Unnati Garg (ICH Guidelines)

Amity Institute of Pharmacy
ICH GUIDELINES
UNNATI GARG
M. Pharm (Pharmaceutics)
A10647021011
1
INTRODUCTION
• The International Council for Harmonisation of Technical

Requirements for Pharmaceuticals for Human Use (ICH) is
unique in bringing together the regulatory authorities and
pharmaceutical industry to discuss scientific and technical
aspects of drug registration.
• ICH is a joint initiative involving both regulators and research-

based industry representatives of the EU, Japan and USA.
• ICH's mission is to achieve greater harmonisation worldwide

to ensure that safe, effective, and high-quality medicines are
developed and registered in the most resource-efficient
manner.
2
OBJECTIVES Amity Institute of Pharmacy
To develop and register To prevent unnecessary

pharmaceuticals in efficient duplication of clinical trials
& cost-effective manner. on humans.
To promote public health.
To harmonize technical To minimize the use of animal

requirements for registration testing without compromising
or marketing approval safety and effectiveness of drug.
3
STRUCTURE OF ICH
ICH Steering Committee: The Steering Committee, made of

six ICH Parties, governs the ICH, determining the policies and
procedures, selecting topics for harmonisation and monitoring
progress of harmonisation initiatives.
ICH Secretariat: The ICH 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.
4
ICH Coordinators: 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.
ICH Working Groups: These are created by the Steering

Committee when a new topic is accepted for harmonisation,
and is charged with developing a harmonised guideline that
meets the objectives outlined in the Concept Paper and
Business Plan.
5
GUIDELINES
QUALITY SAFETY
MULTI-
EFFICACY
DISCIPLINARY
6
QUALITY GUIDELINES
• Those relating to chemical & pharmaceutical quality

assurance (Stability testing, Impurity testing, etc.)
• Q1A – Q1F – Stability
• Q2 – Analytical Validation
• Q3A – Q3D – Impurities
• Q4 – Pharmacopoeias
• Q5A – Q5E – Quality Of biotechnological Products
7
• Q6 – Specifications for New Drug Substances And Products
• Q7 – Good Manufacturing Practice Guide for

Active Pharmaceutical Ingredients
• Q8(R2) – Pharmaceutical development
• Q9 – Quality Risk management
• Q10 – Pharmaceutical quality System
• Q11 – Development and Manufacture of Drug Substances
• Q12 – Lifecycle Management

8
Q1A-Q1F Amity Institute of Pharmacy
Q1A(R2): Stability testing of new drug substances and products.

This Guideline provides recommendations on stability testing
protocols including temperature, humidity and trial duration for
Climatic Zone I and II.
Q1B: Photostability testing of new drug substances and products.

This document is an annex to the main stability Guideline and gives
guidance on the basic testing protocol required to evaluate the light
sensitivity and stability of new drugs and products.
9
Q1A-Q1F
Q1C: Stability testing for new dosage forms

It extends the main stability Guideline 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.
This document is intended to address recommendations on the
application of bracketing and matrixing to stability studies
conducted in accordance with principles outlined in the main
stability Guideline.
10
Q1E: Evaluation of stability data.
This document extends the main stability Guideline by

explaining possible situations where extrapolation of retest
periods or shelf-lives beyond the real-time data may be
appropriate. Furthermore, it provides examples of statistical
approaches to stability data analysis.
Q1F: Stability data package for registration applications in

climate zones III & IV.
The ICH Steering Committee endorsed the withdrawal of the

Q1F Guideline at Yokohama meeting in June 2006
11
Q2 – ANALYTICAL
VALIDATION Amity Institute of Pharmacy
Q2(R1): Validation of analytical procedures: Text and

Methodology
It discusses the characteristics that must be considered during the
validation of the analytical procedures which are included as part
of registration applications. It also include the actual experimental
data required, along with the statistical interpretation, for the
validation of analytical procedures.
12
Q3A – Q3E – IMPURITIES
Q3A(R2): Impurities in New Drug Substances

The Guideline addresses the chemistry and safety aspects of
impurities, including the listing of impurities in specifications
and defines the thresholds for reporting, identification and
qualification.
Q3B(R2): Impurities in New Drug Products

