This document provides an overview of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). It defines ICH as a program involving regulatory authorities and the pharmaceutical industry to discuss scientific and technical aspects of drug registration. The document outlines ICH's objectives, members, structure, guidelines, and quality guidelines related to good manufacturing practices, specifications, analytical validation, stability testing, and impurities.

1. Monika Maan
Associate Professor
Faculty of Pharmacy
Dr.A.P.J.Abdul Kalam University, Indore

2.  What is ICH
 Objective
 Members of ICH
 Where is the ICH located
 ICH Structure
 ICH Guidelines
 ‘Q-Series’ Guidelines
 Q1-Q14

3.  ICH denotes for “ InternationalConference on
Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human
Use.”
 It is a unique harmonization project involving
regulatory authorities and pharmaceutical
industry.

4.  ICH’s logo has been contrived with a view to
symbolizing the letter “I” ,”C” , “H” in a
manner which embodies the letters in an
outline human form.The main color of the
logo is blue, a color often used with
healthcare.

5.  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.
 Harmonization process – founded April 1990

6.  To improve efficiency of new drug development and
registration processes.
 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
marketing approval.
 To developed and registered pharmaceuticals in the
most efficient and cost effective manner.
 To promote public health.
 To prevent unnecessary duplication of clinical trials on
humans.
 To minimize the use of animal testing without
compromising safety and effectiveness of drug.

7.  Members of ICH: ICH is comprised of representatives from
the six parties as well as three Observers and the
International Federation of Pharmaceutical Manufacturers
Associations (IFPMA)
 JAPAN: the Ministry of Health & Welfare (MHW) and the
Japan Pharmaceutical ManufacturersAssociation (JPMA)
 EU: the European Commission (EC) and the European
Federation of Pharmaceutical Industries’ Associations
(EFPIA)
 USA: the Food & Drug Administration (FDA) and the
Pharmaceutical Research and Manufacturers of America
(PhRMA)
 Observers:WHO, EFTA and Canada

8.  ICH does not have "offices" as such because it
is a voluntary cooperative effort of
cosponsors from the three regions.
 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.

9.  The ICH structure consists of the
 ICH Steering Committee
 ICH Coordinators
 ICH Secretariat
 ICHWorking Groups.

10.  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 Steering Committee.

11.  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

12.  The Secretariat is primarily concerned with
preparations for, and documentation of,
meetings of the Steering Committee as well
as coordination of preparations forWorking
Group and Discussion Group meetings.
 Information on ICH Guidelines and the
general ICH process can be obtained from the
ICH Secretariat.

13.  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.,
 ExpertWorking Group (EWG)
 Implementation Working Group (IWG)
 Informal Working Group.

14.  ICH operates through the ICH Steering Committee with
administrative support from the ICH Secretariat and ICH
Coordinators.
 The Steering Committee meets at least twice a year
 During these meetings, new topics will be considered for adoption,
reports are received on the progress of existing topics, and
maintenance and implementation of the guidelines are discussed.
 The topics identified for harmonization by the Steering Committee
are selected from Safety, Quality, Efficacy, and Multidisciplinary
matters.

15.  The four categories are
 Quality (Q)
 Safety (S)
 Efficacy (E)
 Multidisciplinary (M)

16.  "Quality"Topics, i.e., those relating to chemical and pharmaceutical
QualityAssurance
(StabilityTesting, ImpurityTesting, etc.)
 “ Efficacy"Topics, i.e., those relating to clinical studies in human subject
(Dose Response Studies, Good Clinical Practices, etc.)
 “ Safety"Topics, i.e., those relating to in vitro and in vivo pre-clinical
studies
(CarcinogenicityTesting, GenotoxicityTesting, etc.)
 “ Multidisciplinary"Topics, i.e., cross-cuttingTopics which do not
fit uniquely into one of the above categories.

17.  "Quality"Topics, i.e., those relating to
chemical and pharmaceuticalQuality
Assurance (StabilityTesting, ImpurityTesting,
etc.)

