Schedule y -_priti_gupta


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Schedule y -_priti_gupta

  1. 1. By : - Priti Puneet Gupta
  5. 5. <ul><li>122-A Application for permission to import new drug </li></ul><ul><li>122-B Application for approval to manufacture new drug </li></ul><ul><li>122-C Deleted </li></ul><ul><li>122-D Permission to import or manufacture FDC </li></ul><ul><li>122-DA Permission to conduct clinical trials for New Drug / Investigational New Drug </li></ul><ul><li>122-DAA Clinical Trial Definitions </li></ul><ul><li>122-E New Drug Definitions </li></ul>
  6. 6. <ul><li>1940 - Drugs and Cosmetic Act </li></ul><ul><li>1985 - Narcotic drugs and psychotropic substances act </li></ul><ul><li>2000 - Ethical guidelines for biomedical research on human subjects, ICMR </li></ul><ul><li>2001 - Indian GCP guidelines </li></ul><ul><li>2002 - Amendment to D & C act </li></ul><ul><li>2005 - Revised schedule Y </li></ul><ul><li>Guidelines for pre-clinical data for r- DNA vaccines, diagnostics & biological, DBT </li></ul><ul><li>Draft guidelines for stem cell research/ regulation </li></ul>
  7. 7. 1.        Application for permission 2. Clinical trials 1)       Approval for clinical trails 2)       Responsibility of sponser 3)       Responsibility of investigator 4)       Informed consent- new 5)       Responsibility of ethics committee - new 6) human pharmacology (phase I) 7) therapeutic exploratory trials (pahse II) 8) therapeutic exploratory trials (phase III) 9) post marketing trials (pahse IV) - new 3. studies in special population 1) geriatric 2) pediatric 3) pregnant or nursing women 4) post marketing surveillance 5) special studies (BA/BE studies) - new 1.        Clinical trials 1.1 nature of clinical trials 1.2 permission for trials 1.3 responsibility of sponser/ investigator       5) human clinical pharmacology (phase 1) 6) exploratory trials (phase II) 7) confirmatory trials (phase III)   8) special studies       12) post marketing surveillance   old
  8. 8. revised data to be submitted along with the application to conduct clinical trial/ import/ manufacture of new drug for marketing in country 2.1 information on active ingredient 2.2 physicochemical data 2.3 analytical data - new 2.4 complete monograph specification 2.5 validation - new 2.7 data on formulation 3.4 safety pharmacology - new 4.3 male fertility studies - new 4.6 allergenicity/ hypersensitivity 11 sample and testing protocols older data required to be submitted with application to for permission to market a new drug 2.3 specifications of active and inactive ingedients 2.1 physicochemical proportion   2.4 tests of identification of active ingedients and method of its assay   2.2 and 2.5       sample with testing protocol
  9. 9. <ul><li>122-DAA </li></ul><ul><ul><li>“ Clinical trial” means a systematic study of new drug(s) in human subject(s) to generate data for discovering and / or verifying the clinical, pharmacological (including pharmacodynamic and pharmacokinetic) and /or adverse effects with the objective of determining safety and / or efficacy of the new drug. </li></ul></ul>
  10. 10. <ul><li>New chemical entity or a product having therapeutic indication but which has never been earlier tested on human beings </li></ul>
  12. 12. <ul><li>Implementing and maintaining quality assurance systems - Good Clinical Practice (GCP) Guidelines issued by CDSCO, INDIA. </li></ul><ul><li>Sponsors are required to submit a status report on the clinical trial to the Licensing Authority at the prescribed periodicity (annual). </li></ul><ul><li>In case of studies prematurely discontinued for any reason including lack of commercial interest in pursuing the new drug application, a summary report should be submitted within 3 months . The summary report should provide a brief description of the study, the number of patients exposed to the drug, dose and duration of exposure, details of adverse drug reactions and the reason for discontinuation of the study or non-pursuit of the new drug application. </li></ul><ul><li>Any unexpected serious adverse event (SAE) (as defined in GCP Guidelines) 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 </li></ul>
