Indian GCP

PRESENTED BY: ANJALI RARICHAN FIRST YEAR M.PHARM DEPT. OF PHARMACY PRACTICE GRACE COLLEGE OF PHARMACY

Why separate GCP for India? GCP is an ethical and scientific quality standard for

designing, conducting and recording trials that involve participation of human subjects

Formulated by expert committee set up by Central Drugs Standard Control Organisation (CDSCO)

Guidelines have been evolved with consideration of WHO, ICH, USFDA and European GCP guidelines& Ethical Guidelines for Biomedical Research on Human subjects issued by ICMR

Primary Aim : To streamline clinical studies in India

Advantage of India India offers unique opportunities for

conducting Clinical trials in view of– Large patient pool– Well trained enthusiastic investigators– Premiere Medical institutes– Considerable low per patient trial cost

when compared to developed countries

Contents1. Definitions2. Pre-requisites for the study

2.1) Investigational Product2.2) Pre-Clinical Supporting data2.3) Protocol2.4)Ethical and safety considerations

2.4.1) Ethical Principles2.4.2) Ethics Committee2.4.3) Informed Consent Process2.4.4) Essential Information on

Confidentiality2.4.5) Compensation for participation2.4.6) Selection of Special groups as

research Subjects2.4.7) Compensation for accidental

injury

3. Responsibilities3.1) Sponsor3.2) Monitor3.4) Investigator4. Record keeping & data handling5. Quality Assurance6. Statistics7. Special Concerns7.1) Clinical Trials of Vaccines7.2) Clinical Trials of Contraceptives7.3) CT of Surgical procedures/ Medical devices7.4) CT for Diagnostic Agents7.5) CT for Herbal remedies & Medicinal Plants

Appendices

Appendix I : Declaration of Helsinki Appendix II : Schedule Y Appendix III : Format for submission of

pre-clinical and clinical data for r-DNA based vaccines, diagnostics and other biologicals

Appendix IV : Investigators Brochure Appendix V : Essential Documents

GCP, Main Aims… Ensure that studies are scientifically and

ethically sound and the clinical properties of the pharmaceutical substances under the investigation are properly documented.

The main two cardinal principles are– Protection of the rights of human subjects– Authenticity of biomedical data generated

Prerequisites for the study2.1) Investigational Pharmaceutical Product:Physical, chemical, pharmaceutical properties and the formulation of the Investigational Product & Instructions for the storage and handling of the dosage form must be documented. Any structural similarity(ies) to the other known compounds should be mentioned. 2.2) Pre-clinical supporting dataavailable pre-clinical data and clinical information on the Investigational Product should be adequate and convincing to support the proposed study.2.3) Protocol well-structured and complete protocol.

Relevant components of Protocol

1. General Informationa) Protocol title, protocol identifying number and date.b) Name, address & contact numbers of the sponsor and the

monitor / CROc) Name and title of the persons authorised to sign the protocold) Name, title, address and contact numbers of the sponsor's

medical expert for the studye) Name(s), title(s), address(es) and contact numbers of the

investigator(s)f) Name(s), address(es) and contact numbers of the

institution(s) - clinical laboratories2. Objectives and Justification

a)  Aims and objectives of the study,b) Name and description of the investigational productc) A summary of findings from non-clinical studiesd) Description of the IE criteria of the study populatione) Summary of the known and potential risks and benefits, if

any, to human subjects

3. Ethical Considerationsa) General ethical considerations related to the

studyb) how patients / healthy volunteers will be

informed and how their consent will be obtained

c) Possible reasons for not seeking informed consent

4. Study designd) primary and secondary end points, if any, to

be measured during the studye) Description of the type of the studyf) schematic diagram of the study design,

procedures and stagesg) Medications/treatments permitted and not

permittedh) Duration of the subject participation and  

Proposed date of initiation of the studyi) Discontinuation criteria for study subjectsj) Procedures for monitoring subjects’

compliance

5. Inclusion, Exclusion and Withdrawal of Subjectsa) Includes subject inclusion criteria, Exclusion

criteria, withdrawal criteria6. Handling of the Product(s)7. Assessment of Efficacyb) Description of how effects are measured and

recorded and Time and periodicity of effect recording

8. Assessment of Safety9. Statistics10. Data handling and managementc) Persons having direct access to source data /

documentsd) Procedures for handling and processing

records of adverse events to the productse)   Procedures for the keeping of patient lists

and patient records

11. Quality control and quality assurance12. Finance and insurancea) Mention all financial aspects of conducting

and reporting a study 13. Publication policy14. Evaluationb) specified account for how the response is to

be evaluated including methods of computation and calculation of effects.

c) Description of how to deal with and report subjects withdrawn from the study

Documents to be provided with protocol– Information to the Study Subjects– Instructions to staff– Descriptions of special procedures

