Schedule Y

Requirements And Guidelines For Permission To Import / or Manufacture of New Drugs For Sale or To Undertake Clinical Trials
Schedule Y was introduced under the Drugs and Cosmetics Act 1940, to
introduce requirements for countries to get permission for:
Importing
Manufacturing new drugs
Conducting Clinical Trials.
Application for permission
Clinical Trial
Studies in specific population
Post marketing surveillance
Special studies: BA/BE studies

1. Clinical Research Regulation in India: Schedule Y Presented by: Vanshika Gupta 1 st sem M.Pharm (RA ) CRR (MRA103T) 1 PARUL INSTITUTE OF PHARMACY PARUL UNIVERSITY

2. Content Schedules under D&C Act 1940 Rules under Schedule-Y Amendments in 2013 & 2014 Introduction to Schedule Y Schedule Y 1. Application for permission 2. Clinical Trial 3. Studies in special populations 4. Post Marketing Surveillance 5. Special studies: Bioavailability / Bioequivalence Studies 2

3. Schedules under Drugs and Cosmetics Act 1940  Schedule A:  Describes application forms and licenses types. Schedule-B:  Fees for test or analysis by the Central Drugs Laboratories or State Drugs Laboratories. Schedule-C: Contains various biological products and their regulation. Examples : Serums , Adrenaline , Vitamins etc. Schedule-D: List of drugs exempted from the provision of import of drugs. Schedule-E: List of poisonous substances under the Ayurvedic, Siddha and Unani systems. Schedule-F: This contains regulations and standards for running a blood bank. 3

4. Cont... Schedule-F I: Provisions applicable to the production of bacterial vaccines Schedule-F II: Standards for surgical dressings Schedule-F III: Standards for umbilical tapes Schedule-FF: Standards for ophthalmic preparations Schedule-G:  List of drugs falls under Schedule-G (taken only under the supervision of a Registered Medical Practitioner) Most of these drugs are hormonal preparations. Schedule-H:  List of drugs falls under Schedule-H (sold by retail only on the prescription of Registered Medical Practitioner) 4

5. Cont... Schedule-J: Contains a list of various diseases and conditions that cannot be treated under any drug currently in market and No drug may legally claim to treat these diseases Schedule-K:   Contains various substances and drugs and their corresponding regulation. Schedule-L I: It prescribes list of drugs to be sold on prescription only- omitted. Schedule-M:  (GMP) Good manufacturing practices requirements of factory premises, plant, equipments, etc for manufacturing of drugs. Schedule-N: List of minimum equipment for the efficient running of a pharmacy 5

6. Cont... Schedule-O: Contains various regulations and requirements for disinfectant fluids. Schedule-O I:  Provisions applicable to Black Fluids and White Fluid (disinfectants) Schedule-P:  Storage conditions of drugs Schedule-P I:  Pack size of drugs Schedule-Q: List of dyes, colours and pigments permitted to be used in cosmetics and soaps. Schedule-R: Standards for condoms made of rubber latex intended for single use and other mechanical contraceptives Schedule-S: Standards for cosmetics 6

7. Cont... Schedule-T:  The requirements of factory premises, plant, equipments and hygienic conditions for manufacture of Ayurvedic, Siddha, and Unani Schedule-U: Particulars to be shown in manufacturing records Schedule-V: Standards for patent or proprietary medicines Schedule-X:  List of drugs falls under Schedule-X ( Narcotic drugs and Psychotropic ) Schedule-Y:  Requirements and guidelines for permission to import and / or manufacture of new drugs for sale or to undertake clinical trials. 7

8. Rules under Schedule-Y 8 Section 122A: Application for Permission to import new drug Section 122B: Application for approval to manufacture new drug Section 122D: Permission to import or manufacture fixed dose combination Section 122DA: Application for permission to conduct clinical trials for New Drug/ Investigational New Drug. Section 122DAA: Definition of Clinical trial. Section 122DB: Suspension or cancellation of permission/approval Section 122-E: Definition of new drug

