SCHEDULE - Y

Aditi Sawardekar

OVERVIEW OF PRESENTATION
Drug Regulatory Laws The Drugs And Cosmetics Act, 1940 Drugs & Cosmetics Rule 1945

Various Schedules Under Drugs & Cosmetics Act 1940

The Drugs And Cosmetics Act, 1940 (Amendments) Schedule Y What it Covers And Associated Rules Responsibilities of Sponsor, Investigator And Ethics Committee

Application For Permission Under Form 44, Regulatory Authorities, Fees And Test License
Appendices Of Schedule Y

DRUG REGULATORY LAWS

1940 - Drugs and Cosmetic Act 1985 - Narcotic Drugs and Psychotropic Substances Act

2000 - Ethical Guidelines for Biomedical Research on Human Subjects, ICMR 2001 - Indian GCP Guidelines 2002 - Amendment to Drugs & Cosmetics Act 2005 - Revised Schedule Y

Future :
Guidelines for pre-clinical data for r- DNA vaccines, diagnostics & biologicals, DBT. Draft Guidelines for Stem Cell Research/ Regulation, ICMR.

THE DRUGS AND COSMETICS ACT, 1940

An Act to regulate import, manufacture, distribution and sale of drugs and cosmetics. Passed by the Indian Parliament. It extends to the whole of India Both the Act and the Rules came into force from April 1947

DRUGS & COSMETICS RULE 1945

168 Rules has been divided in to Parts from I XIX as per the different subjects pertaining to Schedule (organized plan for matters to be attended to) are from A to Y

 Act: a law or formal decision made by a parliament or other group of elected lawmakers
Rule: an accepted principle or instruction that states the way things are or should be done, and tells you what you are allowed or are not allowed to do

VARIOUS SCHEDULES UNDER DRUGS & COSMETICS ACT 1940

Schedules A-Y Schedule A Applications and Licenses Schedule B Fees for Analysis Schedule C Biological, Immunological and parenteral
products Schedule D Exemptions Schedule E Poisons Schedule F Vaccines, sera etc Schedule G Under medical supervision - Caution

 Schedule H Prescription drugs Schedule J Name of the diseases/ailments which a

drug may not purport to prevent or cure by means of claims made on the label of the container. Schedule K Generics Schedule M GMP Schedule N Requirements for Running Pharmacy Schedule O Standards for Disinfectant fluids Schedule P Packaging and Shelf life Schedule Q Colours used in drugs

Schedule R Labeling Schedule S Cosmetics Schedule T Factory Premises Schedule U Manufacturing records Schedule V Standards for patent and proprietary
drugs

Schedule X Control Measures taken for

Psychotropic Drugs

Schedule Y Requirements and guidelines on clinical

trials for import and manufacture of drugs

THE DRUGS AND COSMETICS ACT, 1940 (AMMENDMENTS)

The Drugs (Amendment) Act, 1955, The Drugs (Amendment) Act, 1960, The Drugs (Amendment) Act, 1962, Drugs and Cosmetics (Amendments) Act, 1964, The Drugs and Cosmetics (Amendments) Act, 1972,

THE DRUGS AND COSMETICS ACT, 1940 (AMMENDMENTS)

The Drugs and Cosmetics (Amendments) Act, 1982, The Drugs and Cosmetics (Amendments) Act, 1986, The Drugs and Cosmetics (Amendments) Act, 1995

SCHEDULE - Y

SCHEDULE - Y
REQUIREMENTS AND GUIDELINES FOR PERMISSION TO IMPORT AND / OR MANUFACTURE OF NEW DRUGS FOR SALE OR TO UNDERTAKE CLINICAL TRIALS

Schedule Y
SCOPE UTILITY

NEW DRUG DEVELOPMENT PROCESS IN INDIA

RIGHTS SAFETY WELL BEING OF HUMAN SUBJECTS

 In Drugs & Cosmetics Rules (Part X-A) : 122A-122E

122-A 122-B Application for permission to import new drug Application for approval to manufacture new drug other than the drugs classifiable under Schedules C (biologics, etc)

122-C
122-D 122-DA

Deleted
Permission to import or manufacture Fixed Dose combination: Defined FDC Application for permission to conduct clinical trials for ND/IND.

