ICH-GCP and Indian GCP Guidelines

Dr Arun Bhatt MD (Med) FICP (Ind)

Member, Faculty of Pharmaceutical
Medicine
President
ClinInvent Research Pvt Ltd
 Structure of Presentation

• Definition
• Evolution and Needs
• Principles and Content
• Responsibilities
Ø Sponsor
Ø Investigator
Ø Ethics committee
• Processes
Ø Documentation
Ø Informed consent
Ø Monitoring
Ø Audits
• Implementation
 Guidelines for Clinical Trials

• 1996 : ICH Guidelines

• 2000 : ICMR guidelines
• 2001 : Indian GCP guidelines
• 2005 : Amendment to Schedule Y
 ICH GCP : Definition

A standard for the design, conduct,

performance, monitoring, auditing,
recording, analyses, and reporting of clinical
trials, that provides assurance that the data and
reported results are credible and accurate, and
that the rights, integrity and confidentiality
of trial subjects are protected
Life must be lived forwards,
but can only be
understood backwards

Soren Kierkegaard
 Need for GCP

• Tuskegee syphilis trials - 1930s

• German prisoner's trials - 1940s
• Harvard fraud - 1980s
• California investigator - 1999
• Johns Hopkins - 2001
• Kerala controversy - 2001
• Letrozole lapses - 2004
 A Doctor’s Drug Trials Turn into Fraud
(NY Times May 17 1999)

“ For Dr Fiddes was conducting research fraud of

audacious proportions, cutting corners and
inventing data to keep the money flowing from drug
industry. Fictitious patients were enrolled in studies.
Blood pressure readings were fabricated. Bodily
fluids that met certain lab values were kept on hand
in the office refrigerator, ready to be substituted for
the urine or blood of patients who did not qualify for
the studies. “
 Kerala Controversy:
Inquiry Commission’s Findings
• Trial at RCC started without approval from Drugs
Controller
• No clearance from Health Ministry for collaboration
with a foreign Institute
• Banned drug smuggled by the Johns Hopkins
scientist
• Patients signed informed consent in language other
than their native language
• Neither ICH-GCP nor the ICMR guidelines for
biomedical research on human subjects followed
• Clinical trials suspended at RCC for 6 months
 Nuremberg Code 1947

•Voluntary consent •No intentional death or

disability
•Anticipate scientific
benefits •Protection from harm

•Benefits outweigh risks •Subject free to stop

•Qualified investigators
•Animal experiments first
•Investigator will stop if
•Avoid suffering harm occurs
 Declaration of Helsinki 1964 - 2000
World Medical Association

• Duty of physician to protect the life, health, privacy and

dignity of the human subject
• Review of proposed research by independent ethics
committee
• Medical research involving human subjects only by
scientifically qualified persons and under the supervision
of a clinically competent medical person
• Physician to obtain the subject’s freely-given consent,
preferably in writing
• Stress on publication of results - negative or positive
 ICH

International Conference on Harmonization

Primary participants
Ø USA, European Union, Japan
Ø Regulatory and industry representatives
Observers
Ø Canada, Australia, Nordic countries
Others
Ø WHO as facilitator
Ø IFPMA as secretariat
 ICH Topics

• Q - Quality
• S- Safety
• E - Efficacy
ØE6 : GCP
• M - Multidisciplinary
 Principles of GCP

• Ethical principles - Declaration of Helsinki, GCP &

regulatory requirements
• Benefits vs. Risks
• Safety of subjects vs. interest of science / society
• Adequacy of non-clinical & clinical information
• Clinical trials scientifically sound & described in clear,
detailed protocol
• Compliance with protocol that has received prior
approval of EC / IRB
• Medical care responsibility of qualified physician /
dentist
 Principles of GCP

• Each individual involved in trial qualified by

education, training and experience
• Informed consent freely given
• Information recorded, handled, stored for accurate
reporting, information and verification
• Protection of subject’s confidentiality
• Investigational products manufactured, stored and
handled as per GMP
• Systems with procedures for quality assurance
 Indian GCP Guidelines

• Evolved with consideration of WHO, ICH, USFDA ,

European GCP and Ethical Guidelines of Biomedical
Research on Human Subjects of ICMR

• Should be followed for carrying out biomedical

research in India at all stages of drug development,
whether prior or subsequent to product registration in
India
 Ethical Principles of Indian GCP

• Essentiality
• Voluntariness, Informed consent and
community agreement
• Non-exploitation
• Privacy and confidentiality
• Precaution & risk minimisation
• Professional competence
 Ethical Principles of Indian GCP

• Accountability and transparency

• Maximisation of the public interest and
Distributive justice
• Institutional arrangements
• Public domain
• Totality of responsibility
• Compliance
 Structure

ICH E6 Indian GCP

Glossary Definitions
Principles Pre-requisites
IRB/IEC Responsibilities
Investigator Records & Data
Sponsor Quality Assurance
Protocol Statistics
Investigators’ Brochure Special Concerns
Essential Documents Appendices
 Critical Path of a Clinical Trial
Planning
Protocol • CRF
Regulatory and
Ethical Approval
Trial Documents • Materials
Select
Investigators
Initial Visits
Site Assessments
Patient Recruitment
Periodic Monitoring
Study
Termination
Data Data Statistical Final
Entry Clean-up Analysis Report

*START *END
 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. “
 Clinical Trial : Participants
• Chefs to design protocols

• Lovers clinical investigators

• Organisers project managers

• Mechanics computer people

• Policemen monitors / ethics

committee / regulators
 Heaven Hell

Chefs French British

Lovers Italians Swiss

Organizers Swiss Italians

Mechanics Germans French

Policemen British German

 Sponsor Responsibilities
Study design
Study Report
Select sites
Termination Regulatory
Study management
DE & DM
QC & QA
GCP Information
Monitoring Documentation
AE reporting Communication
Clinical trial supplies
 Investigator Responsibilities
Monitoring / Audit

Records Reports Regulatory compliance

Safety reporting
Investigator Ethics approval
Investigational
product Informed consent

Medical care
Staff supervision
Investigator =
Protective Physician
+
Responsible Researcher
 Ethics Committee
• Composition
• Quorum
• SOPs
• Assessment of investigator competence
• Review of documents
• Decision making process
• Reporting of adverse events
• Continuing review
 Informed Consent

• Essential elements
• Prior approval by EC
• Responsibility of investigator
• Process of explanation and documentation
 Documentation

If it is not written,
it did not happen!

Do what you write

Write what you do.
 Monitoring

Verification of
Ø Protection of rights and well-being of trial subjects
Ø Accuracy, completeness of data confirmed with
source documents

Conduct of trial as per

Ø Approved / amended valid protocol
Ø Good Clinical Practice
Ø Regulatory requirements
 Audit

A systematic and independent examination of

trial-related activities and documents to
determine whether the evaluated trial-related activities
were conducted, and the data were recorded, analyzed
and accurately reported, according to the protocol,
sponsor’s SOP, GCP and the applicable regulatory
requirement(s)
 Indian GCP : Special Populations

• Children
• Pregnant or nursing women
• Socio-economically disadvantaged
• Mentally challenged
• Students, Subordinates, Employees
• Army personnel
• Prisoners
 Indian GCP : Special Research Areas

• Vaccines
• Contraceptives
• Herbal
• Surgical procedures / Medical devices
• Diagnostic agents – radioactive material
 GCP Implementation
Want to

Attitude

Performance

Knowledge Skills
What to Why to How to
GCP - A Shared Responsibility

Sponsor
Investigator
Regulatory Authority
Ethics Committee