18. • StabilityQ1
• Analytical ValidationQ2
• ImpuritiesQ3
• PharmacopoeiasQ4
• Qualityof BiotechnologicalProductsQ5
• SpecificationsQ6
• Good Manufacturing PracticeQ7
• Pharmaceutical DevelopmentQ8
• QualityRiskManagementQ9
• Pharmaceutical Quality SystemQ10

19. Q11 Development & ManufactureofDrugSubstances
Q12 Lifecycle Management
Q13 Continuous Manufacturing of Drug Substance and Drug Product
Q14 Analytical Procedure Development

20. Q1A(R2) StabilityTesting of New Drug Substances and
Products
Q1B StabilityTesting : Photo stabilityTesting of New Drug
Substances and Products
Q1C StabilityTesting for New Dosage Forms
Q1D Bracketing and Martyring Designs for StabilityTesting
of New Drug Substances and Products
Q1E Q1E Evaluation of Stability Data
Q1F Q1F Stability Data Package for Registration
Applications in Climatic Zones III and IV

21.  Q1A (R2)
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 product.

22.  Q1B:
Give guidance on the basic testing protocol
required to evaluate the light sensitivity and
stability of new drugs and products

23.  Q1C:
Gives guidelines for new formulations of
already approved medicines and defines the
circumstances under which reduced stability
data can be accepted

24.  Q1D:
 The ICH Harmonised Guideline was finalised under Step
4 in February 2002.
 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.
 Bracketing and Matrixing Designs for StabilityTesting of
New Drug Substances and Products

25.  Q1E:
 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 “room temperature”

26.  Q1F:
 Describes harmonized 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-humid
regions.

27. Q2(R1) Validation of Analytical Procedures:Text and
Methodology Impurities
Q2(R1): Validation of Analytical Procedures:Text and
Methodology
 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
methods.
 It also discusses the characteristics that must be considered
during the validation of the analytical procedures

28.  This topic was endorsed by the Assembly in
June 2018.
 The Q2(R2)/Q14 EWG will develop a new ICH
Quality Guideline, ICH Q14, on Analytical
Procedure Development, and revise the ICH
Q2(R1) Guideline onValidation of Analytical
Procedures, with a view to potentially
combine both documents into one, for
simplification and clarity.

29.  Types of Analytical Procedures to be validated are:
 Identification tests
 Quantitative tests for impurities content
 Limit tests for the control of impurities
 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 analytical
procedures :
 Accuracy, Precision(Repeatability, Intermediate
Precision), Specificity, Detection Limit,
Quantitation Limit, Linearity,Range.

30. Q3A(R2) Impurities in New Drug
Substances
Q3B(R2) Impurities in New Drug Products
Q3C(R5) Impurities: Guideline for Residual
Solvents
Q3D Guideline for Elemental
Impurities

31.  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
 Organic impurities
(process- and drug-related)
 Inorganic impurities
 Residual solvents

32.  This Guideline has been first revised and
finalised under Step 4 in February 2003.
 It complements the Guideline on impurities in
new drug substances and provides advice in
regard to impurities in products containing new,
chemically synthesized drug substances.
 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.

33.  This ICH Guideline was finalised under Step 4 in July 1997.
 This recommends the use of less toxic solvents in the
manufacture of drug substances and dosage forms, and sets
pharmaceutical limits for residual solvents (organic volatile
impurities) in drug products.
Benzene 2ppm
Carbon tetrachloride 4ppm
Dichloromethane 5ppm
Dichloroethane 8ppm
Acetonitrile 410ppm
Chloroform 60ppm
Chlorobenzene 360ppm

34.  The pharmacopoeial authorities, working together
through the Pharmacopoeial Discussion Group
(PDG), have been closely involved with the work of
ICH since the outset and harmonization between
the major pharmacopoeias, which started before
ICH, has proceeded in parallel.

35.  This ICH Harmonized Guideline was finalized
under Step 4 in November 2007.
 This document describes a process for the
evaluation and recommendation by the Q4B
ExpertWorking Group (EWG) of selected
pharmacopoeial texts to facilitate their
recognition by regulatory authorities for use
as interchangeable in the ICH regions.

36.  Q4B Annex 1R1: Residue on Ignition/SulphatedAsh
 Q4B Annex 2R1: Test for ExtractableVolume of Parenteral Preparations
 Q4B Annex 3R1: Test for Particulate Contamination: Sub-Visible Particles
 Q4B Annex 4AR1: Microbiological Examination of Non-Sterile Products
Microbial EnumerationTests
 Q4B Annex 4BR1 : Microbiological Examination of Non-Sterile Products
Tests for Specified Micro-Organisms
 Q4B Annex 4CR1 : Microbiological Examination of Non-Sterile Products
 Q4B Annex 6R1 : Uniformity of Dosage Units
 Q4B Annex 7R2 : DissolutionTest
 Q4B Annex 8R1 : SterilityTest
 Q4B Annex 9R1 : Tablet Friability
 Q4B Annex 10R1: Polyacrylamide Gel Electrophoresis
 Q4B Annex 11 : Capillary Electrophoresis
 Q4B Annex 12 : Analytical Sieving
 Q4B Annex 13 : Bulk Density andTapped Density of Powders
 Q4B Annex 14 : Bacterial EndotoxinsTest

