2. • ICH is the “International Conference on
Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use”.
• ICH is a joint initiative involving both regulators
and research-based industry representatives of
the EU, Japan and the US in scientific and
technical discussions of the testing procedures
required to assess and ensure the safety, quality
and efficacy of medicines.
• The ICH Secretariat is based in Geneva. The
biennial meetings and conferences of the ICH
Steering Committee rotate between the EU,
Japan, and the USA.
• To increase international harmonization of technical
requirements to ensure that safe, effective and high
quality medicines are developed.
• To harmonize technical requirements for registration or
• To develop and register pharmaceuticals in the most
efficient and cost effective manner.
• To promote public health.
• To prevent unnecessary duplication of clinical trials on
• To minimize the use of animal testing without
compromising safety and effectiveness of drug.
To promote international harmonization by bringing
together representatives from the three ICH regions
(EU, Japan and USA)
To discuss and establish common guidelines.
To make information available on ICH, ICH activities and
ICH guidelines to any country or company that requests
To promote a mutual understanding of regional initiatives
in order to facilitate harmonization processes related to
ICH guidelines regionally and globally
To strengthen the capacity of drug regulatory authorities
and industry to utilize them.
• ICH is comprised of representatives from six parties that represent the
regulatory bodies and research-based industry in the European Union,
Japan and the USA.
• In Japan, the members are the Ministry of Health, Labour and Welfare
(MHLW), and the Japan Pharmaceutical Manufacturers Association (JPMA).
• In Europe, the members are the European Union (EU), and the European
Federation of Pharmaceutical Industries and Associations (EFPIA).
• In the USA, the members are the Food and Drug Administration (FDA), and
the Pharmaceutical Research and Manufacturers of America (PhRMA).
• Additional members include Observers from the World Health Organization
(WHO), European Free Trade Association (EFTA), and Canada. The
Observers represent non-ICH countries and regions.
7. ICH structure
The ICH structure consists of the ICH Steering Committee, ICH
Coordinators, ICH Secretariat and ICH Working Groups.
ICH Steering Committee
The Steering Committee is the body that governs the ICH,
determines the policies and procedures for ICH, selects topics for
harmonization and monitors the progress of harmonization
initiatives. Each of the six ICH parties has two seats on the ICH
The Coordinators are fundamental to the smooth running of the ICH
and are nominated by each of the six parties. An ICH Coordinator
acts as the main contact point with the ICH Secretariat.
8. ICH Secretariat
The Secretariat is primarily concerned with preparations
for, and documentation of, meetings of the Steering
Committee as well as coordination of preparations for
Working Group and Discussion Group meetings.
Information on ICH Guidelines and the general ICH
process can be obtained from the ICH Secretariat.
ICH Working Group
Depending on the type of harmonization activity needed,
the Steering Committee will endorse the establishment
of one of three types of working group i.e., Expert
Working Group (EWG), Implementation Working Group
(IWG) or Informal Working Group.
Q1A (R2): Stability Testing of New Drug Substances and
The purpose of stability testing is to provide evidence on how
the quality of a drug substance or drug product varies with
time under the influence of a variety of environmental factors
such as temperature, humidity, and light, and to establish a re-
test period for the drug substance or a shelf life for the drug
Q1B: Photostability Testing of New Drug Substances and
• Give guidance on the basic testing protocol required to
evaluate the light sensitivity and stability of new drugs and
10. Q1C: Stability Testing for New Dosage Forms
Gives guidelines for new formulations of already approved
medicines and defines the circumstances under which reduced
stability data can be accepted.
Q1D: Bracketing and Matrixing Designs for Stability Testing of
New Drug Substances and Products
Q1E: Evaluation of Stability Data
• This guideline addresses the evaluation of stability data that
should be submitted in registration applications for new
molecular entities and associated drug products. The guideline
provides recommendations on establishing shelf lives for drug
substances and drug products intended for storage at or below
11. Q1F: Stability Data Package for Registration Applications in
Climatic Zones III and IV
• Describes harmonised global stability testing requirements in
order to facilitate access to medicines by reducing the number
of different storage conditions. WHO conducted a survey
amongst their member states to find consensus on 30°C/65%
RH as the long-term storage conditions for hot-dry and hot-
12. Q2-Analytical validation
Q2(R1): Validation of Analytical Procedures: Text and
• The objective of validation of an analytical procedure is to
demonstrate that it is suitable for its intended purpose
• Gives validation parameters needed for a variety of analytical
• It also discusses the characteristics that must be considered
during the validation of the analytical procedures
13. • Types of Analytical Procedures to be validated
o Identification tests;
o Quantitative tests for impurities content;
o Limit tests for the control of impurities;
o Quantitative tests of the active moiety in samples of
drug substance or drug product or other selected
components in the drug product.
