ICH

International Conference
on
Harmonization
Q- What is ICH?
1. International Conference of Harmonization.
2. It is a joint initiative involving regulators & industry as equal
partners in the scientific & technical discussions of the testing
procedures which are required to ensure and assess the safety,
quality & efficacy of medicines.
GOALS
Remove redundancy / duplication in development and review process
For new medicinal products, single set of data should demonstrate:
–Safety
–Quality
–Efficacy
 The need to Harmonize:
 Rapid increase in laws, regulations & guidelines for reporting &
evaluating data on safety, quality & efficacy
 Diff. regulatory systems with divergent technical requirements
made it necessary for Industry to duplicate time-consuming &
expensive test procedures for diff. markets
 Rising costs of healthcare, R&D costs & minimum delay in
making safe & effective new treatments available to patients.
 ICH-Steering Committee
Established - 17th January 1997

Structure
Three countries, USA, Japan and EU, with their 6 founding member parties
(EU, EFPIA, MHLW, JPMA, FDA and PhRMA)

Observers : (WHO, EFTA, Canada) - Non-voting members.

IFPMA (Intl. Federation of Pharmaceutical mfg. Association) representative

USA (FDA & Pharmaceutical Research & Manufacturers of America)

EU (European Federation of Pharmaceutical Industry Associates)

Japan (Japanese Pharmaceutical Manufacturers Association & MHLW)

Parties: -
 European Commission – European Union (EU)

 European Federation of Pharmaceutical Industries Associations (EFPIA)

 Ministry of Health, Labour and Welfare, Japan (MHLW)
 Japan Pharmaceutical Manufacturers Association (JPMA)
 US Food & Drug Administration (FDA)
 Pharmaceutical Research & Manufacturers of America (PhRMA)
 International Federations of Pharmaceutical Manufacturers Association
(IFPMA)

To facilitate data acceptance by regulatory authorities in these jurisdictions

 The regulatory harmonization is achieved by developing guidelines.
These guidelines are divided into four categories as follows:
 Q – Quality Guidelines: Defining relevant thresholds for impurities
testing and a more flexible approach to pharmaceutical quality based on
Good Manufacturing Practice (GMP) risk management.
 S – Safety Guidelines: ICH has produced a comprehensive set of safety
guidelines to uncover potential risks like carcinogenicity, genotoxicity
and reproductive toxicity.
 E – Efficacy Guidelines: The work carried out by ICH under the
Efficacy heading is concerned with the design, conduct, safety and
reporting of clinical trials.
 M – Multidisciplinary Guidelines: Those are the cross-cutting topics
which do not fit uniquely into one of the Quality, Safety and Efficacy
categories. It includes the ICH medical terminology (MedDRA) and the
Common Technical Document (CTD) 25
Finalized Guidelines:

 Efficacy (E1 to E12) GCP=E6 (1996)

 Quality (Q1 to Q6)
 Safety (S1 to S7 & M3)
 Multidisciplinary (M1, M2, M4)
 Clinical Safety E1 – E2F
 Clinical Study Reports E3
 Dose-Response Studies E4
 Ethnic Factors E5
 Good Clinical Practice E6
 Clinical Trials E7 – E11
 Guidelines for Clinical Evaluation by Therapeutic Category
E12
 Clinical Evaluation E14
 Pharmacogenomics E15 – E16
 Joint Safety/Efficacy Topic M3
 GCP demands ….
ETHICAL PRINCIPLES OF
DECLARATION OF HELSINKI

Trial must be Should be conducted

scientifically sound after favorable
and described in a
CLINICAL TRIAL
approval of IEC
detailed protocol

All information should be recorded, handled, reported and

stored so as to allow its accurate interpretation and
verification
 Good Clinical Practice (GCP)
International ethical and scientific quality standard
for:
Designing
Conducting
Performance
Monitoring
Auditing
Recording
Reporting
Compliance with this standard provides public assurance
that the rights, safety and well-being of trial subjects are
protected and that the clinical trial data are credible.
 Table of Contents - 8 sections
1. Glossary
2. The Principles of ICH-GCP
3. Institutional Review Board/Independent Ethics Committee
(IRB/IEC)
4. Investigator
5. Sponsor
6. Clinical Trial Protocol & Protocol Amendment(s)
7. Investigator’s Brochure
8. Essential Documents for Conduct of a Clinical Trial
 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
requirement(s).

 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.

 The rights, safety, and well-being of the trial subjects are the
most important considerations and should prevail over interests
of science and society.
 The available nonclinical and clinical information on an
investigational product should be adequate to support the
proposed clinical trial.

 Clinical trials should be scientifically sound, and described

in a clear, detailed protocol.

 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.
 The medical care given to, and medical decisions made on
behalf of, subjects should always be the responsibility of a
qualified physician or, when appropriate, of a qualified dentist.
 Each individual involved in conducting a trial should be
qualified by education, training, and experience to perform his
or her respective task(s).
 Freely given informed consent should be obtained from every
subject prior to clinical trial participation.

 All clinical trial information should be recorded, handled, and

stored in a way that allows its accurate reporting,
interpretation and verification.
 The confidentiality of records that could identify subjects
should be protected, respecting the privacy and
confidentiality rules in accordance with the applicable
regulatory requirement(s).

