schedule y of drugs and cosmetic acts

schedule y of drugs and cosmetic acts

1. DRUGS AND COSMETIC ACTS SCHEDULE Y Presented by- DEBASHIS DAS M.Pharm 1 st Sem RIPANS

2. Objective… What actually schedule Y is? Why changes in schedule Y? Rules under schedule Y… Appendices of schedule Y… Conclusion references OUTLINE OF PRESENTATION

3. The main objectives of the drugs and cosmetic acts 1940, is to regulate the import, manufacture, distribution and sale of drugs & cosmetics in the country It also ensure that the drugs that are available to the people are safe and efficacious and the cosmetics marketed are safe for use OBJECTIVES

4. Schedule Y It’s a law Not merely a Guideline What Actually Schedule Y is

5. Schedule Y ,the current regulator (of CDSCO), enforced law in India has been established under Drug and Cosmetic Act, 1945. The regulations to be followed when conducting Clinical Trial. Schedule Y – requirements and guidelines for permission to import and/or manufacture of new drugs for sale or to undertake clinical trial Date 20 January, 2005 Schedule Y

6. To frame guidelines for the current scenario of Clinical research. CDSCO and DTAB formulated GCP under Schedule Y in 2005. Schedule Y 1988 relevant to predominantly generic industry. GCP trials since 1995 , and arrival of IPR regime in 2005. Integration of India in global clinical development and legal support to GCP guidelines. Improvements in quality of clinical trials. It has outlined extensive study criteria in line with the globally accepted formats such as ICH and US FDA guidelines Why changes in schedule Y

7. 122A - Application for permission to import new drug 122 B - Application for approval to manufacture new drug 122 D -Permission to import or manufacture FDC 122 DA- Permission to conduct clinical trials for New Drug / Investigational New Drug 122 DAA –Definition Of “CLINICAL TRIAL” “Clinical trial” - a systematic study of new drug(s) in human subject(s) to generate data for discovering and / or verifying the clinical, pharmacological effect (including pharmacodynamic and pharmacokinetic) and /or adverse effects with the objective of determining safety and / or efficacy of the new drug. Rules under schedule Y

8. 122-E Definition of new drugs Not been used in the country under labeling conditions Approved but now proposed to be marketed with modified or new claims – indications, dosage, dosage form , route of administration , FDC , individually approved to be combined for the first time in a fixed ratio or if ratio is changed

9. APPENDICES of schedule y

10. It contains data to be submitted along with the application to conduct clinical trials / import / manufacture of new drugs for marketing in the country. 1. Introduction a . A brief description of the drug and the therapeutic class to which it belongs. 2. Chemical and pharmaceutical information 2.1 Information on active ingredients Drug information (Generic Name, Chemical Name etc.) Physicochemical Data A. Chemical name and Structure Empirical formula Molecular weight B. Physical properties Solubility Rotation Partition coefficient Dissociation constant Appendix I

11. 2.3 Analytical Data Elemental analysis Mass spectrum NMR spectra IR spectra UV spectra Polymorphic identification 2.4 Complete monograph specification including Identification Identity/quantification of impurities Enantiomeric purity Assay 2.5 validation 2.6 stability studies ( for details refer appendix IX)

12. 3 . Animal pharmacology (for details refer appendix IV) Summary Specific pharmacological actions General pharmacological actions Follow-up and Supplemental Safety Pharmacology Studies Pharmacokinetics: absorption, distribution; metabolism; excretion 2.7 data on formulation dosage form, composition, master manufacturing formula, In process quality control check, Excipients compatibility study Finished product specification Validation of the analytical method

13. 4. Animal toxicology (for detail refer appendix IV) General Aspects Systemic Toxicity Studies Male Fertility Study Female Reproduction and Developmental Toxicity Studies Local toxicity Allergenicity /Hypersensitivity Genotoxicity Carcinogenicity

14. 5. Human/clinical pharmacology (phase I) Summary Specific Pharmacological effects General Pharmacological effects Pharmacokinetics, absorption, distribution, metabolism, excretion Pharmacodynamics /early measurement of drug activity

15. 6. Therapeutic exploratory trial (phase II) Summary Study report(s) as given in Appendix II 7. Therapeutic confirmatory trial (phase III) Summary Individual study reports with listing of sites and Investigators . 8. Special studies Summary Bio-availability / Bio-equivalence. Study on special group of population e.g. geriatrics, pediatrics , pregnant or nursing women

16. Geriatrics Geriatric patients should be included in Phase III clinical trials (and in Phase II trials, at the Sponsor's option) in meaningful numbers, If the disease intended to be treated is characteristically a disease of aging; or the population to be treated is known to include substantial numbers of geriatric patients;

17. The pediatric studies should include - clinical trials, relative bioequivalence comparisons of the pediatric formulation with the adult formulation performed in adults definitive pharmacokinetic studies for dose selection across the age ranges of pediatric patients in whom the drug is likely to be used. These studies should be conducted in the pediatric patient population with the disease under study The timing of pediatric 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. Pediatrics

18. Pregnant or Nursing Women Pregnant or nursing women should be included in clinical trials only when the drug is intended for use by pregnant/nursing women or fetuses/nursing infants and where the data generated from women who are not pregnant or nursing, is not suitable. For new drugs intended for use during pregnancy, follow-up data (pertaining to a period appropriate for that drug) on the pregnancy, fetus and child will be required.

19. 9. Regulatory status in other countries 9.1 countries where the drug is a. marketed b. Approved c. approved as IND d. withdrawn, if any , with reason 9.2 restriction use, if any , in countries where marketed/ approved 9.3 free sale certificate or certificate of analysis , as appropriate. 10. Prescribing information 10.1 proposed full prescribing information 11. Samples and testing protocol NOTE : All items may not be applicable to all drugs. For explanation, refer text of Schedule Y. For requirements of data to be submitted with application for clinical trials we should refer text of this Schedule

20. Data required to be submitted by an applicant for grant of permission to import and/or manufacture a new drug already approved in the country Introduction ( About the drug and its therapeutic class) Chemical and pharmaceutical information (Chemical name, Generic name, Structure , Physico chemical properties) Marketing information (Promotional literature) Special studies conducted with approval of licensing authority Bioavailability/ Bioequivalance and comparative dissolution studies for oral dosage forms Sub acute animal toxicity studies for intravenous infusions and injectables . Appendix I A

21. 1. Title page :- title of the study, the protocol code, name of the investigational product tested, development phase, indication studied, a brief description page, the start and end date of patient accrual and the names of the sponsor and the participating institute 2. Study synopsis(1 to 2 pages) :- a brief review of study from the protocol development to the trial closure should be given here. This section will only summarize the important conclusions derived from the study 3. statement of compliance 4.list of abbreviation and definitions Table of contents Appendix II structure, contents and format for clinical study reports

22. 6. ethics committee: 7.study team 8.study objective 9.investigational plan Trial subjects Efficacy evaluation Safety evaluation Discussion and overall conclusion List of references appendices

23. ANIMAL TOXICOLOGY (NON-CLINICAL TOXICITY STUDIES) Acute toxicity Long-term toxicity Reproduction studies Fertility studies Teratogenicity studies: Local toxicity: Mutagenicity and Carcinogenicity Application Of Good Laboratory Practices (GLP) Appendix III- Animal toxicology (non-clinical toxicity studies)

24. Animal pharmacology General Principles Specific and general pharmacological studies should be conducted to support the use of therapeutics in human Safety pharmacological studies investigates potential undesirable pharmacodynamic effect of as substance on physiological function in relation to exposer within the therapeutic range or above. Specific Pharmacological Actions  Are those which demonstrate the therapeutic potential for humans. General pharmacological Actions Essential Safety Pharmacology To study the effect of the test drug on vital functions such as cardiovascular, respiratory and central nervous system are studied Appendix IV- animal pharmacology

25. Supplemental Safety Pharmacology Studies Investigation of the adverse pharmacological effect that are not assessed in the in the essential safety pharmacological studies and are a cause for concern  Urinary System Includes urine volume, specific gravity , osmolality , pH , proteins, cytology, and blood urea nitrogen , creatinine , plasma protein estimation . Autonomic Nervous System Binding to receptor relevant to ANS and functional response to agonist or antagonist responses in in vitro or in vivo.  Gastrointestinal System Studies of gastric secretion, gastric pH, bile secretion, gastric emptying time etc Other Organ Systems

26. Trial involves research Purpose Trial treatment and randomization Trial procedures Risk Benefit Alternative treatments Compensation /treatment for injury Subject responsibilities Experiment aspects Any payment Appendix V INFORM CONSENT

27. Confidentiality New information Voluntary participation Persons to contact for study information Rights of subjects, if study related injury Reasons for termination Duration of study Number of subjects Any other pertinent information Essential elements of informed consent

28. Study title Subject initials e.g. subjects name/date of birth/age Consent statement with initials in A) signature of the subject B) Legally acceptable representative Signature of the investigator Study investigators name Signature of the witness Name of the witness Format of informed consent form