122-DAA Definition of Clinical trial

122-E Definition of New Drug

122-DAA
Definition of Clinical trial 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.

122 - E
NEW DRUG
- 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
Vaccines are new drugs unless otherwise certified
Considered new drug for 4 years or inclusion in IP

INVESTIGATIONAL NEW DRUG

New chemical entity or a product having therapeutic indication but which has never been earlier tested on human beings

RESPONSIBILITIES OF SPONSOR, INVESTIGATOR AND ETHICS COMMITTEE

RESPONSIBILITIES OF THE SPONSOR

Implementing and maintaining quality assurance systems - Good Clinical Practice (GCP) Guidelines issued by CDSCO, INDIA
Sponsors are required to submit a status report on the clinical trial to the Licensing Authority at the prescribed periodicity (annual).

RESPONSIBILITIES OF THE SPONSOR

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

RESPONSIBILITIES OF THE SPONSOR

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

DEFINITION SAE / SADR / AE / ADR

SAE / SADR: An adverse event / adverse reaction associated with death, in patient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect or is otherwise life threatening Adverse Event (AE) : any untoward medical occurrence (including a symptom / disease or an abnormal lab finding) during treatment with a pharmaceutical product in a patient or a human volunteer that does not necessarily have a relationship with the treatment being given.

DEFINITION SAE / SADR / AE / ADR

Adverse Drug Reaction (ADR) :
Approved product: Noxious / unintended
response at doses normally used or tested in humans

Unapproved product: Noxious / unintended

response at any dose There is reasonable possibility that the adverse event is related with medicinal product studied

RESPONSIBILITIES OF INVESTIGATOR
Responsible for the conduct of the trial according to the protocol and the GCP Guidelines and also for compliance.

Standard operating procedures are required to be documented by the investigators for the tasks performed by them. Ensure that adequate medical care is provided to the participant for any adverse events.
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.

RESPONSIBILITIES OF ETHICS COMMITTEE

Safeguard the rights, safety and well being of all trial subjects. Particular care to protect the rights, 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.

APPLICATION FOR PERMISSION UNDER FORM 44, REGULATORY AUTHORITIES, FEES AND TEST LICENCE

REGULATORY AUTHORITIES
Ministry of Chem & Fertilizers Ministry of Health Health Secretary NPPA National Pharmaceutical Pricing Authority DGHS Director General of Health Services DCGI Drug Controller General of India CDL/CDTL Gov. Drug Testing Laboratories State Drug Regulatory Authority : FDA

Ministry of Sci & Tech DBT Department of Biotechnology

Ministry of Enviro

Additional Secretary

Pricing Regulations

GEAC Genetic Engineering Approval Committee

FEES
Import ff/ Mfg ff/ Import bulk + Mfg ff of new drug Application by same applicant, for modified dosage form or with new claim Secondary applicants after 1 year of approval Import / Mfg FDC Conduct Clinical trial with ND/IND Phase I Phase II Phase III = Rs 50,000/= Rs 15,000/= Rs 15,000/= Rs 15,000/= Rs 50,000/= Rs 25,000/= Rs 25,000/-

No separate fee to be paid along with application for import / mfg based on successful completion

APPLICATION IN FORM 44
FORM 44 (See Rules 122A, 122B, 122D and 122DA) Application for grant of permission to import or manufacture a New Drug or to undertake clinical trial 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 : 1. Particulars of New Drug : 1. Name of the drug : 2. Dosage Form : 3. Composition of the formulation : 4. Test specifications : Active ingredients : Inactive ingredients : 5. Pharmacological classification of the drug : 6. Indications for which proposed to be used : 7. Manufacturer of the raw material : 8. Patent status :

FORM 44 Contd.
2. A 1. 2. 3. 4. 5. 6. 7. 8. 9. Data submitted along with the application Permission to market new drug

Chemical and Pharmaceutical information Animal Pharmacology Animal Toxicology Human / Clinical Pharmacology Exploratory Clinical Trials Confirmatory Clinical Trials Bioavailability / dissolution and stability data Regulatory status in other countries Marketing information : (a) Proposed product monograph (b) Drafts of labels and cartons 10. Application for test licence :

FORM 44 Contd.
B Subsequent approval / permission for manufacture of already approved new drug a) Formulation : a) Bioavailability / bioequivalence b) Name of the investigator / centre c) Source of raw materials and stability b) Raw Material Manufacturing Method QC parameters, specifications, stability Animal toxicity C Approval / permission for FDC

1. 2. 3.

