Schedule y, mk sharma

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REGULATION OF CLINICAL RESEARCH

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  • A-ayurvedic U-unani S-siddha, LOD- list of drugs
  • MFS- male fertility studies DRS- dose ranging studies, FFS- female fertility studies
  • DFD- dosage form design ROA- route of adminstration SADR-suspectedADR
  • Schedule y, mk sharma

    1. 1. Schedule Y Presented By-MANISH KUMAR SHARMA Presented To CENTER FOR CLINICAL RESEARCH SHARDA UNIVERSITY, GREATER NOIDA,UP6/1/2012
    2. 2. Outline of Presentation1. History2. Drug and cosmetic Act,1940 and Schedules3. What actually Schedule Y is ?4. Old/New(amended) Schedule Y5. Why Changes in Schedule Y ?6. Rules under it7. Divisions of Schedule Y8. New Amendments9. Conclusion6/1/2012
    3. 3. Lets revise the History Drug and Cosmetic Act, 1940 was enacted(D/C Act) Pharmacy Act , 1948 Drug and Magic Remedies Act, 1954 The Narcotic and Psychotropic Substance Act and Rules, 1985 Ethical guidelines for Biomedical Research on Human Participants,2000 by ICMR 6/1/2012
    4. 4.  Indian GCP Guidelines,2001  Amendments to Drug and Cosmetic Act,2002  Revised Schedule Y, 2005  Guidelines for Pre Clinical Data for r-DNA Vaccines,20076/1/2012
    5. 5. Drug and Cosmetics Act,1940 In 1940 D/C Act Was enacted in 1945 Drug Rules were Promulgated in December and enforcement Start in 1947 Now have been called as D/C ActObjective- To ensure that the drug is available to the People are safe and cosmetics marketed for safer use. 6/1/2012
    6. 6. Schedules to Rules, 1945 Schedule A- Forms for marketing application for licenses, issue, and renewal  B- Fee for test/analysis by CDL or SDL  C/C1- talk about I/M/S/D of sera, vaccines  D-List of drugs exempted from the provisions that are applicable to import of other drug  E- Omitted , E1- list of poisonous substance under Ayurveda,Unani,Sidha system  F- Production/testing/storage/packaging/labeling F1-biological preparations F2- SD F3- umbilical tapes  G- List of drug used under medical supervision  H- List of drug sold under Prescription  I-Omitted  J-Diseases may not cure/prevent by drugs  K-List of drugs exempted from the provisions that are applicable to6/1/2012 manufacture of other drug
    7. 7.  M-GMP  N-List of minimum equipment in Pharmacy  O-Standards for disinfections  P- Life period of drug  Q-List of dyes/coloring agents in soap/cosmetics  R-Standards for Mechanical contraceptives  S-Standards for cosmetics  T-GMP for A/U/S system of medicines  U- Records for manufacturing/raw materials in drugs  V- Standards for potent medicines  X- List of drugs whose I/M/S are governed by special provision  W- Omitted  Y- About CT6/1/2012
    8. 8. Schedule Y The enforcement that came into existence in 1988 was an essential provision for providing support to the upscale of generic pharma scenario present in those days.  With the entry of large pharmaceutical companies along with the multiple multinationals in field of clinical research the needs changed and a revised version of Schedule Y in line with ICH-GCP (International Council of Harmonization and Good Clinical Practice) standard was put forth in 1995.  Since then multiple revisions to Schedule Y took place to provide a healthy environment for clinical research to be conducted in India.6/1/2012
    9. 9. 6/1/2012
    10. 10. Schedule Y It’s a Law not merely a Guideline6/1/2012
    11. 11. Schedule Y 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 in India.6/1/2012
