ICH-GUIDELINES OF ICH-S

PRESENTED BY GUIDED BY
SAMIKSHA D. MORE Dr. S.D.PANDE
M.PHARM 1ST YEAR M.PHARM PhD
1ST SEMESTER Roll No- 13106
BRANCH-PHARMACEUTICS
VIDYABHARTI COLLEGE OF PHARMACY AMRAVATI
CONTENTS
INTRODUCTION
ICH MISSION
ORIGIN OF ICH
HISTORY OF ICH
ORGANIZATION OF ICH
PROCESS OF HARMONIZATION
ICH GUIDELINES
(Q,S,E,M)
Conclusion
INTRODUCTION

ICH Stands for “International conference on

Harmonization of Technical Requirements of
Pharmaceuticals for Human Use”.

ICH’s logo has been contrived with a view to

symbolizing the letters I, C, H in a ,manner which
embodies the letters in an outline human form.
Main color of logo is blue often used with
healthcare.
 ICH MISSION

 ICH’s Mission is to make suggestion towards accomplishing greater

harmonization in the interpretation and application of technical
Guidelines and requirements for medicinal product registration.
 ORIGIN OF ICH
 In the late 1950s the drug thalidomide was introduced to the
world as a safe sedative and anxiolytic.
 In the 1960s the drug was marketed in 46 countries and, as occurs
with many popular drugs, began to be used off-label.
 The particular indication was morning sickness.
 Not long after, doctors began to notice horrible birth defects such
as phocomelia shortening or (absence of limbs) and flipper-like
limbs in children born to mothers taking thalidomide.
 Initially ICH was partnership between Europe, Japan and USA.
 But today it is Global Organization.
 HISTORY OF ICH
 In the 1980s the European Union began harmonizing regulatory requirements. In
1989, Europe, Japan, and the United States began creating plans for
harmonization.
 The International Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH) was created in April 1990 at
a meeting in Brussels.
 ICH had the initial objective of coordinating the regulatory activities of the
European, Japanese and United States regulatory bodies in consultation with the
pharmaceutical trade associations from these regions, to discuss and agree the
scientific aspects arising from product registration.
 Since the new millennium, ICH's attention has been directed towards extending
the benefits of harmonization beyond the founding ICH regions.
ORGANIZATION OF ICH
 REGULATORY BODIES AND RESEARCH BASED
INDUSTRIES

Region Regulatory Body Research Based Industry

Japan Ministry of Health, Labour Japan Pharmaceuticals

and Welfare Manufacturers Association

Europe European Union European Federation of

Pharmaceutical Industries
and Association

USA Food and Drug Pharmaceutical Research

Administration and Manufacturers of
America
Process of Harmonization
Building Scientific Consensus

Agreeing on Drafting Text

Consulting Regional Regulating Authorities

Adopting Harmonized Guidelines

Implementation of Guidelines
ICH-GUIDELINES

ICH Guidelines are categorized into four types they are -

 Quality guidelines (ICH-Q)
 Safety guidelines (ICH-S)
 Efficacy guidelines (ICH-E)
 Multidisciplinary guidelines (ICH-M)
ICH-S Guidelines

Safety Guidelines

 ICH has produced a comprehensive set of safety

Guidelines to uncover potential risks like carcinogenicity,
genotoxicity and reprotoxicity. A recent breakthrough has
been a non-clinical testing strategy for assessing the QT
interval prolongation liability: the single most important
cause of drug withdrawals in recent years.
Safety Guidelines
Carcinogenicity Studies (S1A-S1C)

S1A : Guideline on the Need for Carcinogenicity studies of

Pharmaceuticals
 These studies should be performed for any pharmaceutical whose
clinical use is expected for at least 6 months.
 This document provides a consistent definition of the circumstances
under which it is necessary to undertake carcinogenicity studies on
new drugs.
 These recommendations take into account the known risk factors as
well as the intended indications and duration of exposure.
 The Objectives of Carcinogenicity studies is to study potential
factors in animals and assess the relevant risk in humans.
 S1B : Testing for Carcinogenicity of Pharmaceuticals