Justification Pcokinetic / Pcodynamic data Any other data

FORM 44 Contd
D Subsequent approval or approval for new indication new dosage form : Number and date of Approval already granted Justification Data on safety, efficacy and quality
A total fee of Rs has been credited to the Government under the Head of Account (receipt enclosed) Signature Designation Date

IMPORTANT CONSIDERATIONS - 1
HUMAN CLINICAL PHARMACOLOGY :(a) Phase I (Human Pharmacology) Safety and Tolerability with the initial administration of IND MTD, Kinetics and Dynamics (b) Phase II (Therapeutic Exploratory Trials) Effectiveness for a particular indication, small group (c) Phase III (Therapeutic Confirmatory Trials) Therapeutic benefit in large number of patients (d) Phase IV (Post Marketing Trials) Related to approved indication

IMPORTANT CONSIDERATIONS
HUMAN CLINICAL PHARMACOLOGY :(a) for new drug substances discovered in India : Data from Phase I (b) 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 (c) Application for permission to initiate specific phase of clinical trial should also accompany Investigators brochure, proposed protocol, case record form, study subjects informed consent document(s) investigators undertaking and ethics committee clearance, if available (d) Sample size depends on type of study (e) EC application can be in parallel to DCGI application (f) Amendments notified to DCGI and EC within 30 days and approval obtained

IMPORTANT CONSIDERATIONS - 2
PSUR
New drugs should be closely monitored for their clinical safety; submission of Periodic Safety Update Reports (PSURs) in order to report all the relevant new information (patient exposure) summarize the market authorization status in different countries and any significant variations related to safety; and indicate whether changes should be made to product information

PSURs shall be submitted every 6 months for the first two years after approval For subsequent two years the PSURs need to be submitted annually PSURs due for a period must be submitted within 30 calendar days of the last day of the reporting period.

IMPORTANT CONSIDERATIONS
PSUR Structure:(a) A title page stating: Periodic safety update report for the product, applicants 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.

IMPORTANT CONSIDERATIONS - 3
DRAFTS OF LABEL AND CARTONS : Should comply with Rules 96 of the D&C Rules, 1945 After Approval no changes in the package insert shall be effected without such changes being approved

IMPORTANT CONSIDERATIONS - 4
BE / BA
(i) For drugs approved elsewhere in the world and absorbed systemically, bioequivalence with the reference formulation should be carried out. (ii) Evaluation of the effect of food

(iii) Dissolution and bioavailability data to be submitted

(iv) All bioavailability and bioequivalence studies should be conducted according to the Guidelines for Bioavailability and Bioequivalence studies as prescribed (ICMR guidelines)

APPENDICES OF SCHEDULE Y

APPENDIX I DATA SUBMITTED WITH APPLICATION FOR PERMISSION TO MARKET A NEW DRUG
1. INTRODUCTION
A brief description of the drug and the therapeutic class to which it belongs.

2. CHEMICAL AND PHARMACEUTICAL INFORMATION.

2.1. Chemical name, code name or number, if any, non-proprietary or generic name, if any, structure, physio-chemical proportion. 2.2. Dosage form and its composition. 2.3. Specifications of active and inactive ingredients. 2.4. Tests for identification of the active ingredient and method of its assay. 2.5. Outline of the method of manufacture of the active ingredient. 2.6. Stability data

3. ANIMAL PHARMACOLOGY
3.1. Summary 3.2. Specific pharmacological actions. 3.3. General pharmacological actions. 3.4. Pharmacokinetics, absorption, distribution, metabolism, excretion.

APPENDIX I DATA SUBMITTED WITH APPLICATION FOR PERMISSION TO MARKET A NEW DRUG
4. ANIMAL TOXICOLOGY (See Appendix III and IV)
4.1. Summary 4.2. Acute Toxicity 4.3. Long Term Toxicity 4.4. Reproduction Studies. 4.5. Local Toxicity 4.6. Mutagenicity and Carcinogenicity.

