schedule y Presentation Transcript

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1. BY SAIDULU& SHIVA DEEPTHI CLINCAL PHARMACOLOGY DEPARTMENT 2. Requirements and guidelines for permission to import and/ or manufacture of new drugs for sale or to undertake clinical trials To3. frame guidelines for conduct of clinical research control and regulation for new drugs CDSCO and DTAB formulated GCP under schedule y in 2005 4. It shall made in Form 44 accompanied with the following data in accordance with appendices, namely Clinical and pharmaceutical information Animal pharmacology data Animal Toxicology data Human Clinical pharmacology data Regulatory status in other countries Prescribing information FORM 12- To import Study drug for examination , test or analysis 5. Definition: Any investigation in human subjects intended to discover or verify the clinical, pharmacological, and/ or other Pharmacodynamics effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. 6.   CT on a New drug shall be initiated only after permission by licensing authority and approval from EC. All trial Investigator(s) should possess appropriate qualifications, training and experience and should have access to such investigational and treatment facilities as are relevant to the proposed trial protocol. A qualified physician who is an investigator or a sub-investigator for the trial, should be responsible for all trial-related medical decisions. 7.  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. Laboratories used for generating data for clinical trials should be compliant with Good Laboratory Practices. 8.  No deviations to the protocol should be implemented without prior written approval of the ethics committee and the Licensing Authority except when it is necessary to eliminate immediate hazards to the trial. Administrative and/or logistic changes in the protocol should be notified to the Licensing Authority within 30 days. 9. Definition of Sponsor: An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. 10.   Sponsors are required to submit a status report on the clinical trial to the Licensing Authority at the prescribed periodicity. Implementing and maintaining quality assurance systems -Good Clinical Practice (GCP) Guidelines issued by CDSCO, INDIA. 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. 11.  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. The summary report should provide a brief description of the study, the number of patients

and dated informed consent form. an unconscious person or a minor or those suffering from severe mental illness or disability). 18. safety and well being of all trial subjects. and wellbeing of human subjects involved in a trial by.         exposed to the drug. Where a subject is not able to give informed consent (e. the same may be obtained from a legally acceptable representative. and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects. The Investigator must provide information about the study verbally as well as using a patient information sheet. dose and duration of exposure. 15. Informed consent is documented by means of a written. Definition: An independent body constituted of medical.   In all trials.g. 16. approving. Investigator 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 occurrences. reviewing. details of adverse drug reactions and the reason for discontinuation of the study or non-pursuit of the new drug application 12. in a language that is non-technical and understandable by the study subject. 13. Standard operating procedures are required to be documented by the Investigators for the tasks performed by them. informed written consent is required to be obtained from each study subject. Responsible for the conduct of the trial according to the protocol and the GCP Guidelines.an impartial witness should be present during the entire informed consent process who must append his/her signatures to the consent form.   Any changes in the informed consent documents should be approved by the ethics committee and submitted to the Licensing Authority before such changes are implemented. Definition: A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial. among other things. 17. after having been informed of all aspects of the trial that are relevant to the subject's decision to participate. safety. 20.  Ensure that adequate medical care is provided to the participant for any adverse events.  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). scientific. If the Subject or his/her legally acceptable representative is unable to read/write . and nonscientific members.   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 . a freely given. signed.     Reviews and its approval to a trial protocol to safeguard the rights. Particular care to protect the rights. whose responsibility it is to ensure the protection of the rights. 14. Studies in this Phase of development usually have non-therapeutic objectives and conducted in healthy volunteers subjects or certain types of patients. and providing continuing review of trials. 19. safety and well being of all vulnerable subjects Obtain ‘Standard Operating Procedures’ and maintain a record Ongoing review based on periodic study progress reports 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. of protocols and amendments. 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.   Definition: A person responsible for the conduct of the clinical trial at a trial site.

