The presentation is intended for B.Pharm Third Year students of PCI Syllabus for subject Quality Assurance of Sixth Semester.

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Dr.K.B.Gabhane

3. Syllabus Contents
ICH Guidelines:
1. Purpose,
2. Participants,
3. Process of harmonization,
4. Brief overview of QSEM, with special emphasis on Q-series guidelines, ICH
stability testing guidelines
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4. Objectives:
• Upon completion of this section, student should be able to :
1. Define the term ICH and its purpose.
2. Explain how the concept of harmonization was adopted in practice
3. Describe the organizational setup of ICH
4. List and explain the steps in the harmonization process
5. Explain the important ICH guidelines
6. List the ICH Quality guideline components
7. Outline stability testing guidelines as per ICH
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6. ICH and its purpose :
ICH : International Conference on Harmonization of Technical
Requirements for Registration of Pharmaceuticals for Human use.
Rational : The differences in technical requirements across countries meant that
drug makers had to spend lot of time and money to duplicate test
procedures if they wanted to market their products at an international
level. Hence A need was felt to rationalize and harmonize
Purpose The body was set upto bring together representatives of pharmaceutical
industry and regulatory bodies to discuss technical and scientific aspects
of registration of drugs in order to have
: Harmonization of technical requirements
: Ensure safety, efficacy, and quality of medicines
: Prevent duplication of clinical trials in humans
: Minimize the use of animal testing without compromising safety and
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8. HISTORY
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9. EVOLUTION OF
ICH
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10. EVOLUTION OF
ICH
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11. FOUNDING MEMBERS
OF ICH
• United States of America
• Japan
• European region
MEMBER
COUNTRIES
• EMA : European Commission and European
Medicine Agency
• USFDA : United States Food and Drug
Administration
• MHLW: Ministry of health, Labour and
welfare, Japan
REGULATORY
REPRESENTATIVES
• EFPIA: European federation of pharmaceutical
industries association
• PhRMA: USA’s Pharmaceutical Research and
Manufacturers of America
• JPMA : Japan’s Pharmaceutical Manufacturers
Associations
INDUSTRIAL
REPRESENTATIVES
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12. Organization of
ICH
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13. Process of Harmonization
HARMONIZATION ACTIVITIES
Formal ICH Procedure New topic for harmonization
Q and A Procedure Clarification foe an existing ICH guideline
Revision Procedure Adding new information to an existing ICH guideline
Maintenance Procedure Changes to be made to maintain a guideline
Formal ICH procedure
than begins in following
steps
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14. Harmonization
Process
Step 1: Building Scientific Consensus
Based on the objective specified, a worker group
prepares a consensus (general agreement) draft called
the technical document. The document further is
submitted to the ICH assembly with a request for
adoption
Step 2 : Agreeing on the draft
The draft is examined and endorsed by regulatory members of Assembly. Assembly confirms
that the scientific consensus (general agreement) exist for technical issues and may proceed
further for adoption.
Step 3 : Consulting regional regulatory agencies
Consultation, discussion and finalization of the expert draft guidelines by regulatory members
at different levels:
Stage 1: Draft goes to different ICH regions for discussion in their respective regulatory
regions.
Stage 2: Comments obtained during stage 1 are addressed by the expert working group and
after discussion, consensus (general agreement) is reached to prepare the expert draft
guidelines Continue…………………………
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15. Step 3 : Consulting regional regulatory agencies
Consultation, discussion and finalization of the expert draft guidelines by regulatory members
at different levels:
Stage 3 : This draft guidelines is finalized and signed by the ICH regulatory member experts.
Step 4 : Adopting Harmonized Guidelines
ICH assembly if agree that sufficient scientific consensus exists on the draft
guideline, and it gets adopted as the ICH Harmonized Guideline.
Step 5 : Implementing Guidelines in ICH regions
ICH harmonized guideline is implemented an all
the ICH regions through the respective regulatory
procedures. Effective tenure is sent to ICH
assembly and published on ICH website.
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16. Brief overview of QSEM The ICH guidelines are covered under four headings under the
acronym QSEM –
• These guidelines covers the areas of quality of drug products such as
:Impurity testing and stability study
• These guidelines have flexible approach on basis of GMP risk
management.
