STABILITY TESTING OF

NEW DRUG SUBSTANCES AND

PRODUCTS

Mr. AGNIMITRA DINDA

SCHOOL OF PHARMACEUTICAL
SCIENCES
INDIA
STABILITY STUDIES :
• Stability is defined as the extent to
which a product retains, within
specified limits and throughout its
period of storage and use (i.e., its
shelf-life), the same properties and
characteristics that it possessed at
the time of its manufacture.
CRITERIA FOR ACCEPTABLE LEVELS OF
STABILITY:

• Chemical
• Physical
• Microbiological
• Therapeutic
• Toxicological
PURPOSE OF STABILITY STUDIES
IN ACTIVE INGREDIENT :

• To ascertain suitability of the

active ingredient for particular
product shelf life.
• To ascertain shelf life of the
product.
• To determine storage condition of
the product.
QUALITY OF PHARMACEUTICAL
PREPARATION TO BE ASSESSED :
• The active ingredient content;
• Product safety (e.g. appearance of toxic
degradation products);
• Physical appearance of the product;
• The content of other important components
of the formulation ( e.g. antimicrobial
preservatives);
• Purity (limits or absence of degradation
products of the active ingredient);
• Physical properties of the dosage form,
Microbial properties;
• Properties of the container/closure system;
• Organoleptic properties (taste, odour, etc.)
CLASSIFICATION OF CLIMATIC
ZONES :

1. Tropical Humid Climates-

Tropical Wet: Average
temperature 26°C, Relative
Humidity (RH) 70-100%
Tropical Wet and Dry :
Temperature range 8-40°C, RH 50-
100% RH
2. Dry climates -
♦Arid (hot and dry): Temperatures up to
50°C, RH 10-50%,
♦Semi-arid: Temperatures 10-35°C.

3. Subtropical Climates
♦Subtropical Dry: Temperatures 10-40°C,
RH 50-80%
♦Subtropical Humid: Temperatures 10-
40°C, RH higher than in Subt Dry.
4. Temperate Climates:
♦ Temperate Oceanic:
Temperatures from 0-18°C, RH 60-
80%,
♦ Temperate Continental:
Temperatures 12-24°C, RH 60-
90%.
5. Sub Arctic Climate
6. Polar Climate: Average
temperature below 0°C.
7. Highland Climates
Mean Kinetic Temperature:
• It is defined as a singled calculated
temperature at which, the
degradation of an article would be
equivalent to the actual
degradation that would, result
from temperature fluctuations
during the storage period.
Climatic
Conditions
Zone I Zone II Zone III Zone IV

Mean annual 20.50C 20.5 - 240C > 240C >240C

Temperature
Kinetic mean 210C 260C 310C 310C
Temperature
Mean annual 45% 60% 40% 70%
Relative
Humidity
DEGRADATION PRODUCTS :
• Identity and chemical structure-
• Cross-reference to any available
information about biological effect and
significance at the concentrations likely
to be encountered.
• Procedure for isolation and purification.
• Mechanism of formation, including order
of reaction.
• Specifications and directions for testing
for their presence at the levels or
concentrations expected to be present.
• Indication of pharmacological action or
inaction.
STABILITY REPORT AS FDA SUGGEST:

• A. General product information:

1. Name of the drug substance/product.
2. Dosage form and strength (including
formulation).
3. Labeling.
4. Composition, type and size of
container and closure
STABILITY REPORT AS FDA SUGGEST:

• B. Specifications and test

methodology information:
1. Physical, chemical and
microbiological characteristics and
proposed specification.
2. Test methodology used on each
sample.
3. Analytical validation data on test
methods used.
4. Description of any biological potency
tests.
STABILITY REPORT AS FDA SUGGEST:

C. Study design and study conditions

:
1. Description of the sampling plan
including
(a) Batches and number selected.
(b) Container-closure and number
selected.
(c) Number of dosage units selected and
whether test conducted on individual
units or on a composite sample-
(f) Sampling times.
2. Expected duration of the study.
STABILITY REPORT AS FDA SUGGEST:

D. Stability data/information:
1. Lot number, scale of manufacture
(research, pilot, production), and date
of manufacture.
2. For antibiotic products, the age of
the bulk antibiotic used in the
manufacture.
3. Analytical data and source of each
data point (e.g. lot, container,
composite, etc.).
4. Summary of information previously
STABILITY REPORT AS FDA SUGGEST:

E. Data analysis and conclusions:

1 Documentation of appropriate
scientific methods used and their
formulas.
3. Evaluation of data, including
calculations, statistical analysis, plots
and graphics.
3. Statistical analysis of biological
potency estimates.
4. Proposed expiration data and its
justification.
GUIDELINES OF ICH FOR
STABILITY TESTING

(A) NEW ACTIVE DRUG

SUBSTANCE
1. Formal Studies:
• Primary stability studies are done
to show that drug substance will
remain within specifications during
the retest period if stored under
recommended storage conditions.
2. Selection of Batches:
• At least 3 batches over at least 12
months under accelerated & long
term (real) storage.

3. Batch Size :
• Pilot scale batch size,
manufactured by the same
synthetic route that simulates the
final process to be used on a
manufacturing scale.
4. Test Method :
• Testing should cover all aspects
likely to be changed during storage
and also likely to influence quality,
safety & efficacy of the drug
substance.
5. Specification for the Drug:
• The limit of acceptance set from the
stability data. Limits of degradation
products to be justified from the levels
seen in clinical studies.
6. Storage Test Condition:
• The length should cover storage,
shipment & subsequent use.

7. Testing Frequency:
• 3 monthly for first year.
• 6 monthly over the second year
and then annually.
8. Packaging Containers:
• The actual packaging container used for
storage and distribution.

9. Labeling:
• Specific storage temperature to be
mentioned as' Store below 30°C. ,
Additional warning about light exposure,
humidity etc. should also be given. The
use of terms such as 'ambient
temperature' or 'room temperature' is
unacceptable.
TESTING CONDITIONS FOR DRUG
SUBSTANCE(AN EXAMPLE) :
Designation Conditions Minimum time
storage period at
submission
Long-term testing 25°C ± 2°C/60% RH ± 5% 12 months
Accelerated testing 40°C ± 2°C/75% RH ± 5% 6 months

• Where signified changes occurs during six

months storage under conditions accelerated
testing at 40°C + 2°C/75% RH + 5%,
additional testing at an intermediate condition,
e.g., 30°C + 2°C/60 + 5% RH should be
conducted. Significant change, 40°C/75% RH
or 30°C/60% RH is defined as failure to meet
the specifications.