  13. 13. <ul><li>Responsible for the conduct of the trial according to the protocol and the GCP Guidelines and also for compliance. </li></ul><ul><li>Standard operating procedures are required to be documented by the investigators for the tasks performed by them. </li></ul><ul><li>Ensure that adequate medical care is provided to the participant for any adverse events. </li></ul><ul><li>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. </li></ul>
  14. 14. <ul><li>Safeguard the rights, safety and well being of all trial subjects. </li></ul><ul><li>Particular care to protect the rights, safety and well being of all vulnerable subjects. </li></ul><ul><li>Obtain ‘standard operating procedures’ and maintain a record. </li></ul><ul><li>Ongoing review based on periodic study progress reports. </li></ul><ul><li>In case an ethics committee revokes its approval it must record the reasons for doing so and at once communicate such a decision to the Investigator as well as to the Licensing Authority. </li></ul>
  16. 16. Ministry of Chem & Fertilizers NPPA National Pharmaceutical Pricing Authority Pricing Regulations Ministry of Sci & Tech DBT Department of Biotechnology Ministry of Enviro Additional Secretary State Drug Regulatory Authority :FDA GEAC Genetic Engineering Approval Committee DCGI Drug Controller General of India DGHS Director General of Health Services Health Secretary Ministry of Health CDL/CDTL Gov. Drug Testing Laboratories REGULATORY AUTHORITIES
  17. 17. <ul><li>APPLICATION FORM 44 </li></ul><ul><li>Imp ff </li></ul><ul><li>Imp rm </li></ul><ul><li>Mfg ff </li></ul><ul><li>Mfg rm </li></ul><ul><li>CT </li></ul>NOC FOR CT + Test Licence for Import APPLICATION FORM 46 A (MFG RM) APPROVAL FORM 46 (MFG FF) APPROVAL FORM 45 A (IMP RM) APPROVAL FORM 45 (IMP FF)
  18. 18. <ul><li>Import ff/ Mfg ff/ Import bulk + Mfg ff = Rs 50,000/- </li></ul><ul><li>of new drug </li></ul><ul><li>Application by same applicant, = Rs 15,000/- </li></ul><ul><li>for modified dosage form or with new claim </li></ul><ul><li>Secondary applicants after 1 = Rs 15,000/- </li></ul><ul><li>year of approval </li></ul><ul><li>Import / Mfg FDC = Rs 15,000/- </li></ul><ul><li>Conduct Clinical trial with ND/IND </li></ul><ul><ul><li>Phase I = Rs 50,000/- </li></ul></ul><ul><ul><li>Phase II = Rs 25,000/- </li></ul></ul><ul><ul><li>Phase III = Rs 25,000/- </li></ul></ul><ul><ul><li>No separate fee to be paid along with application for import / mfg based on successful completion </li></ul></ul>
  19. 19. <ul><li>FORM 44 </li></ul><ul><li>(See Rules 122A, 122B, 122D and 122DA) </li></ul><ul><li>Application for grant of permission to import or manufacture a New Drug or to undertake clinical trial </li></ul><ul><li>I/We..……….. of ……….. , hereby apply for grant of permission for import and / or clinical trial or for approval to manufacture of a new drug or fixed dose combination or subsequent permission of already approved new drug. The necessary information / data is given below : </li></ul><ul><li>1. Particulars of New Drug : </li></ul><ul><ul><li>Name of the drug : </li></ul></ul><ul><ul><li>Dosage Form : </li></ul></ul><ul><ul><li>Composition of the formulation : </li></ul></ul><ul><ul><li>Test specifications : </li></ul></ul><ul><ul><ul><li>Active ingredients : </li></ul></ul></ul><ul><ul><ul><li>Inactive ingredients : </li></ul></ul></ul><ul><ul><li>Pharmacological classification of the drug : </li></ul></ul><ul><ul><li>Indications for which proposed to be used : </li></ul></ul><ul><ul><li>Manufacturer of the raw material : </li></ul></ul><ul><ul><li>Patent status : </li></ul></ul>
  20. 20. <ul><li>Data submitted along with the application </li></ul><ul><li>A Permission to market new drug </li></ul><ul><li>Chemical and Pharmaceutical information </li></ul><ul><li>Animal Pharmacology </li></ul><ul><li>Animal Toxicology </li></ul><ul><li>Human / Clinical Pharmacology </li></ul><ul><li>Exploratory Clinical Trials </li></ul><ul><li>Confirmatory Clinical Trials </li></ul><ul><li>Bioavailability / dissolution and stability data </li></ul><ul><li>Regulatory status in other countries </li></ul><ul><li>Marketing information : </li></ul><ul><ul><li>(a) Proposed product monograph </li></ul></ul><ul><ul><li>(b) Drafts of labels and cartons </li></ul></ul><ul><li>Application for test licence : </li></ul>