• Typical validation characteristics of
Intermediate Precision), Specificity, Detection
Limit, Quantitation Limit, Linearity, Range.
14. Q3A- Q3D----Impurities
Q3A(R2): Impurities in New Drug Substances
• The guideline addresses the chemistry and safety aspects of
impurities, including the listing of impurities, threshold limit,
identification and quantification.
• Classification of Impurities: are of 3 types
o Organic impurities (process- and drug-related)
o Inorganic impurities
o Residual solvents
15. Q3B(R2): Impurities in New Drug Products
Q3C(R4): Impurities: Guideline for Residual
Carbon tetrachloride 4ppm
Formamide, Hexane 290ppm
16. Q4: Pharmacopoeias
Q4A: Pharmacopoeial Harmonisation
Q4B: Evaluation and Recommendation of
Pharmacopoeial Texts for Use in the ICH
• This document describes a process for the evaluation
and recommendation given by the Q4B Expert
Working Group (EWG) for selecting pharmacopoeial
texts to facilitate their recognition by regulatory
authorities for use, interchangeable in the ICH
18. Q5A-Q5E---Quality of biotechnological
Q5A(R1): Viral Safety Evaluation of
Biotechnology Products Derived from Cell
Lines of Human or Animal Origin
• This document is concerned with testing and evaluation of the
viral safety of biotechnology products derived from cell lines
of human or animal origin (i.e., mammalian, avian, insect)
• The objective is to provide a general framework for virus
testing experiments for the evaluation of virus clearance and
the design of viral tests and clearance evaluation studies.
19. • Three principal, complementary approaches have evolved to
control the potential viral contamination of biotechnology
a) selecting and testing cell lines and other raw materials,
including media components, for the absence of undesirable
viruses which may be infectious and/or pathogenic for
b) Testing the capacity of the processes to clear infectious
c) testing the product at appropriate steps for absence of
contaminating infectious viruses.
20. Q5B: Quality of Biotechnological Products :
Analysis of the Expression Construct in Cells Used for
Production of r-DNA Derived Protein Products
• This document presents guidance regarding the
characterization of the expression construct for the
production of recombinant DNA protein products in
eukaryotic and prokaryotic cells.
• expression construct should be analysed using nucleic acid
21. Q5C: Quality of Biotechnological Products :
Stability Testing of
Q5D: Derivation and Characterisation of Cell
Substrates Used for Production of
• The objective of this guideline is to provide broad
guidance on appropriate standards for cell
22. Q5E: Comparability of Biotechnological/
Biological Products Subject to Changes in
Their Manufacturing Process
• The objective of this document is to provide principles for
assessing the comparability of biotechnological/ biological
products before and after changes are made in the
manufacturing process for the drug substance or drug product.
• Therefore, this guideline is intended to assist in the collection
of relevant technical information which serves as evidence
that the manufacturing process changes will not have an
adverse impact on the quality, safety and efficacy of the drug
23. Q6 : Specifications for New Drug Substances
• Bulk drug substance and final product specifications
are key parts of the core documentation for world-
wide product license applications.
• This leads to conflicting standards for the same
product, increased expenses and opportunities for
error as well as a potential cause for interruption of
24. Q6A: Specifications : Test Procedures and Acceptance
Criteria for New Drug Substances and New Drug
Products : Chemical Substances
• The main objective of this guideline is to establish a single
set of global specifications for new drug substances and
new drug products.
• A specification is defined as a list of tests, references to
analytical procedures, and appropriate acceptance
criteria, which are numerical limits, ranges
• This guideline addresses specifications, i.e., those tests,
procedures, and acceptance criteria which play a major
role in assuring the quality of the new drug substance and
new drug product during shelf life.
