ICH Guidelines for stability testing

ICH GUIDELINES FOR
STABILITY TESTING
Presented by-
Ankita Kawtikwar
Roll no. 504
M.Pharm (Sem-I) Seminar
Department of Pharmaceutics
Dr. D.Y.Patil Institute of Pharmaceutical and Sciences and
Research, Pimpri, Pune,411018
1

WHAT IS ICH?
 International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for human use.
 brings together the regulatory authorities and
pharmaceutical industry to discuss scientific and
technical aspects of drug registration.
2

NEED TO HARMONISE?
 Independent evaluation of medicinal product before
they enter the market.
 Industry becoming Global
 Duplicate test procedures
Time consuming
Expensive
 Increasing R & D costs
 Meeting public demand
3

INITIATION OF ICH
 - 1980: European Community
Discussions between Europe, Japan and the US
 - 1989: WHO conference of Drug Regulatory Authorities, Paris
(ICDRA)
 International Federation of Pharmaceutical Manufacturers
and Association(IFPMA)
 - 1990: Birth of ICH at meeting hosted by European Federation
of Pharmaceutical Industries (EFPIA) and Associations at
Brussels
Europe
Japan
US
 Topics of Harmonisation divided into : Safety, Efficacy and Quality
4

DRUG STABILITY
 A measure of how a
pharmaceutical product
maintains its quality
attribute over a period
of time.
5

STABILITY TESTING
 To provide evidence on how the quality of a
drug substance or drug product varies with
time.
 Establish shelf life for the drug product
 Determine recommended storage
conditions
 Determine container closure system
suitability
7

ICH GUIDELINES FOR STABILITY TESTING
10

Q1A(R2)
STABILITY TESTING OF DRUG
SUBSTANCE AND DRUG PRODUCT
11

STRESS TESTING
Helps in
 Identification of degradants
 Identification of degradation pathways
 Determination of which type(s) of stress affect the
molecule
- Photo-stability
- High Temperature
- Low Temperature
- Oxidation
- pH extremes
- Water 12

 STRESS TESTING FOR NEVIRAPINE
14

Data from stability studies should be provided on at
least three primary batches of the active substance.
CONTAINER CLOSURE SYSTEM
Studies should be conducted on the substance
packaged in a container closure system that is the
same or simulates the packaging proposed for
storage and distribution.
SELECTION OF BATCHES
15

STORAGE CONDITIONS
*It is upto the applicant to decide whether long term stability
studies are performed at 25±2°C/ 60%RH±5%RH or
30°C±2°C/65%±5%RH.
**If 30°C±2°C/65%±5%RH is the long term condition, there
is no intermediate condition.
GENERAL CASE
17

If significant change occurs within the first 3 months
testing at the accelerated storage condition, it is
considered unnecessary to continue to test a drug
substance through 6 months.
DRUG SUBSTANCES INTENDED FOR
STORAGE IN A REFRIGERATOR
18

In the absence of an accelerated storage condition
for drug substances intended to be stored in a freezer,
testing on a single batch at an elevated temperature
(e.g., 5°C ± 3°C or 25°C ± 2°C) for an appropriate
time period should be conducted to address the effect
of short term excursions outside the proposed label
storage condition, e.g., during shipping or handling.
DRUG SUBSTANCES INTENDED FOR
STORAGE IN A FREEZER
19

 Testing of attributes that are susceptible to change during
storage and likely to influence quality , safety and/or
efficacy.
 E.g. Appearance, assay, degradation
 STABILITY COMMITMENT
 1. If the submission includes data from stability studies on
at least three production batches, a commitment should be
made to continue these studies through the proposed re-
test period.
 2. Fewer than three production batches, a commitment
should be made to continue these studies through the
proposed retest period and to place additional production
batches, to a total of at least three, on long term stability
studies through the proposed re-test period.
 3. If no data on production batches, a commitment to place
the first three production batches on long term stability
studies through the proposed re-test period.
SPECIFICATION
20

EVALUATION
 Should include results from physical, chemical,
biological and microbiological tests.
STATEMENT AND LABELLING
 Storage statement
Established for labelling should be in accordance
with national/regional requirement.
 Re-test date
-Statement based on stability evaluation
-Should be displayed on the container label
21

FOR DRUG PRODUCT
SELECTION OF BATCHES
 Data from stability studies should be provided on at least
three primary batches of pharmaceutical product.
 Primary batches should be of same formulation and
packaged in the same container closer system as
proposed for marketing
 Two of three batches should be at least pilot scale
batches and the third one can be smaller, if justified.
TESTING FREQUENCY
STORAGE CONDITIONS
(general case- same as that of drug substance)
22

A 5% loss in water from its initial value is considered a significant change for
a product packaged in a semi-permeable container after an equivalent of 3
months’ storage at 40°C/NMT 25%RH.
 Drug products intended for storage below -20
 Stability commitment
 Evaluation
 Statements/Labelling
DRUG PRODUCTS PACKAGED IN
SEMI-PERMEABLE CONTAINERS
25%RH
23

 If significant change occurs between 3 &6 months’
testing at the accelerated storage condition, the
proposed shelf life should be based on the real time
data available from the long term storage condition.
DRUG PRODUCTS INTENDED FOR
STORAGE IN A REFRIGERATOR
24

Q1B: STABILITY TESTING: PHOTOSTABILITY TESTING OF
NEW DRUG SUBSTANCES AND PRODUCTS
A systematic approach to stability testing is
recommended covering as appropriate studies such as:
1) Tests on the active substance
2) On exposed product outside of the immediate pack
and if necessary
3) On the product in the immediate pack and if
necessary
4) On the product in the marketing
Light sources
D65/ID65, fluorescent lamp combining visible and UV
outputs, Xenon or metal halide lamp
25

PHOTOSTABILITY TESTING OF DRUG
SUBSTANCE
FORCED DEGRADATION
TEST
CONFIRMATORY TEST
To evaluate photosensitivity
for method development
and/or degradation pathway
elucidation
Sample should be in
chemically inert and
transparent containers
Variety of exposure conditions
may be used
Provide information
necessary for handling,
packaging and labelling
If clearly photo stable and
photo labile then it should be
confirmed in single batch.
If results are equivocal two
additional batches should be
conducted
27

Q1C: STABILITY FOR NEW DOSAGE
FORMS
 NEW DOSAGE FORM
-Administration route
- New specific functionality/delivery systems
- Different dosage form
 STABILITY PROTOCOL
Stability protocols should follow the guidance in
the principle of parent stability guideline. However a
reduced stability database at submission time (e.g.
6 months accelerated and 6 months long term data
from ongoing studies) may be acceptable in certain
justified cases.
Same
active
substance
28

Q1D:BRACKETING AND MATRIXING DESIGNS
FOR STABILITY TESTING OF NEW DRUG
SUBSTANCES AND PRODUCTS
BRACKETING: The design of a stability schedule such that
the samples on the extremes of certain factors (e.g. Strength,
container size or fill) are tested at all time points as in a full
design.
29

 MATRIXING
The design of a stability schedule such that a selected subset
of the total number of possible samples for all factor
combinations would be tested at specified time point.
30

Q1E: EVALUATION OF STABILITY DATA
 Presentation
 Extrapolation
 No significant change at accelerated condition (For
RT storage)
 Significant change at accelerated condition(RT)
 No significant change at intermediate condition (RT)
 Significant change at intermediate condition(RT)
 No significant change at accelerated condition(for
storage in refrigerator)
 Drug substances or products intended for storage in a
freezer
 Drug substances or products intended for storage
below -20°C 32

ICH Guidelines for stability testing

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ICH Guidelines for stability testing