  21. 21. <ul><li>B Subsequent approval / permission for manufacture of already approved new drug </li></ul><ul><li>Formulation : </li></ul><ul><ul><li>Bioavailability / bioequivalence </li></ul></ul><ul><ul><li>Name of the investigator / centre </li></ul></ul><ul><ul><li>Source of raw mat and stability </li></ul></ul><ul><li>b) Raw Material </li></ul><ul><ul><li>Manufacturing Method </li></ul></ul><ul><ul><li>QC parameters, specs, stability </li></ul></ul><ul><ul><li>Animal toxicity </li></ul></ul><ul><li>C Approval / permission for FDC </li></ul><ul><li>Justification </li></ul><ul><li>PK / PD data </li></ul><ul><li>Any other data </li></ul>
  22. 22. <ul><li>D Subsequent approval or approval for new indication – new dosage form : </li></ul><ul><ul><ul><li>Number and date of Approval already granted </li></ul></ul></ul><ul><ul><ul><li>Justification </li></ul></ul></ul><ul><ul><ul><li>Data on safety, efficacy and quality </li></ul></ul></ul><ul><ul><ul><li>A total fee of Rs………………… has been credited to the Government under the Head of Account …… (receipt enclosed) </li></ul></ul></ul><ul><ul><ul><li>Signature </li></ul></ul></ul><ul><ul><ul><li>Designation </li></ul></ul></ul><ul><ul><ul><li>Date </li></ul></ul></ul>
  23. 23. <ul><li>HUMAN CLINICAL PHARMACOLOGY :- </li></ul><ul><li>Phase I (Human Pharmacology) – Safety and Tolerability with the initial administration of IND – MTD, Kinetics and Dynamics </li></ul><ul><li>Phase II (Therapeutic Exploratory Trials) – Effectiveness for a particular indication, small group </li></ul><ul><li>Phase III (Therapeutic Confirmatory Trials) – Therapeutic benefit in large number of patients </li></ul><ul><li>Phase IV (Post Marketing Trials) – Related to approved indication </li></ul>
  24. 24. <ul><li>HUMAN CLINICAL PHARMACOLOGY :- </li></ul><ul><li>for new drug substances discovered in India : Data from Phase I </li></ul><ul><li>for new drug substances discovered in countries other than India : Phase I data generated outside India, permission may be granted for Phase II trials and subsequently Phase III trials concurrently with other global trials </li></ul><ul><li>Application for permission to initiate specific phase of clinical trial should also accompany Investigator’s brochure, proposed protocol, case record form, study subject’s informed consent document(s) investigator’s undertaking and ethics committee clearance, if available </li></ul><ul><li>Sample size depends on type of study </li></ul><ul><li>EC application can be in parallel to DCGI application </li></ul><ul><li>Drugs indicated in life-threatening, serious disease or diseases of special relevance to Indian health scenario, toxiciological / clinical data abbreviated, deferred or omitted </li></ul><ul><li>Amendments notified to DCGI and EC within 30 days and approval obtained </li></ul>
  25. 25. <ul><li>PSUR :- </li></ul><ul><li>New drugs should be closely monitored for their clinical safety; submission of Periodic Safety Update Reports (PSURs) in order to- </li></ul><ul><li>report all the relevant new information (patient exposure) </li></ul><ul><li>summarize the market authorization status in different countries and any significant variations related to safety; and </li></ul><ul><li>indicate whether changes should be made to product information </li></ul><ul><li>  </li></ul><ul><li>  </li></ul><ul><li>PSURs shall be submitted every 6 months for the first two years after approval </li></ul><ul><li>For subsequent two years – the PSURs need to be submitted annually </li></ul><ul><li>PSURs due for a period must be submitted within 30 calendar days of the last day of the reporting period. </li></ul><ul><li>  </li></ul>
  26. 26. PSUR Structure:- (a) A title page stating: Periodic safety update report for the product, applicant’s name, period covered by the report, date of approval of new drug, date of marketing of new drug and date of reporting; (b) Introduction, (c) Current worldwide market authorization status, (d) Update of actions taken for safety reasons, (e) Changes to reference safety information, (f) Estimated patient exposure, (g) Presentation of individual case histories, (h) Studies, (i) Other information, (j) Overall safety evaluation, (k) Conclusion, (l) Appendix providing material relating to indications, dosing, pharmacology and other related information.