• This document provides guidance on the need to carry out carcinogenicity

studies in both mice and rats, and guidance is also given on alternative testing
procedures which may be applied without jeopardizing safety.
•
The Guideline embraces all pharmaceutical agents that need carcinogenicity
testing as indicated in Guideline S1A.
•
This document provides guidance on approaches for evaluating the
carcinogenic potential of pharmaceuticals.
 (S1B)(R1)EWG : Rodent Carcinogenicity studies for
Human Pharmaceuticals

 This topic was endorsed by the ICH Steering Committee in April 2012.
 A change to the current S1 Harmonized Guidelines on rodent
carcinogenicity testing is proposed to introduce a more comprehensive
and integrated approach to addressing the risk of human carcinogenicity
of pharmaceuticals, clarify and update, without compromising safety.
 The criteria for deciding whether the conduct of a two-year rodent
carcinogenicity study of a given pharmaceutical would add value to this
risk assessment.
 S1C(R2) : Dose selection for Carcinogenicity Studies
of Pharmaceuticals

 This document addresses the criteria for the selection of the high
dose to be used in carcinogenicity studies on new therapeutic
agents to harmonize current practices and improve the design of
studies.
 S2-Genotoxicity

S2(R1) : Guidance on Genotoxicity Testing and Data Interpretation for

Pharmaceuticals intended for Human Use.
 This guidance replaces and combines the ICH (S2A) and (S2B)
Guidelines. The purpose of the revision is to optimize the standard
genetic toxicology battery for prediction of potential human risks, and
to provide guidance on interpretation of results, with the ultimate goal
of improving risk characterization for carcinogenic effects that have
their basis in changes in the genetic material.
 The revised guidance describes internationally agreed upon standards
for follow-up testing and interpretation of positive results in vitro and
in vivo in the standard genetic toxicology battery, including assessment
of nonrelevant findings. This guidance is intended to apply only to
products being developed as human pharmaceuticals.
S2A : Guidance on specific aspects of Regulatory
Genotoxicity Tests for Pharmaceuticals

 This document provide specific guidance on in-vivo and

in-vitro studies and their evaluation test results.
 It includes a glossary of terms related to genotoxicity tests
to improve consistency in applications.
 S2B : Guideline on Genotoxicity
 A Standard Battery for Genotoxicity Testing for Pharmaceuticals
was finalised under Step 4 in July 1997.
 This document addressed two fundamental areas of genotoxicity
testing: the identification of a standard set of assays to be
conducted for registration.
 The extent of confirmatory experimentation in any particular
genotoxicity assay in the standard battery.
 purpose of the revision is to optimise the standard genetic
toxicology battery for prediction of potential human risks, and to
provide guidance on interpretation of results, with the ultimate
goal of improving risk characterization for carcinogenic effects.
S3A-S3B : Toxicokinetics and Pharmacokinetics

 S3A : Note for Guidance on toxicokinetics. The assessment of

systemic exposure in toxicity studies
 ICH guidelines do not require toxicokinetics studies to be
conducted expect in lactating, pregnant animals. Before initiating
reproductive studies.
 This document gives guidance on developing test strategies in
toxicokinetics and highlights the need to integrate
pharmacokinetics into toxicity testing, in order to aid in the
interpretation of the toxicology findings and promote rational
study design development.
 S3B : Pharmacokinetics Guidance for repeated dose
tissue distribution studies

 Tissue distribution studies are essential in providing information

on distribution and accumulation of the compounds and
metabolites especially in relation to potential sites of action.
 This information is useful in desigining toxicology studies.
 This documents guides on when repeated dose distribution studies
are to be conducted.
 S4 : Duration of Chronic Toxicity Testing in
animals (Rodent and Non-Rodent toxicity
studies
 The objective of this guidance is to set out the considerations that
apply to chronic toxicity testing in rodents and non rodents as part of
the safety evaluation of a medicinal products.
 Rodents : a study for 6 months.
 Non-Rodents : a study for 9 months.
 S5 : Detection of Toxicity to Reproduction for Medicinal
products and Toxicity to Male Fertility

 This document provides guidance on tests for reproductive toxicity.

