1

Overview of ICH
Guidelines-
QSEM

PRESENTED BY -ASHWIN D. DIGARSE

M.PHARMA IST YEAR {QA}
SMT. KISHORIAI BHOYAR COLLEGE OF PHARMACY,
KAMPTEE
ICH 2

What is ICH?

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 was created in April 1990.

 ICH Guidelines 3
The ICH topics are divided into four categories and ICH
topic codes are assigned according to these categories.

Quality Guidelines Safety Guidelines

Efficacy Guidelines Multi Disciplinary Guidelines

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Quality Guidelines
Harmonization achievements in the Quality area include pivotal
milestones such as the conduct of stability studies, defining relevant
thresholds for impurities testing and a more flexible approach to
pharmaceutical quality based on Good Manufacturing Practice
(GMP) risk management.
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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.
 Efficacy Guidelines 7

The work carried out by ICH under the Efficacy heading

is concerned with the design, conduct, safety and
reporting of clinical trials.
It also covers novel types of medicines derived from
biotechnological processes and the use of
pharmacogenetics/genomics techniques to produce
better targeted medicines.
Multidisciplinary Guidelines 8

Those are the cross-cutting topics which do not fit

uniquely into one of the Quality, Safety and Efficacy
categories.
It includes the ICH medical terminology (MedDRA), the
Common Technical Document (CTD) and the
development of Electronic Standards for the Transfer of
Regulatory Information (ESTRI).
 Special emphasis on Q-series 9

guidelines
 The “Q-Family”
 Q 1 – Stability Testing
 Q 2 – Analytical Validation
 Q 3 – Impurities
 Q 4 – Pharmacopoeias
 Q 5 – Biotechnological Products
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 Q 6 – Specifications
 Q 7 – Good Manufacturing Practices
 Q 8 – Pharmaceutical Development
 Q 9 – Quality Risk Management
 Q 10 – Pharmaceutical Quality System
ICH Q 1 – Stability Testing ICH 11

Q 1 – Stability Testing

 A set of originally five guidelines (Q1A to Q1F)

Defining
 General aspects of stability testing (storage conditions, batch size and
number, length of time...)
 Photostability
 Application to new dosage forms
 Possibilities for reduced test designs (bracketing and matrixing)
 Stability Testing - Statistical evaluation of stability data and possibilities
for extrapolation
 Storage conditions for stability testing in climatic zones III and IV
(withdrawn)
ICH Q1A Stability Testing for New 12

Drug Substances and Products:

 Stability Testing for New Drug Substances and Products Developed with in
the Expert Working Group of ICH Stability testing requirement for a
Registration Application within Tripartite Objective is to provide evidence of
how the quality of a drug substance or drug product varies with time under
variety of environmental forces (temp., humidity, light) and enables
recommended storage conditions, re-test periods and shelf lives to be
established.
CH Q2 (R1) Validation of Analytical 13

Procedures : Text and Methodology:

 ICH Q2 (R1) Validation of Analytical Procedures :
 Text and Methodology
 Demonstrate that it is suitable for its intended purpose. Four most common
types of analytical procedures: 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 component(s) in the drug product
 ICH Q3A 14


Impurities in New Drug
Provide guidance for registration applications on the content and qualification
Substances
of impurities in new :
drug substances produced by chemical
not previously registered in a region or member state.
syntheses and

 Impurities in new drug substances are addressed from two perspectives:

Chemistry aspects include classification and identification of impurities,
report generation, listing of impurities in specifications, and a brief discussion
of analytical procedures
Safety aspects include specific guidance for qualifying those impurities that
were not present, or were present at substantially lower levels, in batches of
a new drug substance used in safety and clinical studies.
 Second revision of the Q3A guidance, which was published in 1996 and
revised in 2003.
 Impurities can be classified into the following categories:
Organic impurities (process- and drug-related
Inorganic impurities
Residual solvents
 ICH Q4B
Regulatory Acceptance of Analytical 15
Procedures and/or Acceptance Criteria
(RAAPAC) :
 Pharmacopeial Discussion Group (PDG) comprised of representatives of the United
States Pharmacopeia (USP), Japanese Pharmacopoeia (JP), and the European
Pharmacopoeia (Ph.Eur. or EP)
 Activity of Q4B are as follows:
 Effective way to raise and resolve issues that might impact both industry and
regulators.
 For FDA, interchangeability means the possible use of the harmonized methods of JP
and EP, where deemed appropriate and based on our scientific review, to be
considered as equivalent to the USP method.
 A savings in time and effort: Given the unified approach and strength of working
directly with the three regulatory regions, it is an effective way to partner in the
pharmacopeial process to effect change, where single, independent efforts might not
be as successful.
 Maintains FDA's review authority