    12. 12. contt..‘REQUIREMENTS AND GUIDELINES FOR PERMISSION TO IMPORT AND / OR MANUFACTURE OF NEW DRUGS FOR SALE OR TO UNDERTAKE CLINICAL TRIALS IN INDIA’6/1/2012
    13. 13. Amended Schedule Y  ‘Regulations and Guidelines for permission for development (preclinical and/or clinical), import and manufacture of New Drugs for Marketing in India’ DATE- 20TH JAN,20056/1/2012
    14. 14. Why Changes in Schedule Y  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.6/1/2012
    15. 15. Rules under Schedule Y Rule Permission 122 A To Import New Drugs 122 B To manufacture New Drugs To import or manufacture fixed dose 122 D Combinations 122 DA To conduct Clinical Trials for New Drug/Investigational New Drug 122DAA Definition of Clinical Trial 122 E Definition of New Drug6/1/2012
    16. 16. Rule 122DA To conduct Clinical Trials for New Drug/Investigational New Drug New chemical entity or a product having therapeutic indication but which has never been earlier tested on human beings.6/1/2012
    17. 17. 122-E.  122-E. -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 changed6/1/2012
    18. 18. 6/1/2012
    19. 19. Old schedule Yin the older version there are only 5 appendicesAppendix I: Declaration of HelsinkiAppendix II: Schedule YAppendix III: Format for submission of Pre-clinical and clinical data for r-DNA based vaccines, diagnostics and other biologicals.Appendix IV: Investigator’s BrochureAppendix V: Essential Documents6/1/2012
    20. 20. 6/1/2012
    21. 21. Significant changes New concept Older concept1)Clinical trials 1.1 Nature of CTa) Definition of CT 1.2 Permission of CTb) ICD – New 1.3 ICD but no detailsc) responsibilities of ethical 1.4 Responsibilities of committee- New sponsor/investigatord) PMS- New2) Studies in special populations No PMSa) Geriatric 2) Special Studiesb) Pediatrics No Separationc) Pregnantd) PMS - Newe) BA/BE - New3)Formats for critical documents 6/1/2012
    22. 22. Appendix I Data to be submitted along with the application to conduct clinical trials / import / manufacture of new drugs for marketing in the country.a. Introduction about the drugb. Chemical and pharmaceutical information (e.g. Enatiometry)c. Animal pharmacologyd. Animal toxicologye. Human /clinical pharmacology(Phase-I)f. Therapeutics exploratory(Phase-II)g. Therapeutics confirmatory(Phase-III)h. Special studies( paediatrics, pregnant)i. Regulatory status in other countries if availablej. Prescribing information(drug labeling and prescribing inf.) 6/1/2012
    23. 23. APPLICATION FOR PERMISSION UNDER FORM 44, REGULATORY AUTHORITIES, FEES AND TEST LICENCE6/1/2012
    24. 24. Regulatory authoritiesMinistry of Chem & Ministry of Health Ministry of Sci & Ministry ofFertilizers Tech Enviro Health Secretary DBTNPPA DGHS Department of AdditionalNational Director General of Biotechnology SecretaryPharmaceutical Health ServicesPricing Authority GEAC DCGI Genetic Drug Controller Engineering Pricing General of India Approval Regulations Committee CDRL/CDTL Gov. Drug Testing Laboratories State Drug Regulatory Authority :FDA
    25. 25. PROCESS Approval Form 45APPLICATION (IMP FF)FORM 44-Imp FF Approval Form 45-Imp Rm A (IMP RM)-Mfg FF-Mfg Rm Approval Form 46-CT (MFG FF) Application Form NOC FOR CT + Test 46 A (MFG RM) Licence for Import
    26. 26. Fee according to Schedule Y Import ff/ Mfg ff/ Import bulk + Mfg ff = Rs 50,000/- of new drug Application by same applicant, = Rs 15,000/- for modified dosage form or with new claim Secondary applicants after 1 = Rs 15,000/- year of approval Import / Mfg FDC = Rs 15,000/- Conduct Clinical trial with ND/IND  Phase I = Rs 50,000/-  Phase II = Rs 25,000/-  Phase III = Rs 25,000/-  No separate fee to be paid along with application for import / mfg based on successful completion