  27. 27. <ul><li>DRAFTS OF LABEL AND CARTONS :- </li></ul><ul><li>Should comply with Rules 96 and 96 of the D&C Rules, 1945 </li></ul><ul><li>After Approval no changes in the package insert shall be effected without such changes being approved </li></ul>
  28. 28. <ul><li>BE / BA </li></ul><ul><li>For drugs approved elsewhere in the world and absorbed systemically, bioequivalence with the reference formulation should be carried out. </li></ul><ul><li>Evaluation of the effect of food </li></ul><ul><li>  </li></ul><ul><li>(iii) Dissolution and bioavailability data to be submitted   </li></ul><ul><li>   </li></ul><ul><li>(iv) All bioavailability and bioequivalence studies should be conducted according to the Guidelines for Bioavailability and Bioequivalence studies as prescribed (ICMR guidelines </li></ul>
  29. 29. <ul><li>Application : </li></ul><ul><li>Form 12 application </li></ul><ul><li>Material Justification Plan </li></ul><ul><li>Treasury Challan of Rs 100 for first drug, followed by Rs 50 for additional drug </li></ul><ul><li>Test Licence obtained in FORM 11 </li></ul>
  30. 30. <ul><li>APPENDICE OF SCHEDULE Y </li></ul>
  31. 31. Appendix-I : Data to be submitted along with the application to conduct clinical trial/ import/ manufacture of new drugs for marketing in country Appendix- IA : 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 Appendix – II : Structure, contents and format for clinical study reports Appendix – III : Animal toxicology Appendix – IV : Animal pharmacology Appendix – V : Informed consent Appendix – VI : Fixed dose combinations (FDC) Appendix –VII : Undertaking by investigator Appendix – VIII : Ethics committee Appendix – IX : Stability testing of new drugs Appendix – X : contents of the proposed protocol for conducting clinical trials Appendix – XI : data elements for reporting SAE occurring in clinical trials
  32. 32. 1.    Introduction <ul><li>2.   Chemical and pharmaceutical information </li></ul><ul><li>Information on active ingredients </li></ul><ul><li>Physicochemical Data </li></ul><ul><li>Analytical Data </li></ul><ul><li>Complete monograph specification including </li></ul><ul><li>Validations </li></ul><ul><li>Stability Studies </li></ul><ul><li>Data on Formulation </li></ul>
  33. 33. 1.Title Page: Protocol code, name of the investigational product tested, development phase, indication studied, a brief description of the trial design, the start and end date of patient accrual, names of the Sponsor and the participating Institutes (Investigators).   2. Study Synopsis (1 to 2 pages): summarize important conclusions   3. Statement of compliance with the ‘Guidelines for Clinical Trials on Pharmaceutical Products in India – GCP Guidelines’ issued by CDSCO.   4. List of Abbreviations and Definitions   5.Table of contents   6.Ethics Committee: Study conducted in accordance with the ethical principles of Declaration of Helsinki. A detailed description of the Ethics Committee constitution and date(s) of approvals of trial documents for each of the participating sites should be provided. A declaration should state that EC notifications as per Good Clinical Practice Guidelines issued by Central Drugs Standard Control Organization and Ethical Guidelines for Biomedical Research on Human Subjects, issued by Indian Council of Medical Research have been followed.  
