1.

PURPOSE:
1.1. To lay down the procedure for collection, storage and analysis of stability samples of finished product
and estimation of shelf life.
2. SCOPE:
2.1. This procedure is applicable to all experimental lots from R & D Department, Registration batches and
commercial finished product.
2.2. This SOP covers Zone IVb (Hot and Higher humidity) climatic conditions. Therefore, the studies are
carried out at 30 °C + 2 °C / 60 % RH + 5 RH for long term and 40 °C + 2 °C / 75 % RH + 5 RH for
accelerated condition.

3. RESPONSIBILITIES:
3.1. All personnel directly and indirectly involved in QC to comply with the SOP.
3.2. QA Manager to ensure implementation and compliance with the SOP.
3.3. Responsible Pharmacist to ensure compliance with the SOP.
3.4. QC Manager to ensure implementation of the SOP

4. DEFINITIONS/ABBREVIATIONS:
4.1. Abbreviations
4.2. Definitions
4.2.1.Stability: The capability of a given formulation in specified container/ closure system to remain,
within its physical, chemical, microbiological specifications. In other words, it is the extent to which
a product retains, within the specified limits, throughout its period of storage and use, the same
properties and characteristics possessed at the time of its packing.
4.2.2.Stability Study: An evaluation done to provide evidence on how the quality of a Finished Product
varies with time under the influence of different environmental factors such as temperature,
humidity, light and to establish storage conditions.
4.2.3.Long Term Testing: Evaluation of the physical, chemical and microbiological (if required)
characteristics of a pharmaceutical product over the expected duration of the shelf life under
recommended storage conditions and in the proposed container/closure system
4.2.4.. Accelerated Testing: Studies designated to increase the rate of chemical degradation or
physical change of a drug product by using stress (exaggerated) conditions of storage. The basic
objective is to reduce the time of study and extrapolate the result for the long term, i.e., till shelf
life. The data provides tentative expiration date.
4.2.5.Established product: The drug product manufactured using a standardized process and formula
and not showing significant change after assigned shelf life during long term stability testing and
completed the accelerated stability study.
4.2.6.Stable Product: A product is considered to be stable when during long term stability testing the
product is within specification limits up to its designated storage period and for accelerated testing
there is no significant change in any parameter.
4.2.7.Bracketing: The design of a stability schedule such that only samples on the extremes of certain
design factors (e.g., strength, container size and/or fill) are tested at all time points as in a full
 design. The design assumes that the stability of any intermediate levels is represented by the
stability of the extremes tested.
4.2.8.5.6 Stability data must demonstrate stability of the medicinal product throughout its intended shelf
life under climatic condition prevalent in the target countries. Merely applying the same
requirements applicable to other market could potential lead to substandard products.

