Ich quality guidelines

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use

1. ICH GUIDELINES 1 PRESENTED TO: Dr. PRAKASH S GOUDANAVAR HEAD OF THE DEPARTMENT PHARMACEUTICS SACCP PRESENTED BY : SAMEER M PHARM PHARMACEUTICS

2. ICH is the “International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.” ICH is a joint initiative involving both regulators and research-based industry representatives of the EU, Japan and the US in scientific and technical discussions of the testing procedures required to assess and ensure the safety, quality and efficacy of medicines. WHAT IS ICH……? 2

3. The ICH Secretariat is based in Geneva. The biennial meetings and conferences of the ICH Steering Committee rotate between the EU, Japan, and the USA. ICH located 3

4. To increase international harmonization of technical requirements to ensure that safe, effective and high quality medicines are developed. To harmonize technical requirements for registration or marketing approval. To develop and register pharmaceuticals in the most efficient and cost effective manner. To promote public health. To prevent unnecessary duplication of clinical trials on humans . Objectives of ICH 4

5. To promote international harmonization by bringing together representatives from the three ICH regions (EU, Japan and USA) To discuss and establish common guidelines. To make information available on ICH, ICH activities and ICH guidelines to any country or company that requests the information To promote a mutual understanding of regional initiatives in order to facilitate harmonization processes related to ICH guidelines regionally and globally To strengthen the capacity of drug regulatory authorities and industry to utilize them. Goal of ICH 5

6. ICH is comprised of representatives from six parties that represent the regulatory bodies and research-based industry in the European Union, Japan and the USA. In Japan, the members are the Ministry of Health, Labour and Welfare (MHLW), and the Japan Pharmaceutical Manufacturers Association (JPMA). In Europe, the members are the European Union (EU), and the European Federation of Pharmaceutical Industries and Associations (EFPIA). In the USA, the members are the Food and Drug Administration (FDA), and the Pharmaceutical Research and Manufacturers of America (PhRMA). Additional members include Observers from the World Health Organization (WHO), European Free Trade Association (EFTA), and Canada. The Observers represent non-ICH countries and regions. Members of ICH 6

7. GUIDELINES MULTIDISCIPLINARY EFFICACY SAFETY QUALITY 7

8. "Quality" Topics i.e., those relating to chemical and pharmaceutical Quality Assurance (Stability Testing, Impurity Testing, etc. “Efficacy" Topics , i.e., those relating to clinical studies in human subject (Dose Response Studies, Good Clinical Practices, etc.) “Safety" Topics , i.e., those relating to in vitro and in vivo pre-clinical studies (Carcinogenicity Testing, Genotoxicity Testing, etc.) “Multidisciplinary" Topics , i.e., cross-cutting Topics which do not fit uniquely into one of the above categories. 8

9. Harmonisation achievements in the Quality area include pivotal milestones such as the conduct of stability studies, defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management. Consists of Q1A-Q1F, Q2, Q3A-Q3D, Q4-Q4B, Q5A-Q5E, Q6A-Q6B, Q7, Q8, Q9, Q10, Q11 , Q12 ,Q13 & Q14 Quality Guidelines 9

10. QUALITY GUIDELINES Q1A - Q1F : Stability Q2 : Analytical Validation Q3A - Q3D : Impurities Q4 - Q4B : Pharmacopoeias Q5A - Q5E : Quality of Biotechnological Products Q6A- Q6B : Specifications Q7 : Good Manufacturing Practice Q8 : Pharmaceutical Development Q9 : Quality Risk Management Q10 : Pharmaceutical Quality System Q11 : Development and Manufacture of Drug Substances. Q12 : Lifecycle management Q13 : Continuous manufacturing of drug substance and drug products Q14 : Analaytical procedure development 10

11. Q1A-Q1F: Stability Q1A(R2): Stability Testing of New Drug Substances and Products Q1B: Stability Testing : Photostability Testing of New Drug Substances and Products Q1C: Stability Testing for New Dosage Forms Q1D: Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products Q1E: Evaluation of Stability Data Q1F: Stability Data Package for Registration Applications in Climatic Zones III and IV. 11

12. Q1A-Q1F STABILITY Q1A – STABILITY TESTING OF NEW DRUGS SUSBTANCES AND PRODUCTS Stability testing   provides evidence on how the quality of a drug substance or product varies over a given time period and under the influence of environmental factors including temperature, humidity and light. This Guideline provides recommendations on stability testing protocols including temperature, humidity and trial duration for climatic Zone I and II. Furthermore, the revised document takes into account the requirements for stability testing in Climatic Zones III and IV in order to minimise the different storage conditions for submission of a global dossier . 12

13. Q2: Analytical Validation T he collection and evaluation of data generated from the process/method used in making a product whether it is commercial, experimental or a scientific study.   Analytical validation  consists of multiple steps and starts with a  validation master plan. The discussion of the validation of analytical procedures is directed to the four most common types of analytical procedures: - Identification tests; - Quantitative tests for impurities' content - Limit tests for the control of impurities - Quantitative tests of the active moiety in samples of drug substance or drug product. 13

14. 14 Q3A-Q3D : Impurities Impurities in a pharmaceutical product may be defined as unwanted chemicals in the product that are not the active pharmaceutical ingredient (API) itself (or the excipients used to manufacture it), or which develop during formulation or upon aging of both API and formulation. They are unwanted chemicals that remain within the formulation or API in small amounts and which can influence quality, safety and efficacy (QSE), thereby causing serious health hazard. Objective: The objective recommendation of the guide line makes to applicant on reporting, identifying and qualifying information on impurities in new drug substance. Q3A(R2): Impurities in New Drug Substances Q3B(R2): Impurities in New Drug Products Q3C(R5): Impurities: Guideline for Residual Solvents Q3D: Guideline for Elemental Impurities Q3D: Implementation of Guideline for Elemental Impurities.

15. 15 Q4A-Q4B : Pharmacopoeias • Derived from Greek word 'Pharmakon' means drug and ' Poiea ' means to make. • It is a legal and official book issued by recognized authorities usually appointed by Government of each country. • It comprises list of pharmaceutical substances, formulae along with their description and standards. Q4A:- Pharmacopeial Harmonisation Q4B:-Evaluation and Recommendation of Pharmacopeial Texts for Use in the ICH Regions.

16. Q5A-Q5E: Quality of Biotechnological Products Q5A(R1):-Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal OriginQ5A Q5B:- Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products Q5C:-Stability Testing of Biotechnological/Biological Products Q5D:- Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products Q5E:-Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process. 16

17. Q6A-Q6B: Specifications Q6A:-Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Q6B:-Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. 17

18. Q7: Good Manufacturing Practice Good manufacturing practice  ( GMP ) is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product. This document is intended to provide guidance regarding Good Manufacturing Practice (GMP) for the manufacturing of Active Pharmaceutical Ingredients (APIs) under an appropriate system for managing quality. In February 1998, the ICH Steering Committee agreed that GMP for Active Pharmaceutical Ingredients (APIs) should be adopted as an ICH Topic. 18

19. Q8: Pharmaceutical Development The aim of pharmaceutical development is to design a quality product and its manufacturing process to consistently deliver the intended performance of the product. The information and knowledge gained from pharmaceutical development studies and manufacturing experience provide scientific understanding to support the establishment of the design space*, specifications, and manufacturing controls . 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. 19

20. Q9 : Quality Risk Management “ A systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle.” OR “ QRM is integral to an effective pharmaceutical quality system. It can provide a proactive approach to identifying, scientifically evaluating & controlling potential risks to quality. It facilitates continual improvement of process performance & product quality throughout the product life cycle .” QRM can be applied to different aspects of pharmaceutical quality 20

21. 21 CONT…. 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 labelling materials.

22. Q1O:- PHARMACEUTICAL QUALITY SYSTEM A Pharmaceutical Quality System (PQS) is a management system to direct and control a pharmaceutical company in terms of quality.” This definition of ICH Q10 is based on the definition from the family of ISO 9000 standards, with the primary objective of ensuring the quality and efficacy of the medicinal product , and patient safety, while improving the overall level of quality and the performance of the business . This Guideline applies to pharmaceutical drug substances and drug products, including biotechnology and biological products, throughout the product lifecycle. 22

23. Q11 : Development and Manufacture of Drug Substances This new guidance is proposed for Active Pharmaceutical Ingredients (APIs) harmonising the scientific and technical principles relating to the description and justification of the development and manufacturing process (CTD sections S 2.2. - S 2.6) of Drug Substances including both chemical entities and biotechnological/biological entities. 23

24. 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. Adoption of this new ICH Guideline will promote innovation and continual improvement in the biopharmaceutical sector, and strengthen quality assurance and reliable supply of product, including proactive planning of supply chain adjustments. It will allow regulators (assessors and inspectors) to better understand the firms’ Pharmaceutical Quality Systems (PQSs) for management of post-approval CMC changes. 24 Q12: Life cycle Management

25. Q13 : Continuous manufacturing of drug substance and drug products Regulatory agencies are taking proactive steps to enable the implementation of continuous manufacturing; they see it as a means “to improve product quality and address many of the underlying causes of drug shortages and recalls 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. 25

26. Q14 : : Analaytical procedure development The new 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. This new guideline is intended to improve regulatory communication between industry and regulators and facilitate more efficient, sound scientific and risk-based approval as well as post-approval change management of analytical procedures . 26

27. REFERENCE https://www.ich.org/products/guidelines/quality/article/quality-guidelines.html 27

28. THANK YOU 28