 In case of any question, the local regional method prevails. Establishes a process for
 ICH Q 5 C Quality of 16

Biotechnological Products:
 Applies to well-characterised proteins and Polypeptides,their
derivatives and products of which they are components, and
which are isolated from tissues, body fluids, cell cultures, or
produced using rDNA technology.
 Covers the generation and submission of stability data for all
biotechnological products (vaccines, growth hormones, etc.)
 The document does not cover antibiotics, allergenic extracts,
heparins, vitamins or whole blood.
 Purpose: Guidance to applicants regarding the type of stability
studies that should be provided in support of marketing
applications.
 ICH Q6A
Test Procedures and Acceptance Criteria 17
for New Drug Substances and New Drug
Products: Chemical Substances :
 It 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 United States, the European Union,
or Japan
 "Conformance to specifications" means that the drug substance and / or
drug product, when tested according to the listed analytical procedures,
will meet the listed acceptance criteria.
 Addresses only marketing approval of new drug products and substances
but not during the CT development
 ICH-Q7A 18
Guidance for Active
Pharmaceutical Ingredients:
 Provide guidance regarding GMP for the manufacturing of active
pharmaceutical ingredients (APIs) under an appropriate system for
managing quality
 Define manufacturing operations to include
Receipt of material Production
Packaging and Repackaging Quality control
Labeling and Re-labeling Release Storage
 Distribution of APIs and related controls
 Vaccines are not included
 Should not use a stand-alone section
 Covers cell culture, fermentation (CCF), tissue or animal sources
including transgenic animals
 ICH – Q8(R1) 19

Pharmaceutical Development:
 Pharmaceutical development should include the following
elements:
 Defining the target product profile as it related Q,S and E
 Identifying Critical Quality Attributes (CQA) of the drug product
to study and control the product quality.
 Determining the quality attributes of the drug substance and
Excipients, etc to get desired quality.
 Selecting an appropriate manufacturing process and a control
strategy.
 Q8(R2) 20

Pharmaceutical
 Development
Describes science and risk-based approaches:for pharmaceutical
product and manufacturing process
 Development to consistently deliver the intended performance of
the product
 Introduced concepts of design space and flexible regulatory
approaches
 Scientific understanding to support the establishment of design
space, specifications and manufacturing controls
 Introduced concepts of Quality by Design (QbD) and provided
examples of QbD development approaches and design space
ICH-Q9 Quality Risk 21

Management
 Describes systematic processes for the assessment, control,
communication and review of quality risks
 Applies over product lifecycle: development, manufacturing and
distribution
 Includes principles, methodologies and examples of tools for quality
risk management
 Assessment of risk to quality should:
- Be based on scientific knowledge
- Link to the protection of the patient
- Extend over the lifecycle of the product
 Risk: Combination of the probability of occurrence of harm and
severity of that harm.
 ICH-Q10 Pharmaceutical 22

Quality System
 Incorporates the concepts behind Q8 and Q9 by providing a
pharmaceutical quality system that can be implemented through out
the product life cycle.
 Facilitates continual improvement and strengthen the link between Q8
and Q9.
 Quality attributes to meet patients need.
 Establish and maintain State of Control (Process performance and
Product quality).
- Track and trend product quality
- Maintain and update models as needed
- Internally verify that process changes are successful
 Good scientific development (Q8) in combination with QRM (Q9) and
PQS (Q10) will improve drug quality and efficiency of pharmaceutical
manufacturing
 ICH-Q11 Development and 23

Manufacture of Drug
 Substances
High level technical guidance relevant to the design, development
and manufacture of drug substances as a part of total strategy.
 Provide guidance for drug substances (Q6A & Q6B)
 Identify similarities and differences of biologics and chemical entities.
 Facilitate regulatory evaluation process
 To demonstrate process and product understanding
 Address the complexity of different manufacturing process & product
 Outline science based concepts
 Address systematic and enhances approaches for design space,
control strategies and real-time release
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Thank you