  34. 34. 7. Study Team: Administrative structure of the study (Investigators, site staff, Sponsor/ designates, Central laboratory etc.).   8. Introduction: Description of the product development rationale 9.Study Objective: Overall purpose of the study, primary and secondary objectives   10.Investigational Plan: Trial design, the Subject selection criteria, the treatment procedures, blinding / randomization techniques if any, allowed/ disallowed concomitant treatment, the efficacy and safety criteria assessed, the data quality assurance procedures and the statistical methods planned for the analysis of the data obtained.   11.Trial Subjects : Enumerate the patients screened, randomized, and prematurely discontinued. State reasons for premature discontinuation of therapy in each applicable case.   12. Efficacy evaluation : Results
  35. 35. 13. Safety Evaluation : Complete list 13.1 all serious adverse events, whether expected or unexpected and 13.2 unexpected adverse events whether serious or not 14. Discussion and overall Conclusion 15. List of References   16. Appendices a. Protocol and amendments b. Specimen of Case Record Form c. Investigators’ name with contact addresses, phone, email d. Patient data listings e. List of trial participants treated with investigational product f. Discontinued participants g. Protocol deviations h. CRFs of cases involving death / life threatening AE cases i. Publications from the trial j. Important publications referenced in the study k. Audit certificate, if available l. Investigator’s certificate on accuracy of the study
  36. 36. <ul><li>Toxicity studies to comply with GLP </li></ul><ul><li>Systemic Toxicity Studies </li></ul><ul><ul><li>Single dose ( 2 rodent species); 2g/kg or 10 times dose in humans – 14 days observation; Minimum lethal dose / Maximum tolerated dose </li></ul></ul><ul><ul><li>Repeated dose (2 mammalian species, 1 non-rodent); administration for 7 days) </li></ul></ul><ul><li>Dose Ranging Study : Identify target organ and establish MTD </li></ul><ul><li>Male Fertility Study </li></ul><ul><li>Female Reproduction and Developmental Toxicity Study </li></ul>
  37. 37. <ul><li>Perinatal study </li></ul><ul><li>Local toxicity – Dermal, vaginal, rectal, ocular, inhalation </li></ul><ul><li>Allergenicity / hypersensitivity </li></ul><ul><li>Genotoxicity </li></ul><ul><li>Carcinogenicity </li></ul>
  38. 38. <ul><li>Cardiovascular System </li></ul><ul><li>Central Nervous System </li></ul><ul><li>Respiratory System </li></ul><ul><li>Follow up and Supplemental Safety Pharmacology </li></ul>
  39. 39. <ul><li>Essential Elements: </li></ul><ul><li>Study involves research and its purpose </li></ul><ul><li>Expected duration of participation </li></ul><ul><li>Description of the procedures </li></ul><ul><li>Description of foreseeable risks or discomforts </li></ul><ul><li>Description of any benefits to subject / mankind </li></ul><ul><li>Alternative procedures or therapies </li></ul><ul><li>Statement describing confidentiality of records </li></ul><ul><li>Trial treatment schedule(s) </li></ul><ul><li>Compensation and/or treatment(s) in the event of a trial-related injury </li></ul><ul><li>Whom to contact, rights of Subjects and in the event of any injury </li></ul><ul><li>anticipated prorated payment, if any, to the Subject for participating in the trial </li></ul><ul><li>Subject's responsibilities </li></ul><ul><li>Voluntary participation, no penalty or loss of benefits to which the Subject is otherwise entitled </li></ul>
  40. 40. <ul><li>Additional elements, which may be required </li></ul><ul><li>Foreseeable circumstances under which the Subject's </li></ul><ul><li>Participation may be terminated without the Subject's consent </li></ul><ul><li>  Additional costs to the Subject </li></ul><ul><li>Consequences to withdraw from the research and procedures for orderly termination   </li></ul><ul><li>Notification in a timely manner if significant new findings develop which may affect the Subject's willingness to continue participation </li></ul><ul><li>  Particular treatment or procedure may involve risks to the Subject (or to the embryo or fetus, if the Subject is or may become pregnant), which are currently unforeseeable </li></ul><ul><li>  Approximate number of Subjects enrolled in the study </li></ul>
  41. 41. FORMAT – See Word file
  42. 42. Fixed Dose Combinations refer to products containing one or more active ingredients used for a particular indication(s).  
  43. 43. <ul><li>GROUP 1 : One or more of the active ingredients is a new drug. </li></ul><ul><li>Marketing data will be similar to data required for any new drug (including clinical trials) </li></ul><ul><li>  </li></ul>
  44. 44. <ul><li>GROUP 2 : Active ingredients already approved/marketed individually, combined for the first time, for a particular claim and where the ingredients are likely to have significant interaction of a pharmacodynamic or pharmacokinetic nature </li></ul><ul><li>If Marketed abroad : </li></ul><ul><li>Clinical trial reports of other countries </li></ul><ul><li>Regulatory status in other countries </li></ul><ul><li>If not Marketed abroad : </li></ul><ul><li>Chemical and pharmaceutical data will be submitted - chemical and pharmaceutical data, stability of the proposed dosage form </li></ul><ul><li>  Clinical trials (pharmacological, toxicological and clinical data on the individual ingredients along with the rationale for combining them in the proposed ratio. Acute toxicity data (LD 50) and pharmacological data should be submitted on the individual ingredients as well as their combination in the proposed ratio. </li></ul><ul><li>  </li></ul>
  45. 45. GROUP 3 : Already marketed, but in which it is proposed either to change the ratio of active ingredients or to make a new therapeutic claim. For such FDCs, the appropriate rationale including published reports (if any) should be submitted to obtain marketing permission. Permission will be granted depending upon the nature of the claim and data submitted.  
