The document discusses the International Council for Harmonization (ICH), which brings together regulatory authorities and the pharmaceutical industry to discuss technical requirements for drug development and approval. The ICH aims to harmonize these requirements across regions to increase efficiency and reduce duplication. It develops guidelines on quality, safety, efficacy and other areas that are implemented by regulatory agencies. Over 70 guidelines have been produced covering topics like stability testing, clinical trials and good manufacturing practices. The document provides details on the ICH organization, guideline development process, and some examples of quality guidelines.

1. ICH GUIDELINES
BY: KIRANKUMAR SOLANKI

2. WHAT IS ICH?
• It is the international council for
harmonization of technical requirements
for pharmaceuticals for human use.
• Originally founded in 1990.
• It brings together the regulatory authorities and
pharmaceutical industries to discuss scientific
and technical aspects of pharmaceuticals and
develop ICH guidelines.
• ICH guidelines are provided for: Quality. Safety
and Efficacy of medicines.

3. Purpose of ICH
• Promotion of public health through
international harmonization that
contributes to:
▫ Prevention of unnecessary duplication of clinical
trials and post market clinical evaluations.
▫ Development and manufacturing of new medicines.
▫ Registration and supervision of new medicines.
▫ Reduction of unnecessary animal testing without
compromising safety and effectiveness.
• Accomplished through Technical Guidelines that
are implemented by the regulatory authorities.

4. Aim of ICH
• Achieving greater harmonisation in the interpretation and
application of technical guidelines and requirements for
pharmaceutical product registration.
• To maintain a forum for a constructive dialogue on scientific
issues between regulatory authorities and the pharmaceutical
industry.
• To contribute to the protection of public health .
• Greater mutual acceptance of research and development data
between the members.
• To avoid divergent future requirements through harmonisation.
• To facilitate the adoption of new or improved technical
research and development approaches .
• To encourage the implementation and integration of common
standards .

5. ICH Members (as of June 2020)
• 17 Members:
• Founding Regulatory: EC, Europe;
MHLW/PMDA, Japan; FDA, United States.
• Founding Industry: EFPIA; JPMA; PhRMA.
• Standing Regulatory: Swissmedic,
Switzerland; Health Canada, Canada
• Regulatory: ANVISA, Brazil; NMPA, China;
HSA, Singapore; MFDS, Republic of Korea;
TFDA, Chinese Taipei; TITCK, Turkey
• Industry: BIO; Global Self-Care Federation;
IGBA

6. ICH Observers
• 2 Standing Observers:
• WHO, International Federation of
Pharmaceutical Manufacturers & Associations
(IFPMA).
• Other Observers:
• Regulatory authorities; Regional Harmonization
Initiatives; international industry
pharmaceutical organizations; international
organizations regulated or affected by ICH
Guidelines.

7. Parts of ICH Organization
• Assembly is overarching body of the association,
composed of all members that take decisions
regarding articles of association, rules of
procedure, admission of new member, adoption of
new guideline.
• Assembly takes decisions:
• By consensus (All members agree).
• In the absence of consensus voting is done only by
regulatory members.

8. Parts of ICH Organization
• Management Committee is the body that
oversees operational aspects of the association
on behalf of all members, including
administrative and financial matters and
oversight of the Work Groups. (WGs works
directly on development new guidelines).
• Management Committee provides:
• Recommendations on the selection of new topics
for harmonization as well as on the adoption,
withdrawal or amendments of ICH Guidelines.

9. Steps involved in the development of ICH
guideline
• Step 1: The WG works to prepare a consensus
draft of the technical document.
• Step 2: The Members of the ICH Assembly (both
industries & regulatory) are invited to endorse the
technical document & draft Guideline.
• Step 3: Public consultation by the ICH Regulatory
Members and ICH Secretariat. All comments are
considered by the WG.
• Step 3 is finalized once consensus is reached by
the regulatory experts of the WG.

10. Steps involved in the development of ICH
guideline
• Step 4: The Regulatory Members of the ICH
assembly adopt the final ICH harmonized
Guideline.
• Step 5: Implementation by the ICH Regulatory
Members.

11. Some of the benefits of ICH guidelines
• Clinical trials conducted in one ICH region can be
used in other ICH regions by setting the common
standards on science and ethics.
• CTD (Common technical document) brings together
all Quality, Safety and Efficacy information in a
common, harmonized format, accepted by regulators
in all ICH regions.
• It has revolutionized regulatory review processes for
regulators and industry.
• MedDRA (Medical Dictionary for Regulatory
Activities) It is used for registration, documentation
and safety monitoring of medical products both before
and after marketing authorization.

12. ICH Guidelines(as of Nov,2019)
• There are over 70 Guidelines available on
technical requirements for :
• Quality - 24 Guidelines (12 main).
▫ Involves stability, impurity testing & GMP.
• Safety – 15 Guidelines.
▫ Involves Carcinogenicity, Genotoxicity,
Reprotoxicity & other toxicity studies.
• Efficacy – 21 Guidelines.
▫ Involves clinical trials & pharmacogenomics.
• Multidisciplinary - 7 Guidelines.
▫ Involves MedDRA, CTD & Electronic standards.

