Schedule y

Schedule y

1. Schedule 1 Dr. Ashishkumar Baheti Md Pharmacology

2. What is Schedule Y ? 2

3. It’s a Law not merely Guidelines Schedule Y 3

4. Schedule Y 4 “REQUIREMENTS AND GUIDELINES FOR PERMISSION TO IMPORT AND / OR MANUFACTURE OF NEW DRUGS FOR SALE OR TO UNDERTAKE CLINICAL TRIALS "

5. Schedule Y Schedule Y is law established under Drug and Cosmetic Act, 1945 enforced by CDSCO to be followed when conducting Clinical Trial in India. Enforced since 1988 Amended on 2005,2009 and 2011. 5

6. Purpose of schedule y 6 Enabling India to adopt more sophisticated regulations to better protect their citizens and invite more industry , while at the same time ensuring that the data from India is more acceptable internationally .

7. Why India is hottest destination for conducting global clinical trials ?  Trials registered in Clinicaltrials.gov (USFDA) with India as one of the locations From 2001 to 2011 7

8. Why India is hottest destination for conducting global clinical trials ? 8 Large patient pool High level of ICH GCP and US FDA standards compliance Well trained and experienced Investigators Favourable regulatory environment Cost effectiveness (30-50% cost advantage over a similar trial in Europe or US ) Increasing prevalence of diseases .

9. Difference between older and amended Schedule Y 9 Older Schedule Y ( 1988) Amended Schedule Y (2005) Narrow and restrictive definitions of clinical trial phases . Provide pragmatic definition of all phases Restriction on number of patients and centers in early phases of trials No such restriction , depend on protocol requirements Details of Informed consent Form was not given Details of Informed consent Form is given . Ethical committee responsibility not mentioned Responsibilities of ethical committee mentioned. Post marketing study (Phase 4 ) not mentioned. Post marketing study (Phase 4 ) mentioned. Guidelines for Studies in special populations not given . Guidelines for Studies in special populations given .e.g. geriatric , child, pregnant etc.

10. Structure of schedule Y 10 Application for permission Clinical Trial C onduct of clinical trial Responsibilities of Sponsor Investigator(s), Ethics Committee Informed Consent Phases of clinical trial Studies in special populations: Geriatrics Paediatrics Pregnant or nursing women Post Marketing Surveillance- Periodic Safety Update Reports Special studies: Bioavailability / Bioequivalence Studies Appendix I to XI

11. Application for permission under FORM 44 and accompanied data as per Appendix I Chemical and pharmaceutical Information Animal pharmacology data Animal toxicology data Human clinical pharmacology data Regulatory status in other countries Prescribing Information 11

12. Fees to be deposited to regulatory authority for Conducting Clinical trial with ND/IND Phase I = Rs 50,000/- Phase II = Rs 25,000/- Phase III = Rs 25,000 12

13. CLINICAL TRIAL 13 Clinical trial shall be initiated only after the permission by the Licensing Authority (LA ) and the approval from Ethics committee (EC ) . Investigator should possess appropriate qualifications, training and experience and should have access to proper facilities relevant to protocol. Laboratories should be compliant with Good Laboratory Practices. Protocol amendments if any , should be notified to the Licensing Authority in writing along with the approval by EC

14. Responsibilities of 14 Sponsor Investigator Ethics Committee

15. Responsibilities of Sponsor 15 Selection of Investigator(s) and study sites. Making legal agreement with the Investigator . Sponsor should establish detailed SOP’s . Study management, data handling and record keeping . Compensation for Participation. Supply, storage and handling of Pharmaceutical Products

16. Sending status reports to regulatory authorities periodically. If any SAE , report to authority within 14 working day Properly monitoring study sites . Sponsor should perform an audit as a part of QA system. If Premature Termination or Suspension of a Study ,should notify the investigator, the ethics committee and the regulatory authorities accordingly. Responsibilities of Sponsor cont’d . 16

17. Medical care of the study subjects . Conducting of trial according to the protocol and GCP guidelines . Communication with sponsor and EC Promptly reporting of any deviations from protocol to eliminate immediate hazards to the subjects . SAE and unexpected AE should be reported to the sponsor within 24hours and to EC within 7 working days Ensure the accuracy, completeness, legibility of the data reported to the sponsor . Accountability of investigational product at the study site . Responsibilities of Investigator 17

18. Responsibilities of Ethics Committee 18 To ensure a competent review of all ethical aspects of the project and execute the same free from any bias . To protect the dignity, rights and well being of the potential research participants . Protect vulnerable subjects. Obtain and maintain record and SOPs . Ongoing review of project based on Periodic progress report .

