INDIAN GCP (CDSCO Guidelines)

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

2. 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

3. 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

4. Contents
1. Definitions
2. Pre-requisites for the study
2.1) Investigational Product
2.2) Pre-Clinical Supporting data
2.3) Protocol
2.4)Ethical and safety considerations
2.4.1) Ethical Principles
2.4.2) Ethics Committee
2.4.3) Informed Consent Process
2.4.4) Essential Information on Confidentiality
2.4.5) Compensation for participation
2.4.6) Selection of Special groups as research
Subjects
2.4.7) Compensation for accidental injury

5. 3. Responsibilities
3.1) Sponsor
3.2) Monitor
3.4) Investigator
4. Record keeping & data handling
5. Quality Assurance
6. Statistics
7. Special Concerns
7.1) Clinical Trials of Vaccines
7.2) Clinical Trials of Contraceptives
7.3) CT of Surgical procedures/ Medical devices
7.4) CT for Diagnostic Agents
7.5) CT for Herbal remedies & Medicinal Plants

6. 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

7. 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

8. Prerequisites for the study
2.1) 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 data
available 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.

9. Relevant components of Protocol
1. General Information
a) Protocol title, protocol identifying number and date.
b) Name, address & contact numbers of the sponsor and the monitor
/ CRO
c) Name and title of the persons authorised to sign the protocol
d) Name, title, address and contact numbers of the sponsor's medical
expert for the study
e) 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 laboratories
2. Objectives and Justification
a) Aims and objectives of the study,
b) Name and description of the investigational product
c) A summary of findings from non-clinical studies
d) Description of the IE criteria of the study population
e) Summary of the known and potential risks and benefits, if any, to
human subjects

10. 3. Ethical Considerations
a) General ethical considerations related to the study
b) how patients / healthy volunteers will be informed and
how their consent will be obtained
c) Possible reasons for not seeking informed consent
4. Study design
a) primary and secondary end points, if any, to be
measured during the study
b) Description of the type of the study
c) schematic diagram of the study design, procedures and
stages
d) Medications/treatments permitted and not permitted
e) Duration of the subject participation and Proposed date
of initiation of the study
f) Discontinuation criteria for study subjects
g) Procedures for monitoring subjects’ compliance

11. 5. Inclusion, Exclusion and Withdrawal of Subjects
a) Includes subject inclusion criteria, Exclusion criteria,
withdrawal criteria
6. Handling of the Product(s)
7. Assessment of Efficacy
a) Description of how effects are measured and recorded
and Time and periodicity of effect recording
8. Assessment of Safety
9. Statistics
10. Data handling and management
a) Persons having direct access to source data / documents
b) Procedures for handling and processing records of
adverse events to the products
c) Procedures for the keeping of patient lists and patient
records

12. 11. Quality control and quality assurance
12. Finance and insurance
a) Mention all financial aspects of conducting and
reporting a study
13. Publication policy
14. Evaluation
a) specified account for how the response is to be
evaluated including methods of computation and
calculation of effects.
b) 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

13. . 2.4) Ethical & Safety Considerations
2.4.1) Ethical principles
a) 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

14. f) Principles of professional competence : should
be conducted by professionally qualified people
g) Principles of accountability and transparency :
research conducted in honest, impartial &
transparent manner
h) 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

15. 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

16. .
– 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

17. 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
contain
1. Aims & methods of research
2. Expected duration
3. Reasonably expected benefits
4. Alternative procedures if any
5. Foreseeable risks
6. Right of prevent use of his/her biological samples
7. Extend of confidentiality of the subjects
8. Free treatment to research related injury
9. Compensation
10. Voluntary participation

18. 11) Phone numbers & address of contact persons
12) All information about the biological material and data
generated from the person
13) Risk of discovery of biologically sensitive information
14) Publication if any, including photographs & pedigree
chart
Informed consent in non therapeutic trials
Consent 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

19. Responsibilities
 Sponsor
1. Investigator/Institution Selection
2. Allocation of duties & responsibilities
3. Study management, data handling and record keeping
4. Compensation for participation
5. Confirmation of review by the ethics committee
6. Information on Investigational products
7. Supply, storage and handling of Pharmaceutical
products
8. ADR reporting
9. Study Reports
10. Monitoring& Audits

20. 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 requirements
a) Verify Investigators Qualifications
b) Ascertain institutional facilities
c) Verify that
1. IP is available and stored properly
2. IP is supplied to only persons eligible to receive it
3. Subjects are provided necessary information
4. Receipt, use, return & disposal of products
5. Investigator receives current IB

21. 6. Investigator follows protocol
7. Investigator maintains ED
8. All parties are informed about study & follow GCP
guidelines & SOP’s
9. Verifying each party is performing specialized
function in accordance with protocol/ agreement
10. Verifying none of parties delegate any assigned
function to unauthorized individuals
d) Promptly inform sponsor & EC any unwanted
deviation from protocol/ GGCP’s
e) Observe & report subject recruitment rate to sponsor
f) Ensure that CRF’s are correctly filled
g) Should submit a written report to sponsor after each
site visit

22. 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 include
a) Medical care of study subjects
b) Monitoring and auditing of records
c) Communication with EC
d) Conduct study in accordance with protocol
e) IP accountability at trial site
f) Selection and recruitment of study subjects
g) Accuracy and completeness of records and reports

23. 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) Documentation
2) Corrections
3) Electronic Data Processing
4) Validation of Electronic Data Processing Systems
5) Language
6) Responsibilities of the Investigator
7) Responsibilities of the Sponsor and the Monitor

24. STATISTICS
 1) Role of a Biostatistician
Involvement 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

25. SPECIAL CONCERNS
1)Clinical Trials of Vaccines
a) 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 I
2. PHASE II
3. PHASE III

26.  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.

27. 3) Clinical trials with surgical procedures/ medical devices
 Definitions
 Guidelines
4) Clinical trials for Diagnostic Agents - Use of Radio-active
Materials and X- Rays
In 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

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

29. 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

30.  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

31.  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

32.  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)

33.  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

34. APPENDIX III to Schedule Y
Animal toxicity requirements for clinical
trials and marketing of a new drug
APPENDIX IV to Schedule Y
 Number of animals for long term toxicity
studies
APPENDIX V to Schedule Y
 Patient consent form for participation in
a Phase I Clinical Trial

35. APPENDIX VI to Schedule Y
Data requirements of Fixed Dose
Combinations

36. 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 enzyme
mapping, PCR etc.)
c) Description on Identity-Physical, Chemical, Immunological
and Biological wherever
applicable.
d) Potency.
e) General Safety Test.
f) Data on sterility tests as per Indian Pharmacopeia guidelines.

37. 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 TESTING
1. 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/Immunotoxicity
5. Reproductive and developmental toxicity
6. Genotoxicity studies
7. Carcinogenicity studies

38. C: RECOMBINANT IMMUNODIAGNOSTIC REAGENTS
D: CLINICAL TRIALS
1. Phase I : Human/Clinical Pharmacology Immunogenic
Potency
2. Phase II: Exploratory Clinical Trials-
Preventive/Therapeutic Efficacy (Data to be
generated in subjects residing in endemic/ non-endemic
areas)
3. Phase III: Confirmatory Trials

39. APPENDIX IV
 INVESTIGATOR’S BROCHURE (IB)
APPENDIX V
 ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A
CLINICAL TRIAL

40. COMMENT ON THERAPY
• V