9. Amendments in 2013 & 2014 Rule 122DAB – Compensation in case of injury or death during clinical trial Rule 122DAC – Condition of clinical trial permission and inspection. Rule 122DD – Registration of ethic Committee - Requirement and guidelines for registration of ethic committee 9

10. Introduction Requirements And Guidelines For Permission To Import / or Manufacture of New Drugs For Sale or To Undertake Clinical Trials Schedule Y was introduced under the Drugs and Cosmetics Act 1940, to introduce requirements for countries to get permission for: Importing Manufacturing new drugs Conducting Clinical Trials. 10

11. Requirements And Guidelines 11

12. SCHEDULE Y (1) Application for permission : Application for permission to import or manufacture new drugs for sale or to undertake clinical trials shall be made in Form 44 accompanied with following data in accordance with the appendices It includes: (i) Chemical and pharmaceutical information (ii) Animal pharmacology data (iii) Animal toxicology data 12

13. Cont... (iv) Human Clinical Pharmacology Data (v) Regulatory Status in other country (vi) Prescribing Information Form 12 – To import study drug for examination, test or analysis. 13

14. Cont... 2. Clinical Trial : (i) Approval for clinical trial: - Clinical trial on a new drug shall be initiated only after the permission has been granted by the Licensing Authority under rule 21 (b) - All trial Investigator(s) should possess appropriate qualifications, training and experience. 14

15. Cont... - Protocol amendments if become necessary before initiation or during the course of a clinical trial, all such amendments should be notified to the Licensing Authority in writing along with the approval by the ethics committee which has granted the approval for the study. (ii)Responsibilities of Sponsor: The clinical trial Sponsor is responsible for implementing and maintaining quality assurance systems to ensure that the clinical trial is conducted and data generated, documented and reported in compliance with the protocol 15

16. Cont... - Standard operating procedures (SOPs) should be documented to ensure compliance with GCP and applicable regulations. - Sponsors are required to submit a status report on the clinical trial to the Licensing Authority - Any unexpected serious adverse event (SAE) occurring during a clinical trial should be communicated promptly (within 14 calendar days) by the Sponsor to the Licensing Authority and to the other Investigator(s) participating in the study. 16

17. Cont... (iii) Responsibilities of the Investigator(s): Responsible for the conduct of the trial according to the protocol and the GCP Guidelines SOP are required to be documented by the investigators for the tasks performed by them. To ensure adequate medical care is provided to the subject. Investigator(s) shall report all serious and unexpected adverse events to the Sponsor within 24 hours and to the Ethics Committee that accorded approval to the study protocol within 7 working days of their occurrence 17

18. Cont... (iv) Informed Consent: Informed consent should be Non-technical and in understandable language. Investigator must provide information about the study verbally and in written . The Subject’s consent must be obtained in writing using an ‘Informed Consent Form. Legally acceptable representative. The patient information sheet as well as the Informed Consent Form should have been approved by the ethics committee and furnished to the Licensing Authority. 18

19. Cont... (v) Responsibilities of the Ethics Committee: The responsibility of the ethics committee that to reviews and grant its approval to a trial protocol to safeguard the rights, safety and well being of all trial subjects. Conduct ongoing review of the trial. Ethics committee(s) should get document ‘standard operating procedures’ and should maintain a record of its proceedings. (vi) Human Pharmacology (Phase I) : The objective of studies in this Phase is the estimation of safety and tolerability with the initial administration of an investigational new drug into human(s). Phase I trials should preferably be carried out by Investigators trained in clinical pharmacology with access to the necessary facilities to closely observe and monitor the Subjects. 19

20. Cont... (vii) Therapeutic exploratory trials (Phase II) : The primary objective of Phase II trials is to evaluate the effectiveness of a drug for a particular indication or indications in patients with the condition under study and to determine the common short-term side-effects and risks associated with the drug. An important goal for this Phase is to determine the dose(s) and regimen for Phase III trials. (viii) Therapeutic confirmatory trials (Phase III) : - Phase III are designed to confirm the preliminary evidence accumulated in Phase II that a drug is safe and effective for use in the intended indication and recipient population. 20