 It defines the periods of treatment to be used in animals to better
reflect human exposure to medical products and allow more specific
identification of stages at risk.
 It should encourage the full assessment on the safety of chemicals on
the development of the offspring.
 S6 : Preclinical safety Evaluation of Biotechnology
derived pharmaceuticals
• This document covers the preclinical safety testing requirements for
biotechnological products. It addresses the use of animal models of
disease, determination of when genotoxicity assays and
carcinogenicity studies should be performed, and the impact of
antibody formation on duration of toxicology studies.
• Primary goals of preclinical evaluation are:
• To identify initial safe dose and subsequent dose in humans.
• Identification of potential organs for drugs toxicity and to find
whether toxicity is reversible or not.
• Safety parameters for clinical monitoring.
S7A : Safety Pharmacology Studies for Human
Pharmaceuticals
• This guidance was developed to protect clinical trial
participants and patients receiving marketed products from
potential adverse effects of pharmaceuticals.
• This documents addresses the definition, objectives and
scope of safety pharmacology studies.
• It also addresses which studies are needed before initiations
of Phase 1 clinical studies as well as information needed for
marketing.
S7B : The Nonclinical Evaluation of the Potential for
Delayed Ventricular Repolarization (QT interval
Prolongation) By Human Pharmaceuticals

 This guideline describes a non-clinical testing strategy for

assessing the potential of a test substance to delay ventricular
repolarization.
 This guideline includes information concerning non-clinical
assasy and integrated risk assessments.
S8 : Immunotoxicity Studies for Human
Pharmaceuticals

 This guideline addresses the recommendations on nonclinical

testing for immunosuppressant.
 The guideline might also apply to drugs in which clinical signs
of immunosuppressents are observed during clinical trials and
following approval to market.
 The term immunotoxicity in this guidelines will primarily refer
to immnuosuppressent which is a state of increased
susceptibility to infections or the development of tumors.
 S9 : Non-Clinical Evaluation for Anticancer
Pharmaceuticals

 It describes the type and timing of non-clinical studies in relation to the

development of anticancer pharmaceuticals and references other
guidance as appropriate.
 This Guideline provides information for pharmaceuticals that are
intended to treat cancer in patients with late stage or advanced disease
regardless of the route of administration, including both small molecule
and biotechnology-derived pharmaceuticals.
 S10 : Photo safety Evaluation of Pharmaceuticals

 This guideline applies to new APIs. New excipients clinical formulations

for dermal applications and photodynamic therapy products.
 It is an integrated process that can involve an evaluation of
photochemical characteristics, data from non clinical and human safety
information.
 The photo safety assessment aims to determine weather risk
minimization measures are warranted to prevent adverse events in
humans.
 In-vitro assay for photo-toxicity is the 3T3 neutral red uptake assay.
 In-vivo for species selection irradiation sensitivity, heat tolerance etc.
 S11 : For Non-Clinical safety testing in support of
development of Paediatric Medicines
• The S11 Guideline provides direction on the nonclinical safety studies
important to support a paediatric development program.
• It recommends standards for the conditions under which nonclinical
juvenile animal testing is considered informative and necessary to
support paediatric clinical trials, and also provides guidance on the design
of the studies.
S12 : Non-Clinical Bio-distribution Considerations
for Gene Therapy products

 The S12 EWG is working on the development of a new S12

Guideline on “Nonclinical Bio-distribution Considerations for
Gene Therapy Products” with a view to providing
recommendations on the elements of nonclinical studies
performed that include Bio-distribution assessment, and will
contribute to the streamlined development of the Gene
Therapy products, while maintaining scientific rigor and
minimizing the unnecessary use of animals.
 Conclusion

 As the pharmaceutical industries are growing day by day it is very

important to established guidelines those will create harmonization.
 ICH was formed to develop and implement the guidelines. That will
reduce the time required for the registration of a pharmaceutical
products.
 It also help to minimize the errors and also eliminates the risk of the
drug development.
 References

 International Journal of Drug Regulatory Affairs; by Chaitanya

Prasad Kolla 2014, (Page no 19, 20, 25, 26).
 ICH Official Website.
Thank-You