Guidelines By ICH and special emphasis on Quality.

1. Overview of ICH
Guidelines-
QSEM
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PRESENTED BY -ASHWIN D. DIGARSE
M.PHARMA IST YEAR {QA}
SMT. KISHORIAI BHOYAR COLLEGE OF PHARMACY,
KAMPTEE

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.
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3. ICH Guidelines
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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5. 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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6. 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.
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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.
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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).
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9. Special emphasis on Q-series
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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10.  Q 6 – Specifications
 Q 7 – Good Manufacturing Practices
 Q 8 – Pharmaceutical Development
 Q 9 – Quality Risk Management
 Q 10 – Pharmaceutical Quality System
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11. ICH Q 1 – Stability Testing ICH
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)
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12. ICH Q1A Stability Testing for New
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.
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13. CH Q2 (R1) Validation of Analytical
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
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14. ICH Q3A
Impurities in New Drug Substances
:
 Provide guidance for registration applications on the content and qualification
of impurities in new drug substances produced by chemical syntheses and not
previously registered in a region or member state.
 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
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15. ICH Q4B
Regulatory Acceptance of Analytical
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 multi-
center input into scientific review for determining the interchangeability
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16. ICH Q 5 C Quality of
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.
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17. ICH Q6A
Test Procedures and Acceptance Criteria
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
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18. ICH-Q7A
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
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19. ICH – Q8(R1)
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.
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20. Q8(R2)
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
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21. ICH-Q9 Quality Risk 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.
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22. ICH-Q10 Pharmaceutical 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
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23. ICH-Q11 Development and
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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24. Thank you
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