25. • Universal Tests:
• The following tests are considered generally applicable
to all new drug substances and drug products.
• Specific Tests for drug substances :
o Physicochemical properties
o Particle size
o Polymorphic forms
o Tests for chiral new drug substances
o Water content
o Inorganic impurities
o Microbial limits
26. • Specific Tests for drug products(oral dosage
Particle size distribution:
Uniformity of dosage units:
Antioxidant preservative content:
27. • Specific Tests for drug products (Parenteral Drug
• Uniformity of dosage units
• Particle size distribution
• pH (Osmolarity)
• Particulate matter
• Water content
• Antimicrobial preservative
• Antioxidant preservative content
• Functionality testing of delivery systems
28. Q6B: Specifications : Test Procedures and
Acceptance Criteria for Biotechnological/Biological
• This document provides guidance on justifying and setting
specifications for proteins and polypeptides which are
derived from recombinant or non-recombinant cell cultures.
• A valid biological assay to measure the biological activity
should be provided by the manufacturer.
• Examples of procedures used to measure biological activity
Animal-based biological assays, which measure an
organism's biological response to the product;
Cell culture-based biological assays, which measure
biochemical or physiological response at the cellular level;
Biochemical assays, which measure biological activities such
as enzymatic reaction rates or biological responses induced
by immunological interactions.
29. Q7: Good Manufacturing Practice Guide for
Active Pharmaceutical Ingredients
• The main objective of this guideline is that
to maintain the quality of the active
• Buildings and Facilities:
• Process equipment:
• Documentation and Records:
30. Q8(R2): Pharmaceutical Development
• This guideline is intended to provide guidance on the
contents of Pharmaceutical Development of drug
• The aim of pharmaceutical development is to design
a quality product and its manufacturing process to
consistently deliver the intended performance of the
• The Pharmaceutical Development section also
describe the type of dosage form and the formulation
that are suitable for the intended use.
• Q8 gives information about Drug Substance,
Excipients, Container Closure System.
31. Q9: Quality Risk Management
• The purpose of this document is to offer a
systematic approach to quality risk management.
• This guideline provides principles and tools for
quality risk management that can be applied to
all aspects of pharmaceutical quality including
development, manufacturing, distribution; and
the inspection and submission/review processes
throughout the lifecycle of drug substances and
drug (medicinal) products, biological and
biotechnological products, including the use of
raw materials, solvents, excipients, packaging and
32. • PRINCIPLES OF QUALITY RISK MANAGEMENT
• Two primary principles of quality risk
– The evaluation of the risk to quality should be
based on scientific knowledge and ultimately link
to the protection of the patient; and
– The level of effort and documentation of the
quality risk management process should be
commensurate with the level of risk.
33. General Quality Risk Management Process:
Quality Risk Management Process
Output / Result of the
Quality Risk Management Process
34. Q10: Pharmaceutical Quality System
• This document establishes a new ICH tripartite
guideline describing a model for an effective
quality management system for the
pharmaceutical industry, referred to as the
Pharmaceutical Quality System.
• comprehensive model for an effective
pharmaceutical quality system is based on
International Standards Organization (ISO)
quality concepts, includes applicable Good
Manufacturing Practice (GMP) regulations
35. Status of Safety Topics Safety" Topics, i.e., those
relating to in vitro and in vivo pre-clinical studies (Carcinogenicity
Testing, Genotoxicity Testing, etc.)
S1A-S1C---- Carcinogenicity studies:
S1A: Guideline on the Need for Carcinogenicity
Studies of Pharmaceuticals
• Carcinogenicity studies should be performed for any
pharmaceutical whose expected clinical use is continuous 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.
36. • The objectives of carcinogenicity studies are to identify a
tumorigenic potential in animals and to 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.
S1C(R2): Dose Selection for Carcinogenicity Studies of
• 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.
37. S2– Genotoxicity:
o S2(R1): Guidance on Genotoxicity Testing and Data Interpretation
for Pharmaceuticals Intended for Human Use
• This guidance is a combination of ICH S2A and S2B guidelines:
o S2A: Guidance on Specific Aspects of Regulatory Genotoxicity
Tests for Pharmaceuticals;
• This document provided specific guidance and recommendations
for in vitro and in vivo tests and on the evaluation of test results.