safety considerations. Licensing Authority may require pharmacokinetic studies to be undertaken to verify that the data generated in Indian population is in conformity with the data already generated abroad.e. evaluations should be made in the appropriate age group. 29.   Pharmacokinetics. i. patients with renal or other organ systems failure. When clinical development is . and the efficacy and safety of available treatments . therapeutic regimens (including concomitant medications) and target populations for further studies in Phase II or III. Phase III studies needs to be carried out primarily to generate evidence of efficacy and safety of the drug in Indian patients.   Phase III studies 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. and those on specific concomitant medication is required to be submitted if relevant to the clinical profile of the drug and its anticipated usage pattern. 27. efficacy and dose definition. For new drugs approved outside India. 25. Information supporting the use of the drug in children. 26. Drug expected to be used in children. The primary objective is demonstration or confirmation of therapeutic benefits(s).   Doses used in Phase II are usually (but not always) less than the highest doses used in Phase I. 21. the type of disease being treated. Pharmacodynamics Early Measurement of Drug Activity 22.. These trials may not be considered necessary at the time of new drug approval but may be required by the Licensing Authority for optimizing the drug’s use. characterization of a drug’s absorption. pregnant women. Additional objectives of Phase II studies can include evaluation of potential study endpoints.    Geriatric patients should be included in Phase III clinical trials (and in Phase II trials. distribution. Studies in Phase II should be conducted in a group of patients The main goal for this Phase is to determine the dose(s) and regimen for Phase III trials. if The disease intended to be treated is characteristically a disease of aging or when the new drug is likely to alter the geriatric patient’s response (with regard to safety or efficacy) compared with that of the nongeriatric patient. metabolism and excretion. If the application is for the conduct of clinical trials as a part of multi-national clinical development of the drug. Studies conducted in Phase I. elderly patients. These trials demonstrates the drug’s safety. 24. 28.         Subjects.  Prior to conduct of Phase III studies in Indian subjects. nursing women. at the Sponsor’s option) in meaningful numbers. or the population to be treated is known to include substantial numbers of geriatric patients. the number of sites and patients as well as the justification for undertaking such trials in India should be provided to the Licensing Authority along with the application. These studies should be intended to provide an adequate basis for marketing approval. usually intended to involve one or a combination of the following objectives : Maximum tolerated dose: To determine the tolerability of the dose range expected to be needed for later clinical studies and to determine the nature of adverse reactions that can be expected.   Post Marketing trials are performed after drug approval and related to the approved indication.   The primary objective of Phase II trials is to evaluate the effectiveness of a drug for a particular indication and to determine the common short-term side-effects and risks associated with the drug. 23.   Pediatric studies in the new drug development program will depend on the medicinal product.

If the new drug is intended to treat serious or life-threatening diseases. For clinical trials conduced in the paediatric population.   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. 2. Mutagenicity and Carcinogenicity.3. 36.paediatric studies should be conducted.5.6. code name or number. Acute Toxicity 4. ethical.4. 2. paediatric population should be included in the clinical trials early 31. bioequivalence with the reference formulation should be carried out . These studies may be initiated at various phases of clinical development or after post marketing surveillance in adults if a safety concern exists. if any.3. Summary 3. CHEMICAL AND PHARMACEUTICAL INFORMATION. it is usually appropriate to begin with older children before extending the trial to younger children and then infants. Pharmacokinetics 4.        to include studies in children. 2.2. clinical trial data should be generated in the pediatric population except for initial safety and tolerability data. Paediatric Subjects are legally unable to provide written informed consent. structure. nonproprietary or generic name.4. 35. occurring in both adults and paediatric patients. 2. 3. and are dependent on their parent(s)/legal guardian to assume responsibility for their participation in clinical studies. Dissolution and bioavailability data submitted with the new drug application must provide information that assures bioequivalence or establishes bioavailability All bioavailability and bioequivalence studies should be conducted according to the Guidelines for Bioavailability and Bioequivalence studies as prescribed.2. 33. Tests for identification of the active ingredient and method of its assay. clinical and psychosocial issues. For new drugs intended for use during pregnancy. Stability data 37. 30. if any. 3. Local Toxicity 4. Dosage form and its composition. 3. which will usually be obtained in adults.1. Excretion of the drug or its metabolites into human milk should be examined and the infant should be monitored for predicted pharmacological effects of the drug. 2. 1. Outline of the method of manufacture of the active ingredient. 4. 2. HUMAN/CLINICAL PHARMACOLOGY (PHASE I) 5.   Dissolution Data should be submitted for all solid oral dosage forms. 32. Summary . for which there are currently no or limited therapeutic options. follow-up data on the pregnancy.   For drugs approved elsewhere in the world and absorbed systemically. ANIMAL PHARMACOLOGY 3. foetus and child will be required.1.1. Long Term Toxicity 4. 2. physiochemical proportion. Specific pharmacological actions.  If the new drug has a potential for use in paediatric patients . INTRODUCTION A brief description of the drug and therapeutic class to which it belongs. 5. Reproduction Studies. General pharmacological actions.6. Chemical name.3. These studies should be conducted under the labeled conditions of administration. Specifications of active and inactive ingredients. the reviewing ethics committee should include members who are knowledgeable about pediatric. Summary 4.5. 34.  all paediatric participants should be informed to the fullest extent possible about the study in a language and in terms that they are able to understand. Evaluation of the effect of food on absorption following oral administration should be carried out.1.4.2.  If the new drug is for diseases predominantly or exclusively affecting pediatric patients. ANIMAL TOXICOLOGY (See Appendix III and IV) 4.

