Indian gcp guidelines[647]

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provide assurance that the data and the reported results are credible (able to be believed), accurate and that the rights, integrity and confidentiality of trial subjects are protected.

1. INDIAN GCP GUIDELINES 1 Presented BY :- AKHILESH AKKI 1 ST YEAR M PHARM Dept. of Pharmaceutics, Regulatory Affairs Group. JSS COLLEGE OF PHARMACY MYSURU.

2. A standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provide assurance that the data and the reported results are credible (able to be believed), accurate and that the rights, integrity and confidentiality of trial subjects are protected. 2 What is GCP?

3. GCP is an ethical and scientific quality standard for designing, conducting and recording trials that involve participation of human subjects. Formulated by expert committee set up by Central Drugs Standard Control Organisation (CDSCO) Guidelines have been evolved with consideration of WHO, ICH, USFDA and European GCP guidelines& Ethical Guidelines for Biomedical Research on Human subjects issued by ICMR  Primary Aim : To streamline(design) clinical studies in India 3 Why separate GCP for India?

4. India offers unique opportunities for conducting Clinical trials in view of – Large patient pool – Well trained enthusiastic investigators – Premiere Medical institutes – Considerable low per patient trial cost when compared to developed countries 4 Advantage of India

5. The creation of GCP guidelines not only intended to protect the rights and safety of the study subjects but was also intended to serve the interests of all parties involved in the clinical research. The basic principles governing the concept of GCP are as follows:- To assist, stimulate and achieve a unified standard, at a global level, for the conduct of clinical research studies on human beings. To act as an educational tool for personnel interested in clinical research or for clinicians already engaged in research, by furnishing the requisite information with respect to the requirements of GCP and its efficient implementation. Assist clinical research editors to assess the acceptability of the research submitted for publication, and to enable regulatory personnel to evaluate studies that may affect the use and registration of certain medicinal products. 5 PRINCIPLES GOVERNING GCP:

6. To provide a general summary and any other necessary advice on how to apply and how to implement globally accepted GCP principles for clinical research in human beings. 6

7. Definitions Pre-requisites for the study 2.1 Investigational Product 2.2 Pre-Clinical Supporting data 2.3 Protocol 2.4 Ethical and safety considerations 2.4.1 Ethical Principles 2.4.2 Ethics Committee 7 Contents

8. 2.4.3 Informed Consent Process 2.4.4 Essential Information on Confidentiality 2.4.5 Compensation for participation 2.4.6 Selection of Special groups as research Subjects 2.4.7 Compensation for accidental injury 3. Responsibilities 3.1 Sponsor 3.2 Monitor 3.4 Investigator 8

9. 4. Record keeping & data handling 5. Quality Assurance 6. Statistics 9

10. Appendix I : Declaration of Helsinki Appendix II : Schedule Y Appendix III : Format for submission of pre- clinical and clinical data for r-DNA based vaccines, diagnostics and other biologicals Appendix IV : Investigators Brochure Appendix V : Essential Documents 10 Appendices

11. Ensure that studies are scientifically and ethically sound and the clinical properties of the pharmaceutical substances under the investigation are properly documented. The main two essential principles are – Protection of the rights of human subjects – Authenticity of biomedical data generated 11 GCP, Main Aims

12. 2.1) Investigational Pharmaceutical Product: Physical, chemical, pharmaceutical properties and the formulation of the Investigational Product & Instructions for the storage and handling of the dosage form must be documented. Any structural similarities to the other known compounds should be mentioned.  2.2) Pre-clinical supporting data , available pre-clinical data and clinical information on the Investigational Product should be adequate and convincing to support the proposed study.  2.3) Protocol well-structured and complete protocol. 12 Pre-requisites for the study 

13. 1. General Information Protocol title, protocol identifying number and date. Name, address & contact numbers of the sponsor and the monitor / CRO (Clinical research organisation) Name and title of the persons authorised to sign the protocol Name, title, address and contact numbers of the sponsor's medical expert for the study Name(s), title(s), address( es ) and contact numbers of the investigator(s) Name(s), address( es ) and contact numbers of the institution(s) - clinical laboratories 13 Relevant components of Protocol 

14. 2. Objectives and Justification Aims and objectives of the study, Name and description of the investigational product A summary of findings from non-clinical studies Summary of the known and potential risks and benefits, if any, to human subjects. 3. Ethical Considerations General ethical considerations related to the study How patients / healthy volunteers will be informed and how their consent will be obtained Possible reasons for not seeking informed consent 14