The Guideline specifically deals with those impurities which
might arise as degradation products of the drug substance or
arising from interactions between drug substance and excipients
or components of primary packaging materials.
13
Q3C(R8): Guidelines for Residual Solvent

Providing recommendations on the use of less toxic solvents in
the manufacture of drug substances and dosage forms and setting
pharmaceutical limits for residual solvents (organic volatile
impurities) in drug products.
Q3D(R1): Guidelines for Elemental Impurities

It establishes Permitted Daily Exposures (PDEs) for 24
Elemental Impurities (EIs) for drug products administered by the
oral, parenteral and inhalation routes of administration. In
addition, guidance is provided in Q3D on how to develop an
acceptable level for EIs for drug products administered by other
routes of administration.
14
Q3E EWG: Assessment and control of extractables and

leachables for pharmaceuticals and biologics
This guideline was endorsed in July 2019 and is still under
development.
Q4A: Pharmacopoeial Harmonization
The pharmacopoeial authorities, working together through
the Pharmacopoeial Discussion Group (PDG), have been closely
involved with the work of ICH since the outset and harmonisation
between the major pharmacopoeias, which started before ICH, has
proceeded in parallel.
15
Q4B: Evaluation and Recommendation of Pharmacopoeial Texts

for Use in the ICH Regions
This document describes a process for the evaluation and
recommendation by the Q4B Expert Working Group (EWG) of
selected pharmacopoeial texts to facilitate their recognition by
regulatory authorities for use as interchangeable in the ICH regions.
16
Q5A – Q5E – QUALITY OF BIOTECHNOLOGICAL
PRODUCTS Amity Institute of Pharmacy
Q5A(R1): Viral safety Evaluation of Biotechnological products

derived from cell lines of human or animal origin.
The purpose of this Guideline is to provide a general framework

for virus testing, experiments for the assessment of viral clearance
and a recommended approach for the design of viral tests and viral
clearance studies.
Q5B: Analysis of the expression construct in cells used

for production of r-DNA derived protein products.
This document is intended to describe the types of information that

are considered valuable in assessing the structure of the expression
construct used to produce recombinant DNA derived proteins.
17
Q5C: Stability testing of Biotechnological/Biological
Products.
This document augments the stability Guideline (Q1A) and deals
with the particular aspects of stability test procedures needed to
take account of the special characteristics of products in which
the active components are typically proteins and/or polypeptides.
Q5D: Derivation and characterization of cell substrates used

for production of Biotechnological/Biological Products.
This document provides broad guidance on appropriate standards
for the derivation of human and animal cell lines and microbial
cells used to prepare biotechnological/biological products, and
for the preparation and characterisation of cell banks to be used
for production.
18
Q5E: Comparability of Biotechnological/Biological Products

subject to changes in their manufacturing process.
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 product.
19
Q6A - Q6B - Specifications
Q6A: Specifications: Test Procedures and Acceptance Criteria for

New Drug Substances and New Drug Products: Chemical
Substances
This document provides guidance on the setting and justification of
acceptance criteria and the selection of test procedures for new drug
substances of synthetic chemical origin, and new drug products
produced from them, which have not been registered previously in the
ICH regions.
Q6B: Specifications: Test Procedures and Acceptance Criteria for

Biotechnological/Biological Products
This document provides general principles on the setting and
justification of a uniform set of international specifications for proteins
and polypeptides which are produced from recombinant or non-
recombinant cell-culture expression systems. 20
Q7 – Good Manufacturing Practices
Q7 – Good Manufacturing Practice Guide for Active

Pharmaceutical Ingredients
It is intended to help ensure that APIs meet the requirements for
quality and purity that they purport or are represented to
possess. This Guideline applies to the manufacture of APIs for
use in human drug (medicinal) products.
Q7 Q&A – Questions and Answers: Good Manufacturing

Practice Guide for Active Pharmaceutical Ingredients
Technical issues with regard to GMP of APIs – also in context
with new ICH Guidelines - are addressed in this Questions and
Answers document in order to harmonise expectations during
inspections, to remove ambiguities and uncertainties.
21
Q8 - Q9
Q8(R2) – PHARMACEUTICAL DEVELOPMENT
The Pharmaceutical Development section is intended to provide a
comprehensive understanding of the product and manufacturing
process for reviewers and inspectors.
Q9 – QUALITY RISK MANAGEMENT
This Guideline provides principles and examples of tools for
quality risk management that can be applied to different aspects
of pharmaceutical quality.
These aspects include development, manufacturing, distribution,
and the inspection and submission/review processes throughout
the lifecycle of drug substances
22
Q10 : PHARMACEUTICAL QUALITY SYSTEM

