The document discusses ICH stability testing guidelines for drug substances and products, outlining the types of studies required including long term, intermediate, and accelerated studies under various storage conditions. Key aspects that are evaluated include physical, chemical, and microbial changes that may occur over time and factors that influence stability such as temperature, humidity, and light exposure. The purpose of stability testing is to establish a product's shelf life and ensure it remains safe and effective when stored as recommended.

1. Assignment on
ICHSTABILITYTESTINGGUIDELINES:
Presented by:
Diksha Diwakar Roll No: 1784550007
Class: B-pharma 6th semester Subject: Quality
Assurance
Submitted to:
Mohammad khalid
Assistant Professor.
KRISHNA PHARMACY COLLEGE BIJNOR

2. ICH Stability testing guidelines
Drug Stability
Stability of pharmaceutical product may be defined as the capability of a particular
formulation in a specific container/closure system to remain within it’s physical, chemical,
microbiological therapeutic and toxicology specification.
Stability studies are preformed on
Drug Stability (DS)-
The unformulated drug substance that may subsequent be formulated with
excipient to produce the dosage form.

3. Drug product (DP)-
The dosage form in the final immediate packaging intended for
marketing controlled and documented determination of acceptable change
of the drug substance.
On storage of Drug substance and Drug product the following changes may
be takes place-
Physical changes
■ Appearance
■ Melting point
■ Moisture
■ Particle size
Chemical changes
■ Increase in Degradation
■ Decrease of Assay
Microbial changes

4. ■ Stability testing (ICH):
■ TYPE SIZE, NUMBER OF BATCHES (ICH/WHO GUIDELINES)-
■ At least 3 primary batches of Drug product, should be of the same
formulation packaged in same container proposed for marketing.
■ 2 out of 3 batches should be pilot scale batches.
■ LONG TERM STABILITY STUDIES-
■ Study is performed at 25°C/60% or 30°C/65%.
■ Ideally 12 months data is to be generated but 6 month data is also
acceptable in circumstances for submission registration dossier,
continued till end of shelf life.
■ ACCELERATED STABILITY STUDIES-
■ Storage condition of 40°C +/- 2°C and relative humidity of 75% +/- 5%
has been recommended for all the four zones for drug substance and
Drug product.
■ Studies carried out for 6 month.

5. CLIMATE ZONES / STORAGE CONDITIONS:
DRUG SUBSTANCE – INTENDED FOR STORAGE IN A REFRIGERATOR:
Study Storage condition Minimum time period
covered by data at
submission
Long term 25°C+/- 2°C / 60% +/- 5% R.H. 12 months
Intermediate 30°C +/- 2°C / 65% +/- 5% R.H. 6 months
Accelerated 40°C +/- 2°C / 75% +/- 5% R.H. 6 months
Study Storage Minimum time
period covered by
data at submission
Long term 5°C+/- 3°C 12 months
Accelerated 25°C+/- 2°C / 60% +/-
5% R.H.
6 months

6. DRUG SUBSTANCE / PRODUCTS – INTENDED FOR STORAGE IN FREEZER
DRUG PRODUCTS – GENERAL CASE:
Study Storage Minimum time period covered
by data at submission
Long term -20°C+/- 5°C 12 months
Study Storage Minimum time period
covered by data at
submission
Long term 25°C +/- 2°C / 60% +/- 5% R.H. 12 months
Intermediate 30°C +/- 2°C / 65% +/- 5% R.H 6 months
Accelerated 40°C +/- 2°C / 75 % +/- 5% R.H. 6 months

7. DRUG PRODUCTS – PACKAGED IN SEMI – PERMEABLE CONTAINER
Study Storage Minimum time period
covered by data at
submission
Long term 25°C +/- 2°C / 40% +/- 5%
R.H.
12 months
Intermediate 30°C +/- 2°C / 65% +/- 5%
R.H.
6 months
Accelerated 30°C +/- 2°C / 65% +/- 5%
R.H.
6 months

8. ■ PROTECTION AGAINST HYDROLYSIS:
■ Buffering agent for pH control.
■ Alteration of dielectric constant.
■ Addition of comlexing agent like caffeine.
■ Use of surfactant, good refrigeration.
■ PROTECTION AGAINST OXIDATION:
■ Chelation using EDTA, citric acid, tartaric acid.
■ Use of insert gas like nitrogen.
■ Protection from light by use of amber colored container.
■ Storage at low temperature.