15.   4. Study design Primary and secondary end points, if any, to be measured during the study Description of the type of the study Schematic diagram of the study design, procedures and stages Medications/treatments permitted and not permitted Duration of the subject participation and proposed date of initiation of the study Discontinuation criteria for study subjects Procedures for monitoring subjects’ compliance 15

16. 5. Inclusion, Exclusion and Withdrawal of Subjects Includes subject inclusion criteria, Exclusion criteria, withdrawal criteria  6. Handling of the Products 7. Assessment of Efficacy Description of how effects are measured and recorded and Time and periodicity of effect recording 8. Assessment of Safety 9. Statistics 10. Data handling and management Persons having direct access to source data / documents Procedures for handling and processing records of adverse events to the products 16

17. c) Procedures for the keeping of patient lists and patient records 11. Quality control and quality assurance 12. Finance and insurance Mention all financial aspects of conducting and reporting a study 13. Publication policy 14. Evaluation  specified account for how the response is to be evaluated including methods of computation and calculation of effects. Description of how to deal with and report subjects withdrawn from the study  17

18. Documents to be provided with protocol – Information to the Study Subjects – Instructions to staff – Descriptions of special procedures 18

19. 2.4) Ethical & Safety Considerations 2.4.1) Ethical principles a) Principles of essentiality : research entailing the use of human subjects is absolutely essential for the advancement of knowledge and for the benefit of all members of the human species after the proposed research is dully vetted and consideration of all other alternatives b) Principles of voluntariness, informed consent and community agreement c) Principles of non-exploitation : subjects should be remunerated and apart from the socio economic status, should be well informed about the study d) Principles of privacy and confidentiality : no details of subjects identity should be disclosed without valid scientific and legal reasons 19

20. e) Principles of precaution and risk minimisation : research designed in such a way that subjects are put to the minimum risk, suffer & generally benefit from the research f ) Principles of professional competence : should be conducted by professionally qualified people g) Principles of accountability and transparency : research conducted in honest, impartial & transparent manner h) Principles of the maximisation of the public interest and of distributive justice i) Principles of institutional arrangements j) Principles of public domain k) Principles of totality of responsibility 20

21. Responsibilities – Dignity, rights & well being of research participants – Ensure that universal ethical values & international scientific standards are expressed in terms of local community values & customs – Assist in development & the education of a research community  Composition – Should be multidisciplinary & multi sectorial – 5-7 members, maximum of 12-15 – Chairperson from outside the institution – Composition as follows – Chairperson – 1-2 basic medical scientist ( one pharmacologist)  21 2.4.2) Ethics Committee  

22. – 1-2 Clinicians from various institutes – One legal expert or retired judge – One social scientist – One Philosopher – One lay person – Member Secretary – Adequate representation of age, gender & community Record Retention – At least 5 years after the completion or termination of study if it is not possible to maintain the same permanently 22

23. Sponsor   1. Investigator/Institution Selection 2. Allocation of duties & responsibilities 3. Study management, data handling and record keeping 4. Compensation for participation 5. Confirmation of review by the ethics committee 6. Information on Investigational products 7. Supply, storage and handling of Pharmaceutical products 8. ADR reporting 9. Study Reports 10. Monitoring& Audits 23 Responsibilities

24. Should be qualified enough by education, training & experience for proper conduct of study & should have qualifications prescribed by Medical Council of India (MCI). His main responsibilities include:- a) Medical care of study subjects b) Monitoring and auditing of records c) Communication with EC (ethical comities) d) Conduct study in accordance with protocol e) Selection and recruitment of study subjects f) Accuracy and completeness of records and reports 24 Investigator 

25. The basic concept of record-keeping and handling of data is to record, store, transfer, and where necessary convert efficiently and accurately the information collected on the trial subjects into data that can be used to compile the Study Report. 1) Documentation 2) Corrections 3) Electronic Data Processing 4) Validation of Electronic Data Processing Systems 5) Language 6) Responsibilities of the Investigator 7) Responsibilities of the Sponsor and the Monitor 25 Record keeping and data handling

