Stability plays an important role in the drug development process. Present work aims to compare the stability testing (ST) requirements of International Conference on Harmonization (ICH) with other international regulatory agencies like World Health Organization (WHO), Association of South East Asian Nations (ASEAN) and European Agency for Evaluation of Medicinal and Health Products (EMEA). ICH guidelines describe stability testing requirements for new drug substance and drug product. WHO guidelines describe stability testing requirements for both new and existing Active pharmaceutical ingredients (APIs) and addresses information to be submitted in original and subsequent applications for marketing authorization of their related Finished pharmaceutical products (FPP) for human use. ST requirements for WHO are similar, except for the parameters like selection of batches and storage conditions. WHO guidelines have an additional requirement for long term storage condition (general case) and accelerated storage conditions (substance/product intended to be stored in refrigerator). ASEAN guideline mainly focuses on the requirements for stability testing of drug products along with new chemical entities (NCE’s). The differences were observed in stress testing, selection of batches and real time storage conditions. EMEA guidelines discussed here are an extension of the note for guidance on stability testing requirements for new active substance and related products. It sets out the stability testing requirements for existing active substance and related finished product. The minimum time period to be covered by data at the time of submission during long term storage conditions differs from ICH guidelines.

1. Pharma Times - Vol. 43 - No. 09 - September 2011 21
Article
Comparison of Stability Testing Requirements of ICH
with other International Regulatory Agencies
Patel Henal, Sudeendra Bhat R., Balamuralidhara V* and Pramod Kumar T.M.
Pharmaceutical Quality Assurance Group, Dept. of Pharmaceutics, JSS College of Pharmacy, JSS University,
Mysore.
*Email id: baligowda@gmail.com
Objective
The objective of the present work was
to compare stability testing requirements
of ICH with WHO, ASEAN and EMEA for
various parameters such as: Stress testing
(includes photo stability testing), selection
of batches, container closure system,
specification, storage conditions, testing
frequency, stability commitment, evaluation,
statements and labeling.
Introduction
Stability plays an important role in the
drug development process. It explains
several factors that affect the expiration
dating of drug products, including the
chemical and physical stability during the
pre-clinical formulation stages, process
development, packaging development,
and post-marketing life. It allows the
establishment of recommended storage
conditions, retest periods, and ultimately
product shelf-life and expiry dating. Although
various international regulatory agencies
have their stability testing requirements
derived from parent ICH guidelines, they
differ in some parameters of stability testing
requirements1
.
Comparison of guidelines
Various international guidelines dis-
cussed here have derived their requirements
Stability plays an important role in the drug development process. Present work aims to compare the stability
testing (ST) requirements of International Conference on Harmonization (ICH) with other international regulatory
agencies like World Health Organization (WHO), Association of South East Asian Nations (ASEAN) and
European Agency for Evaluation of Medicinal and Health Products (EMEA). ICH guidelines describe stability
testing requirements for new drug substance and drug product. WHO guidelines describe stability testing
requirements for both new and existing Active pharmaceutical ingredients (APIs) and addresses information
to be submitted in original and subsequent applications for marketing authorization of their related Finished
pharmaceutical products (FPP) for human use. ST requirements for WHO are similar, except for the parameters
like selection of batches and storage conditions. WHO guidelines have an additional requirement for long term
storage condition (general case) and accelerated storage conditions (substance/product intended to be stored
in refrigerator). ASEAN guideline mainly focuses on the requirements for stability testing of drug products along
with new chemical entities (NCE’s). The differences were observed in stress testing, selection of batches and
real time storage conditions. EMEA guidelines discussed here are an extension of the note for guidance on
stability testing requirements for new active substance and related products. It sets out the stability testing
requirements for existing active substance and related finished product. The minimum time period to be covered
by data at the time of submission during long term storage conditions differs from ICH guidelines.
Key words: Stability testing, ICH, WHO, ASEAN, EMEA
for stability testing from ICH guidelines for
stability testing. However, they differ in cer-
tain aspects which are discussed below.
1. ICH guidelines for stability testing2
ICH guidelines define the stability data
package for a new drug substance or drug
product that is sufficient for a registration
application within the three regions of the
EC, Japan and the United States. Stability
testing requirements as per ICH guidelines
are discussed briefly in Table 1.
2. Comparison of ICH and WHO
guidelines3
ICH guidelines discuss stability testing
requirements for new drug substances
and new drug products, whereas WHO
guidelines apply to new and existing API’s
and their related FPP’s for human use
(Table 2).
3. Comparison of ICH and ASEAN
guidelines4
ASEAN guidelines majorly focus on
the stability testing requirements for drug
products. The drug products covered
in this guideline include Generics and
Variations along with NCEs. The difference
in the requirements from ICH guideline is
highlighted in Table 3.
Comparison of ICH and EMEA
guidelines5
Differences in some of the parameters
of stability testing requirements for EMEA
from ICH are given in Table 4.
Conclusion
From the above work it can be concluded
that though WHO guideline is derived from
ICH parent guideline, they have some
significant differences which defines its
individuality as a separate guideline.
ICH guideline defines stability testing
requirements for new drug substances and
drug products whereas WHO guideline
applies to both new and existing API’s
and their related finished products. The
differences were observed in the following
parameters: selection of batches, storage
conditions and statements and labeling.
ASEAN guideline mainly focuses
on the stability testing requirements for
drug products which include generics
and variations along with NCEs. Minor
differences were observed in the parameters
like stress testing, selection of batches,
storage conditions and testing frequency.
Also, there are no intermediate conditions
for carrying out stability testing as per
ASEAN guidelines.

2. Pharma Times - Vol. 43 - No. 09 - September 2011 22
Table 1. Stability testing requirements as per ICH guidelines
Parameters Drug substances Drug products
Stress testing Stress testing recommendations:
• Temperature:Temperatureaboveaccelerated
temperature (50˚C, 60˚C, 70˚C, etc.)
• Humidity: 25˚C/75% RH and 25˚C/90% RH
• Oxidation: Wide range of pH
• Photostability testing should be carried out
on a single batch.
• Temperature: 50˚C or 60˚C
for 1 month
• Temperature/humidity:
40˚C/75%RH, 25˚C/80%RH
• Photostability testing should be carried out.
Selection of batches Data should be provided on at least three primary
pilot scale batches.
Data should be provided on at least three primary
batches. Two should be at least pilot scale
batches.
Container closure system Stability testing should be carried out in the same
container closure system as that proposed for
storage and distribution.
Container closure system for testing should be
same as that proposed for marketing including any
secondary packaging.
Specification It is the list of tests and proposed acceptance
criteria which the drug substance should meet.
List of tests and acceptance criteria for drug
products.
Testing frequency Long term studies: 0, 3, 6, 9, 12, 18, 24 months
and annually through the proposed re-test
period.
Accelerated: 0, 3, 6 months
Intermediate: 0, 6, 9, 12 months
Same as that of drug substances.
Storage conditions a. General case:
Long term:
25°C ± 2°C/60%RH ± 5% RH or 30°C±2°C/
65%RH±5% RH
Intermediate:
30°C ± 2°C/65% RH ±5% RH
Accelerated:
40°C ± 2°C/75%RH ±5% RH
b. For drug substance intended to be stored in
refrigerator:
Long term: 5°C ± 3°C
Accelerated:
25°C ±2°C/60%RH ± 5% RH
c. For drug substance intended to be stored in
freezer:
Long term: - 20°C ± 5°C
Storage conditions for general case, for the product
intended to be stored in refrigerator and freezer is
same as that for drug substance.
a. Drug products packaged in semi-permeable
containers:
Accelerated:40°C±2°C/NMT 25%RH
Stability
commitment
If the data does not cover the proposed re-
test period granted at the time of approval, a
commitment should be made to continue the
stability studies post approval.
If the data does not cover the proposed shelf life
granted at the time of approval, a commitment
should be made to continue the long term studies
through the proposed shelf life and the accelerated
studies for 6 months post approval.
Evaluation Based on the evaluation of data re-test period
should be established.
Based on the evaluation of data shelf life should
be established.
Statements/ labeling A storage statement should be established
based on the stability evaluation of the drug
substance.
