ICH.pptx

ICH GUIDELINES IN DETAIL

1. Presented by : MISS HARSHITA SINGHAI m. Pharm sem. 2 Roll no. Y21254012 DEPARTMENT OF PHARMACEUTICAL SCIENCES DR. HARISINGH GOUR VISHWAVIDYALAYA SAGAR ( M.P. ) ( A CENTRAL UNIVERSITY ) Session 2021-2022 1 ICH GUIDELINES

2. CONTENTS Introduction Objectives Structure ICH Guidelines Quality Guidelines Safety Guidelines Efficacy Guidelines Multidisciplinary Guidelines References 2

3. INTRODUCTION In 1989 , Europe, Japan, and the United States began creating plans for harmonisation . The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was created in April 1990. ICH had the initial objective of coordinating the regulatory activities of the European, Japanese and United States regulatory bodies in consultation with the pharmaceutical trade associations from these regions, to discuss and agree the scientific aspects arising from product registration.

4. In 2015, ICH underwent several reforms and changed its name to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use while becoming a legal entity in Switzerland as a non-profit association. The aim of these reforms was to transform ICH into a truly global initiative supported by a robust and transparent governance structure.

5. Harmonization of legislative and teachnical requirements. Mutual acceptance of data between Europe, Japan and US. To reduce cost of research work duplication. To reduce time frame for global marketing of newer drugs after approval. To maintain and formulate guidelines on quality, safety and efficacy based regulations for consumer and patient benefits.

6. STRUCTURE International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) comprises the following bodies- ICH Assembly ICH Management Committee MedDRA Management Committee ICH Secretariat

7. ICH GUIDELINES ICH has developed over 45 harmonized guidelines . The ICH Topics are divided into four major categories: Quality (Q) : Related to chemical and pharmaceutical Quality Assurance . Safety (S): Related to in vitro and in vivo preclinical studies . Efficacy (E): Related to clinical studies in human subject. Multidisciplinary topics (M): Related to cross-cutting topics which do not fit uniquely into one of the above categories.

8. QUALITY GUIDELINES 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 .

9. ICH has produced a comprehensive set of safety Guidelines to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity . A recent breakthrough has been a non-clinical testing strategy for assessing the QT interval prolongation liability: the single most important cause of drug withdrawals in recent years. SAFETY GUIDELINES

10. EFFICACY GUIDELINES 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. MULTIDISCIPLINARY GUIDELINES 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 ).

11. THE Q FAMILY Q 1 – Stability Testing Q 2 – Analytical Validation Q 3 – Impurities Q 4 – Pharmacopoeias Q 5 – Biotechnological Products Q 6 – Specifications Q 7 – Good Manufacturing Practices Q 8 – Pharmaceutical Development Q 9 – Quality Risk Management Q 10 – Pharmaceutical Quality System

12. ICH GUIDELINES FOR STABILITY STUDIES 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  & IV

13. PRINCIPLES OF THE GUIDELINE Purpose of stability testing is to provide evidence how quality varies with time under influence of temperature, humidity and light . 2. Establish re-test period for drug substances RETEST PERIOD : The period after which samples of the drug substance should be examined to ensure that the material is still in compliance with the specification, and thus suitable for use in manufacturing. A retest period should be proposed on the basis of stability results and may be extended to five years (e.g., Ethambutol 2HCl, or Isoniazid ) . SHELF LIFE (EXPIRY DATE/EXPIRATION DATING PERIOD): The period of time during which a pharmaceutical product, if stored correctly, is expected to comply with the specification as determined by stability studies on a number of batches of the product. The shelf-life is used to establish the expiry date of each .

14. STABILITY Stability of pharmaceutical product may be defined as the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, therapeutic and toxicological specification. Types stability studies: 1) Long term stability study 2) Intermediate stability study 3) Accelerated stability study    Assurance to the patient • Economic considerations • Legal requirement Advantage

15. ICH GUIDELINES Q1A(R2) STABILITY TESTING OF APIS

16. . GENERAL Information on the stability of the drug substance is an integral part of the systematic approach to stability evaluation.   STRESS TESTING Carried out on a single batch and it include the effect of temperature, humidity where appropriate, oxidation and photolysis on DS. Scope: These guidelines help to identify the likely degradation products, to establish the degradation pathway and intrinsic stability of the molecule. SELECTION OF BATCHES- At least 3 primary batches of the drug substance should be selected. The quality should be representative to quality of material used for production scale.

