The document discusses stability testing guidelines for pharmaceutical dosage forms, emphasizing the importance of stability in maintaining drug properties during storage and usage. It outlines various types of stability testing including long-term, intermediate, and accelerated stability, as well as the principles and protocols involved in conducting these tests. Additionally, it details climatic zones and their impact on stability testing conditions, along with the significance of photostability evaluation.

1. ICH Stability Testing Guidelines
P. RAJA SEKHAR
Department of Pharmaceutics
St. Peter’s Institute of Pharmaceutical Sciences,
Vidyanagar, Hanamkonda 506001.

2. What is STABILITY ?
❖ Ability of the pharmaceutical dosage form to maintain the physical,
chemical, therapeutic and microbial properties during the time of
storage and usage by the patient.
❖ It is measured by the rate of changes that take place in
the pharmaceutical dosage forms
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3. Role of Stability in drug development
❖ Stability studies play a Prominent role in drug development,
❖ Permit Understanding of the molecule,
❖ Essential for developing analytical Tools,
❖ Essential for selecting packaging for drug substance and drug product,
❖ Essential for choosing storage conditions for drug substance and drug product.
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4. Role of stress testing
❖ Identification of degradation pathways,
❖ Identification of degradants,
❖ Determine which type of stress affects the API or Drug Product or Finished Pharmaceutical
Product (FPP)
- Light
- High Temperature
- Low temperature
- Humidity (Moisture)
- Oxidation
- pH extremes.
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5. Stability testing Guidelines List
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The guidelines for stability testing falls under the Quality topic (Q)
The stability testing contains Q1A-Q1F are of six different guidelines.
Guideline Title
Q1A(R2) Stability Testing of New Drug Substances and Products
Q1B 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 Applications in Climatic Zones III and IV

6. What are the types of Stability ?
▸ CHEMICAL: Each ingredient retain its chemical integrity and labeled potency
within specified limit.
▸ PHYSICAL: The original physical properties including appearance, palatability,
uniformity, dissolution, and suspendability are retained.
▸ MICROBIOLOGICAL: Sterility or resistance to microbial growth is retained
according to specified requirement.
▸ THERAPEUTIC: Therapeutic effect remains unchanged.
▸ TOXICOLOGY: No significant increase in toxicity occurs.
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7. What are principles of the guidelines?
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1. Purpose of stability testing is to provide evidence how quality varies with time under
influence of temperature, humidity, light.
2. Establish Re-test period for drug substances.
➢ Re-test period, the period after which samples of the drug substances should be examined to
ensure is still in compliance with specification, and thus suitable for manufacturing.
3. Establish shelf life for drug product.
➢ Shelf life is used to establish expiration date of drug product.

8. What are principles of the guidelines?
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4. Recommends storage condition.
5. Give test condition based on analysis of effects of climate conditions
in the three regions of the Europe, Japan, USA.
6. Gives mean kinetic temperature which is derived from climatic
data.
7. Divided world into four different climatic zones I-IV
➢ this guidelines addresses climate zone I and II

9. What are various climate Zones?
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1 hectopascal (hPa) equals 100 Pa
Climatic
Zone
Climate Definition Major Countries/ Region Mean Annual
Temperature/ Partial
Water Vapour Pressure
Long Term Testing
Conditions
I Temperate Uk, US, Northern Europe, Russia <15°C/<11hPa 21°C/45% RH
II Subtropical and
Mediterranean
Japan, Southern Europe 15 -22°C/(11-18) hPa 25°C/60% RH
III Hot and Dry India, Iraq >22°C/<15hPa 30°C/35% RH
Iva Hot and Humid Iran Egypt >22°C/15-27hPa 30°C/65% RH
IVb Hot and Very Humid Brazil, Singapore >22°C/>27hPa 30°C/75% RH

10. STABILITY TESTING PROTOCOL
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Stability testing is the systematic approach towards drug development process.
The protocol for stability testing is a pre-requisite for starting stability testing and is necessarily a written document that describes the key components of
a regulated and well-controlled stability study.
A well designed stability protocol should contain the following information:
➢ Number of Batches
➢ Containers and closures
➢ Orientation of storage of containers
➢ Sampling time points
➢ Test storage conditions
➢ Test parameters
➢ Test methodology
➢ Acceptance criteria

11. TYPES OF STABILITY TESTING
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1. Long term stability
2. Intermediate stability
3. Accelerated stability
4. In-use stability

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Long-term
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 12 months or 6 months.
Intermediate
30°C ± 2 °C/65% RH ± 5% RH 6 months.
Accelerated
40°C ± 2 °C/75% RH ± 5% RH 6 months.
Study Storage condition and Minimum time period
covered by data at submission

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Study Storage condition and Minimum time period covered by data at submission
Long-term
5 °C ± 3°C 12 months or 6 months
Accelerated
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 6 months
Study Storage condition and Minimum time period for
Active pharmaceutical ingredients intended for storage
in a refrigerator

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Study Storage condition and Minimum time period covered by data at submission
Long-term
−20°C ± 5°C 12 months or 6 months
Study Storage condition and Minimum time period for Active
pharmaceutical ingredients intended for storage in a Freezer

15. Long term stability testing
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❖ Stability studies are intended for testing the drug product for longer periods under varying conditions of
temperature and humidity.
❖ If the drug is to be distributed in different geographical regions and if shipping is required for transportation,
in that case long term stability studies are of prime importance.
❖ Long term stability studies are performed by testing the sample at specific time intervals and conditions of
external parameters are changed accordingly.
❖ Main objective of this study is to determine shelf-life of the drug product.