Same as drug substances.

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Table 2. Comparison of ICH and WHO guideline
Parameters ICH WHO
Selection of batches Data from at least three primary batches of the new
drug substance should be provided.
Data from at least two primary batches should be
provided for stability testing of existing API’s.
Storage conditions a. Long term storage conditions for drug substance
and drug product: (general case)
25°C ± 2°C/60% RH ± 5% RH or
30°C ± 2°C/65% RH ± 5% RH
a. Long term storage conditions for drug substance and
drug product: (general case)
25°C ± 2°C/60% RH ± 5% RH or
30°C ± 2°C/65% RH ± 5% RH or
30°C ± 2°C/75% RH ± 5% RH
b. Accelerated storage conditions for drug
substance/product to be stored in refrigerator:
25°C ± 2°C/60% RH ± 5% RH
b. Accelerated storage conditions for drug substance/
product to be stored in refrigerator:
25°C ± 2°C/60% RH ± 5% RH or
30°C ± 2°C/65% RH ± 5% RH or
30°C ± 2°C/75% RH ± 5% RH
Parameters ICH ASEAN
Stress testing Temperature: temperature above accelerated
storage conditions (50ºC, 60ºC, 70ºC)
Humidity: 25˚C/75%RH and 25˚C/90%RH
Stress testing conditions is 40°C ± 2°C/75% RH
± 5% RH which is same as accelerated storage
conditions.
Selection of batches Data from at least three primary batches of the new
drug substance should be provided.
Data on at least two pilot scale batches are acceptable
for conventional dosage forms and for product
containing stable drug substances.
Storage conditions a. Product stored in permeable container:
Not mentioned
a. Product stored in permeable container:
30°C ± 2°C/75%RH ± 5% RH
b. Product stored in impermeable container:
Not mentioned
b. Product stored in impermeable container:
30°C ± 2°C/RH not specified
c. General case (long term storage)
25°C ±2°C/60% RH ± 5% RH or
30°C ± 2°C/65%RH ± 5% RH
c. For NCE (real time storage), generics and
variations:
30°C ± 2°C/75%RH ± 5% RH
Table 3. Comparison of ICH and ASEAN guidelines
Parameters ICH EMEA
S e l e c t i o n o f
batches
Data from at least three
primary batches of the
new drug substance
should be provided.
Option a:
Drug substance (described in an official pharmacopoeial monograph):
Stability information from accelerated and long term testing is to be provided on
at least two production scale batches.
Drug product:
For conventional dosage form and when drug substances are known to be stable,
stability data on at least two pilot scale batches are acceptable.
Option b:
Drug substance (not described in an official pharmacopoeial monograph):
Stability information from accelerated and long term testing is to be provided on
at least three pilot scale batches.
Drug product:
For critical dosage forms or when active substances are known to be unstable,
stability data on three primary batches are to be provided. Two of the three batches
should be of at least pilot scale; the third may be smaller.
Storage conditions L o n g t e r m s t o r a g e
conditions: minimum time
period covered by data for
new drug substances and
drug products at the time
of submission should be
12 months.
Drug substance:
Long term storage conditions: minimum time covered by data at the time of
submission should be 6 months for both option a and b.
Drug product:
Long term storage conditions: minimum time covered by data at the time of
submission should be - Option a: 6 months, Option b:12 months
Table 4. Comparison of ICH and EMEA guidelines

4. Pharma Times - Vol. 43 - No. 09 - September 2011 24
EMEA stability testing requirements
differ in the parameters such as stress
testing, selection of batches and minimum
time period covered by the data at the
time of submission under various storage
conditions for drug substances and drug
products.
Bibliography
1. Kim H. Handbook of Stability Testing
in Pharmaceutical Development-
Regulations, Methodologies and Best
Practices, Springer; 2008:10-13.
2. http://www.ich.org/LOB/media/
MEDIA419.pdf
3. WHO Technical Report Series, No.
953, Annex 2, Stability testing of active
pharmaceutical ingredients and finished
pharmaceutical products, 2009.
4. http://www.aseansec.org/home.htm
5. http://www.emea.eu.int