37. Q5A
(R1)
Viral Safety Evaluation of Biotechnology Products
Derived from Cell Lines of Human or Animal Origin
Q5B Quality of Biotechnological Products : Analysis of the
Expression Construct in Cells Used for Production of r-
DNA Derived Protein Products
Q5C: Quality of Biotechnological Products : Stability Testing of
Biotechnological/Biological Products
Q5D: Derivation and Characterization of Cell Substrates Used
for Production of Biotechnological/Biological Products
Q5E Comparability of Biotechnological/ Biological Products
Subject to Changes inTheir Manufacturing Process

38.  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.

39.  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 analyzed using
nucleic acid techniques.

40.  This ICH Harmonized Guideline was finalized under Step 4 in
November 1995.
 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.

41.  The objective of this guideline is to
Derivation and Characterization of Cell
Substrates Used for Production of
Biotechnological/Biological Products provide
broad guidance on appropriate standards for
cell substrates.

42.  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
product.

43.  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 product supply.

44.  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.

45.  The following tests are considered generally applicable to
all new drug substances and drug products.
 Description
 Identification
 Assay
 Impurities
 SpecificTests for drug substances :
 Physicochemical properties
 Particle size Polymorphic forms
 Tests for chiral new drug substances
 Water content
 Inorganic impurities
 Microbial limits

46.  Particle size distribution:
 Dissolution
 Disintegration
 Hardness/friability
 Uniformity of dosage units
 Microbial limits
 Antioxidant preservative content
 Alcohol content
 Rheological properties:
 Redispersibility

47.  Uniformity of dosage units
 Particle size distribution
 pH (Osmolarity)
 Sterility
 Endotoxins/Pyrogens
 Particulate matter
 Water content
 Antimicrobial preservative
 Antioxidant preservative content
 Functionality testing of delivery systems

48.  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.

49.  The ICH Harmonized Guideline was finalized
under Step 4 in November 2000.This
document is intended to provide guidance
regarding Good Manufacturing Practice
(GMP) for the manufacturing of Active
Pharmaceutical Ingredients (APIs) under an
appropriate system for managing quality.

50.  This guideline is intended to provide guidance on the
contents of Pharmaceutical Development of drug
products
 The aim of pharmaceutical development is to design
a quality product and its manufacturing process to
consistently deliver the intended performance of the
product.
 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

51.  he ICH Harmonized Guideline was finalized under Step
4 in November 2005.
 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 labeling
materials.

52.  Two primary principles of quality risk
management are:
 The evaluation of the risk to quality should be
based on scientific knowledge and ultimately
link to the protection of the patient
 The level of effort and documentation of the
quality risk management process should be
commensurate with the level of risk

53.  The ICH Harmonized Guideline was finalized
under Step 4 in June 2008.
 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

54.  The Guideline reached Step 4 of the ICH
process on 1 May 2012.
 This Guideline describes approaches to
developing and understanding the
manufacturing process of the drug
substance, and also provides guidance on
what information should be provided in
Module 3 of the CommonTechnical
Document (CTD) Sections 3.2.S.2.2 –
3.2.S.2.6 (ICH M4Q).

55.  This topic was endorsed by the ICH Steering
Committee in September 2014.
 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.

56.  This topic was endorsed by the Assembly in
June 2018.This new Guideline is proposed to:
Capture key technical and regulatory
considerations that promote harmonisation,
including certain Current Good
Manufacturing Practices (CGMP) elements
specific to Continuous Manufacturing (CM)

57. Allow drug manufacturers to employ flexible
approaches to develop, implement, or integrate
CM for the manufacture – drug substances and
drug products – of small molecules and
therapeutic proteins for new and existing
products.
Provide guidance to industry and regulatory
agencies regarding regulatory expectations on
the development, implementation, and
assessment of CM technologies used in the
manufacture of drug substances and drug
products.

58.  This topic was endorsed by the Assembly in
June 2018.
 The Q2(R2)/Q14 EWG will develop a new ICH
Quality Guideline, ICH Q14, on Analytical
Procedure Development, and revise the ICH
Q2(R1) Guideline onValidation of Analytical
Procedures, with a view to potentially
combine both documents into one, for
simplification and clarity.

59. Thank you