Stability testing provides evidence on how the quality of a drug substance or product varies over time under different environmental conditions like temperature and humidity. It establishes a re-test period for the drug substance and a shelf life for the product. Studies include long term testing at 25°C/60% RH for at least 12 months, accelerated testing at 40°C/75% RH for 6 months, and intermediate testing at 30°C/65% RH for 6 months. At least three primary batches are tested initially and one batch per year thereafter.

2. The purpose of stability testing is 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.

3. Long term Stability
Accelerated Stability
Intermediate
Stability

4. To establish the i) Degradation pathways and intrinsic
stability
of molecules .
ii) To test the attributes influencing the
quality &
safety of drug during storage.
iii) The impact of these factors
are modulated
by the type of container or
packaging
quality.All these factors jointly

5. For long term studies, frequency of testing should be
proposed re-test period of at least 12 months, normally be
every 3 months over the first year, every 6 months over the
second year, and annually thereafter through the proposed
re-test period.
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.
Where an expectation exists that results from accelerated
studies are likely to approach significant change
criteria,increased testing should be conducted.

6. When testing at the intermediate storage condition is
called for as a result of significant change at the accelerated
storage condition, a minimum of four time points (e.g., 0, 6, 9,
12 months), from a 12-month study is recommended.

7. The choice of test conditions defined,is based on an analysis of
the effects of climatic conditions in the three regions of the EC,
Japan and the United States. The mean kinetic temperature in
any part of the world can be derived from climatic data, and the
world can be divided into four climatic zones, I-IV.
Dividing the world according to temperature and
humidity
zone
• Zone - I : Temperate Climatic zones
• Zone - II : Mediterranean/Sub tropical Climatic
zones
• Zone - III : Hot Dry Climatic zone
• Zone - IV : Hot Tropical humid climatic zone

8. CLIMATIC
CONDITION
ZONE - I ZONE- II ZONE-III ZONE-IV
Mean annual
temp.
20.5°C 20.5°–24.0°C >24.0°C >24.0°C
Kinetic mean
temp.
21.0° C 26.0°C 31.0°C 31.0°C
Mean annual
relative
humidity
45% 60% 40% 70%

9. The long term studies performed at 25°C ± 2°C/60% RH ±
5% RH for minimum of 12 months’ duration and should be
continued for a period of time sufficient to cover the proposed
re-test period.
The Accelerated studies conducted at 40°C ± 2°C/75% RH ±
5% RH 6 months
Intermediate studies conducted at 30°C ± 2°C/65% RH ± 5%
RH for 6 months
The other storage conditions can also be followed if justified.
Heat sensitive drugs are stored at alternative lower temperature
conditions which eventually becomes designated long term
storage condition

10. The six months Accelerated testing carried out at the
temperature at least 15°C above its designated long term storage
temperature together with appropriate relative humidity
conditions for the temperature(e.g. if a product is to be stored at
refrigerated conditions 2-8°C , Accelerated testing is conducted
at 25°C + 2% / 60% + 5% RH )

11. At least three primary production batches of the drug substance
should be taken for stability studies.
Thereafter one batch should be taken every year of each product
from production batches.

12. The stability studies should be conducted on the drug substance
packaged in a container closure system that is the same as or
simulates the packaging proposed for storage and distribution.
Product Sampling
Qty.
Method Study Period
Capsules 400 LTS, ASS & ISS
LTS – 36 Months
ASS – 6 Months
ITS – 12 Months
Tablets 400 LTS, ASS & ISS
Injection 120 LTS, ASS & ISS
Dry Syrup 40 LTS, ASS & ISS

13. The testing should cover, as appropriate, the physical,chemical,
biological, and microbiological attributes.
The possibility of identification of degradation products should
be explored if some degradation product is reported (They
should not be more than 5% in Assay from its initial value /
Change in colour , hardness , pH, Dissolution of 12 dosage )
The stability of drug products after reconstitution or dilution
according to labeling should be addressed to provide appropriate
and supportive information. The stability samples should confirm
to all finished product specifications.
Manufacturers recommendations on these can also
be an alternate criteria for acceptance .

14. Photostability testing should be conducted on at least one
primary batch of the drug product if appropriate.
Selection of Batches
At least three primary batches of the drug product.
Same formulation and packaged in the same container closure
system as proposed for marketing.
Manufacturing process for primary batches should same as
that in production batches.

15. Stability studies should be performed on each individual
strength and container size of the drug product unless
Bracketing or Matrixing is applied.Other supporting
data can be provided.
Specifications :
Stability studies should include testing of those attributes of
the drug product that are susceptible to change during
storage and are likely to influence quality, safety, and or
efficacy,as appropriate, the physical, chemical, biological,
and microbiological attributes, preservative content (e.g.,
antioxidant, antimicrobial preservative), and functionality
tests (e.g., for a dose delivery system).

16. EVALUATION
The purpose of the stability study is to establish, based on
testing a minimum of three batches of the drug substance
and evaluating the stability information (including, as
appropriate, results of the physical, chemical, biological,
and microbiological tests), applicable to all future batches
of the drug substance manufactured under similar
circumstances.