17. . CONTAINER CLOSURE SYSTEM- Stability study conducted on the drug substance packed in a container closure system that is same or simulate packaging proposed for storage and distribution . SPECIFICATION- These guidelines states the list of test, references to analytical procedure and proposed acceptance criteria. STATEMENT AND LABELLING- A storage statement established for labelling in relevant national/regional requirements b ased on the stability evaluation of the drug substance. Terms such as “ambient conditions” or “room temperature” should be avoided. Retest date for DS and Expiry date for DP should be displayed on the container label if appropriate.

18. . TESTING FREQUENCY

19. CLIMATE ZONE

20. ICH GUIDELINES Q1B To demonstrate that light exposure does not result in unacceptable change Testing is carried out on a single batch Testing carried out on: Drug substance Exposed drug product outside of the immediate pack Drug product in the immediate pack Drug product in the marketing pack Light sources: Artificial daylight fluorescent lamp combining visible and ultraviolet (UV) outputs, xenon or metal halide lamp .  Photostability Testing :

21. ICH GUIDELINES Q1C New dosage forms Same active substance Different administration route New specific functionality/delivery systems Reduced stability database Different dosage forms of same administration route.   Stability Testing for New Dosage Forms

22. ICH GUIDELINES Q1C Only samples on the extremes of certain design factors are tested at all time points as in a full design . Design Factors : >Strength > Container Closure Sizes and/or Fills . Bracketing

23. Matrixing Matrixing is t he statistical design of a stability schedule. Each storage condition should be treated separately under its own matrixing design. At a given time point (other than the initial or final ones) not every batch on stability needs to be tested. Full testing must be performed at the maximum storage period at the time of submission 

24. ICH GUIDELINES Q1E Objectives of the Guideline : It describes: How to propose a retest period for drug substances and a shelf life for drug products in the registration application . When and how a extrapolation beyond available data can be considered. Stability Data Package for Registration Applications in Climatic Zones III and IV Objectives of the Guideline Application of ICH Q1A(R) in countries of Climatic zones III and IV ICH GUIDELINES Q1F

25. THE S FAMILY S1A =Need for Carcinogenicity Studies of Pharmaceuticals S1B = Testing for Carcinogenicity of Pharmaceuticals S1C ( R2 )=Dose Selection for Carcinogenicity Studies of Pharmaceutical S2 ( R1 )=Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals intended for Human Use S3A = Note for Guidance on Toxicokinetics : The Assessment of Systemic Exposure in Toxicity Studie S4 = Duration of Chronic Toxicity Testing in Animals ( Rodent and Non-Rodent Toxicity Testing) S5 ( R2 ) S5A , S5B (M)=Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility

26. S6 ( R1 )=Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals S7A =Safety Pharmacology Studies for Human Pharmaceuticals S7B =The Non-Clinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals S8 = Immunotoxicity Studies for Human Pharmaceuticals S9 = NonClinical Evaluation for Anticancer Pharmaceuticals S10 = Photosafety Evaluation of Pharmaceuticals S11 = Nonclinical Safety Testing in Support of Development of Paediatric Medicines THE S FAMILY

27. EFFICACY 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 / pharmacogenomics techniques to produce better targeted medicines.

28. THE FAMILY OF EFFICACY E1 - E2F               Clinical Safety E3                        Clinical Study Reports E4                        Dose-Response Studies E5                         Ethnic Factors E6                         Good Clinical Practice E7 - E11                Clinical Trials E12                       Clinical Evaluation by Therapeutic Category E14                       Clinical Evaluation E15 - E16              Pharmacogenomics  

29. 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 ). ICH Multidisciplinary Guidelines from M1 to M13

30. ICH 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 M13 Bioequivalence for Immediate-Release Solid Oral Dosage Forms

31. REFERENCES WWW.ICH.ORG https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073369.pdf http://www.authorstream.com/Presentation/amol.sabale-1563301-ich-guidelines-stability-testing-ppt/ https://www.slideshare.net/AmanKDhamrait/stability-studies-ich-q1aq1e-guidelines-ppt https://www.gmp-compliance.org/guidelines/gmp-guideline/ich-q1ar2-stability-testing-of-new-drugs-and-products-revised-guideline REFERENCES