29. Combination therapy with two or more agents having complementary mechanism of action is an example of incremental innovation that may extend the range of therapeutic options in the treatment of almost every human disease Fixed dose combination(FDC) fall into four categories one or more of the active ingredients is a new drugs First time combination of individually approved/marketed drugs, where the ingredients are likely to have significant interaction of a pharmacodynamic or pharmacokinetic nature Combination already marketed, but in which it is proposed either to change the ratio of active ingredients or to make new therapeutic claim Combined only for the purpose of convenience Appendix VI: FIXED DOSE COMBINATIONS (FDCs)

30. 1. - Full name - Address - Title of Principal Investigator (or Investigator if no PI) 2. -Name & Address of the medical college, hospital or facility. - Education training & experience of the Investigator 3. Name & address of all clinical laboratory facilities 4. Name and address of EC 5. Name of other members of the research team 6. Protocol title & Study number (if any) 7. Commitments 8. Signature of the Investigator with Date. Appendix VII- UNDERTAKING BY THE INVESTIGATOR

31. Appendix VIII - ETHICS COMMITTEE It should have at least seven members . a chair person (who is from outside the institution) and a member secretary Other member should be mix of medical/ non-medical scientific/ non-scientific persons including lay public , to reflect their different view point The quorum of ethics committee should have at least 5 members Basic medical scientist( pharmacologist) Clinician Legal expert Social scientist/ethicist/philosopher etc. Lay person from the community NOTE : ONLY THOSE ETHICS COMMITTEE MEMBER WHO ARE INDEPENDENT OF THE CLINICAL TRIAL AND THE SPONSOR OF THE TRIAL SHOULD VOTE / PROVIDE OPINION IN MATTERS RELATED TO STUDY .

32. Stability testing is to be performed to provide evidence on how the quality of the drug substance or formulation varies with time under influence of environmental factors such as temperature , humidity , and light , and to establish shelf life for the formulation and recommended storage condition It includes testing of those attributes of the drug that are susceptible to change during storage and are likely to influence quality , safety and / or efficacy . Appendix IX – STABILITY TESTING OF NEW SRUGS

33. Title page Full title of the clinical study Protocol/study number and protocol version number with date The Investigational New Drug (IND) name/number of the investigational drugs Complete name and address of the sponsor and contract research organization if any List of the investigators who are conducting the study Names of clinical laboratories and other departments and/ or facilities participating in the studies Table of content A complete table of content including a list of all appendices Background and Introduction Preclinical experiences Clinical experiences Appendix X - contents of the proposed protocols for conducting clinical trials

34. 2 . Study rationale This section should describe a brief summary of the background information relevant to the study design and protocol methodology 3. Study design Overview of the study design Flowchart of the study A brief description of the methods and procedure used during the study 4. Study population the number of subject required to be enrolled in the study at the investigative site and by all site along with a brief description of the nature of the subject population required is also mentioned 5.Subject eligibility Inclusion criteria Exclusion criteria

35. 6. Study treatment: Dosing schedule , details of product stability, storage requirements , dispensing requirements, possible drug interactions 7. Adverse events: Description of expected adverse events should be given 8. Data analysis 9. Undertaking by the investigator (appendix VII) NOTE- protocol is assigned by sponsor after getting CDA from investigator

36. 1. Patient details Initials & other relevant identifier (hospital/ OPD record number etc) Gender Age &/or date of birth Weight Height 2. Suspected drug(s) Generic name of the drug Indication(s) for which suspect drug was prescribed or tested Dosage form and strength Daily dose & regimen (specify units-e.g. mg, ml, mg/kg) Route of administration Starting date & time of the day Stopping date and time, or duration of treatment Appendix XI – data elements for report serious adverse events occurring in a clinical trial

37. 3. Details of suspected Adverse Drug Reaction(s) Full Description of reaction(s) including: - body site - severity - criterion for considering the report as serious. In addition to the description of signs & symptoms whenever possible describe a specific diagnosis for the reaction. Start date (& time) of onset of reaction Stop date (& time) of duration of reaction 4. Details about Investigator Name Address Telephone number Profession (Specialty) Date of reporting the event to the Licensing Authority Date of reporting the event to Ethics Committee over seeing the site Signature of the Investigator

38. CONCLUSION “With The Schedule Y The Efforts Are Aligned In a Single Direction To Ensure That Irrespective Of The Country, The Data Generated is Of Good Quality And Standard Which Can Be Accepted World Wide”

39. GUPTA S. K. BASIC PRINCIPLE OF CLINICAL RESEARCH AND METHODOLOGY http://www.slideshare.net/slideshare006/schedule-y-mk-sharma.(date-08.12.2016) http://www.cdsco.nic.in/html/D&C_Rules_Schedule_Y.pdf(11.12.2016) REFERENCES