  46. 46. GROUP4 : Individual active ingredients (or drugs from the same class) have been widely used in a particular indication(s) for years, their concomitant use is often necessary and no claim is proposed to be made other than convenience. It will have to be demonstrated that the proposed dosage form is stable and the ingredients are unlikely to have significant interaction of a pharmacodynamic or pharmacokinetic nature.   No additional animal or human data are generally required for these FDCs, and marketing permission may be granted if the FDC has an acceptable rationale.  
  47. 47. <ul><li>1. Full name, address, title </li></ul><ul><li>  </li></ul><ul><li>2. Name / address of medical college, hospital or other facility where the clinical trial will be conducted. Education, training & experience, qualification and MCR number </li></ul><ul><li>  </li></ul><ul><li>3. Name / address of clinical laboratory facilities </li></ul><ul><li>  </li></ul><ul><li>Name / address of the Ethics Committee </li></ul><ul><li>  </li></ul><ul><li>Names of other members of the research team </li></ul><ul><li>  </li></ul><ul><li>6. Protocol Title and Study number (if any) of the clinical trial to be conducted by the Investigator. </li></ul><ul><li>  </li></ul>
  48. 48. <ul><li>At least seven members </li></ul><ul><li>Should appoint Chairperson (who is from outside the institution) and a Member Secretary.   </li></ul><ul><li>Quorum at least 5 members with the following representations: </li></ul><ul><li>basic medical scientists (preferably one pharmacologist). </li></ul><ul><li>clinicians </li></ul><ul><li>legal expert </li></ul><ul><li>social scientist / representative of NGO voluntary agency /philosopher / ethicist / theologian or a similar person </li></ul><ul><li>lay person from the community. </li></ul><ul><li>  </li></ul><ul><li>Must include at least one non-scientific member and at least one member who is independent of the institution / trial site. </li></ul><ul><li>Appropriate gender representation on the Ethics Committee.   </li></ul><ul><li>EC members who are independent of trial and sponsor should vote / provide opinion in matters related to the study. </li></ul>
  49. 49. Refer Word Doc for EC approval format
  50. 50. <ul><li>Evidence on how the quality of a drug substance or formulation varies with time under the influence of various environmental factors </li></ul><ul><li>To establish shelf life for the formulation / recommended storage </li></ul><ul><li>Validated stability-indicating analytical procedures   </li></ul><ul><li>  </li></ul><ul><li>Stress testing of the drug substance on single batch to identify degradation products </li></ul><ul><li>Photostability on at least one primary batch of the drug substance as well as the formulation, </li></ul>Pilot Batch : 1/10 th of commercial / production batch Primary Batch : Batch used in stability study for registration / establish shelf life.
  51. 51. Study Study conditions Duration   Long term 30°C ± 2°C/65% RH ± 5% RH 12 months Accelerated 40°C ± 2°C/75% RH ± 5% RH 6 months   If at any time during 6 months’ testing under the accelerated storage condition, such changes occur that cause the product to fail in complying with the prescribed standards, additional testing under an intermediate storage condition should be conducted and evaluated against significant change criteria.
  52. 52. Pdt intended to be stored in a refrigerator   Study Study conditions Duration of study   Long term 5°C ± 3°C 12 months Accelerated 25°C ± 2°C/60% RH ± 5% RH 6 months     Pdt intended to be stored in a freezer   Study Study conditions Duration of study   Long term - 20°C ± 5°C 12 months     Pdts for storage below -20°C shall be treated on a case-by-case basis.  
