Transcript Stability Trials

Stability Trials
ASEAN Guidelines
The Objective of a stability study

To determine the shelf life, namely the
time period of storage at a specified
condition within which the drug product
still meets its established specifications
Design
The design should be based on knowledge
of the behavior and properties of the drug
substance and dosage form.
 Photostability testing should be conducted
on at least one primary batch of the
product if appropriate. The standard
conditions were described by ICH

Selection of Batches
For NCE stability data should be provided
on at least 3 primary batches of the drug
products
 For generic and variations;
- For conventional dosage forms
(immediate release solid and solutions),
when the drug substances are known to
be stable stabiliy data on at least 2 pilot
scale batches are acceptable

Selection of Batches (contd)
- For critical dosage forms (prolonged
release forms) or when the drug
substances are known to be unstable,
stability data on 3 primary batches are to
be provided. Two or 3 batches should be
at least of a pilot scale; the third batch
may be smaller
Testing parameter
Stability study should include testing of those
attributes of the drug product that are
susceptible to change during storage and are
likely to influence quality, safety and/or efficacy.
 The testing should cover, the physical, chemical,
biological and microbiological attributes,
preservatives content (antioxidant &
antimicrobial) and functionality test (dose
delivery system)

Testing parameter (contd)

1.
The analytical procedures should be fully
validated and stability indicating
according to ASEAN guideline on
Analytical validation.
Tablet
Should be evaluated for appearance,
odor, color, assay, degradation products,
dissolution, moisture and
hardness/friability
Testing parameter (contd)
2. Capsules
Hard gelatin capsules: appearance (incl
brittleness), odor, color, assay, degradation
products, dissolution, mosture and microbial
content.
Soft gelatin capsules: appearance (incl
brittleness), odor, color, assay, degradation
products, dissolution, mosture and microbial
content, pH, leakage, and pellicle formation.
Testing parameter (contd)
3. Emulsions :
Appearance (incl. phase separation), color,
odor, assay, degradation products, pH,
viscosity, microbial limits, preservative
content, and mean size and distribution of
dispersed globules
Testing parameter (contd)
4. Oral solutions and Suspensions
Appearance (incl. formation of precipitate, clarity
for solutions), color, odor, assay, degradation
products, pH, viscosity, preservative content and
microbial limits.
Additional for suspensions: redispersibility,
rheological properties, mean size and distrib of
particles. After storage sample of suspensions
should be prepared for assay according to the
recommended labelling (shake well before
using).
Testing parameter (contd)
5. Oral powders for reconstitution
Oral powders: appearance, color, odor,
assay, degradation products, moisture and
reconstitution time.
Reconstituted products (suspensions): as
described in oral solutions and
suspensions above, after preparation
Testing parameter (contd)
6. Metered dose inhalations and Nasal aerosols
Appearance (content, container, valve), color,
taste, assay, degrad. Products, assay for
cosolvent, labeled number of medication
actuations per container meeting dose content
uniformity, aerodynamic particle size distrib.,
microscopic evaluation, water content, leak rate,
microbial limits, valve delivery, and
extractable/leachables from plastic and
elastomeric components
Testing parameter (contd)
7. Nasal Sprays: Solutions and Suspensions
Appearance, color, clarity for solution, assay,
degrad. Products, preservative and antioxidant
content, microbial limits, pH, particulate matter,
unit spray medication content uniformity,
number of actuations meeting unit spray content
uniformity per container, droplet and/or particle
size distrib., weight loss, pump delivery,
microscopic evaluation, foreign particulate
matter, bleachable form plastic and closure &
pump.
Testing parameter (contd)
8. Topical, Ophtalmic and Otic preparations
(included ointments, cream, lotions, paste, gel,
solutions and non-metered aerosols for
application to the skin)
Topical prep: appearance, clarity, color,
homogenity, odor, pH, resuspendability (for
lotions), consistency, viscosity, particle size
distrib, assay, degrag. Products, preservative
and antioxidant content, microbial limits/sterility
and weight loss
Testing parameter (contd)
Ophtalmic or otic products: additionally
sterility, particulate matter and extractable
Non-metered topical aerosols:
appearance, assay, degrad. Products,
pressure, weight loss, net weight
dispensed, delivery rate, microbial limits,
spray pattern, water content, and particle
size distrib.
Testing parameter (contd)
9. Suppositories
- appearance, color, assay, degradation
products, particle size, softening range,
dissolution (at 37oC) and microbial limits.
Testing parameter (contd)
10. Small Volume Parenterals (SVPs)
appearance, clarity, color, assay,
preservative content (if present),
degradation products, particulate matter,
pH, sterility and pyrogen/endotoxin.
(additional for injectable
suspension/emulsion as in
suspension/emulsion)
Testing parameter (contd)
11. Large Volume Parenterals (LVPs)
appearance, color, assay, preservative
content (if present), degradation products,
particulate matter, pH, sterility,
pyrogen/endotoxin, clarity and volume
Testing parameter (contd)
12. Drug Admixture
should be evaluated for stability and
compatibility in admixture with the other drug
products or with dilents, both in upright and in
inverted orrientations.
A stability protocols should be conducted at 0-,
6- to 8- and 24 hour time points. Tests include
appearance, color, clarity, assay, degradation
products, pH, particulate matter, interaction w/
container, sterility.
Testing parameter (contd)
13. Transdermal Patches
appearance, assay, degradation products,
in-vitro release rates, leakage, sterility,
peel and adhesive forces, and the drug
release rates
Testing parameter (contd)
14. Freeze-dried Products
appearance for both freeze-dried and its
reconstituted products, pH, water content
and rate of solution.
Testing Frequency
Storage
Condition
Products
Testing
Frequency
Real Time
NCE, Generics,
and variations
0, 3, 6, 9, 12, 18, 24
months and annually
through the proposed
shelf-life
Accelerated
NCE, Generics,
and variations
0, 3 and 6
months
Alternatives to
accelerated
study
NCE, Generics,
and variations
0, 1 and 3
months
Storage Condition
Type of container/study
Storage Condition
Products in primary containers
permeable to water vapour
30oC + 2oC/75% RH +
5% RH
30oC + 2oC/RH not
specified
40oC + 2oC/75% RH +
5% RH
40oC + 2oC/75% RH +
5% RH
Products in primary containers
impermeable to water vapour
Accelerated studies
Stress studies
For NCE Drug Products
Study
Storage
Condition
Minimum time
period covered
by data at
submission
Number of
Batches
Real Time
30oC +
2oC/75% RH
+ 5% RH
12 months
Min. 3
6 months
Min. 3
Accelerated 40oC +
2oC/75% RH
+ 5% RH
For generics and variation products
Study
Storage
Condition
Minimum time
period covered
by data at
submission
Number of
Batches
Real Time
30oC +
2oC/75% RH
+ 5% RH
12 months
Min.2 for
conventional &
stable drug subs
Min 3 for critical
dosage form or
unstable drug s
Accelerated 40oC +
2oC/75% RH
+ 5% RH
12 months
6 months
Min 2
Drug Products Intended for storage in a
refrigerator
Study
Storage
Condition
Minimum time
period covered
by data at
submission
Number of
Batches
Real Time
5oC + 3oC
12 months
Min. 3
6 months
Min. 3
Accelerated 25oC +
2oC/60% RH
+ 5% RH
Drug Products Intended for storage in a
Freezer
Study
Storage
Condition
Minimum time
period covered
by data at
submission
Real Time
-20oC + 5oC
12 months