It includes terms related to genotoxicity tests to improve
consistency in applications.
38. • S2B: Genotoxicity: A Standard Battery for Genotoxicity Testing for
• This document addresses two fundamental areas of genotoxicity
testing: the identification of a standard set of assays to be
conducted for registration, and the extent of confirmatory
experimentation in any particular genotoxicity assay in the
• Registration of pharmaceuticals requires a comprehensive
assessment of their genotoxic potential. It is clear that no single
test is capable of detecting all relevant genotoxic agents.
Therefore, the usual approach should be to carry out a battery of
in vitro and in vivo tests for genotoxicity
39. • The purpose of this guideline is to optimize the standard
genetic toxicology battery for prediction of potential
human risks, and for interpretation of results, with the
ultimate goal of improving risk characterization for
carcinogenic effects that have their basis in changes in the
40. • S3A –S3B--- Toxicokinetics and Pharmacokinetics:
• S3A: Note for Guidance on Toxicokinetics: The
Assessment of Systemic Exposure in Toxicity Studies
• ICH guidelines do not require toxicokinetic studies to be
conducted, except in pregnant, lactating animals, before
initiating reproductive studies.
• In this context, toxicokinetics is defined as the generation
of pharmacokinetic data, either as an integral component
in the conduct of non-clinical toxicity studies or in
specially designed supportive studies, in order to assess
• This document gives guidance on developing test
strategies in toxicokinetics and the need to integrate these
pharmacokinetics into toxicity testing, in order to aid in
the interpretation of the toxicology findings and and their
relevance to clinical safety issues
41. • The primary objective of toxicokinetics is: to describe the
systemic exposure achieved in animals and its relationship
to dose level and the time course of the toxicity study.
42. • S3B: Pharmacokinetics: Guidance for Repeated
Dose Tissue Distribution Studies
• Tissue distribution studies are essential in providing information
on distribution and accumulation of the compound and/or
metabolites, especially in relation to potential sites of action; this
information may be useful for designing toxicology and
pharmacology studies and for interpreting the results of these
• This document gives guidance, when the repeated dose tissue
distribution studies should be considered (i.e., when appropriate
data cannot be derived from other sources). It also gives
recommendations on the conduct of such studies
43. S4: Duration of Chronic Toxicity Testing in Animals
(Rodent and Non-Rodent Toxicity Testing)
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 product
• Rodents(a study of 6 months duration)
• Non-rodents(a study of nine months duration).
44. • S5: Detection of Toxicity to Reproduction for
Medicinal Products & Toxicity to Male Fertility
• This document provides guidance on tests for
• 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
• It should encourage the full assessment on the safety of
chemicals on the development of the offspring.
45. • S6: Preclinical Safety Evaluation of
This document covers the pre-clinical 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.
The primary goals of preclinical safety evaluation are:
1) to identify an initial safe dose and subsequent dose in
2) to identify potential target organs for toxicity and for the
study of whether such toxicity is reversible;
3) to identify safety parameters for clinical monitoring.
46. • S7A: Safety Pharmacology Studies for Human
• This guideline was developed to protect clinical trial
participants and patients receiving marketed products from
potential adverse effects of pharmaceuticals
• This document addresses the definition, objectives and scope
of safety pharmacology studies.
• It also addresses which studies are needed before initiation of
Phase 1 clinical studies as well as information needed for
47. S7B : The Nonclinical Evaluation of the Potential
for Delayed Ventricular Repolarization (QT
By Human Pharmaceuticals
• This guideline describes a non-clinical testing strategy for
assessing the potential of a test substance to delay ventricular
• This guideline includes information concerning non-clinical
assays and integrated risk assessments.
48. • S8 : Immunotoxicity Studies for Human
• This guideline addresses the recommendations on nonclinical
testing for immunosuppressant.
• The guideline might also apply to drugs in which clinical signs
of immunosuppressant are observed during clinical trials and
following approval to market.
• The term immunotoxicity in this guideline will primarily refer
to immunosuppressant, i.e. a state of increased susceptibility
to infections or the development of tumors.