5. REFERENCES:
5.1. WHO TRS 986 ANNEX 2
5.2. ICH Q1A-Q1E

6. INTERNAL DOCUMENT REFERENCES:

6.1.
7. PROCEDURE:
7.1. Selection criteria: Carry out stability studies of development batches for a single or multiple batches
as per the formulation. Carry out stabilities studies of registration batches for three batches. Data on
experimental batches serves to provide supportive information.
7.1.1.Accelerated stability studies
7.1.1.1. Will be done for 6 months at 40°C±2°C / 75% RH±5%RH
7.1.1.2. Testing intervals will be at 0; 3 and 6 months ± 2 days.
7.1.1.3. New commercial product – first 3 validation batches will be put on accelerated stability.
7.1.1.4. Change in Manufacturing Process – first 3 batches will be put on accelerated stability.
7.1.1.5. Change in formulation – first 3 batches will be put on accelerated stability.
7.1.1.6. Change in primary packaging – first 3 batches will be put on accelerated stability.
7.1.1.7. Reprocessed / reworked batch – that batch will be put on accelerated stability.
7.1.1.8. Established product – one batch per year
7.1.2.Long Term Stability Studies
7.1.2.1. These will be done up to end of shelf life plus one year at 30°C±2°C / 60% RH±5%RH.
7.1.2.2. Testing intervals will be at 0; 3;6;9;12;18;24;48;60 months ± 2 days
7.1.2.3. New commercial product – first 3 validation batches.
7.1.2.4. Change in Manufacturing Process – first 3 batches will be put on real time stability.
7.1.2.5. Change in formulation – first 3 batches will be put on real time stability.
7.1.2.6. Change in primary packaging – first 3 batches will be put on real time stability.
7.1.2.7. Reprocessed / reworked batch – that batch will be put on real time stability.
7.1.2.8. Established product – one batch per year will be put on real time stability.
7.1.3.Container Size
7.1.3.1. When the same product is marketed in more than one pack size, e.g., a bottle containing
100 tablets and a bottle containing 1000 tablets. The smaller container has a higher
surface area to internal volume ratio than the larger container. Thus the smallest
marketed container is the most critical in terms of container properties contributing to
product degradation.
 7.1.3.2. Thus, moisture or oxygen permeation through bottle for 100 tablets is more critical than
through bottle for 1000 tablets of similar constructions.
7.2. Significant Change
7.2.1.A 5% change in assay value form the initial figure.
7.2.2.Any degradation product exceeding its specification values.
7.2.3.Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test
(e.g., colour, hardness, crack, pocket budging etc.)
7.3. Bracketing
7.3.1.The use of a bracketing design is only considered appropriate when it can be demonstrated that
the strengths or container sizes and/or fills selected for testing are indeed the extremes.
7.3.2.Bracketing can be applied to studies with multiple strengths of identical or closely related
formulations. Such as;
7.3.2.1. Capsules of different strengths made with different fill plug sizes from the same powder
blend,
7.3.2.2. Tablets of different strengths manufactured by compressing varying amounts of the
same granulation,
7.3.2.3. Oral solutions of different strengths with formulations that differ only in minor excipients
(e.g., colourants, flavourings).
7.3.2.4. The same container closure system where either container size or fill varies while the
other remains constant.
7.3.2.4. However, if a bracketing design is considered where both container size and fill vary, it
should not be assumed that the largest and smallest containers represent the extremes
of all packaging configurations. Select the extremes by comparing the various
characteristics of the container closure system that may affect product stability. These
include container wall thickness, closure geometry, surface area to volume ratio,
headspace to volume ratio, water vapour permeation rate or oxygen permeation rate
per dosage unit or unit fill volume, as appropriate.
7.3.3.Bracketing should not be applied in cases where different excipients are used among strengths.
7.3.4.If the stability of the extremes is shown to be different, the intermediates will be considered to be
as stable the least stable extreme (i.e., the shelf life for the intermediates should not exceed that
for the least stable extreme.
7.4. Stability sample
7.4.1.Sample will be collected by IPQA chemist on the packing line or from R&D immediately after
packaging
7.4.2.Sample quantity is determined as per the approved stability protocol as per Annexure 5 by the
type of stability and quantity required for the tests at each interval.
7.4.3.Stability samples are used once per interval and cannot be returned to the chamber for re-use at a
later time period.
7.4.4.Always collect extra buffer samples (quantity sufficient to perform twice the stability tests per
interval) in case of spillages or OOS results that require investigations.
 7.4.5.The samples should be charged into the respective stability chambers on the day of
commencement of the study as prescribed in the respective stability study protocol. The
commencement date should be within 15 days of the date of approval of the batch which is
considered as initial month.
7.4.6.The sample shall be packed simulating the dispatch conditions or as per the proposed packing in
which it will be marked including primary and secondary packing and identified with a label
showing the type of study.
7.4.6.1. The label shall contain details such as date of charging, month of analysis, batch No.
and also the instructions regarding the storage: Temperature and Relative Humidity.
7.4.7.Samples to be logged into the stability sample register as per Annexure 1 for real time Stability
and Annexure 2 for Accelerated stability.

7.5. Withdrawal and Testing of Samples

7.5.1.After completion of incubation period, withdraw the selected samples from stability chamber on
due date ± 2 days and hand over to responsible QC analyst for testing. Ensure that the chamber
internal glass door is opened for as short a time as possible and close before setting off alarms.
7.5.2.Withdraw all samples for that particular day in one go to avoid multiple opening and closing of the
stability chamber door.
7.5.3.After the sample withdrawal from stability chamber, allow the sample to acquire the room
temperature and then only start the analysis.
7.5.4.Complete the analysis within 5 days after the withdrawal of sample. If the results are found to be
Out of Specification, then carry out the investigation as per SOP 4010 of Handling Out of
Specification.
7.5.5.If the results are within the specification enter into the stability data sheet as per Annexure 3 Long
term stability, and Annexure 4 accelerated stability for trending of data of the Stability Study.
7.5.6.If the trend results are Out of Trend, then carry out the investigation as per Handling of Out of
Trend SOP 4014.
7.5.7.If any significant change is observed at accelerated stability study at any interval, analyze the
samples of long term stability study.
7.5.8.If any significant change is observed during stability study, discontinue the stability study and carry
out the risk assessment study as per the Quality Risk Management SOP 1007.
7.5.9.Carry out the tests specified in the relevant stability study protocol as per Annexure 5. The
analytical method adopted should be stability indicating.
7.5.10. Submit the completed test data sheet, Stability Trend, and report as per Annexure 6 to QA
Manager for review.
7.6.

8. RECORDS:
8.1. N/A
9. ANNEXURES:
 9.1. ANNEXURE 1 REAL TIME STABILITY SAMPLE REGISTER
9.2. ANNEXURE 2 ACCELERATED STABILITY SSMPLE REGISTER
9.3. ANNEXURE 3 REAL TIME STABILITY DATA SHEET
9.4. ANNEXURE 4 ACCELERATED STABILITY DATA SHEET
9.5. ANNEXURE 5 STABILITY PROTOCOL FORMAT
9.6. ANNEXURE 6 STABILITY REPORT FORMAT

10. DISTRIBUTED TO
10.1. WAREHOUSE MANAGER
10.2. QA MANAGER
10.3. QA OFFICER
10.4. OPERATIONS
10.5. QC MANAGER
11. CHANGE CONTROL HISTORY
Change Control Version Effective Reason for Change
Date: