Origin and Principles Of

International Conference On
Harmonisation –Good Clinical
Practice (ICH-GCP) Guidelines

SUBMITTED BY
SYAMA. J.S
1ST M.PHARM
DPS Cheruvandoor

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 ICH

ICH denotes for "International Conference on Harmonisation of

Technical Requirements for Registration of Pharmaceuticals for
Human consumption".

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 ICH MISSION

 ICH’s mission is to make suggestions towards accomplishing

greater harmonisation in the interpretation and application of
technical Guidelines and requirements for medicinal product
registration.

 Need for laws, regulations and guidelines for Reporting &

evaluating the safety, quality and efficacy data of new drugs.

 The focus of ICH has been on the Technical requirements for

medicinal products contain new drugs.
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 HISTORY OF ICH

 ICH's origin in 1990, the ICH process has step by step evolved.

 ICH's first 10 years saw substantial progress in the growth of Tripartite

ICH Guidelines on Safety, Quality and Efficacy topics (QSEM).

 Work was also undertaken on a number of important multidisciplinary

subjects, which admitted MedDRA (Medical Dictionary for Regulatory
Activities) and the CTD (Common Technical Document).

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As the second tenner the exploitation of ICH Guidelines continued, but
with more care given to the following need to:

 Maintain already present Guidelines as science and technology

continued to develop

 Expand communication and spreading of information on ICH

Guidelines with non-ICH regions became a key focus

 Provide the implementation of ICH Guidelines in ICH's own region

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 460 BC- Oath of Hippocrates
 1930- US Food Drugs and Cosmetic Act
I st conference of ICH in 1990 in Brussels
 1947 -Nuremberg code
3 regions participated
 1948-Declaration of Human Rights Representatives from- Industry
 1962- US FDA IND Guidelines Academia
Ministry of health
 1964- Declaration of Helsinki
 1968- Committee on Safety of Medicines, UK
 1978 - GCP, US FDA
 1982 -International Guidelines for Biomedical Research Involving Human Subjects
 1990- ICH
 1991- GCP, Europe
 1996 - ICH GCP
 1997 - ICH GCP Guideline 6
PURPOSE OF ICH
•To provide a form for regulatory authorities and the pharmaceutical
industry to discuss the requirements for drug development.

•To update harmonized technical requirements in the light of advances in

science and technology.

•To ensure that there is a harmonized approach to the development of new

guidelines/requirements.

•To facilitate the adoption of new or improved research and development

approach.

•To facilitate the dissemination of harmonized guideline and encourage

common standards

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 ICH PARTIES
Key players in ICH process are the six parties drawn from regulatory bodies and
pharmaceutical companies in Europe, Japan and the United states.

•European commission(EU)
•European federation of pharmaceutical industries and association(EFPIA).
•Japanese ministry of health, labour and welfare(MHLW).
•Japan pharmaceutical manufactures association(JPMA).
•United states of food and drug administration(US FDA).
•Pharmaceutical research and manufactures of America (PhRMA)

OBSERVERS
•WHO ,TPP (Canada)
•International federation of Pharmaceutical manufacturer’s association
•EFTA(European Free Trade Association) 8
 WORK PRODUCTS

 Guidelines: ICH has originated over 50 harmonised Guidelines aiming

at eliminating gemination in the development and registration process,
so that a single set of reports can be generated to demonstrate the
quality, safety and efficacy of a new pharmaceutical product.

 ICH has also developed Questions and Answers (Q&A) when

additional guidance and advice were considered required helping the
interpretation of certain harmonised tripartite Guidelines.

 CTD: The Common Technical Document (CTD) describes the common

format for the formulation of a well integrated CTD for applications
that will be submitted to regulatory bodies.
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 eCTD: The Electronic Common Technical Document (eCTD) has been
prepared for the electronic submission of the Common Technical
Document (CTD) from applicant to drug regulator, in order to provide
international electronic communication through the provision of
Electronic Standards for the Transfer of Regulatory Information (ESTRI).

 MedDRA: The Medical Dictionary for Regulatory Activities (MedDRA)

Terminology has also been developed under the aegis of International
conference on harmonization

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 ICH GUIDE LINES

 Quality

 Safety

 Efficacy

 Multidisciplinary
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QUALITY
Mainly relates to
 Chemical & pharmaceutical QA.(Raw materials, Impurities,
Residual Solvents)
 Stability & Specifications .
Quality guidelines
 Q1:Stability-photostability
 Q2:Analytical validation
 Q3:Impurities
 Q4:Biotechnological Quality
 Q5:Specifications
 Q7:GMP for active Pharma ingredients
 Q8:Pharmaceutical development 12

 Q9:Quality risk management

 SAFETY
These are topics dealing with invitro & in vivo Pre-clinical testing.
Pharmacovigilance
ADR Reporting

 SAFETY GUIDELINES ARE

 S1:Carcinogenicity studies- need, testing& dose selection.

 S2:Genotoxicity-regulatory ,battery of tests.

 S3A:Toxicokinetics
 S4:Chronic toxicity testing
 S5A:Toxicity to reproduction
 S5B:Toxicity to male fertility.
 S6:Pre-clinical biotech derived drugs.
 S7A:Safety pharmacology
 S7B:QT interval prolongation
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 S8:Immunotoxicity
 EFFICACY

 Includes topics relating to clinical studies in human subjects

 Design
 Conduct Safety & Reporting
 Clinical Trials
 E1:Exposure to assess clinical safety
 E2:Clinical safety data management
 E3:Study reports
 E5:Ethnic factors
 E6:Good clinical practice(GCP)
 E8: Clinical trial design
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 MULTIDISCIPLINARY
Common technical document
Electronic Submission
Coding System
 M1:Medical terminology
 M2:Electronic standards for transfer of regulatory information &data
 M3:Maintenance of ICH guidelines
 M4:Common technical document
 Common Technical Document(CTD)
 M4Q:Quality
 M4S:Safety
 M4E:Efficacy
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DEFINITION OF GOOD CLINICAL PRACTICE & ICH GCP
“ICH GCP is an international ethical and scientific quality standard for the
design, conduct, performance, monitoring, auditing, recording, analyses and
reporting of clinical trials that provide assurance that the data and the
reported results are credible, accurate and that the rights, integrity and
confidentiality of trial subjects are protected.

 Consistent with the principles that have their origin in the Declaration Of
Helsinki, and the clinical trial data are credible.

 To ensure the rights, safety and well being of the trial subjects are protected

 Ensure the credibility of clinical trial data 16

Declaration of Helsinki - 1964
 Developed to guide physicians in biochemical research involving
human subjects
Requires:
 All physicians to conform to accepted scientific principles
 A research protocol to be reviewed by an independent committee
 Research performed by “clinically competent person”
 Objective proportional to risk
 Rights of patients protected
 Participants to be fully informed, and to consent to take part

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 ICH GCP The History & Development
 1536 Ambroise Paré , Wound healing

 1747 James Lind , Scurvy treatment

( Perhaps the first ever clinical trial was James Lin’s demonstration that
citrus fruits cure scurvy .He compared the effects of various different
acidic substances, ranging from vinegar to cider, on groups of afflicted
sailors, and found that the group who were given oranges and lemons had
largely recovered from scurvy after 6 days.)

 1894 Placebo control

 1931 Flip of a coin randomisation 18

 The Disasters

 1937 -100 patients died, due to diethylene in sulpha preparation

 1950 -Aplastic anaemia on Chloramphenicol

 1961 -Softenon (thalidomide) catastrophe in Europe

 March 2006 -The drug TGN1412 caused catastrophic systemic failures in

the subjects during its first human clinical trials (phase I). Following this,
an Expert Group on Phase in One Clinical Trials published a report.

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 ICH – GCP : Evolution
1980s - EC
Pioneered harmonization of regulatory requirements
Develop single market for medicinal products
Demonstrated feasibility of harmonization
1989, Paris - WHO Conference of Drug Regulatory Authorities
IFPMA – discuss joint regulatory-industry initiative
ICH conceived
Apr, 1990, Brussels – EFPIA
Birth of ICH
ICH Steering Committee established

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 1990/91 Guidelines on GCP in Europe
 1996 ICH GCP conference
 1997 All clinical trials in Europe must comply to the ICH /GCP
guidelines

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OBJECTIVES OF ICH GCP
Protect the patient

To provide a unified standard for the European Union (EU), Japan & United States
to facilitate mutual acceptance of clinical data by the authorities in these
jurisdictions

Facilitate the mutual acceptance of clinical data across ICH GCP regions

Avoid trial duplication (saving time, money, resource)

Facilitate global submissions through mutual acceptance of data

Technical requirements for medicinal products containing new drug

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Before the trial is initiated
 Risk Vs. Benefit
 Right; Safety and well being of trial subject
 Ethical awareness
 Clear and scientific protocol
 Trials should have REC approval
 Medical care is the responsibility of a qualified Physician.
 Research Physicians should be qualified
During the trial
 Patients should freely give their Consent
 Appropriate and careful recording and storage of trial information.
 Confidentiality
 GMP
 Applicable Systems and procedures 23
 ICH –GCP GUIDELINES
Provide a unified standard for the EU, Japan and USA regions to facilitate
mutual acceptance of clinical trial data by the regulatory authorities in these
regions.