49. • S9: Nonclinical Evaluation for Anticancer
• This guideline provides information for pharmaceuticals
that are only intended to treat cancer in patients with late
stage or advanced disease regardless of the route of
administration, including both small molecule and
• It describes the type and timing of nonclinical studies in
relation to the development of anticancer pharmaceuticals
and references other guidance as appropriate.
• This guideline aims to facilitate and accelerate the
development of anticancer pharmaceuticals and to protect
patients from unnecessary adverse effects, while avoiding
unnecessary use of animals and other resources
50. • Efficacy Guidelines Efficacy" Topics, i.e., those
relating to clinical studies in human subject
(Dose Response Studies, Good Clinical Practices,
51. Clinical safety:
E1: The Extent of Population Exposure to Assess
Clinical Safety for Drugs Intended for Long-Term
Treatment of Non-Life-Threatening Conditions
• This document gives recommendations on the number of
patients and duration of exposure for the safety
evaluation of drugs intended for the long-term treatment
of non-life-threatening conditions
• This guidelines gives information on duration of drug
exposure and its relationship to both time and magnitude
of occurrence of adverse events
52. E2A: Clinical Safety Data Management :
Definitions and Standards
• This document gives standard definitions and
terminology for key aspects of clinical safety reporting.
• It also gives guidance on mechanisms for handling
adverse drug reactions in the investigational phase of
53. E2B(R3): Clinical Safety Data Management
Data Elements for Transmission of Individual
Case Safety Reports
• The objectives of the working group is to identify, define and
standardize the data elements for the transmission of individual
case safety reports(adverse reactions, adverse event reports).
• Following its submission to ISO for development as an
International Standard. Key parts of this updated guideline will be
incorporated into the Implementation Guide for Electronic
Transmission of Individual Case Safety Reports Message
Specification which is currently available for public awareness.
54. E2C(R1): Clinical Safety DataManagement:
Periodic Safety Update Reports for Marketed
• This document gives guidance on the format and
content of safety updates, which need to be
provided at regular intervals to regulatory authorities
to ensure maximum efficacy and to avoid duplication
of marketed drugs .
55. E2D: Post-Approval Safety Data Management: Definitions and
• This document provides a standardized procedure for post-
approval safety data management.
• The definitions of the terms specific to post-approval phase
are also provided.
• The practices of the data management were standardized in
such cases obtained from consumers, literatures, internets
which are all specific to post-approval data management.
56. E2E: Pharmacovigilance Planning
• This guideline is intended to aid in planning
pharmacovigilance activities, especially in preparation
for the early post marketing of a new drug (in this
guideline, the term "drug" denotes chemical entities,
biotechnology-derived products, and vaccines).
• The main focus of this guideline is on a Safety
Specification and Pharmacovigilance Plan that might be
submitted at the time of license application.
• The guideline describes a method for summarizing the
important identified risks of a drug, important potential
risks, and important missing information, including the
potentially at-risk populations and situations where the
product is likely to be used that have not been studied.
57. E2F: Development Safety Update Report
• The main focus of the DSUR is collection of data from clinical trials of
investigational drugs including biological’s, with or without a marketing
• The DSUR should provide safety information from all ongoing clinical trials
that the sponsor is conducting or has completed during the review period
clinical trials conducted using an investigational drug whether with or
without a marketing approval, i.e., human pharmacology, therapeutic
exploratory and therapeutic confirmatory trials (Phase I – III)
clinical trials conducted using marketed drugs in approved indications, i.e.,
therapeutic use trials (Phase IV);
other therapeutic use of an investigational drug;
comparability trials conducted to support changes in the manufacturing
process of medicinal products
58. E3: Structure and Content of Clinical Study
• This document describes the format and content of a study
report that will be acceptable in all three ICH regions. It
consists of a core report suitable for all submissions and
• The clinical study report described in this guideline is an
integrated full report of an individual study of any
therapeutic, prophylactic or diagnostic agent (referred to
herein as drug or treatment) conducted in patients.