This Guideline applies to the systems supporting the
development and manufacture of pharmaceutical drug substances
and drug products, including biotechnology and biological
products, throughout the product lifecycle.
Q8/9/10 Q&As (R4): Q8/Q9/Q10-Implementation

The Questions and Answers developed by the Quality
Implementation Working Group (IWG) are intended to facilitate
the implementation of the Q8(R2), Q9 and Q10 Guidelines, by
clarifying key issues.

23
Q11 – Development and Manufacture
of Drug Substances Amity Institute of Pharmacy
Q11 – Development and Manufacture of Drug Substances

(Chemical entities and Biotechnological/Biological entities)
It addresses aspects of development and manufacture that pertain to
drug substance, including the presence of steps designed to reduce
impurities. This Guideline is applicable to drug substances as
defined in the Scope sections of ICH Guidelines Q6A and Q6B.
24
Q12 – Lifecycle Management
Q12: Technical and Regulatory considerations for

Pharmaceutical Product Lifecycle Management
This new Guideline is proposed to provide a framework to
facilitate the management of post-approval Chemistry,
Manufacturing and Controls (CMC) changes in a more
predictable and efficient manner across the product lifecycle.
25
SAFETY GUIDELINES
• Those relating to adverse effects of the products.
• S1A – S1C – Carcinogenecity studies
• S2 – Genotoxicity
• S3A – S3B – Toxicokinetics and pharmacokinetics
• S4: Duration of Chronic Toxicity Testing in Animals
• S5 – Detection of Toxicity to Reproduction for

Medicinal Products & Toxicity to Male Fertility
26
• S6 – Preclinical Safety Evaluation of Biotechnology-

Derived Pharmaceuticals
• S7A: Safety Pharmacology Studies for Human Pharmaceuticals
• S7B: The Nonclinical Evaluation of the Potential for

Delayed Ventricular Repolarization by Human Pharmaceuticals
• S8 – Immunotoxicity Studies for Human Pharmaceuticals
• S9 – Nonclinical Evaluation for Anticancer Pharmaceuticals
• S10: Photosafety Evaluation
• S11: Non-clinical Paediatric Safety

27
S1A – S1C – CARCINOGENECITY
STUDIES Amity Institute of Pharmacy
S1A: Need for Carcinogenicity Studies of Pharmaceuticals

This document provides a consistent definition of the
circumstances under which it is necessary to undertake
carcinogenicity studies on new drugs.
S1B: Testing for Carcinogenicity of Pharmaceuticals

This document provides guidance on approaches for evaluating
the carcinogenic potential of pharmaceuticals. The Guideline
embraces all pharmaceutical agents that need carcinogenicity
testing as indicated in Guideline S1A.
28
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 harmonise current practices and improve the design of
studies.
S2(R1) – Guidance on Genotoxicity testing Data

Interpretation for Pharmaceuticals intended for human use
This document provided specific guidance and recommendations
for in vitro and in vivo tests and on the evaluation of test results.
It includes a glossary of terms related to genotoxicity tests to
improve consistency in applications.
29
S3A – S3B – Toxicokinetics and
Pharmacokinetics Amity Institute of Pharmacy
S3A: Note for Guidance on Toxicokinetics: The assessment of

systemic exposure in Toxicity 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
This document gives guidance on circumstances when repeated dose
tissue distribution studies should be considered (e.g., when
appropriate data cannot be derived from other sources). It also gives
recommendations on the conduct of such studies.
30
S4 – Toxicity Testing Amity Institute of Pharmacy
S4: Duration of Chronic Toxicity Testing in Animals (Rodent

and Non-Rodent Toxicity Testing)
This guidance has been prepared for the development of
medicinal products with the exception of those already covered
by the ICH Guideline on Safety Studies for Biotechnological
Products, e.g., Monoclonal antibodies, recombinant DNA
proteins.
31
S5 – Reproductive
Toxicology Amity Institute of Pharmacy
S5(R3): Revision of S5 Guideline on Detection of Toxicity to