    27. 27. Appendix I-A Data required to be submitted by an applicant for grant of permission to import &/or manufacture a new drug already approved in the country.a) Introductionb) Chemical and pharmaceutical informationc) Marketing informationd) Special studies 6/1/2012
    28. 28. Appendix IIIAnimal toxicology (Non-clinical toxicity studies) 1) SDTS- Minimum 5 animal, 24hr observation 2) DRS- On one Rodent Species 3) RDTS- a) 14 to 28 days- on 1 Rodent and 1 Non Rodent b)90 days- same as above but introduction of HIGH DOSE REVERSAL . 4) MFS- Rodent Species, Dose selection should be done on basis of 14 to 28 days studies. 5) FFS- should be carried out for all drugs( Appendix I- 4.4)6/1/2012
    29. 29. Animal toxicology (Non-clinical toxicity studies) Other Studies a. Hypersensitivity b. Genotoxicity c. Carcinogenicity 6/1/2012
    30. 30. Appendix IV-Animal Pharmacology Animal pharmacology studies are done to see the effect if IP on different systems like CVS CNS ANS RS US GIT6/1/2012
    31. 31. Appendix V- INFORM CONSENT  Trial involves research  Purpose  Trial treatments and randomization  Trial procedures  Risk  Benefit  Alternative treatments  Compensation / treatment for injury  Subject’s responsibilities  Experimental aspects  Any payment6/1/2012
    32. 32. Essential Elements of Informed Consent  Confidentiality  New information  Voluntary participation  Person/s to contact for study information  Rights of subject, if study related injury  Reasons for termination  Duration of study  Number of subjects  Any other pertinent information6/1/2012
    33. 33. Format of Informed Consent Form Study Title Subject’s Initials e.g. Subject’s Name/ Date of Birth / Age Consent Statements with initials ina) Signature (or Thumb impression) of the Subjectb) Legally Acceptable Representative Signature of the Investigator Study Investigator’s Name Signature of the Witness Name of the Witness 6/1/2012
    34. 34. Appendix VI- FDC’sCombination therapy with two or more agents having complementary mechanisms of action is an example of incremental innovation that may extend the range of therapeutic options in the treatment of almost every human diseaseData requirements of Fixed Dose CombinationsFixed Dose combinations (FDC) fall into four groups and their data requirements accordingly. The first group of FDC includes those in which one or more of the active ingredients is a new drug. The second group of FDC includes those in which active ingredients already approved/marketed . The third group of FDC includes those which are already marketed 6/1/2012
    35. 35. Appendix VII Undertaking By The Investigator1) Full name, address and title of the Principal Investigator2) Name and address of the medical college, hospital or other facility where the clinical trial will be conducted: Education, training &experience that qualify the Investigator for the clinical trial (Attach details including Medical Council registration number, and / any other statement of qualification3) Name and address of all clinical laboratory facilities to be used in the study.4) Name and address of the Ethics Committee ,responsible for approval and continuing review of the study.5) Names of the other members of the research team (Co- or sub-Investigators) who will be assisting the Investigator in the conduct of the investigation.