59. • The guideline is intended to assist sponsors for the
development of a report that is complete, free from
ambiguity, well organized and easy to review
STRUCTURE AND CONTENT OF CLINICAL STUDY REPORTS
• Title page
• Table of contents for the individual clinical study report
• List of abbreviations and definition of terms
• Ethics (ethical conduct of the study, patient information and
60. • Investigators and study administrative structure
• Study objectives
• Overall study design and plan - description
• Selection of study population
• Selection of doses in the study
• Efficacy and safety variables
• Efficacy results and tabulations of individual patient
• Safety evaluation
61. E4: Dose-Response Information to Support Drug
• This document gives recommendations on the design
and conduct of studies to assess the relationship
between doses, blood levels and clinical response
throughout the clinical development of a new drug.
• This information can help in identifying an appropriate
starting dose, to adjust dosage to the needs of a
particular patient, and a dose beyond which
unacceptable side effects are seen.
62. E5(R1): Ethnic Factors in the Acceptability of
Foreign Clinical Data
• The purpose of this guidance is to facilitate the
registration of medicines among ICH regions.
• This document addresses the intrinsic characteristics of
the drug recipient and extrinsic characteristics
associated with environment and culture that could
affect the results of clinical studies carried out in
• Describes the concept of the "bridging study" that a
new region may request to determine whether data
from another region are applicable to its population.
63. E6(R1): Good Clinical Practice : Consolidated Guideline
• Good Clinical Practice (GCP) is an international ethical
and scientific quality standard for designing,
conducting, recording and reporting trials that involve
the participation of human subjects.
• This Good Clinical Practices document describes the
responsibilities and expectations of all participants in
the conduct of clinical trials, including investigators,
monitors, sponsors .
• GCPs cover aspects of monitoring, reporting and
achieving of clinical trials and incorporating these into
Essential Documents and on the Investigator's
64. E7-E11----CLINICAL TRIALS:
E7: Studies in Support of Special Populations :
• This document provides recommendations on the special
considerations which apply in the design and conduct of clinical
trials of medicines that are likely to have significant use in the
• E.g.: New Molecular Entities that are likely to have significant use
in the elderly, because the disease intended to be treated is
characteristically a disease of ageing ( e.g., Alzheimer's disease)
65. E8: General Considerations for Clinical Trials
This document sets out the general scientific principles for the
conduct, performance and control of clinical trials.
The guideline addresses a wide range of subjects in the design and
execution of clinical trials.
The ICH document "General Considerations for Clinical Trials" is
(a) describe internationally accepted principles and practices in the
conduct of both individual clinical trials and overall
development strategy for new medicinal products
66. (b) facilitate the evaluation and acceptance of foreign clinical
trial data by promoting common understanding of general
c) present an overview of the ICH clinical safety and efficacy
documents and facilitate the user's access to guidance
(d) provide a separate glossary of terms used in the ICH clinical
safety and efficacy related documents that pertain to clinical
67. E9: Statistical Principles for Clinical Trials
• This biostatistical guideline describes essential considerations on
the design and analysis of clinical trials, especially the
"confirmatory" (hypothesis-testing) trials that are the basis for
68. E10: Choice of Control Group and Related Issues
in Clinical Trials
• This document addresses the choice of control groups in clinical
• Control groups in clinical trials can be classified on the basis of
two critical attributes: (1) the type of treatment used and (2) the
method of determining who will be in the control group.
• The type of control treatment may be any of the following four:
(1) placebo, (2) no treatment, (3) different dose or regimen of
the study treatment, or (4) a different active treatment.
69. E11: Clinical Investigation of Medicinal Products in
the Pediatric Population
• This document addresses the conduct of clinical
trials of medicines in pediatric populations.
• This document will facilitate the development of
safe and effective use of medicinal product in
• Specific clinical study include:
• (1) timing of initiation of pediatric studies during
medicinal product development;
• (2) types of studies (pharmacokinetic,
pharmacokinetic/ pharmacodynamic (PK/PD),
• (3) age categories;
• (4) ethics of pediatric clinical investigation.
70. • E12-Guidelines for Clinical Evaluation by
• The ICH Efficacy Guidelines are applicable to all therapeutic
classes of drugs, but there are some therapeutic classes which
need individual drug evaluation guidelines among the three
71. E12: Principles for Clinical Evaluation of New
• This document provides general principles for the
clinical evaluation of new anti-hypertensive drugs.
• It describes core principles for the evaluation of
antihypertensives that are accepted in the three ICH
regions, but some region-specific differences remain,
therefore this document should be considered an "ICH
Principle Document" rather than an "ICH Guideline".