Reproduction for Human Pharmaceuticals
Guideline incorporates experience gained with the testing of
pharmaceuticals using the current and novel testing paradigms as
well as the advances of scientific, technological and regulatory
knowledge over the past years. The ICH S5(R3) provides human
safety assurance at least equivalent to that provided by current
testing paradigms.
32
S6 – Biotechnological
Products Amity Institute of Pharmacy
S6 (R1): Preclinical Safety Evaluation of Biotechnology-

Derived Pharmaceuticals
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.
33
S7A – S7B – Pharmacology
Studies Amity Institute of Pharmacy
S7A: Safety Pharmacology Studies for Human Pharmaceuticals

This Guideline generally applies to new chemical entities and
biotechnology-derived products for human use. It can be applied to
marketed pharmaceuticals when appropriate.
S7B: The Nonclinical Evaluation of the Potential for Delayed

Ventricular Repolarization 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 assays and integrated risk assessments.
34
S8 - Immunotoxicology
Studies Amity Institute of Pharmacy
S8 – Immunotoxicity Studies for Human Pharmaceuticals

This Guideline provides recommendations on nonclinical testing
approaches to identify compounds which have the potential to be
immunotoxic, and guidance on a weight-of-evidence decision
making approach for immunotoxicity testing.
35
S9 – Nonclinical Evaluation
for Anticancer Amity Institute of Pharmacy
Pharmaceuticals
S9 – Nonclinical Evaluation for Anticancer Pharmaceuticals

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.
S9 Q&As – Questions and Answers: Nonclinical Evaluation for

Anticancer Pharmaceuticals
The Questions and Answers developed by the S9 Implementation
Working Group (IWG) are intended to facilitate the implementation
of the S9 Guideline clarifying its scope as well as its interpretation
and implementation.
36
S10 – Photosafety
Evaluation Amity Institute of Pharmacy
S10: Photosafety Evaluation of Pharmaceuticals

This Guideline provides international standards for photosafety
assessment and harmonises such assessments supporting human
clinical trials and marketing authorizations for pharmaceuticals.
It includes factors for initiation of and triggers for additional
photosafety assessment
37
S11 – Nonclinical
Paediatric Safety Amity Institute of Pharmacy
S11: Nonclinical Safety Testing in Support of Development of

Paediatric Medicines
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.
38
EFFICACY GUIDELINES
• Those relating to clinical studies in Human subject (Dose

Response studies, Good Clinical Practices, etc.)
• E1 – Clinical Safety for Drugs used in Long Term Treatment

• E2A- E2F – Pharmacovigilance
• E3 - Clinical Study Reports
• E4: Dose-Response Studies
• E5 – Ethnic Factors
• E6 – Good Clinical Factors
• E7 – Clinical Trials in Geriatric Population
• E8 – General Considerations for Clinical Trials
39
• E9 – Statistical Principles for Clinical Trials

• E10 – Choice of Control Group in clinical Trials
• E11 – Clinical Trials in Pediatric Population
• E12 – Clinical Evaluation by Therapeutic Category
• E14 - Clinical Evaluation of QT
• E15 – Definitions in Pharmacogenetics/Pharmacogenomics
• E16 – Qualification of Genomic Biomarkers
• E17 – Multiregional Clinical Trials
• E18 – Genomic Sampling
40
E1 – Clinical Safety for Drugs used in
Long Term Treatment Amity Institute of Pharmacy
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 numbers of
patients and duration of exposure for the safety evaluation of
drugs intended for the long-term treatment of non-life-
threatening conditions.
41
E2A- E2F -
Pharmacovigilance Amity Institute of Pharmacy
E2A: Clinical Safety Data Management: Definitions and

Standards for Expedited Reporting
It also gives guidance on mechanisms for handling expedited
(rapid) reporting of adverse drug reactions in the investigational
phase of drug development.
E2B(R3): Clinical Safety Data Management: Data elements

for Transmission of Individual case safety reports.
The ICH Steering Committee had taken a key decision that
technical specifications should no longer be developed solely
within ICH but should be created in collaboration with Standards
Development Organisations (SDOs) to enable wider inter-
operability across the regulatory and healthcare communities.
42
E2C(R2): Periodic Benefit - Risk Evaluation Report