     APPENDIX III –ANIMAL TOXICOLOGY APPENDIX IV –ANIMAL PHARMACOLOGY Cardiovascular System •Central Nervous System •Respiratory System •Follow up and Supplemental Safety Pharmacology 44. Chemical name. Safety Evaluation : Complete list 13. for oral dosage form. CHEMICAL AND PHARMACEUTICAL INFORMATION. 4.). 5. 39. 9. Investigational Plan: 11. General Pharmacological effects. Table of contents 6. List of Abbreviations and Definitions 5. Test specifications. Trial Subjects 12. Investigator-wise reports.1. (a) Active ingredients. with reasons. if any.2 Draft specimen of the label and carton. Investigator-wise reports 8. with phase. Title Page: Protocol code. 4. Specific Pharmacological effects. 40. 2. name of the investigational product tested. Summary 8. MARKETING INFORMATION 3. rights of Subjects and in the event of any injury Anticipated prorated payment. Sponsor/ designates. Summary 7.3.2. Investigator-wise reports.2. whether expected or unexpected and 13. (d) Withdrawn. if any. names of the Sponsor and the participating Institutes (Investigators).1.4. structure. (b) Inactive ingredients 2. Study Synopsis (1 to 2 pages): summarize important conclusions 3.4.1.2. Bioavailability/Bioequivalance and comparative Dissolution Studies. INTRODUCTION A brief description of the drug and the therapeutic class.       5. Ethics Committee 42. 3. site staff. Bioavailability and dissolution studies.1. Statement of compliance with the ‘Guidelines for Clinical Trials on Pharmaceutical Products in India – GCP Guidelines’ issued by CDSCO.            7. 7. code name or number. Tests for identification of the active ingredients and method of its assay. 2. REGULATORY STATUS IN OTHER COUNTRIES (a) Marketed (b) Approved. Central laboratory etc.5. EXPLANATORY CLINICAL TRIALS (PHASE II) 6. Introduction: Description of the product development rationale 9. Outline of the method of manufacture of active ingredients. 6. Stability data. 2. 8. Discussion and overall Conclusion 15. 41. 5. Dosage from its composition 2. 2.3. the start and end date of patient accrual.2. SPECIAL STUDIES 8.2 unexpected adverse events whether serious or not 14. 2. if any. a brief description of the trial design. 4. primary and secondary objectives 10. CONFIRMATORY CLINICAL TRIALS (PHASE III) 7. indication studied. Study Team: Administrative structure of the study (Investigators.3. Study Objective: Overall purpose of the study.1 all serious adverse events. development phase. Appendices 43.1 Proposed package insert/promotional literature 3. Sub-acute animal toxicity studies for intravenous infusions and injectables. physiochemical properties. List of References 16. 1.2. Pharmacokinetics 38. nonproprietary or generic name. to the Subject for participating in the trial Subject's responsibilities . Efficacy evaluation: Results 13.2. if any. (c) Under trial.             Essential Elements: Study involves research and its purpose Expected duration of participation Description of the procedures Description of foreseeable risks or discomforts Description of any benefits to subject / mankind Alternative procedures or therapies Statement describing confidentiality of records Trial treatment schedule(s) Compensation and/or treatment(s) in the event of a trial-related injury Whom to contact. SPECIAL STUDIES CONDUCTED WITH APPROVAL OF LICENSING AUTHORITY 4.1. 2. Summary 6. 8.6.