The guidance was developed with consideration of current GCP of the European
Union , Japan, and the United States as well as those of Australia, Canada , the
Nordic countries and the WHO

The guidance should followed when generating clinical trial data that are
intended to be submitted to regulatory authorities.

The principle established in this guidance may also be applied to other clinical
investigations that may have an impact on the safety and well being of human
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subjects
 ICH – GCP COVERS
1. Glossary
Common language for investigators/sponsors/ethics committees
2.Principles of Good Clinical Practice
13 tenets of ICH GCP
3.Requirements for IRB/IEC(Institutional Review Board/Independent Ethics
Committee)
Roles responsibilities and composition
4.Responsibilities of the investigator
5.Responsibilities of the sponsor
6.Requirements for clinical trial protocol and protocol amendments
7.Responsibility of the sponsor in the development of investigator’s brochure.
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8.Essential documents for the conduct of a clinical trial.

Regulatory Authorities Review submitted clinical data and conduct
inspections
The Sponsor Company or institution organization which takes
responsibility for initiation management and financing
of clinical trial
The Project monitor Usually appointed by sponsor
The investigator Responsible for conduct of clinical trial at the trial site.
Team leader.
The pharmacist at trial Responsible for maintenance, storage and dispensing
location of investigational products eg. Drugs in clinical trials
Patients Human subjects
Ethical review board or Appointed by Institution or if not available then the
Committee for protection Authoritative Health Body in that Country will be
of subjects responsible
Committee to monitor Overseas Sponsors eg. Drug Companies
large trials
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 13 ICH GCP PRINCIPLES
1.Ethical Principle
Clinical trials should be conducted in accordance with the ethical principles
that have their origin in the Declaration of Helsinki, and that are consistent with
GCP and the applicable regulatory requirements.

2. Risk Benefit
Before a trial is initiated ,foreseeable risks and inconveniences should be
weighed against the anticipated benefit for the individual trial subject and
society. A trial should be initiated and continued only if the anticipated benefits
justify the risks.

1. 3.Rights of subjects first

The rights ,safety and well-being of the trial subjects are the most important
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considerations and should prevail over interests of science and society

4.Suitable IMP
The available nonclinical and clinical information on an investigational
product should be adequate to support the proposed clinical trial

5.Scientific protocol
Clinical trial should be scientifically sound and described in a clear, detailed
protocol

6.Independent Review
A trial should be conducted in compliance with the protocol that has received
prior Institutional Review Board(IRB)/Independent Ethics
Committee(IEC)approval/ favourable opinion.

7.Qualified medical care

The medical care given to, and medical decisions made on behalf of, subjects
should always be the responsibility of a qualified physician or ,when 28
appropriate ,of a qualified dentist
8.Qualified Investigators
Each individual involved in conducting a trial should be qualified by
education ,training and experience to perform his or her respective task.

9.Informed consent
Freely given informed consent should be obtained from every subject
prior to clinical trial participation

10.Accurate Data
All clinical trial information should be recorded, handled and stored in
a way that allows its accurate reporting, interpretation and
verification.

11.Confidentiality
The confidentiality of records that could identify subjects should be
protected, respecting the privacy and confidentiality rules in
accordance with the applicable regulatory requirements. 29
12.IMP to GMP
Investigational products should be manufactured , handled and stored
in accordance with applicable Good Manufacturing Practice (GMP).
They should be used in accordance with the approved protocol .

13.Systemic Quality Procedure

.Systems with procedures that assure the quality of every aspect of the
trial should be implemented.

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 Indian GCP guidelines

 Released in Dec 2001(Developed by CDCSO and endorsed by DCGI)

 In general, in line with ICH GCP

 Has Revised Schedule Y (Jan 2005) addressed discrepancies.

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CONCLUSION

 The events that led up to the culmination of the ICH-GCP guidelines brought
forth public awareness that there was a need to control and regulate clinical
trials dealing with drugs and human subjects.

 The violation of human rights played a large role and that is why the
Declaration of Helsinki and The Nuremberg Code remain as the framework of
the present guidelines.

 The ICH-GCP guidelines are therefore considered the ‘bible’ of clinical trials,
and have become a global law which safeguards humanity as we know it
today. 32
 REFERENCE

 INTERNATIONAL CONFERENCE ON HARMONISATION: AN OVERVIEW

www.ijdra.com REVIEW ARTICLE

 1)Guideline for Good Clinical Practice E6(R1),ICH Expert working

group,ICH Harmonized tripartite guideline, International Conference on
Harmonization of Technical requirements for registration of pharmaceuticals
for human use, June 1996,page no;1-8.

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