This document gives guidance on the format and content of
safety updates, which need to be provided at intervals to
regulatory authorities after products have been marketed.
E2D: Post-Approval Safety Data Management: Definitions

and Standards for Expedited Reporting
This document provides a standardised procedure for post-
approval safety data management and the guidance for gathering
and reporting information.
43
E2E: Pharmacovigilance Planning

This Guideline is intended to aid in planning pharmacovigilance
activities, especially in preparation for the early post-marketing
period of a new drug
E2F: Development Safety Update Report (DSUR)

DSUR proposed in this Guideline is intended to be a common
standard for periodic reporting on drugs under development
(including marketed drugs that are under further study) among
the ICH regions.
44
E3 – E4
E3: Structure and content of clinical study Reports

This document describes the format and content of a clinical study
report that will be acceptable to all regulatory authorities of the
ICH regions. It consists of a core report suitable for all submissions
and appendices that need to be available but will not be submitted
in all cases.
E4: Dose – Response Information to Support drug Registration

This document gives recommendations on the design and conduct
of studies to assess the relationships among dose, drug-
concentration in blood, and clinical response throughout the
clinical development of a new drug
45
E5 - E6 Amity Institute of Pharmacy
E5(R1): Ethnic Factors in the Acceptability of foreign

Clinical Data
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 regions
E6(R2): Good Clinical Practice (GCP)

This guideline encourages implementation of improved and more
efficient approaches to clinical trial design, conduct, oversight,
recording and reporting, while continuing to ensure human
subject protection and reliability of trial results.
46
E7 - E8
E7: Studies in Support of Special Populations : Geriatrics

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
elderly
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.
47
E9 - E10
E9: Statistical Principles for Clinical Trials

The principles outlined in this guidance are primarily relevant to
clinical trials conducted in the later phases of development, many
of which are confirmatory trials of efficacy.
E10: Choice of Control Group and Related Issues in clinical

Trials
It points out the assay sensitivity problem in active control
equivalence / non-inferiority trials that limits the usefulness of
trial design in many circumstances.
48
E11(R1): Addendum: Clinical Investigation of Medicinal Products

in the Pediatric Population
This Addendum is proposed to address new scientific and technical
knowledge advances in pediatric drug development.
E12: Principles for Clinical Evaluation of New Antihypertensive

Drugs
This therapeutic area document considers the Clinical Evaluation of
New Antihypertensive Drugs. It provides a set of "Principles" on which
there is general agreement among all ICH regions covering endpoints
and trial designs.
49
E14: The Clinical Evaluation of QT/QTc Interval Prolongation

and Proarrhythmic 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 repolarisation.
E15: Definitions for Genomic Biomarkers, Pharmacogenomics,

Pharmacogenetics, Genomic Data and Sample Coding
Categories
The validation and qualification processes for genomic biomarkers,
evidence for their intended use and acceptance criteria across ICH
regions are outside of the scope of this guideline.
50
E16 - E17
E16: Biomarkers Related to Drug or Biotechnology Product

Development: Context, Structure and Format of Qualification
submissions
The Guideline describes recommendations regarding context,
structure, and format of regulatory submissions for qualification of
genomic biomarkers, as defined in ICH E15.
E17: General Principles for Planning and Design of Multi-

Regional Clinical Trials
This Guideline provides guidance on general principles on
planning/designing Multi-Regional Clinical Trial (MRCT). Drug
development has been globalised and MRCT for regulatory
submission has widely been conducted in ICH regions and beyond.
51
E18 – Genomic
Sampling Amity Institute of Pharmacy
E18: Genomic sampling and Management of Genomic Data

This Guideline will facilitate the implementation of genomic
studies by enabling a common understanding of critical
parameters for the unbiased collection, storage, and optimal use
of genomic samples and data.
52
MULTIDISCIPLINARY
GUIDELINES Amity Institute of Pharmacy
• Topics which do not fit uniquely into one of the above

stated categories.
• M1: MedDRA Terminology
• M2: Electronic Standards
• M3: Nonclinical Safety Studies
• M4: Common Technical Document
• M5: Data Elements and Standards for Drug Dictionaries

53
• M6: Gene Therapy
• M7: Mutagenic Impurities
• M8: Electronic Common Technical Document
• M9: Biopharmaceutics Classification System-based Biowaivers
54
M1 - M2
M1: MedDRA – Medical Dictionary for Regulatory Activities

MedDRA is a rich and highly specific standardised medical
terminology developed by ICH to facilitate sharing of regulatory
information internationally for medical products used by humans. It is
used for registration, documentation and safety monitoring of medical
products both before and after a product has been authorised for sale.
M2 EWG: Electronic Standards for the Transfer of Regulatory

Information
objective of this guideline is facilitating international electronic
communication by evaluating and recommending, open and non-
proprietary - to the extent possible - Electronic Standards for the
Transfer of Regulatory Information (ESTRI) that will meet the
requirements of the pharmaceutical companies and regulatory
authorities. 55
M3: Nonclinical
Safety Studies Amity Institute of Pharmacy
M3(R2): Guidance on Non-Clinical Safety Studies for the

Conduct of Human Clinical Trials and Marketing
Authorization for Pharmaceuticals
The recommendations of this revised Guidance further harmonise
the nonclinical safety studies to support the various stages of
clinical development among the ICH regions. 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
authorisation for pharmaceuticals.
56
M4: CTD Amity Institute of Pharmacy
CTD: The Common Technical Document

The agreement to assemble all the Quality, Safety and Efficacy
information in a common format (called CTD - Common
Technical Document ) has revolutionised the regulatory review
processes, led to harmonised electronic submission that, in turn,
enabled implementation of good review practices.
57
M5: Data Elements and Standards
for Drug Dictionaries Amity Institute of Pharmacy
M5: Data Elements and Standards for Drug Dictionaries

The aim of this guideline is to develop ICH requirements for
the standardisation of medicinal product identifiers and related
terminology. In particular, a need was identified
to harmonise product information that would facilitate the
electronic exchange of Individual Case Safety Reports (ICSRs)
within and across ICH regions using the ICH E2B format in post-
marketing pharmacovigilance.
58
M6: Gene Therapy
M6: Virus and Gene Therapy Vector Shredding and

Transmission
ICH Steering Committee endorsed the development of an ICH
Guideline on this topic with the aim of providing more extensive
information to improve harmonisation amongst the ICH regions.
In April 2011, this topic was ceased following the ICH Steering
Committee discussion. he decision was based on the opinion that
the current state of science and related resource allocation would
not allow this topic to be supported as a topic for harmonisation.
59
M7: Mutagenic
Impurities Amity Institute of Pharmacy
M7: Assessment and control of DNA Reactive (Mutagenic)

Impurities in Pharmaceuticals to Limit Potential
Carcinogenic Risk
It is intended to resolve questions such as whether impurities
with similar alerts that potentially have similar mechanism of
action should not be combined in calculating a Threshold of
Toxicological Concern (TTC) and whether the TTC may differ
based on differences in the approved duration of use.
60
M8: Electronic Common
Technical Document Amity Institute of Pharmacy
M8 eCTD v3.2.2: Electronic Common Technical Document

(eCTD) v3.2.2
The eCTD is defined as an interface for industry to agency
transfer of regulatory information while at the same time taking
into consideration the facilitation of the creation, review, life
cycle management and archiving of the electronic submission.
The eCTD specification lists the criteria that will make an
electronic submission technically valid. The focus of the
specification is to provide the ability to transfer the registration
application electronically from industry to a regulatory authority.
Industry to industry and agency to agency transfer is not
addressed.
eCTD v3.2.2 Page
61
M8 eCTD v4.0: Electronic Common Technical

Document (eCTD) v4.0
The ICH M8 EWG/IWG was formed in November 2010 to
assume responsibility for the continued development of the next
major version of the eCTD.
eCTD v4.0 Page
62
M9: Biopharmaceutics Classification
System-based Biowaivers Amity Institute of Pharmacy
M9: Biopharmaceutics Classification System-based

Biowaivers
This new multidisciplinary Guideline addresses
Biopharmaceutics Classification System (BCS)-based
biowaivers. BCS-based biowaivers may be applicable to BCS
Class I and III drugs, however BCS-based biowaivers for these
two classes are not recognised worldwide. This means that
pharmaceutical companies have to follow different approaches in
the different regions.
This Guideline provides recommendations to support the
biopharmaceutics classification of medicinal products and to
support the waiver of bioequivalence studies.
63
M9: Biopharmaceutics Classification
System-based Biowaivers Amity Institute of Pharmacy
M9 Q&As: Questions and Answers: Biopharmaceutics

Classification System-based Biowaivers
The ICH M9 Q&As provide clarity to suport the implementation
of the ICH M9 Gudieline on Biopharmaceutics Classification
System (BCS)-based biowaivers in ICH Regulatory Member
countries/regions.
64
REFERNCE
• ICH Official web site : ICH
65
66

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Amity Institute of Pharmacy

• The International Council for Harmonisation of Technical

• ICH is a joint initiative involving both regulators and research-

• ICH's mission is to achieve greater harmonisation worldwide

To develop and register To prevent unnecessary

To promote public health.

To harmonize technical To minimize the use of animal

ICH Steering Committee: The Steering Committee, made of

ICH Secretariat: The ICH Secretariat is primarily concerned

ICH Coordinators: The coordinators are fundamental to the

ICH Working Groups: These are created by the Steering

• Those relating to chemical & pharmaceutical quality

• Q1A – Q1F – Stability

• Q3A – Q3D – Impurities

• Q5A – Q5E – Quality Of biotechnological Products

• Q6 – Specifications for New Drug Substances And Products

• Q7 – Good Manufacturing Practice Guide for

• Q10 – Pharmaceutical quality System

• Q11 – Development and Manufacture of Drug Substances

• Q12 – Lifecycle Management

Q1A(R2): Stability testing of new drug substances and products.

Q1B: Photostability testing of new drug substances and products.

Q1C: Stability testing for new dosage forms

Q1D: Bracketing and Matrixing designs for stability testing

Q1E: Evaluation of stability data.

This document extends the main stability Guideline by

Q1F: Stability data package for registration applications in

The ICH Steering Committee endorsed the withdrawal of the

Q2(R1): Validation of analytical procedures: Text and

Q3A(R2): Impurities in New Drug Substances

Q3B(R2): Impurities in New Drug Products

Q3C(R8): Guidelines for Residual Solvent

Q3D(R1): Guidelines for Elemental Impurities

Q3E EWG: Assessment and control of extractables and

Q4B: Evaluation and Recommendation of Pharmacopoeial Texts

Q5A(R1): Viral safety Evaluation of Biotechnological products

The purpose of this Guideline is to provide a general framework

Q5B: Analysis of the expression construct in cells used

This document is intended to describe the types of information that

Q5D: Derivation and characterization of cell substrates used

Q5E: Comparability of Biotechnological/Biological Products

Q6A: Specifications: Test Procedures and Acceptance Criteria for

Q6B: Specifications: Test Procedures and Acceptance Criteria for

Q7 – Good Manufacturing Practice Guide for Active

Q7 Q&A – Questions and Answers: Good Manufacturing

Q10 : PHARMACEUTICAL QUALITY SYSTEM

Q8/9/10 Q&As (R4): Q8/Q9/Q10-Implementation

Q11 – Development and Manufacture of Drug Substances

Q12: Technical and Regulatory considerations for

• Those relating to adverse effects of the products.

• S1A – S1C – Carcinogenecity studies

• S3A – S3B – Toxicokinetics and pharmacokinetics

• S4: Duration of Chronic Toxicity Testing in Animals

• S5 – Detection of Toxicity to Reproduction for

• S6 – Preclinical Safety Evaluation of Biotechnology-

• S7A: Safety Pharmacology Studies for Human Pharmaceuticals

• S7B: The Nonclinical Evaluation of the Potential for

• S8 – Immunotoxicity Studies for Human Pharmaceuticals

• S9 – Nonclinical Evaluation for Anticancer Pharmaceuticals

• S10: Photosafety Evaluation

• S11: Non-clinical Paediatric Safety

S1A: Need for Carcinogenicity Studies of Pharmaceuticals

S1B: Testing for Carcinogenicity of Pharmaceuticals