ICH Guidelines: purpose, participants, process of harmonization, Brief overview of QSEM, with special emphasis on Q-series guidelines, ICH stability testing guidelines

1. ICH Guideline
Dr Bindiya Chauhan
Pharmaceutical Quality Assurance

2. ICH Guidelines
 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.
 In the simple word, it provide all types of guidelines that one can
implement and use to get and quality product to the customers

3. Purpose/ Mission
 To make recommendations towards achieving greater harmonisation in the
interpretation and application of technical guidelines and requirements for
pharmaceutical product registration and the maintenance of such registrations;
 To maintain a forum for a constructive dialogue on scientific issues between
regulatory authorities and the pharmaceutical industry on the harmonisation of the
technical requirements for pharmaceutical products;
 To contribute to the protection of public health in the interest of patients from an
international perspective;
 To monitor and update harmonised technical requirements leading to a greater
mutual acceptance of research and development data;
 To avoid divergent future requirements through harmonisation of selected topics
needed as a result of therapeutic advances and the development of new
technologies for the production of medicinal products;

4. Purpose/ Mission
 To facilitate the adoption of new or improved technical research and development
approaches which update or replace current practices;
 To encourage the implementation and integration of common standards through the
dissemination of/ spreading of, the communication of information about and coordination
of training on, harmonised guidelines and their use;
 And to develop policy for the ICH Medical Dictionary for Regulatory Activities Terminology
(MedDRA) whilst ensuring the scientific and technical maintenance, development and
dissemination of MedDRA as a standardised dictionary which facilitates the sharing of
regulatory information internationally for medicinal products used by humans.

5. Participants
Members
They are people from the
various contries
For Example –
1. Funding regulatory
members
2. Funding Industrial Members
3. Standing regulatory
members etc.
Observer
These people are the
observer. For example –
1. Standing observer
2. Legislative/
administrative
authorities/obsever etc

6. Brief overview of QSEM/ Process of Harmonization
 ICH provides official guidelines in the form of QSEM.
 Q – Quality Guideline series – Chemicals and Pharmaceutical Quality Assurance
 S – Safety Guideline series – Mainly dealing with In vivo – in vitro preclinical study
 E – Efficacy Guideline series – Clinical study in human being
 M – Multi Disciplinary Guideline series – Terminology, electronic standard and CTD,
common technical document

7. Q series Guidelines

8. Q series Guidelines
EWG - The Expert Working Group

9. Q series Guidelines

10. Q series Guidelines

11. Q series Guidelines

12. Q series Guidelines

13. Q series Guidelines

14. Q series Guidelines

15. Q series Guidelines

16. ICH Stability testing guidelines – Q series guidelines

17. ICH Stability testing guidelines
 Stability study:
 A measure of how pharmaceutical products maintains its quality attribute over a time.
 The purpose off stability testing is to provide evidence on how the quality off drug
substance or product varies with time under the influence off a variety off environment
factor.
 Need/scope of Stability study
 Provide evidence as to how the quality of the drug product varies with time.
 Establish shelf life for the drug product.
 Determine recommended storage conditions.
 Determine container closure system

18. Advantages of Stability Study
 Chemical degradation of the product leads to lowering of the concentration
of the drug in the dosage form which can be minimize by stability study
 Toxic products may be formed due to chemical degradation of the active
ingredient, these kind of toxic products are too dangerous for human being,
one can know these types of toxic products in the form of impurities when
performed stability studies.
 Assurance to the patient safety can be provided
 Economic considerations
 Legal requirement can be considered one of the advantage of stability study

19. VARIABLES AFFECTING THE STABILITY
 Formulation
 Packaging
 Site and method of manufacture
 API
 Finished product
 Batch size
 Batch to batch variability
 Process validation
 Quality risk management
 Container labeling
 Changes to product

20. Adverse effect of instability of drug/ Need of Stability
study
 Loss of active drug (e.g. aspirin hydrolysis, oxidation of adrenaline)
 Loss of vehicle (e.g. evaporation of water from o/w creams, evaporation of
alcohol from alcoholic mixture.)
 Loss of content uniformity (e.g. creaming of emulsions, impaction of
suspensions)
 Reduction in bioavailability (e.g. ageing of tablets resulting in a change in
dissolution profile)

21. Broad classification of Types of Stability
 CHEMICAL: Each active ingredient retains its chemical integrity and labeled potency
within the specified limit.
 PHYSICAL: The physical stability properties includes
appearance, uniformity, dissolution and suspend ability are retained.
 MICROBIOLOGICAL: Sterility or resistance to microbial growth is retained according to
specified requirement.
 THERAPEUTIC: Therapeutic activity remains unchanged
 TOXICOLOGIC: No significant increase in toxicity occurs.

22. ICH GUIDELINES FOE STABILITY TESTING
ICH GUIDELINES TITLE
Q1A
Stability testing of new drug substances and product
Q1B
Stability testing : photo stability testing of new drug substance
and product
Q1C
Stability testing for new dosage form
Q1D
Bracketing and matrixing designs for stability
testing of drug substances and products
Q1E
Evaluation of stability data

23. Stability testing of API
 Following are the consideration -
 General
 Stress Testing
 Selection of Batches
 Container Closure System
 Specification
 Testing Frequency
 Storage Conditions
 Stability Commitment
 Evaluation
 Statements/ Labelling

24. Stability testing of API – Stress testing
 Stress testing of the active substance can help in
 Identification of degrdants.
 Identification of degradation pathways
 Determination of which type(s) of stress affect the molecule:
o Photo-stability
o High Temperature
o Low Temperature
o Oxidation
o pH extremes
o Water

25. Stability testing of API – Specifications
 Stability studies should include testing of those attributes of the drug
substance that are susceptible to change during storage and are likely to
influence quality, safety, and/or efficacy.
 The testing should cover, as appropriate, the physical, chemical, biological,
and microbiological attributes.
 e.g. appearance, assay, degradation.

26. Stability testing of API – Testing frequency
 For long term studies:
Year 1: every 3 months
Year 2: every 6 months
Subsequent years: annually
 At accelerated storage conditions: (6 month study)
Minimum three points including,
e.g. 0 3 6
(initial) (final)
 At intermediate storage conditions: (12 month study)
Four points including ,
e.g. 0 6 9 12
(initial) (final)

27. Stability testing of API – Storage
condition/ specification
 A drug substance should be evaluated
• To test its thermal stability
• Its sensitivity to moisture(if applicable)
 The long-term testing (minimum of 12 months) on at least 3 primary batches at
the time of submission and should be continued for a period of time sufficient
to cover the proposed re-test period.

28. Stability testing of API – Storage
condition/ specification
STUDY
STORAGE CONDITION
MINIMUM TIME PERIOD
COVERED BY DATA AT
SUBMISSION
Long term
25 C ± 2 C
60%RH ± 5%
12 months
Intermediate
(controlled)
30º C ± 2º C
65%RH ± 5%
6 months
accelerated
40º C ± 2º C
75%RH ± 5%
6 months

29. Types of Stability Studies
 Three types of stability studies:
 1. Accelerated
studies designed to know short term excursion temperature on the drug substance.
 2. Intermediate
Studies conducted incase of failure in accelerated studies and the conditions of
temperature and humidity are in between long term and accelerated.
 3. long term
studies designed to check the stability of the drug substance.

30. THANK YOU 