26. Prior to the Subject’s participation in the Study the written Informed Consent form should be signed and personally dated by subject/Impartial witness & the Investigator Essential information that must be provided to the subject should contain:- 1. Aims & methods of research 2. Expected duration 3. Reasonably expected benefits 4. Alternative procedures if any 5. Foreseeable risks 6. Right of prevent use of his/her biological samples 7. Extend of confidentiality of the subjects 8. Free treatment to research related injury 9. Compensation 10. Voluntary participation 26 Informed Consent Process 

27. Role of a Biostatistician Involvement of a appropriately qualified and experienced statistician is necessary in the planning stage as well as throughout the Study. The Bio-statistician’s should make a statistical model to help the Sponsor, CRO and / or the Investigator in writing the Protocol. The number of Subjects to be included in the study is determined in relation to the statistical model on which the Protocol is based. Study Design Randomisation and blinding Statistical Analysis 27 STATISTICS 

28. Appendix I WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI Ethical Principles for Medical Research Involving Human Subjects : It includes: A. INTRODUCTION B. BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH C. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL CARE  28 APPENDICES

29. Appendix II SCHEDULE Y Requirements and guidelines on clinical trials for import and manufacture of new drug Clinical Trials Chemical and Pharmaceutical Information Animal Toxicology Animal Pharmacology Human/Clinical Pharmacology trials (Phase I) 29

30. 6. Exploratory trials (Phase II) 7. Confirmatory trials (Phase III) 8. Special Studies 9. Submission of Reports (Appendix II to Schedule Y) 10. Regulatory status in other counties 11. Marketing Information  30

31. Appendix I to Schedule Y Data required to be submitted with application for permission to market a new drug. 1. Introduction 2. Chemical and pharmaceutical information 3. Animal pharmacology 4. Animal toxicology (See Appendix III and IV to Sch. Y) 5. Human/clinical pharmacology (Phase I) 6. Exploratory clinical trials (Phase II) 31

32. 7. Confirmatory clinical trials (Phase III) 8. Special studies 9. Regulatory status in other countries 10. Marketing information 32

33. APPENDIX III to Schedule Y Animal toxicity requirements for clinical trials and marketing of a new drug APPENDIX IV to Schedule Y Number of animals for long term toxicity studies APPENDIX V to Schedule Y Patient consent form for participation in a Phase I Clinical Trial APPENDIX VI to Schedule Y Data requirements of Fixed Dose Combinations 33

34.   APPENDIX III Format for submission of preclinical and clinical data For r-DNA based vaccines, diagnostics and other biologicals. SPECIFICATION AND CHARACTERIZATION INFORMATION ON R-DNA VACCINES AND BIOLOGICAL PRODUCTS. a) Description in details of the method of r-DNA products b) Description of the method of sequence verification c) Description on Identity-Physical, Chemical, Immunological and Biological wherever applicable. d) Potency. e) General Safety Test. f) Data on sterility tests as per Indian Pharmacopeia guidelines. 34

35. f) Data on purity of recombinant product. g) Description of constituent materials like preservatives etc. h) Data on stability of finished formulation as per IP (Indian pharmacopeia) guidelines. B. DATA ON PRECLINICAL TESTING 1. Biological activity/ pharmacodynamics in vitro and in appropriate animal models. 2. Safety Pharmacology (Functional indices of toxicity). 3. Toxicology and pharmacokinetics (Absorption, Distribution, Metabolism, Excretion ADME) 4. Immunogenicity/ Immunotoxicity 5. Reproductive and developmental toxicity 6. Genotoxicity studies 7. Carcinogenicity studies 35

36. C: RECOMBINANT IMMUNODIAGNOSTIC REAGENTS D: CLINICAL TRIALS 1. Phase I : Human/Clinical Pharmacology Immunogenic Potency 2. Phase II: Exploratory Clinical Trials- Preventive/Therapeutic Efficacy (Data to be generated in subjects residing in endemic/ non-endemic areas) 3. Phase III: Confirmatory Trials 36

37. APPENDIX IV INVESTIGATOR’S BROCHURE (IB) APPENDIX V ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL 37

38. https://www.researchgate.net/publication/327209215_Good_Clinical_Practices_An_Indian_Perspective https://www.iddresearch.com/wp-content/uploads/2018/06/Indian_GCP_Guidelines.pdf http://www.sgpgi.ac.in/sop/GCP-%20Indian.pdf 38 References

39. 39 THANK YOU