Transcript Slide 1

STABILITY TESTING
Dr. Laila Khairy PhD,
Chairman, NODCAR
NATIONAL ORGANIZATION FOR DRUG CONTROL
AND RESEARCH
PURPOSE OF STABILITY STUDIES
OBJECTIVE
TYPE OF
STUDY
FOR
-To select adequate
Accelerated
Development of product
-To determine shelf life
and storage conditions
Accelerated and /
or real-time
Development of product
and registration dossier
-To substantiate the
Real-time
Registration dossier
-To verify that no
Accelerated and
real time
Quality assurance in
general including quality
control.
formulation & container
closure
claimed shelf life
changes have been
introduced in the
formulation or
manufacturing process.
Intended Market
Four climatic zones can be distinguished
for the purpose of worldwide stability
testing
Climatic
zone
Type
Measured data
in open
(Co) (RH%)
I
Temperate
10.9
75
18.7
45
18.8
II
Sub-tropic
17.0
70
21.1
52
III
Hot / dry
24.4
39
26.0
54
IV
Hot / humid
26.5
77
28.4
70
Points of Consideration During
A Stability Study
•
Storage Conditions.
•
Container Closure
•
Extreme Temperature Fluctuations
•
Storage Temperatures
•
Microbial Quality
•
Degradation
•
Statistical consideration
On-going stability studies – WHO
One batch every other year may be
tested for formulations considered to be
stable
( otherwise one batch per year)
One batch every 3 – 5 years may be
tested for formulations when the stability
profile has been established unless a
major product change has been made.
CONTENT OF STABILITY REPORTS
A. General Product Information.
B. Specifications and test methodology.
C. Study Design and Study Conditions.
D. Stability Data / Information.
E. Analytical Methods
F. Data Analysis and Conclusions.
Before You Start
 Rugged and robust methods.
 Trained analysts.
 Effective technology transfer.
 Qualified equipment and instruments.
 Pre-Determined and Written.
- Protocol
- Acceptance Criteria
Pre-validation Assay Acceptance
Criteria
• Assay Characterized for:
– Accuracy
- Specificity
- Ruggedness
- Robustness
- Precision and other parameters as appropriate
- SST parameters.
• Passes repeated SST SETS
Quantitation Limit
• Lowest amount of analyte in a samples
which can be quantitatively determined
with suitable
- Precision.
- Accuracy.
• Approaches.
- Visual evaluation.
- By signal to noise ratio (10:1)
- Based on SD and slope of response.
Accuracy
• Closeness to reference value.
• Methods.
-Assay of reference material.
-Comparison of results to
reference
procedure.
-Infer
from precision,
specificity data.
linearity,
and
Specificity for ID Tests
• Discrimination may be shown by.
• Obtaining
•
- Positive results from samples containing the
analyte.
AND
Negative results from samples not containing the
analyte.
- Obtaining negative results on materials similar
in structure to the analytes.
Specificity for Assay
& Impurity Tests
• Spike with impurities and demonstrate
resolution.
- From active
- From each other
• Spike with degradation product standards
• Perform peak purity tests
- Collection and analysis
- Detection (DAD.MS)
Ruggedness and Robustness
• Ruggedness: ability of assay to perform.
- Person to person
- Instrument to instrument
- Day –to day
• Robustness: capacity to remain unaffected
- By small, deliberate changes in parameters
Linearity
• Ability to obtain test results which are
directly proportional to the concentration
of analyte in the sample.
• Establish across the range (5 conc. Min.).
• Dilution or separate weighings.
• Visual inspection of plot.
• Statistical analysis of regression line.
Reproducibility
• Expresses precision between laboratories.
• Inter – laboratory trial.
• Used for assay standardization.
• Not necessarily part of marketing
application dossier.
Repeatability
( AKA intra-assay precision)
• Precision under
- Same operating conditions
- Over a short time interval
• Methods
- 9 determinations (minimum) covering range
- 6 determinations at 100% test concentration
Generally Acceptable Design
Considerations
1.Tablets: A stability study should include
tests for the following characteristics of
the
tablet:
Appearance,
friability,
hardness, color, odor, moisture, strength,
disintegration and dissolution.
etc…… capsules …………………………
Key
wor
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