5. HUMAN/CLINICAL PHARMACOLOGY (PHASE I)

5.1. Summary 5.2. Specific Pharmacological effects. 5.3. General Pharmacological effects. 5.4. Pharmacokinetics, absorption, distribution, metabolism, excretion.

APPENDIX I DATA SUBMITTED WITH APPLICATION FOR PERMISSION TO MARKET A NEW DRUG
6. EXPLANATORY CLINICAL TRIALS (PHASE II)
6.1. Summary 6.2. Investigator-wise reports.

7. CONFIRMATORY CLINICAL TRIALS (PHASE III)

7.1. Summary 7.2. Investigator-wise reports

8. SPECIAL STUDIES
8.1. Summary 8.2. Bioavailability and dissolution studies. 8.3. Investigator-wise reports.

APPENDIX I DATA SUBMITTED WITH APPLICATION FOR PERMISSION TO MARKET A NEW DRUG
9. REGULATORY STATUS IN OTHER COUNTRIES
9.1. Countries where (a) Marketed (b) Approved. (c) Under trial, with phase. (d) Withdrawn, if any, with reasons. 9.2. Restrictions on use, if any, in countries where marketed/ 9.3. Free sale certificate from country of origin.

10. MARKETING INFORMATION

10.1. Proposed product monograph 10.2. Drafts of labels and cartons. 10.3. Sample of pure drug substance, with testing protocol.

APPENDIX IA DATA SUBMITTED GRANT OF PERMISSION TO IMPORT MANUFACTURE AN ALREADY APPROVED NEW DRUG
1. INTRODUCTION A brief description of the drug and the therapeutic class. 2. CHEMICAL AND PHARMACEUTICAL INFORMATION.
2.1. Chemical name, code name or number, if any, non-proprietary or generic name, if any, structure, physio-chemical properties. 2.2. Dosage from its composition 2.3. Test specifications. (a) Active ingredients. (b) Inactive ingredients 2.4. Tests for identification of the active ingredients and method of its assay. 2.5. Outline of the method of manufacture of active ingredients. 2.6. Stability data.

APPENDIX IA DATA SUBMITTED GRANT OF PERMISSION TO IMPORT MANUFACTURE AN ALREADY APPROVED NEW DRUG
3. MARKETING INFORMATION
3.1 Proposed package insert/promotional literature 3.2 Draft specimen of the label and carton.

4. SPECIAL STUDIES CONDUCTED WITH APPROVAL OF LICENSING AUTHORITY

4.1. Bioavailability/Bioequivalance and comparative Dissolution Studies, for oral dosage form, 4.2. Sub-acute animal toxicity studies for intravenous infusions and injectables.

APPENDIX II FORMAT OF STUDY REPORT

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.

APPENDIX II FORMAT OF STUDY REPORT

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, randomised, and prematurely discontinued. State reasons for premature discontinuation of therapy in each applicable case. 12. Efficacy evaluation : Results

APPENDIX II FORMAT OF STUDY REPORT

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. Investigators certificate on accuracy of the study

APPENDIX III ANIMAL TOXICOLOGY

Toxicity studies to comply with GLP Systemic Toxicity Studies Single dose (2 rodent species); 2g/kg or 10 times dose in humans 14 days observation; Minimum lethal dose / Maximum tolerated dose Repeated dose (2 mammalian species, 1 non-rodent); administration for 7 days

Dose Ranging Study : Identify target organ and establish MTD

Male Fertility Study Female Reproduction and Developmental Toxicity Study

APPENDIX III ANIMAL TOXICOLOGY

Perinatal study Local toxicity Dermal, vaginal, rectal, ocular, inhalation Allergenicity / hypersensitivity Genotoxicity

Carcinogenicity

APPENDIX IV ANIMAL PHARMACOLOGY

Cardiovascular System

Central Nervous System

Respiratory System Follow up and Supplemental Safety Pharmacology

APPENDIX V INFORMED CONSENT

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, rights of Subjects and in the event of any injury Anticipated prorated payment, if any, to the Subject for participating in the trial Subject's responsibilities

APPENDIX V INFORMED CONSENT

Voluntary participation, no penalty or loss of benefits to which the Subject is otherwise entitled Additional elements, 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, if the Subject is or may become pregnant), which are currently unforeseeable Approximate number of Subjects enrolled in the study

APPENDIX VI FIXED DOSE COMBINATIONS

Fixed Dose Combinations refer to products containing one or more active ingredients used for a particular indication(s).

