of the potential for delayed ventricular repolarization (qt interval prolongation) by human pharmaceuticals S(8): Immunotoxicity studies for human pharmaceuticals S(9): Nonclinical evaluation for anticancer pharmaceuticals 5.2 SAFETY SERIES
- 18. • E(1): The extent of population exposure to assess clinical safety • E2(A): clinical safety data management • E2(B)(R2): maintenance of the ICH guideline on clinical safety data management • E2(B)(R3): revision of the ICH guideline on clinical safety data management ,Data elements for transmission of individual case safety reports • E2(C)(R1): clinical safety data management: periodic safety update reports for marketed drugs • E2(D): post-approval safety data management: definitions and standards for expedited reporting • E2(E): pharmacovigilance planning • E2(F): development safety update report • E(3): structure and content of clinical study reports • E(4): dose-response information to support drug registration • E(5)(R1): ethnic factors in the acceptability of foreign clinical data • E(6)(R1): guideline for good clinical practice 5.3 EFFICACY SERIES
- 19. • E(7): studies in support of special populations: geriatrics • E(8): general considerations for clinical trials • E(9): statistical principles for clinical trials • E(10): choice of control group and related issues in clinical trials • E(11): clinical investigation of medicinal products in the pediatric population • E(12): principles for clinical evaluation of new antihypertensive drugs • E(14): the clinical evaluation of qt/qtc interval prolongation and proarrhythmic potential for non- antiarrhythmic drugs • E(15): definitions for genomic biomarkers, pharmacogenomics, pharmacogenetics, genomic data and sample coding categories • E(16): genomic biomarkers Related to drug response
- 20. • M(1) : Medical Terminology • M(2): Electronic Standards for the Transfer of Regulatory Information • M(3)- (R2): Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals • M(4): The Common Technical Document • M(5): Data Elements and Standards for Drug Dictionaries 5.4 MULTIDISCIPLINARY SERIES
- 21. THANK YOU