19. Informed Consent 19

20. Informed Consent 20 In all trials, informed written consent is required to be obtained from each subject . The Investigator must provide information about study verbally and using a patient information sheet (PIS) in a language that is nontechnical and understandable by the subject. Both PIS and ICF should have been approved by the ethics committee and submit to the Licensing Authority .

21. Where a subject is not able to give informed consent (e.g. unconscious person or a minor or those suffering from severe mental illness or disability), the same may be obtained from a legally acceptable representative (LAR) If the Subject is unable to read/write - an impartial witness should be present during consent process who must append his/her signatures to the consent form. A checklist of essential elements to be included in ICF given in Appendix V. 21

22. Human Pharmacology (Phase I) To estimate safety and tolerability . Often carried out in healthy adult volunteers using clinical, physiological and biochemical observations. At least 2 subjects should be used on each dose. Carried out by investigators trained in clinical pharmacology and having the necessary facilities to closely observe and monitor the subjects . Phases of clinical trial 22

23. Phases of clinical trial 23 Therapeutic exploratory trials (Phase II) To evaluate the effectiveness of a drug for particular indication. To determine the short term side effects and risk associated with drug . These studies are usually limited to 3-4 centres and carried out by clinicians specialized on the concerned therapeutic areas .

24. Phases of clinical trial 24 Therapeutic confirmatory trials (Phase III) To obtain evidence about the efficacy and safety of the drug in a larger number of patients . Carried out by clinicians in the concerned therapeutic area s If the drug is already approved in other countries, phase III data on at least 100 patients distributed over 3-4 centres should be provided in Indian patients .

25. Phases of clinical trial 25 Post Marketing Trials (lV) Performed after drug approval and related to the approved indication . To study drug-drug interaction, dose-response or safety studies, mortality/morbidity studies . Should use the same scientific and ethical standards as applied in pre-marketing studies

26. Studies in special populations 26

27. Studies in special populations : Geriatrics 27 Geriatric patients can be included in clinical study only if Disease to be treated is characteristically a disease of aging Population to be treated having substantial numbers of geriatric patients When the new drug is likely to alter the geriatric patient’s respons e .

28. Paediatrics patients can be included in clinical trials only if If the new drug is for disease exclusively affecting paediatric patients . If the new drug is intended to treat serious or life-threatening diseases , occurring in both adults and paediatric patients . Studies in special populations : Paediatrics 28

29. Written informed consent should be obtained from the parent/legal guardian. However, paediatric patients should be informed to fullest extent . If a paediatric patient wishes to withdraw from study of serious or life-threatening diseases , continued parental/legal guardian consent . Studies in special populations : Paediatrics 29 Carried out after the phase III clinical trials in adults , can be studied earlier only if , disease occurs primarily in children .

30. Studies in special populations : Pregnant or nursing women 30 Drug is intended for use by pregnant/nursing women or foetuses/nursing infants . E .g. To test the efficacy and safety of a drug for reducing perinatal transmission of HIV infection . Follow-up data on the pregnancy, foetus and child will be required . Where applicable, excretion of the drug or its metabolites into human milk should be examined . Pregnant or nursing women should be included in clinical trials only when

31. New drugs should be closely monitored for their safety once they are marketed. The applicants shall furnish Periodic Safety Update Reports (PSURs) in order to Report all the relevant new information (patient exposure) Summarize the market authorization status in different countries and any significant variations related to safety Indicate whether changes should be made to product information   PSURs shall be submitted every 6 months for the first two years For subsequent two years – annually . Post marketing surveillance : Periodic Safety Update Reports 31

32. Special studies: Bioavailability/Bioequivalence Studies 32 For drugs approved elsewhere in the world and absorbed systemically, bioequivalence study with the reference formulation should be carried out. Evaluation of the effect of food should be carried out Dissolution and bioavailability data to be submitted All BA / BE studies should be conducted according to the prescribed guidelines (ICMR guidelines)

33. Appendices 33 APPENDIX I -Data to be submitted along with the application to conduct clinical trials/import/ manufacture of New drugs . APPENDIX ll - Structure, Contents and Format for Clinical Study Reports APPENDIX lll -Format of Animal Toxicology APPENDIX lV - Format of Animal Pharmacology APPENDIX V - Format of Informed Consent APPENDIX Vl - Requirements for approval of Fixed Dose Combination s APPENDIX Vll - Undertaking by Investigator APPENDIX Vlll - Ethics Committee APPENDIX lX - Stability testing of New Drugs APPENDIX X - Contents of the proposed protocol for conducting clinical trials APPENDIX Xl - Data elements for reporting serious adverse events occurring in a Clinical Trial.