APPENDIX VI FIXED DOSE COMBINATIONS

GROUP 1 : One or more of the active ingredients is a new drug.
Marketing data will be similar to data required for any new drug (including clinical trials)

APPENDIX VI FIXED DOSE COMBINATIONS contd

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 If Marketed abroad : Clinical trial reports of other countries Regulatory status in other countries If not Marketed abroad : Chemical and pharmaceutical data will be submitted - chemical and pharmaceutical data, stability of the proposed dosage form 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.

APPENDIX VI FIXED DOSE COMBINATIONS

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.

APPENDIX VI FIXED DOSE COMBINATIONS

GROUP 4 : 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.

APPENDIX VII UNDERTAKING BY INVESTIGATOR

1. Full name, address, title 2. Name / address of medical college, hospital or other facility where the clinical trial will be conducted. Education, training & experience, qualification and MCR (Medical Council Registration) number 3. Name / address of clinical laboratory facilities 4. Name / address of the Ethics Committee

5. Names of other members of the research team

6. Protocol Title and Study number (if any) of the clinical trial to be conducted by the Investigator.

APPENDIX VIII ETHICS COMMITTEE

At least seven members Should appoint Chairperson (who is from outside the institution) and a Member Secretary. Quorum at least 5 members with the following representations: 1. basic medical scientists (preferably one pharmacologist). 2. clinicians 3. legal expert 4. social scientist / representative of NGO voluntary agency /philosopher / ethicist / theologian or a similar person 5. lay person from the community. Must include at least one non-scientific member and at least one member who is independent of the institution / trial site. Appropriate gender representation on the Ethics Committee. EC members who are independent of trial and sponsor should vote / provide opinion in matters related to the study.

APPENDIX IX STABILITY TESTING OF NEW DRUGS

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,

Pilot Batch : 1/10th of commercial / production batch

Primary Batch : Batch used in stability study for registration / establish shelf life.

APPENDIX X PROPOSED PROTOCOL

1. Title Page a. Full title b. Protocol / Study number, and protocol version number with date c. The IND name/number of the investigational drug d. Complete name and address of the Sponsor and CRO e. List of the Investigators, institutional affiliations and site locations f. Name(s) of clinical laboratories and/or facilities participating in study. 2. Table of Contents 3. Background and Introduction Preclinical experience Clinical experience 4. Study Rationale 5. Study Objective(s) 6. Study Design

APPENDIX X PROPOSED PROTOCOL

7. 8. Study Population Subject Eligibility a. Inclusion Criteria b. Exclusion Criteria

9. Study Assessments 10. Study Conduct 11. Discontinued Subjects 12. Study Treatment (Dosing Schedule, Drug supplies, administration, dose modification, possible drug interactions, concomitant therapy, blinding / unblinding procedures)

APPENDIX X PROPOSED PROTOCOL

13. Adverse Events 14. Ethical Considerations (Risk/benefit assessment, EC review and communications, Informed consent process, Statement of Subject confidentiality including ownership of data and coding procedures) 15. Study Monitoring and Supervision 16. Investigational Product Management 17. Data Analysis 18. Undertaking by the Investigator

19. 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)

APPENDIX XI DATA FOR REPORTING SAE

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. Start date (and time) of onset of reaction Stop date (and time) or duration of reaction De-challenge and re-challenge information Setting (e.g., hospital, out-patient clinic, home, nursing home)

5. Outcome Information on recovery and any sequelae; results of specific tests and/or treatment that may have been conducted For a fatal outcome, cause of death and a comment on its possible relationship to the suspected reaction; Any postmortem findings.

6. 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

UNATTENDED AREAS
Regulations for :
1. Biologics :
Vaccines Blood products Tissue Cellular/Gene therapy

2. Herbals 3. Medical devices 4. Pharmacovigilance 5. Electronic records

THANK YOU !!!