Education. Study Objective(s) 6. Appropriate gender representation on the Ethics Committee.      Fixed Dose Combinations refer to products containing one or more active ingredients used for a particular indication(s).              1.clinicians 3. GROUP 1 : One or more of the active ingredients is a new drug. Quorum at least 5 members with the following representations: 1.      45.Name / address of medical college. training & experience.Name / address of the Ethics Committee 5. title 2. 47. Must include at least one non-scientific member and at least one member who is independent of the institution / trial site. for a particular claim and where the ingredients are likely to have significant interaction of a pharmacodynamic or pharmacokinetic nature GROUP 3: Already marketed.     1. hospital or other facility where the clinical trial will be conducted. no penalty or loss of benefits to which the Subject is otherwise entitled Additional elements. Table of Contents 3. GROUP 4 : Individual active ingredients (or drugs from the same class) have been widely used in a particular indication(s) for years. if the Subject is or may become pregnant). qualification and MCR (Medical Council Registration) number 3.lay person from the community. 2.Study Population .social scientist / representative of NGO voluntary agency /philosopher / ethicist / theologian or a similar person 5.basic medical scientists (preferably one pharmacologist).Name / address of clinical laboratory facilities 4.           At least seven members Should appoint Chairperson (who is from outside the institution) and a Member Secretary.     Evidence on how the quality of a drug substance or formulation varies with time under the influence of various environmental factors To establish shelf life for the formulation / recommended storage Validated stability-indicating analytical procedures Stress testing of the drug substance on single batch to identify degradation products Photostability on at least one primary batch of the drug substance as well as the formulation 50. 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. EC members who are independent of trial and sponsor should vote / provide opinion in matters related to the study.Protocol Title and Study number (if any) of the clinical trial to be conducted by the Investigator. their concomitant use is often necessary and no claim is proposed to be made other than convenience. but in which it is proposed either to change the ratio of active ingredients or to make a new therapeutic claim. which are currently unforeseeable Approximate number of Subjects enrolled in the study 46. Title Page 2. Background and Introduction 4. Study Rationale 5. which may be required Foreseeable circumstances under which the Subject's Participation may be terminated without the Subject's consent Additional costs to the Subject Consequences to withdraw from the research and procedures for orderly termination Notification in a timely manner if significant new findings develop which may affect the Subject's willingness to continue participation Particular treatment or procedure may involve risks to the Subject (or to the embryo or fetus.        Voluntary participation.Full name. Marketing data will be similar to data required for any new drug (including clinical trials) GROUP 2 : Active ingredients already approved/marketed individually.legal expert 4. 48.Names of other members of the research team 6. address. Study Design 7. 49. combined for the first time.

Ethical Considerations 15. mg/kg)  Route of administration  Starting date and time of day  Stopping date and time. Exclusion Criteria 9.Undertaking by the Investigator 19. Study Assessments 10.Data Analysis 18.     8. results of specific tests and/or treatment that may have been conducted For a fatal outcome. Any postmortem findings. Discontinued Subjects 12. Investigational Product Management 17.  Start date (and time) of onset of reaction  Stop date (and time) or duration of reaction  54.  4. cause of death and a comment on its possible relationship to the suspected reaction. mg. as well as the criterion (or criteria) for regarding the report as serious. as for the suspected drug(s). ml.Appendices 52. Study Conduct 11.       13.Subject Eligibility a. Study Treatment 51. Adverse Events 14.. In addition to a description of the reported signs and symptoms. Outcome Information on recovery and any sequelae. Other Treatment(s) Provide the same information for concomitant drugs (including non prescription/OTC drugs) and non-drug therapies.)  Gender  Age and/or date of birth  Weight  Height 2. Inclusion Criteria b. Details of Suspected Adverse Drug Reaction(s)  Full description of reaction(s) including body site and severity. 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.           5. 6.              1. YOU ! . describe a specific diagnosis for the reaction. whenever possible. Study Monitoring and Supervision 16.g. Patient Details  Initials & other relevant identifier (hospital/OPD record number etc. or duration of treatment 53. 3. Details about the Investigator Name Address Telephone number Profession (specialty) Date of reporting the event to Licensing Authority: Date of reporting the event to Ethics Committee overseeing the site: Signature of the Investigator THANK55.

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