9. ■ Testing scope for solid dosages:
■ Physical – chemical properties
■ Appearance
■ Elasticity
■ Moisture
■ Hardness
■ Dissolution
■ Chemical properties
■ Assay
■ Degradation
■ Microbial properties
■ Container closure system properties
■ Functionality tests

10. ■ Testing scope for liquid form:
■ Physical – chemical properties
■ pH
■ Loss on weight
■ Sterility tests
■ Chemical properties
■ Assay
■ Degradation product
■ Content antioxidants
■ Microbial properties
■ Pyrogen testing
■ Container closure system properties
■ Functionality test
■ Leakage test

11. ■ Testing scope for oral liquid form:
■
■ Physical – chemical properties
■ pH
■ Viscosity
■ Particle size distribution
■ Chemical properties
■ Assay
■ Degradation products
■ Degradation preservatives
■ Microbial properties
■ Container closure system properties
■ Functionality tests

12. ■ Testing scope for semi liquid form
■ Physical – chemical properties
■ Appearance
■ Loss of weight
■ Viscosity
■ Chemical properties
■ Assay
■ Degradation products and preservative
■ Content preservatives
■ Microbial properties
■ Container closure system properties
■ Functionality tests

13. STABILITY:
Ideally any commercial pharmaceutical product should have a shelf life 5 years
and should not fall below 90-95 % potency under recommend storage .
In designing a solid dosage form it is necessary to know the inherent stability of
the drug substance, excipient to be used, formulation procedure.
CHEMICAL DEGRADATION STUDY:
Hydrolysis-
Usually drug such as ester, amides, and lactams undergo hydrolysis.
Oxidation reduction-
Loss of electron, gain of electron. Auto oxidation also is responsible.
Photolysis-
Compound such as ascorbic acid, riboflavin, folic acid undergo
degradation on exposure to light.
Isomerisation-
Compound get converted into a less effective form.

14. ELEVATED TEMPERATURE STUDIES:
Test are usually performed at 40, 50, 60°C in conjuction with ambient humidity.
Higher temperature are also used, samples kept at highest temperature examined for chemical
and physical Changes at weekly intervals – if no change is seen after 30 days at 60°C stability
prognosis is excellent.
STABILITY UNDER HIGH HUMIDITY CONDITION:
In presence of moisture, many drug substance hydrolyze react with other excipients or oxidize.
These tests are preformed by exposing the drug to different relative humidity condition.
PHOTOLYTIC STABILITY –
Many drug fade or darken on exposure to light and this leads to an aesthetic problem which
can be controlled by using –
• Amber glass container.
• Opaque container.
• Incorporating a Dye.

15. PHOTO DEGRADATION PATHWAYS-:

16. STABILITY TO OXIDATION-
Stability to oxidation must be evaluated to establish that the final product
should be packaged under insert atmosphere or it requires an antioxidants.
A 40 % oxygen atmosphere allows for rapid evaluation.
EFFECT of ph:
Most of the drug are stable at pH 4- 8.
Weakly acidic and basic drug are most soluble in inonized form and
instability is likely as they are charged.
STRESS TESTING-
Helps to identify the likely degradation product and degradation pathways
and intrinsic stability of molecules.
Carried out on single batch.
Humidity.

17. SHELF LIFE-
Shelf life is the time period during which a drug product is expected to
remain within the approved specification for use, provided that it is stored
under the condition defined on the container label.
Maximum and minimum time at which potency must be at least 90% of
level claim at the temperature indicated to predict to self life at room
temperature:
Temperature in °c Maximum time for
study
Minimum time for
study
37 12 months 64 months
45 8.3 months 2.9 months
60 4.1 months 3 weeks
85 06 weeks 2.5 days

18. LIMITATIONS:
-Temperature
-energy of activation is about 1 to 30 kcal / moles.
- degradation due to
1. Diffusion
2. Microbial contamination
3. Photochemical reaction
4. Excessive agitation
- higher temperature
Example-
Coagulation of suspending agent
Denaturation of protein
Breaking of emulsion
Loss of consistency of ointment