 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.

 Systems with procedures that assure the quality of every

aspect of the trial should be implemented.
General Frameworks
 WHO GCP
 ICH GCP

Regional/Applied Frameworks
 EU GCP
 US CFR

National/Applied GCP Guidelines

 India, China, Russia, Singapore, Malaysia,
Indonesia, South America, South Africa,
Turkey
 ‘A need was, however, felt to develop our
own Indian Guidelines to ensure uniform
quality of clinical research throughout the
country and to generate data for registration
for new drugs before use in the Indian
population.’
Dr. S.P. Agarwal, Director General of Health Services and
Chairman, Drug Technical Advisory Board (DTAB)
 The enforcement that came into existence in 1988
 Regulations and Guidelines for permission for
development (preclinical and/or clinical), import and
manufacture of New Drugs for Marketing in India.
 Significant Changes
◦ Clinical trials – definition, conduct
◦ Responsibilities of Ethics Committee (EC), Investigator
and Sponsor
◦ Formats for critical documents
 “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”.
 Definition of Phases I – IV
 Concurrent Phase II-III
 Central lab and trial samples
 Compliance to GCP / GLP
 Flexibility in data requirements for new drugs for life
threatening / serious conditions or disease of relevance
to India
 Clinical trials required if the indication is
relevant to special population e.g. pediatrics,
geriatrics, pregnancy
 EC for pediatric trials to include members
knowledgeable about pediatric, ethical, clinical and
psychosocial issues
 Mature minors and adolescents to sign an
 assent form
 Other –Post-marketing surveillance, BA/BE
 Quality assurance to ensure compliance to GCP
guidelines of CDSCO.

 Submission of status report at prescribed periodicity;

reasons for premature termination to be communicated.

 Serious adverse event to be communicated promptly

(within 14 calendar days) to DCGI and other
investigators
 Responsible for conduct of trial according
to protocol and GCP
 Compliance as per undertaking format
(Indian version of FDA form 1572)
 Medical care for AEs
 SAE reporting to
◦ Sponsor within 24 hrs
◦ EC within 7 days
 Informed consent
 Safeguard rights, safety, wellbeing of
subjects
 Special care for vulnerable subjects
 Ongoing review
 Reason’s for revoking approval and information to
investigator / regulatory authority
 EC approval of protocol / informed consent form
(ICF) and notification to DCGI prior to initiation
 Approval for sites without EC by institutional /
independent EC
 EC approval of protocol amendments
and notification to DCGI
1.Title page
2. Synopsis
3. Statement of Compliance to GCP
4. Abbreviations
5. Table of contents
6. Ethics committee
7. Study team
A. Protocol and amendments
B. Specimen of Case Record Form
C. Investigators’ name(s) with contact addresses, phone, email etc.
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 and life threatening adverse
event cases
I. Publications from the trial
J. Important publications referenced in the study
K. Audit certificate, if available
L. Investigator’s certificate that he/she has read the report and that
the report accurately describes the conduct and the results of
the study.
 Trial involves research
 Purpose
 Trial treatments and randomization
 Trial procedures
 Risk
 Benefit
 Alternative treatments
 Compensation / treatment for injury
 Subject’s responsibilities
 Experimental aspects
 Any payment
 Confidentiality
 New information
 Voluntary participation
 Person/s to contact
◦ for study information
◦ rights of subject
◦ if study related injury
 Reasons for termination
 Duration of study
 Number of subjects
 Any other pertinent information
1. Full name, address and title of the Principal Investigator (or
Investigator(s) when there is no Principal Investigator)
2. Name and address of the medical college, hospital or other facility
where the clinical trial will be conducted: Education, training &
experience that qualify the Investigator for the clinical trial (Attach
details including Medical Council registration number, and / or any
other statement(s) of qualification(s))
3. Name and address of all clinical laboratory facilities to be used in
the study.
4. Name and address of the Ethics Committee that is responsible for
approval and continuing review of the study.
5. Names of the other members of the research team (Co- or sub-
Investigators) who will be assisting the Investigator in the conduct
of the investigation (s).
6. Protocol Title and Study number (if any) of the clinical trial to be
conducted by the Investigator
7. Signature with Date
i. Study not to begin until EC / DCGI approval
ii. Adherence to protocol
iii. Personal supervision
iv. Ensure requirements of IC and EC review
v. Report of AE to sponsor
vi. Understanding of investigator’s brochure
vii. Ensure that all associates, colleagues and
employees suitably qualified and experienced and
aware of their obligations
viii. Maintenance of records and availability for
audits / sponsor inspection / EC and DCGI ;
Cooperation in audits
ix. Report to EC promptly about changes and
unanticipated problems
x. Report all unexpected serious adverse events to
the Sponsor in 24 hrs and EC within 7 days
xi. Confidentiality of data and patients
xii. Compliance with all other obligations of clinical
investigators
 No of members at least 7 members
 Chairperson from outside the institution)
 Other members a mix of medical/non-medical,
scientific and non-scientific persons, including lay
public
 Quorum for EC
 Documents for Review by Ethics Committee
Sponsor
Investigator
Regulatory Authority
Ethics Committee
Thank you!