21. Cont... - These studies should be intended to provide an adequate basis for marketing approval. - Studies in Phase III may also further explore the dose response relationships (relationships among dose, drug concentration in blood and clinical response) - Use of the drug in wider populations, in different stages of disease, or the safety and efficacy of the drug in combination with other drug(s). 21

22. Cont... (ix) Post Marketing Trials (Phase IV): Post Marketing trials are studies These trials go beyond the prior demonstration of the drug’s safety, efficacy and dose definition Phase IV trials include additional drug-drug interaction(s), dose-response or safety studies and trials designed to support use under the approved indication(s), e.g. mortality/morbidity studies, epidemiological studies etc. 22

23. Cont... (3) Studies in Special Populations : The use of the drug in children, pregnant women, nursing women, elderly patients, patients with renal or other organ systems failure , and those on specific concomitant medication is required to be submitted. Geriatrics- Geriatric patients should be included in Phase III clinical trials in meaningful numbers, if- The disease intended to be treated is characteristically a disease of aging . When there is specific reason to expect that conditions common in the elderly are likely to be encountered. When the new drug is likely to alter the geriatric patient's response compared with that of the non-geriatric patient. 23

24. Cont... - Pediatrics: Studies in the new drug development program will depend on the medicinal product - The type of disease being treated - Safety considerations, and - The efficacy and safety of available treatments. - Pregnant or nursing women - Should be included in clinical trials only when the drug is intended for use by pregnant/nursing women or foetuses/nursing infants. - Follow-up data (pertaining to a period appropriate for that drug) on the pregnancy, foetus and child will be required. 24

25. Cont... (4) Post Marketing Surveillance : Subsequent to approval of the product, new drugs should be closely monitored for their clinical safety once they are marketed. The applicants shall furnish Periodic Safety Update Reports (PSURs). Submitted every 6 months for first 2 years. (5) Special studies: Bioavailability / Bioequivalence Studies : For drugs approved elsewhere in the world and absorbed systemically, bioequivalence with the reference formulation should be carried out wherever applicable. All bioavailability and bioequivalence studies should be conducted according to the Guidelines for Bioavailability and Bioequivalence studies as prescribed. 25

26. Appendix Some highlights of Schedule Y in terms of its appendices; which provide the guidelines to conduct clinical trials are: APPENDIX 1 - Conduct clinical trials/import/manufacture of new drugs APPENDIX IA - For grant of permission to import and / or manufacture a new drug APPENDIX II - Structure, contents and format for clinical study reports APPENDIX III- Animal toxicology (non-clinical toxicity studies) 26

27. Cont... APPENDIX IV- Animal pharmacology APPENDIX V- Informed consent APPENDIX VII - Undertaking by the Investigator APPENDIX VIII- Ethics Committee APPENDIX X - Contents of Protocol APPENDIX XI - Data elements for reporting SAE APPENDIX XII - Compensation in case of injury or death during clinical trial 27

28. Data To Be Submitted Along With The Application To Conduct Clinical Trials / Import / Manufacture Of New Drugs For Marketing In The Country. Introduction Chemical and pharmaceutical information Animal Pharmacology (for details refer Appendix Animal Toxicology (for details refer Appendix Human / Clinical pharmacology (Phase I) Therapeutic exploratory trials (Phase II) Therapeutic confirmatory trials (Phase III) Special studies Regulatory status in other countries Prescribing information Samples and Testing Protocol/s 28

29. Reference https://rgcb.res.in/documents/Schedule-Y.pdf Schedule Y. Requirements and guidelines for permission to import and/or manufacture of new drugs for sale or to undertake clinical trials. New Delhi, India: Central Drug s Standard Control Organization. 2013. https://ccrps.org/clinical-research-blog/difference-between-ich-gcp-and-schedule-y 29

30. 30 THANKYOU