16. Intermediate stability testing
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❖ Studies conducted at 30°C/65% RH and designed to moderately increase the rate of chemical degradation or
physical changes for a drug substance or drug product intended to be stored long term at 25°C.
❖ The intermediate storage condition has been changed between different temperature and relative humidity
conditions.

17. Accelerated stability testing
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❖ These studies include use of exaggerated storage conditions designed to study increased rate of physical and
chemical degradation.

18. ICH Q1A Summary of stability parameters:
Study type and storage conditions
Study type and Condition Storage Condition Time
Period
(Months)
Comments
General Long Term 25°C ± 2°C/60% RH ± 5% RH or
30°C ± 2 °C/65% RH ± 5% RH
12 Must cover retest or shelf life period at a
minimum and includes storage, shipment
and subsequent use.
Intermediate 30°C ± 2°C/65% RH ± 5% RH 6
Accelerated 40°C ± 2°C/75% RH ± 5% RH 6
Refrigeration Long term 5°C ± 3°C 12 Must cover retest or shelf life period at a
minimum and includes storage, shipment
and subsequent use.
Accelerated 25°C ± 2°C/60% RH ± 5% RH 6
Freezer Long Term -20°C ± 5°C 12 Must cover retest or shelf life period at a
minimum and includes storage, shipment
and subsequent use.

19. TEST SCHEDULE FOR STABILITY TESTING OF
NEW PRODUCTS:
Sampling times vs climatic zones
Environment Sampling time points (in
Months)
Method and Climatic Zone
25°C ± 2°C/60% RH 3,6,9,12,18,24,36 Long term fore Zones I and IV
30°C ± 2°C/35% RH 3,6,9,12,18,24,36 Long term fore Zones III
30°C ± 2°C/65% RH 3,6,9,12,18,24,36 Long term fore Zones IVa, or
intermediate condition for Zone I
and II
30°C ± 2°C/75% RH 3,6,9,12,18,24,36 Long term fore Zones IVa, or
intermediate condition for Zone I
and II
40°C ± 2°C/75% RH 3,6 Accelerated conditions for all
zones

20. Systemic approach to photostability testing:
i) Tests on the drug substance
ii) Tests on the exposed drug product outside of the
immediate pack
iii) Tests on the drug product in the immediate pack
iv) Tests on the drug product in the marketing pack
❖ For drug substances, photostability testing consist of two parts:
1. forced degradation testing and
2. confirmatory testing.
Photostability Testing

21. Light source used for photostability testing:
▸ Option 1 : Any light source that is designed to produce an output
similar to the D65/ID65 emission standard
(e.g. xenon, or metal halide lamp)
*D65 is the internationally recognized standard for outdoor daylight as
defined in ISO 10977 (1993).
*ID65 is the equivalent indoor indirect daylight standard.
Photostability Testing

22. Light source used for photostability testing:
▸ Option 2:the cool white fluorescent and near ultraviolet lamp.
1. A cool white fluorescent lamp designed to produce an output similar to
that specified in ISO D65 10977(1993).
2. A near UV fluorescent lamp having a spectral distribution from 320 nm
to 400 nm
Photostability Testing

23. EVALUATION
▸ A Systematic approach should be adopted in the presentation and evaluation of the stability
information which covers the physical, chemical & biological parameter.
▸ A minimum of three batches of drug product is tested.
▸ The analyst must found the batch to batch variability and if it is small than only it is accepted
and it can be done by different statistical test’s
▸ Where the data shows so little degradation & so variability that is apparent from looking the
data the requested shelf life will be granted. & it is normally unnecessary to go through the
formal statistical analysis.
Photostability Testing

24. Significant change for a drug product:
▸ A 5% change in assay from its initial value.
▸ Any degradation product exceeding its acceptance criterion.
▸ Failure to meet the acceptance criteria for appearance, physical attributes, and
functionality test (e.g., color, phase separation, resuspendibility, caking, hardness, dose
delivery per actuation)
▸ However, some changes in physical attributes (e.g., softening of suppositories, melting of
creams) may be expected under accelerated conditions.
Significant Change

25. STATEMENTS / LABELLING:
▸ A storage statement should be established based on the stability
evaluation of the drug substances.
▸ Terms such as “ambient conditions” or “room temperature” should be
avoided.
▸ Retest date should be displayed on the container label if appropriate.
Conclusion

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THANK You All!
Dr. P. Rajasekhar
Professor, Department of Pharmaceutics
St. Peter’s Institute of Pharmaceutical
Sciences, Hanumakonda