Ich Guidelines Au. Vivek Jain

Ich guidelines syllabus accor. to PCI

1. As Per PCI Regulations /B. Parm . VI Sem./Pharmaceutical Quality Assurance UNIT-1 ICH Guideline Presented By : VIVEK JAIN M.Pharm . (Pharmaceutical Analysis) Associate Professor ADINA Institute Of Pharmaceutical Sciences, Sagar (M.P.) EMAIL:[email protected]

2. ICH (April 1990)   International Conference on Harmonisation (ICH) was created in april 1990 The European Medicines Agency publishes scientific guidelines that are harmonised between Europe, Japan and the United States of America ICH guidelines are provided for: Quality. Safety and Efficacy of medicines.

3. MISSION Harmonisation for Better Health 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

4. PURPOSE To Harmonize of technical requirements for registration or marketing approval To Ensure quality, safety, efficacy of medicines To prevent unnecessary duplication of clinical trials on humans To Minimize the use of animal testing without compromising safety and effectiveness To promote public health

5. history Need to harmonize, Because of the following reasons: Industry becoming global Duplicate test procedures time consuming expensive Increase R &D costs Meeting public demand Initiation of ICH 1980s Formulate European community 1989s WHO conference on DRA, Paris 1990s birth of ICH (created by all three Japan, USA & Europe) Topic of harmonization divided into : safety, quality and efficacy

6. ICH structure region Regulatory body Japan MHLW ( ministry of health, labour and welfare) Europe EU (European unions) US FDA

7. ICH members

8. Process of Harmonisation ICH harmonisation activities fall into 4 categories; 1.Formal ICH Procedure 2.Q&A Procedure 3.Revision Procedure 4,.Maintenance Procedure

9.   BRIEF OVERVIEW OF QSEM WITH SPECIAL EMPHASIS ON Q-SERIES GUIDELINES The ICH topics are divided into four categories Q – QUALITY GUIDELINES S – SAFETY GUIDELINES E - EFFICACY GUIDELINES M - MULTIDISCIPLINARY GUIDELINES Carcinogenicity (carcinogen any substance that produce cancer) Genotoxicity (genetic toxicity) Reprotoxicity toxicity related to reproduction ICH medical terminology ( MedDRA ) Common Technical Document ( CTD) The development of Electronic Standards for the Transfer of Regulatory Information (ESTRI).

10. Q – QUALITY GUIDELINES Q 1 S Stability Q 2 A Analytical validation Q 3 I Impurities Q 4 P Pharmacopoeias Q 5 B Quality of Biotechnology Products Q 6 S Specifications Q 7 API Good Manufacturing Guide for Active Pharmaceutical Ingredients   Q 8 PD Pharmaceutical Development Q 9 QRM Quality Risk Management   Q 10 PQS Pharmaceutical Quality System Q 11 DMDS Development and Manufacture of Drug Substances (Chemical Entities Biotechnological/Biological Entities) Q 12 LCM Life Cycle Management

11. Q – QUALITY GUIDELINES Q 1 A – Q 1 F Stability Q1A – Stability Testing of New Drug Substances and Products Q1 B –  Stability Testing : Photo Stability 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 Application in Climatic Zones III and IV Q2 (R1) – Validation of Analytical Procedures: Text and Methodology

12. Q3A- Q3D Impurities Q3A - Impurities in New Drug Substances Q3B – Impurities in New Drug Products Q3C – Impurities : Guideline for Residual Solvents Q3D – Impurities : Guideline for Elemental Impurities  Q4 – Pharmacopoeias Q4A  – Pharmacopoeial Harmonisation Q4B  – Evaluation and Recommendation of Pharmacopoeial Text for use in the ICH Regions   Q4B Annex 2(R1)  – Test for Extractable Volume of Parenteral Preparation General Chapter  Q4B – Annex 3(R1)  – Test for Particulate Contamination : Sub- Visibal Particales General Chapter 

13. Q4B – Annex 4A(R1)  – Microbiological Examination of Non-Sterile Products : Microbial Enumeration Tests General Chapter Q4B – Annex 4B(R1)  – Microbiological Examination of Non-Sterile Products : Test for Specified Micro-Organism General Chapter 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

14. Q4B Annex 6 (R1)  – Uniformity of Dosage Units General Chapter Q4B Annex 7(R2) –  Dissolution Test General Chapter Q4B Annex 8(R1)  – Stability Test General Chapter Q4B Annex 9(R1)  – Tablet Friability General Chapter Q4B Annex 10(R1)  – Polyacrylamide Gel Electrophoresis General Chapter Q4B Annex 11  – Capillary Electrophoresis General Chapter Q4B Annex 12  – Analytical Sieving General Chapter Q4B Annex 13  – Bulk Density and Tapped Density of Powders General Chapter Q4B Annex 14  – Bacterial Endotoxin Test General Chapter

15. Q5A-Q5E Quality of Biotechnology Products Q5A (R1) –  Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin Q5B –  Quality of Biotechnology Products : Q5C  – Quality of Biotechnology Products :Quality of Biotechnological Q5D  – Derivation and Characterisation of Cell Substrates used for Production of Biotechnological/Biological Products Q5E  – Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process

16. Q6A-Q6B Specifications Q6A  – Specifications : Test Procedure and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Q6B  – Specifications : Test Procedure and Acceptance Criteria for Biotechnological/Biological Q7  – Good Manufacturing Guide for Active Pharmaceutical Ingredients Q8(R2) – Pharmaceutical Development Q9 – Quality Risk Management Q10 – Pharmaceutical Quality System Q11 – Development and Manufacture of Drug Substances (Chemical Entities Biotechnological/Biological Entities) Q12 – Life Cycle Management

17. S – SAFETY GUIDELINES S1A - S1C Carcinogenicity Studies   S2 Genotoxicity Studies S3A - S3B Toxicokinetics and Pharmacokinetics S4 Toxicity Testing S5 Reproductive Toxicology S6 Biotechnological Products. S7A - S7B Pharmacology Studies S8 Immunotoxicology Studies S9 Nonclinical evaluation for anticancer pharmaceuticals S10 Photo safety evaluation S11 Nonclinical paediatric safety

18. E - 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. Code. E6 Good Clinical Practice. E7 Clinical Trials In Geriatric Population. E8 General Considerations For Clinical Trials E9 Statistical Principles For Clinical Trials E10 Choice Of Control Group In Clinical Trials E11 Clinical Trials In Paediatric Population E12 Clinical Evaluation By Therapeutic Category E14 Clinical Evaluation Of QT E15 Definitions Of Pharmacogenetics E16 Qualification Of Genomic Biomarkers E17 Multiregional Clinical Trials E18 Genomic Sampling E19 Safety Data Collection

19. M - 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 Genotoxic Impurities M8 Electronic Common Technical Document ( eCTD ) M9 Biopharmaceutics Classification System-based Biowaivers \ M10 Bioanalytical Method Validation

20. Stability guideline General: Definition: Stability of pharmaceutical product may be defined as the ability of pharmaceutical dosage form to maintain the physical, chemical, microbiological and therapeutics properties during the time of storage and usage by the patient Purpose of stability testing is: To provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light, and to establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions.

21. Stability protocol For Drug Substance General Stress testing Selection of batches Container and closure system Specifications Testing frequency Storage conditions Stability Commitment Evaluation Statements/Labeling

22. Stress Testing It is also known as force degradation study Stress testing of the drug substance can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic/natural stability of the molecule. Stress testing is likely to be carried out on a single batch of the drug substance. It should include the effect of temperatures, humidity (e.g., 75% RH or greater) where appropriate oxidation, and photolysis on the drug substance.

23. Selection of Batches At least three primary batches of the drug substance should be representative to quality of the material used for production scale. Container Closure System The stability studies should be conducted on the drug substance packaged in a container closure system that is the same as the packaging proposed for storage and distribution. Specification Specification, which is a list of tests, reference to analytical procedures, and proposed acceptance criteria, is addressed in ICH Q6A and Q6B.

24. Testing Frequency frequency of testing should be sufficient to establish the stability profile of the drug substance. For long-term studies , (For drug substances with a proposed re-test period) at least 12 months, the frequency of testing at the long term storage condition should normally be every 3 months over the first year, every 6 months over the second year , and annually thereafter through the proposed re-test period. At the accelerated storage condition , a minimum of three time points, including the initial and final time points (e.g., 0, 3, and 6 months), from a 6-month study is recommended. For intermediate studies: Min. 4 time points (0, 6, 9, 12 months) for a 12 months study

25. Storage Conditions General case . Study Long term* Storage conditions 25°C ± 2°C 60 % RH ± 5% RH Minimum time period 12 months Intermediate** 30°C ± 2°C/65% RH ± 5% RH 6 months Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months

26. . Drug substances intended for storage in a refrigerator Long term 5°C ± 3°C 12 months Accelerated 25°C±2°C 6 months

27. Drug substances intended for storage in a freezer Long term - 20°C ± 5°C 12 months

28. Stability Commitment In case where data submitted for registration do not cover the proposed shelf life it is necessary to give commitment to continue the stability studies post approval in order to firmly establish the shelf life. Where the submission includes long term stability data from three production batches covering the proposed shelf life, a post approval commitment is considered unnecessary.

29. Evaluation The purpose of the stability study is to establish re-test period for DS and shelf life for drug product for future batched based on evaluation of results obtained from chemical, physical, biological, microbiological tests A systematic approach should be adopted in the presentation and evaluation of the stability information, which should include, as appropriate, results from the physical, chemical, biological, and microbiological tests, including particular attributes of the dosage form (for example, dissolution rate for solid oral dosage forms).

30. Statements/Labeling A storage statement should be established for the labeling in accordance with relevant national/regional requirements. The statement should be based on the stability evaluation of the drug product. There should be a direct link between the label storage statement and the demonstrated stability of the drug product. An expiration date should be displayed on the container label.