1. Drug stability testing involves conducting studies under various temperature, humidity and light conditions to determine a drug's shelf life and optimal storage requirements. 2. The ICH Q1A guideline provides the standard process for stability testing new drug substances and products to obtain registration. It defines testing stages, storage conditions and frequencies to evaluate how quality varies over time. 3. Stability testing helps establish expiration dates and provides evidence for appropriate packaging and labeling to ensure drug quality through a product's shelf life.

1. Guided by: Presented by:
Dr. Arpana Patil Salim Mulla
(M.Pharm, Phd) M.Pharm (SEM-I )
Alard College of Pharmacy
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2.  Drug stability refers to the capacity of a drug substance or
product to remain within established specifications of identity,
strength, quality, and purity in a specified period of time.
 Stability is officially defined as the time during which the drug
product retains the same properties and characteristics that it
possessed at the time of manufacture.
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3.  STAGE 1- Early stage stress and accelerated testing with drug
substances
 STAGE 2- Stability on pre-formulation batches
 STAGE 3- Stress testing on scale-up batches
 STAGE 4- Accelerated and long term testing for registeration
purposes
 STAGE 5- On-going stability testing
 STAGE 6- Follow-up Stabilities
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4.  To gather information during pre-formulation stage to
produce a stable product
 To determine maximum expiration date.
 To get an idea of storage condition.
 To determine the packaging components.
 To establish retest period of pharmaceuticals.
 To establish transport condition.
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5.  Chemical degradation of active drug may reduce the
quality of therapeutic indices like 5- flurouracil,
carbamazepine etc have very small therapeutic range,
sight degradation of drug may produce sub therapeutic
concentration.
 After degradation a drug may produce more toxic
product(s) which may be more toxic than the parent
product.
 Instability of drug product reduce bioavailability. This
may be caused by physical or chemical instability.
 Instability of a product may change the physical
appearance of the product.
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6.  The ICH (International Conference on Harmonization)
Guidelines Q1A(R2) “Stability testing of new drug
substances and products” is the “gold standard” for
conducting stability studies. This is valid for “new drug
substances or drug products” that are sufficient for a
registration application.
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7.  Q1A- Stability testing of new Drug Substances and
Products
 Q1B- Stability Testing : Photostability 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 Substsances and products
 Q1E- Evaluation of stability data
 Q1F- Stability data package for registration
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8. OBJECTIVE OF THE GUIDELINE:
 It defines stability of drug substances and drug
product for registration of application of associated
drug, within three regions of ICH i.e. EU, Japan, USA.
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9. 1. Purpose of stability testing is to provide evidence how quality
varies with time under influences 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 that the material
is still in compliance with the specification, and thus suitable for
use in manufacturing.
A retest period should be proposed on the basis of stability
results and may be extended to five years (e.g. Ethambutol 2HCI, or
isoniazid)
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10. 3. Establish shelf life for drug products:
• SHELF LIFE (EXPIRY DATE/EXPIRATION DATING PERIOD):
The period of time during which a pharmaceutical product,
if stored correctly, is expected to comply with the specification as
determined by stability studies on a number or batches of the
product.
The shelf life is used to establish the expiry date of DRUG
PRODUCT.
4. Recommends storage conditions
5. Gives Test conditions based on analysis of effects of climatic
conditions in the three regions of the EU, japan, USA.
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11. Stress testing:
 These guidelines help to identify the likely degreadation
products, to establish the degradation pathway of the
molecule.
Selection of batches:
 At least 3 primary batches of the drug substances should
be selected. The quality should be representative to
quality of material used for production scale.
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12. Container Closure system:
◦ Should simulate packaging proposed for storage and distribution.
Specification:
◦ List of tests,
◦ Reference to analytical procedure,
◦ Proposed acceptance criteria
◦ Test Attributes
◦ Attributes that are susceptible to changed storage,
◦ Influence quality, safety and/or efficacy
◦ Should cover physical, chemical, biological and microbiological
attributes.
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13. Testing frequency:
Testing frequency for products proposed shelf life of at least 12 months.
FIRST YEAR…. 3 month
SECOND …… 6 month
Thereafter…. Annually through out the proposed retest period .
At accelerated storage condition:
Minimum three time points (0,3 and 6 months)from a 6 month study
At intermediate storage condition:
Minimum of four time points (0,6,9 and 12 months) from a 12 month
study.
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14.  Long term testing should cover a minimum of 12
months duration on at least three primary bacterial
batches at time of submission and should be continue
sufficient to covered the proposed retest period.
 General
Study Storage condition Duration
Long term 25o C ± 2o C/60%
±5%
Or
30oC ± 2oC/65% ± 5%
12 months
Intermediat
e
30oC ± 2oC/65% ± 5% 6 months
Accelerated 40oC ± 2oC/75% ± 5% 6 months
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15. Drugs packed in semi permeable
membrane containers:
Study Storage Condition Duration
Long term 25oC ± 2oC/ 40% RH ± 5%
Or
30oC ± 2oC/ 35% RH ± 5%
12 months
Intermediate 30oC ± 2oC/ 65% RH ± 5% 6 months
Accelerated 40oC ± 2oC/ 75% RH ± 5% 6 months
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16. Drug substance intended for
storage in a refrigerator
 If significant change between 3 and 6 month at
accelerated testing propose re-test data based on real
time data. (LONG TERM STUDY)
 If significant change within 3 month discussion should
address excursion outside label storage. Single batch
shorter than 3 months with more frequent testing
Study Storage condition Duration
Long term 5oC ± 3oC 12 months
Accelerated 25oC ± 2oC/60%± 5% 6 months
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17. Drug substance intended for storage in a
freezer
 Re-test period based on real time data at long term
storage condition.
 In absence of accelerated storage condition testing on a
single batch at an elevated temperature e.g. 5oC 3oC
address short term excursions
Study Storage condition Duration
Long term -20oC ± 5oC 12 month
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18. Stability commitment:
 When retest period not covered or not mentioned.
 Long term stability data do not cover proposed retest
period granted at time of approval to establish re test
period.
 Not required for submission which includes data from 3
production batches commitment to continue through
proposed retest period
 Fewer than three production batches commitment continue
through proposed retest period and place additional
production batches to a total of three on long term stability
through proposed retest period.
 No production batches commitment to place first three
production batches on long term stability studies through
proposed retest period.
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19. 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 3 batches of drug product was 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 tests.
 Where the data shows so little degradation and so little
variability that is apparent from looking the data that the
requestedshelf life will be granted. It is normally
unnecessary to go through the formal statistical analysis.
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20. Significant change of drug
substance or product:
 A 5% change in assay from its initial value.
 Any degradation product exceeding its acceptance
criterion.
 Failure to meet the acceptance criteria for apperance,
physical attributes and functionality test (e.g. colour,
phase separation, hardness).
 As appropriate for the dosage form, e.g. failure to meet
the acceptance criteria for dissolution for 12 dosage
units.
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21. 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.
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24. References:
 www.ich.org/product/guidelines/quality.html
 www.ema.europa.eu/pdfs/human/ich/273699en.pdf
 www.ich.org/fileadmin/.../ICH.../Guidelines/.../Q1BGuidel
ine.pdf
 Apps.who.int/prequal/traninresources/pq…/stabilitystud
ies.ppt
 Drug Stability: Principles and Practices. By Jens T.
Carstensen. Marcel Dekker: New York, 1990, CRC
press publication, Third edition, pg no. 54-110.
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