13. Quality Guidelines
• Q 1 A – Q 1 F Stability
• Q1A – Stability Testing of New Drug Substances
and Products.
• Q1 B – Photo Stability Testing of New Drug
Substances and Products.
• Q1C – Stability Testing for New Dosage Forms.
• Q1D – Bracketing and Matrixing Designs for
Stability Testing of New Drug Substances and
Products.
• Q1E – Evaluation of Stability Data.
• Q1F – Stability Data Package for Registration
Application in Climatic Zones III and IV.

14. Quality Guidelines
• Q 2(R1) Analytical validation-Validation of
Analytical Procedures: Text and Methodology.
• Q 3 Impurities
• Q3A - Impurities in New Drug Substances.
• Q3B – Impurities in New Drug Products.
• Q3C– Guideline for Residual Solvents.
• Q3D –Guideline for Elemental Impurities
• Q 4 Pharmacopoeias
• Q 5 Quality of Biotechnology Products

15. Quality Guidelines
• Q 6 Specifications - Test Procedure and Acceptance
Criteria for New Drug Substances and New Drug Products,
Chemical Substances & biotechnological products.
• Q 7 Good Manufacturing Guide for Active Pharmaceutical
Ingredients.
• Q 8 Pharmaceutical Development
• Q 9 Quality Risk Management.
• Q 10 Pharmaceutical Quality System.
• Q 11 Development and Manufacture of Drug
Substances (Chemical Entities, Biotechnologicals/
Biological Entities)
• Q 12 Life Cycle Management.
• For detailed ICH guidelines visit
https://www.ich.org/page/ich-guidelines.

16. Stability testing guidelines
• Stability of pharmaceutical product may be
defined as the ability of pharmaceutical dosage
form to maintain the physical, chemical,
microbiological and therapeutics properties
during the time of storage and usage by the
patient.

17. Purpose of stability testing
• 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 and recommended
storage conditions.

18. Stability protocol For Drug Substance & Drug products
• Stress testing (only in drug substance)
• Selection of batches
• Container and closure system
• Specifications
• Testing frequency
• Storage conditions
• Stability Commitment
• Evaluation
• Statements/Labeling

19. Stress testing
• It is also known as force degradation study.
• Stress testing of the drug substance can help
identify the likely degradation products,
which can in turn help establish the degradation
pathways and the intrinsic/natural stability of
the molecule.
• Stress testing is likely to be carried out on a
single batch of the drug substance.
• It should include the effect of temperatures (in
10°c increments), humidity (e.g., 75% RH or
greater) where appropriate oxidation, hydrolysis
and photolysis on the drug substance.

20. Selection of batches
• At least three primary batches should be
representative to quality of the material used for
production scale.
• 1st 3 batches manufactured for the sale should be
selected, and 1st batch manufactured in the
current year is selected for stability testing
(excluding trial batches).

21. Container Closure System & specifications.
• Container Closure System:
• Stability testing should be conducted on the drug
product/dosage form packaged in the container
closure system proposed for marketing/sale
(including, as appropriate, any secondary packaging
and container label).
• Specification, which is a list of tests, reference to
analytical procedures, and proposed acceptance
criteria, is addressed in ICH Q6A and Q6B.

22. Testing frequency
• For long term study
• For products with a proposed shelf life of at
least 12 months:
• every 3 months over the first year,
• every 6 months over the second year, and
• annually there after through the proposed shelf
life.

23. Testing frequency
• At the accelerated storage condition,
• a minimum of three time points, including the
initial and final time points (e.g., 0, 3, and 6
months), from a 6-month study is recommended.
• For intermediate studies:
• Min. 4 time points (0, 6, 9, 12 months) for a 12
months study.

24. Storage conditions (General case)
Or 30°C ± 2°C/65% RH ± 5% RH
*It is up to the applicant to decide whether long term stability studies
are performed at 25 ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ±
5% RH.

25. Storage condition
• For drugs intended to be stored in Refrigerator.
• For drugs intended to be stored in Freezer.

26. Stability Commitment
• In case where data submitted for registration do
not cover the proposed shelf life, it is necessary
to give commitment to continue the stability
studies post approval in order to firmly establish
the shelf life.
• Where the submission includes long term
stability data from three production batches
covering the proposed shelf life, a post approval
commitment is considered unnecessary.

27. Evaluation
• The purpose of the stability study is to establish re-
test period for DS and shelf life for drug
product for future batches based on evaluation of
results obtained from chemical, physical, biological,
microbiological tests.
• A systematic approach should be adopted in the
presentation and evaluation of the stability
information, which should include, as appropriate,
results from the physical, chemical, biological,
and microbiological tests, including particular
attributes of the dosage form (for example, dissolution
rate for solid oral dosage forms).

28. Statements/Labeling
• A storage statement should be established for the
labeling in accordance with relevant
national/regional requirements.
• The statement should be based on the stability
evaluation of the drug product.
• There should be a direct link between the label
storage statement and the demonstrated stability
of the drug product.
• An expiration date & re-test date should be
displayed on the container label.