. 2.4) Ethical & Safety Considerations2.4.1) Ethical principlesa) Principles of essentiality : research entailing the use of

human subjects is absolutely essential for the advancement of knowledge and for the benefit of all members of the human species after the proposed research is dully vetted and consideration of all other alternatives

b) Principles of voluntariness, informed consent and community agreement

c) Principles of non-exploitation : subjects should be remunerated and apart from the socio economic status, should be well informed about the study

d) Principles of privacy and confidentiality : no details of subjects identity should be disclosed without valid scientific and legal reasons

e) Principles of precaution and risk minimisation : research designed in such a way that subjects are put to the minimum risk, suffer no AE & generally benefit from the research

f) Principles of professional competence : should be conducted by professionally qualified peopleg) Principles of accountability and transparency : research conducted in honest, impartial & transparent mannerh) Principles of the maximisation of the public interest and of distributive justice i) Principles of institutional arrangements j) Principles of public domain k) Principles of totality of responsibility l) Principles of totality of responsibility

2.4.2) Ethics Committee Responsibilities

– Dignity, rights & well being of research participants

– Ensure that universal ethical values & international scientific standards are expressed in terms of local community values & customs

– Assist in development & the education of a research community

Composition– Should be multidisciplinary & multi sectorial– 5-7 members, maximum of 12-15– Chairperson from outside the institution– Composition as follows

.– Chairperson– 1-2 basic medical scientist ( one

pharmacologist)– 1-2 Clinicians from various institutes– One legal expert or retired judge– One social scientist– One Philosopher– One lay person– Member Secretary– Adequate representation of age, gender &

community Record Retention

– At least 5 years after the completion or termination of study if it is not possible to maintain the same permanently

Informed Consent Process Prior to the Subject’s participation in the Study the

written Informed Consent form should be signed and personally dated by subject/LAR/Impartial witness & the Investigator

Essential information that must be provided to the subject should contain1. Aims & methods of research2. Expected duration3. Reasonably expected benefits4. Alternative procedures if any5. Foreseeable risks6. Right of prevent use of his/her biological samples7. Extend of confidentiality of the subjects8. Free treatment to research related injury9. Compensation 10. Voluntary participation

11) Phone numbers & address of contact persons12) All information about the biological material and data generated from the person13) Risk of discovery of biologically sensitive information14) Publication if any, including photographs & pedigree chart

Informed consent in non therapeutic trialsConsent must always be given by the

subject. Consent of LAR/guardian may be taken into consideration only if

Objective of study cannot be met by subjects who can personally give informed consent

Foreseeable risks are low Ethics committee written approval

Responsibilities Sponsor1. Investigator/Institution Selection2. Allocation of duties & responsibilities 3. Study management, data handling and

record keeping4. Compensation for participation5. Confirmation of review by the ethics

committee6. Information on Investigational products7. Supply, storage and handling of

Pharmaceutical products8. ADR reporting9. Study Reports10. Monitoring& Audits

Monitor Principal communication link between sponsor

and Investigator Responsibilities Main responsibility to oversee progress of

study & to ensure that it conducted in accordance with protocol, GCP’s & RA requirementsa) Verify Investigators Qualificationsb) Ascertain institutional facilitiesc) Verify that1. IP is available and stored properly2. IP is supplied to only persons eligible to

receive it3. Subjects are provided necessary

information4. Receipt, use, return & disposal of products5. Investigator receives current IB

6. Investigator follows protocol7. Investigator maintains ED8. All parties are informed about study & follow GCP guidelines & SOP’s9. Verifying each party is performing specialized function in accordance with protocol/ agreement10. Verifying none of parties delegate any assigned function to unauthorized individualsd) Promptly inform sponsor & EC any unwanted deviation from protocol/ GGCP’se) Observe & report subject recruitment rate to sponsorf) Ensure that CRF’s are correctly filledg) Should submit a written report to sponsor after each site visit

Investigator

Should be qualified enough by education, training & experience for proper conduct of study & should have qualifications prescribed by Medical Council of India (MCI).

His main responsibilities includea) Medical care of study subjectsb) Monitoring and auditing of recordsc) Communication with ECd) Conduct study in accordance with protocole) IP accountability at trial sitef) Selection and recruitment of study subjectsg) Accuracy and completeness of records and

reports

RECORD KEEPING AND DATA HANDLING The basic concept of record-keeping and

handling of data is to record, store, transfer, and where necessary convert efficiently and accurately the information collected on the trial subject(s) into data that can be used to compile the Study Report.

1) Documentation2) Corrections3) Electronic Data Processing4) Validation of Electronic Data Processing

Systems5) Language6) Responsibilities of the Investigator7) Responsibilities of the Sponsor and the

Monitor

STATISTICS 1) Role of a BiostatisticianInvolvement of a appropriately qualified and experienced statistician is necessary in the planning stage as well as throughout the Study. The Bio-statistician’s should make a statistical model to help the Sponsor, CRO and / or the Investigator in writing the Protocol. The number of Subjects to be included in the study is determined in relation to the statistical model on which the Protocol is based. 2) Study Design Randomisation and blinding Statistical Analysis Statistical Analysis

SPECIAL CONCERNS1)Clinical Trials of Vaccinesa) Phases of Vaccine Trials : The guidelines to conduct the clinical trial on

investigational vaccines are similar to those governing a clinical trial. The phase of these trials differ from drug trials as given below:

1. PHASE I2. PHASE II3. PHASE III

2)Clinical Trials of Contraceptives All procedures for clinical trials are

applicable. Subjects should be clearly informed about the alternative available.

In women where implant has been used as a contraceptive for trial, a proper follow up for removal of the implant should be done, whether the trial is over or the subject has withdrawn from the trial.

Children borne due to failure of contraceptives under study should be followed up for any abnormalities if the woman does not opt for medical termination of pregnancy.

3) Clinical trials with surgical procedures/ medical devices Definitions Guidelines4) Clinical trials for Diagnostic Agents - Use of Radio-active Materials and X- RaysIn human beings, for investigation and treatment, different radiations- X-rays, gamma rays and beta rays, radio opaque contrast agents and radioactive materials are used. The relative risks and benefits of research proposal utilizing radioactive materials or X-rays should be evaluated. Radiation limits for the use of such materials and X-Rays should be in accordance with the limits set forth by the regulatory authority (BARC) for such materials. Guidelines

5) Clinical trials of Herbal Remedies and Medicinal Plants Categories of Herbal Products Guidelines

APPENDICES

1.Appendix I WORLD MEDICAL ASSOCIATION DECLARATION

OF HELSINKI Ethical Principles for Medical Research

Involving Human Subjects : It includes: A. INTRODUCTION B. BASIC PRINCIPLES FOR ALL

MEDICAL RESEARCH

C. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL CARE

2. Appendix II SCHEDULE Y Requirements and guidelines on clinical

trials for import and manufacture of new drug

1. Clinical Trials 2. Chemical and Pharmaceutical

Information

3. Animal Toxicology 4. Animal Pharmacology 5. Human/Clinical Pharmacology

trials (Phase I) 6. Exploratory trials (Phase II) 7. Confirmatory trials (Phase III) 8. Special Studies 9. Submission of Reports (Appendix

II to Schedule Y) 10. Regulatory status in other

counties

11. Marketing Information Appendix I to Schedule Y Data required to be submitted with

application for permission to market a new drug.

1. Introduction 2. Chemical and pharmaceutical

information 3. Animal pharmacology 4. Animal toxicology (See Appendix III

and IV to Sch. Y)

5. Human/clinical pharmacology (Phase I)

6. Exploratory clinical trials (Phase II) 7. Confirmatory clinical trials (Phase

III) 8. Special studies 9. Regulatory status in other

countries 10. Marketing information

APPENDIX III to Schedule YAnimal toxicity requirements for clinical trials and marketing of a new drugAPPENDIX IV to Schedule Y Number of animals for long term toxicity

studiesAPPENDIX V to Schedule Y Patient consent form for participation in

a Phase I Clinical Trial

APPENDIX VI to Schedule YData requirements of Fixed Dose Combinations

APPENDIX III Format for submission of preclinical and clinical

data* for r-DNA based vaccines, diagnostics and other biologicals. A : SPECIFICATION AND

CHARACTERIZATION INFORMATION ON R-DNA VACCINES AND BIOLOGICAL PRODUCTS.

a) Description in details of the method of r-DNA products

b) Description of the method of sequence verification (such as restriction enzymemapping, PCR etc.)

c) Description on Identity-Physical, Chemical, Immunological and Biological whereverapplicable.

d) Potency.e) General Safety Test.f) Data on sterility tests as per Indian Pharmacopeia

guidelines.

f) Data on purity of recombinant product.g) Description of constituent materials like preservatives etc.h) Data on stability of finished formulation as per IP (Indian pharmacopeia) guidelines.B : DATA ON PRECLINICAL TESTING1. Biological activity/ pharmacodynamics in vitro and in appropriate animal models.2. Safety Pharmacology (Functional indices of toxicity).3. Toxicology and pharmacokinetics (Absorption, Distribution, Metabolism, Excretion ADME)4. Immunogenicity/Immunotoxicity5. Reproductive and developmental toxicity6. Genotoxicity studies7. Carcinogenicity studies

C: RECOMBINANT IMMUNODIAGNOSTIC REAGENTSD: CLINICAL TRIALS1. Phase I : Human/Clinical Pharmacology Immunogenic

Potency2. Phase II: Exploratory Clinical Trials-

Preventive/Therapeutic Efficacy (Data to begenerated in subjects residing in endemic/ non-endemic areas)

3. Phase III: Confirmatory Trials

APPENDIX IV

INVESTIGATOR’S BROCHURE (IB)

APPENDIX V ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A

CLINICAL TRIAL

COMMENT ON THERAPY• V