72. E14: The Clinical Evaluation of QT/QTc Interval Prolongation and
Pro-Arrhythmic Potential for Non-Antiarrhythmic Drugs
• This document provides recommendations to sponsors concerning
the design, conduct, analysis, and interpretation of clinical studies
to assess the potential of a drug to delay cardiac repolarization.
• This assessment should include testing the effects of new agents
on the QT/QTc interval as well as the collection of cardiovascular
• The investigational approach used for a particular drug should be
individualized, depending on the pharmacodynamic,
pharmacokinetic, and safety characteristics of the product, as well
as on its proposed clinical use.
73. E15: Definitions for Genomic Biomarkers, Pharmacogenomics,
Pharmacogenetics, Genomic Data and Sample Coding
• In order to develop harmonised approaches to drug regulation,
it is important to ensure that consistent definitions of
terminology are being applied across all constituents of the
International Conference on Harmonisation (ICH).
• An agreement on definitions will facilitate the harmonization in
the discipline of pharmacogenomics and pharmacogenetics for
global drug development and approval processes.
74. E16: Genomic Biomarkers Related to Drug
Response: Context, Structure and Format of
• The guideline describes recommendations regarding context,
structure, and format of regulatory submissions for qualification
of genomic biomarkers(E15).
• clinical and non-clinical genomic biomarkers related to drug
response including pharmacokinetics, pharmacodynamics,
efficacy and safety aspects.
76. M1 Medical Terminology
• New Medical Dictionary for Regulatory Activities Terminology
(MedDRA) was developed by the working group of ICH and is
owned by the International Federation of Pharmaceutical
Manufacturers and Associations (IFPMA) acting as trustee for
the ICH steering committee.
• It provides an international medical dictionary applicable to
all phases of product development.
• Its goal is to provide a comprehensive and specific
terminology to help standardize, facilitate and simplify
77. M2 Electronic Standards for Transmission of Regulatory Information
• Facilitate international electronic communication by evaluating
and recommending the specifications
• The first Specification developed by the M2 EWG was the
Individual Case Safety Report (ICSR), created as the electronic
message for the ICH E2B(R2)
• The second Specification developed by the M2 EWG was the
Electronic Common Technical Document (eCTD) created as the
electronic message for the Common Technical Document
developed by the ICH M4.
• ICH M2 has initiated the development of the Next Major Version
of the eCTD (eCTD NMV) to improve robustness, flexibility and
long term stability of the message.
78. • M3(R2): Guidance on Non-Clinical Safety Studies for the
Conduct of Human Clinical Trials and Marketing Authorization
• The present guidance represents the consensus that exists
regarding the type and duration of nonclinical safety studies
and their timing to support the conduct of human clinical trials
and marketing authorization for pharmaceuticals.
• The nonclinical safety assessment for marketing approval of a
pharmaceutical usually includes pharmacology studies, general
toxicity studies, toxicokinetic and nonclinical pharmacokinetic
studies, reproduction toxicity studies, genotoxicity studies and,
for drugs that have special cause for concern or are intended for
a long duration of use
79. • The goals of the nonclinical safety evaluation generally include
a characterisation of toxic effects with respect to target
organs, dose dependence, relationship to exposure, and,
when appropriate,potential reversibility.
• This information is used to estimate an initial safe starting
dose and dose range for the human trials and to identify
parameters for clinical monitoring for potential adverse
80. M4:The Common Technical Document
• The Common Technical Document provides a harmonised
structure and format for new product applications. The
Common Technical Document was agreed upon in November
2000 in San Diego, USA.
• This Common Technical Document is divided into four
separate sections. The four sections address the application
organisation (M4 organise), the Quality section (M4Q), the
Safety section (M4S) and the Efficacy section (M4E) of the
• An electronic version of the Common Technical Document
(eCTD) developed by the eCTD Implementation Working
Group. The Electronic Common Technical Document (eCTD)
allows for the electronic submission of the Common Technical
Document (CTD) by an applicant to regulator
81. M5: Data Elements and Standards for Drug
• This document provides guidance on the harmonized
standards related to core sets of medicinal product
information and medicinal product terminology.
• Facilitate the exchange and practical use of medicinal
product data by regulators and pharmaceutical industry.