  53. 53. <ul><li>1. Title Page </li></ul><ul><li>a. Full title </li></ul><ul><li>b. Protocol / Study number, and protocol version number with date </li></ul><ul><li>c. The IND name/number of the investigational drug </li></ul><ul><li>d. Complete name and address of the Sponsor and CRO </li></ul><ul><li>e. List of the Investigators, institutional affiliations and site locations </li></ul><ul><li>f. Name(s) of clinical laboratories and/or facilities participating in study. </li></ul><ul><li>  </li></ul><ul><li>2. Table of Contents </li></ul><ul><li>3. Background and Introduction </li></ul><ul><ul><ul><ul><ul><li>Preclinical experience </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Clinical experience </li></ul></ul></ul></ul></ul><ul><li>4. Study Rationale </li></ul><ul><li>  </li></ul><ul><li>5. Study Objective(s) </li></ul><ul><li>  </li></ul><ul><li>6. Study Design </li></ul><ul><li>  </li></ul>
  54. 54. <ul><li>Study Population </li></ul><ul><li>Subject Eligibility </li></ul><ul><ul><li>Inclusion Criteria </li></ul></ul><ul><ul><li>Exclusion Criteria </li></ul></ul><ul><li>9.Study Assessments </li></ul><ul><li>10. Study Conduct </li></ul><ul><li>11.Discontinued Subjects </li></ul><ul><li>12.Study Treatment (Dosing Schedule, Drug supplies, administration, dose modification, possible drug interactions, concomitant therapy, blinding / unblinding procedures) </li></ul>
  55. 55. <ul><li>13. Adverse Events </li></ul><ul><li>14. Ethical Considerations (Risk/benefit assessment, EC review and communications, Informed consent process, Statement of Subject confidentiality including ownership of data and coding procedures) </li></ul><ul><li>15. Study Monitoring and Supervision </li></ul><ul><li>16. Investigational Product Management </li></ul><ul><li>Data Analysis </li></ul><ul><li>Undertaking by the Investigator  </li></ul><ul><li>Appendices (Study synopsis, patient information sheet, informed consent form, CRF, other data collection forms, a summary of relevant pre-clinical safety information and any other documents referenced) </li></ul>
  56. 56. 1. Patient Details Initials & other relevant identifier (hospital/OPD record number etc.) Gender Age and/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 and regimen (specify units - e.g., mg, ml, mg/kg) Route of administration Starting date and time of day Stopping date and time, or duration of treatment   3 . Other Treatment(s) Provide the same information for concomitant drugs (including non prescription/OTC drugs) and non-drug therapies, as for the suspected drug(s).   4. Details of Suspected Adverse Drug Reaction(s) Full description of reaction(s) including body site and severity, as well as the criterion (or criteria) for regarding the report as serious. In addition to a description of the reported signs and symptoms, whenever possible, describe a specific diagnosis for the reaction.*
  57. 57. <ul><li>Start date (and time) of onset of reaction </li></ul><ul><li>Stop date (and time) or duration of reaction </li></ul><ul><li>Dechallenge and rechallenge information </li></ul><ul><li>Setting (e.g., hospital, out-patient clinic, home, nursing home) </li></ul><ul><li>  </li></ul><ul><li>5. Outcome </li></ul><ul><li>Information on recovery and any sequelae; results of specific tests and/or treatment that may have been conducted </li></ul><ul><li>For a fatal outcome, cause of death and a comment on its possible relationship to the suspected reaction; Any post-mortem findings. </li></ul><ul><li>  </li></ul><ul><li>6. Details about the Investigator </li></ul><ul><li>Name </li></ul><ul><li>Address </li></ul><ul><li>Telephone number </li></ul><ul><li>Profession (specialty) </li></ul><ul><li>Date of reporting the event to Licensing Authority: </li></ul><ul><li>Date of reporting the event to Ethics Committee overseeing the site: </li></ul><ul><li>  Signature of the Investigator </li></ul>
  58. 58. <ul><li>LOOPHOLES AND FURTHER REFINEMENT </li></ul>
  59. 59. <ul><li>New Drug remains to be New Drug for 4 years. Phase IV trials require permission? Approved drug and approved indication need not require permission </li></ul><ul><li>Unmet medical needs also to be added for CT waiver </li></ul><ul><li>All clinical trial supplies to be included in FORM 11 </li></ul><ul><li>Approvals of Amendments could be a problem </li></ul><ul><li>SOPs for investigators and documentation of tasks – templates required </li></ul><ul><li>EC chairperson outside institute is a rarity </li></ul>
  60. 60. <ul><li>SUSARS within 15 calendar days (Suspected unexpected serious adverse event). 24 hour timeline for reporting to sponsor required. </li></ul><ul><li>PSURs instead of PMS data for new drug. International PSURs to be accepted </li></ul><ul><li>Appendix IA minimal data, exhaustive specs demanded from Innovator (Appendix I) ; not useful for differentiation with generic </li></ul><ul><li>Comparative evaluation to be omitted in Appendix 1 </li></ul><ul><li>Requirement to support data protection </li></ul>