    36. 36. VII.2 Commitments by The Investigator a. Study not to begin until EC / DCGI approval b. Adherence to protocol c. Personal supervision d. Ensure requirements of IC and EC review e. Report of AE to sponsor f. Understanding of investigator’s brochure g. Ensure that all associates, colleagues and employees suitably qualified and experienced and aware of their obligations h. Report all unexpected serious adverse events to the Sponsor in 24 hrs and EC within 7 days. i. Maintenance of records and availability for audits / sponsor inspection / EC and DCGI. Cooperation in 6/1/2012 audits
    37. 37. Appendix VIII ETHICS COMMITTEE COMPOSITION ICH GCP Indian GCP Schedule-Y• At least 5 members. •Fairly small (5-7 •At least 7 members.•At least 1 member - members).nonscientific area. • 1 member from non- •Not Explained.•Quorum members scientific area •The quorum shouldnumber not detailed. have at least 5 •The quorum should have a members.•Maximum number is minimum of 5 members. •Maximum number isnot detailed. not detailed. •12 to 15 is the maximum•Not recommended. recommended number. •Not recommended. •Member Secretary belongs to the same Institution. 6/1/2012
    38. 38. Appendix IX- Stability testing of NewDrugs Stability testing is to be performed to provide evidence on how the quality of a drug substance or formulation varies with time under the influence of various environmental factors such as- a. Temperature b. Humidity and c. Light Objective. - To establish shelf life for the formulation and recommended storage conditions.6/1/2012
    39. 39. STABILITY TESTINGStress testing of the drug substance should be conducted to identify-a. The degradation pathwaysb. Evaluate the intrinsic stability of the molecule andc. Validate the stability indicating power of the analytical procedures used.Stress testing may generality be carried out on a single batch of the drug substance. It should include the effect of- Temperature, humidity, oxidation, photolysis on the drug substance.TWO TYPES OF STUDY IS DONE1)Long-term testing should cover a minimum of 12 months’ duration on at least three primary batches of 6/1/2012
    40. 40. STABILITY TESTING2)Accelerated testing should cover a minimum of 6 months duration at the time of submission.Study conditions for drug substances and formulations intended to be stored under general conditions.Study conditions and Duration of studyi)Long term 30 C 2 C/65% RH 5%RH 12 monthsii)Accelerated 40 C 2 C/75% RH 5% RH 6 monthsIf at any time during 6 months’ testing under the accelerated storage condition, such changes occur then further studies are done.NOTE- The nature of the stress testing will depend on the individual drug substance and the type of formulation involved. 6/1/2012
    41. 41. Appendix X – Contents of the ProposedProtocol Title page Table of contenta) a) introductionb) Study rationalec) Study designd) Study populatione) Subject eligibilityf) Study treatmentg) AEh) Data analysisi) Undertaking by investigatorNOTE- Protocol is assigned by sponsor after getting CDA from investigator 6/1/2012
    42. 42. Appendix XI- Data Elements For Reporting SAE in aClinical Triala) Patient details(Age, sex, weight, height)b) Suspected drug( Generic name, DFD, ROA)c) Detail of SUSPECTED ADR( severity, start date, stop date, hospitalization or not)d) Details about investigator 6/1/2012
    43. 43. New Amendments on 30.06.2009CLINICAL RESEARCH ORGANISATION – REGISTRATIONThese guidelines have been approved by DTAB 1)Rule 122 DAB. – Registration of clinical research organization for conducting clinical trials. The clinical research organisation, contracted in writing by the sponsor to carry out any or all obligations transferred to it by the sponsor, shall perform such functions only, if it is duly registered, under the rules, by the Licensing Authority defined in6/1/2012
    44. 44. Schedule Y-1-Requirements and Guidelinesfor registration of clinical research 2. Criteria fororganisations Registration (I) The Clinical Research Organisation shall be under the charge of a person who is responsible for the overall activities of the organisation. He shall be thoroughly familiar with the investigational product(s), the protocol, written informed consent forms or other information provided to the subjects, the standard operative procedures by the sponsors, GCP guidelines and other rules applicable to the conduct of clinical trials. 6/1/2012 The organisation shall have adequate (ii)
    45. 45. (iii) The organisation shall ensure that the trials are adequately monitored and the trial related responsibilities transferred to it, partially or fully, by the sponsor are discharged effectively and efficiently.(iv) The organisation shall implement quality assurance and quality control as per standard operative procedures designed for the purpose. Such SOPs shall be well documented.6/1/2012
    46. 46. New Amendments on 18th Nov.20111)Rule 122-DAB- compensation during injury or death duringclinical trialIn case of injury in clinical trial the compensation is based asper the recommendation of EC/IRB , it may be financial ormedical.2) In case of death his/her legal heirs are entitled for thefinancial compensation, subject to the confirmation to EC6/1/2012
    47. 47. Conclusion With the Schedule Y, 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 worldwide6/1/2012
    48. 48. ReferencesGupta S.K, Basic principles of Clinical research and Methodology, 2007. 6/1/2012
    49. 49. QUERIES????6/1/2012

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