QULAITY
• They help to detect potential risks such as genotoxicity, carcinogenicity,
and reprotoxicity.
SAFETY
• These guidelines provide guidance about designing, conducting, safety
aspects and reporting of clinical trials for pharmaceutical products.
• Novel drug products derived from biotechnology and genomic /
pharmacogenetic techniques for targeted drug delivery are also covered.
EFFICACY
• Topics in Pharmaceutical field that do not fit into any of the above
categories are covered under this area. Ex: Electronic standards.
MULTI
DISCIPLINARY
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17. GUIDELINE SUBPART AREA COVERED
Q1 Q1 A Stability testing of new drug substances and products
Q1 B Photostability testing of new drug substances and products
Q1 C Stability testing of new dosage forms
Q1 D Bracketing and matrixing designs for stability testing of
new drug substances and products.
Q1 E Evaluation of stability data
Q1 F Stability data package for registration applicationsin
climatic zone III and zone IV.
Q2 Validation of analytical procedures.
QUALITY GUIDELINES
The areas covered are labeled from Q1 to Q11 and deals with important aspects like Stability
testing, analytical validation, impurities, quality systems, risk management, and GMP
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18. QUALITY GUIDELINES
GUIDELINE SUBPART AREA COVERED
Q3 Q3 A Impurities in new drug substances
Q3 B Impurities in new drug products
Q3 C Guidelines for residual solvents
Q3 D Guidelines for elemental impurities
Q4
Pharmacopeias
Q4 A Pharmacopoeial Harmonization
Q4 B Evaluation and recommendation of pharmacopeial texts for
use in ICH regions.
Q5 Q5 A Viral safety evaluation of biotechnology products derived
from cell lines of human or animal origin
Q5 B Analysis of expressions construct in cells used for
production of r-DNA derived protein products 18
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19. QUALITY GUIDELINES
GUIDELINE SUBPART AREA COVERED
Q5 Q5 C Stability testing of biotechnology/ biological products
Q5 D Derivation and characterization of cell substrates used for
production of biotechnology / biological products.
Q5 E Comparability of biotechnological/biological products subject to
changes in their manufacturing process
Q6 Q6 A Test procedure and acceptance criteria for biotechnological
/biological products.
Q6 B Test procedure and acceptance criteria for biotechnological/
biological products.
Q7 Good manufacturing practices for API
Q8 Pharmaceutical Development 19
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20. QUALITY GUIDELINES
GUIDELINE SUBPART AREA COVERED
Q 9 Quality risk management
Q 10 Pharmaceutical Quality system
Q 11 Development and manufacture of drug substances
(Chemical and Biological entities)
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21. ICH guidelines for Stability
1. These guidelines define what information must be provided at the time of applying to
register a new drug molecule.
2. These guidelines were first adopted in1993
3. After revision and updation, the current version Q1A(R2) is adopted since 2003.
4. This guideline harmonizes the registration process for all drugs in the USA, Japan and
EU.
5. This means a drug registered in one of these regions will not require repeated stability
testing when to be sold in any of these regions.
6. The stability testing data submitted under this guideline must provide information
about how the drug molecule changes over time under different storage conditions.
7. The data helps to define the ideal storage condition for the said product and the shelf
life of the product.
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22. ICH guidelines for Stability
TYPES OF STABILITY TESTING :
1. Real – time testing : Testing drug product for longer duration to find out what is the
maximum time for product degradation when stored under recommended storage
conditions
2. Accelerated stability testing : Here product is subjected to stress in the form of
higher temperatures, moisture, agitation, light, pH and packaging conditions to study
its degradation profile
3. Retained sample stability testing : This involves samples that are retained from each
batch that has been sent to the market
4. Cyclic temperature stress testing : Not routinely used, this involves subjecting the
products to temperature stresses in a way to mimic likely market storage conditions.
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23. Overview of ICH Stability guidelines contents :
Some of the areas covered by ICH on stability testing include
1. Stress testing
2. Photostability testing
3. Batch selection for stability testing
4. Testing of container closure system
ICH guidelines for Stability
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24. https://www.ich.org/
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