Stability Data requirement for
New Drug
Substances and Products
Objectives of the Document
On the basis of
revised version of the ICH Q1A guideline and defines the stability data package
for a new drug substance or drug product that is sufficient for a registration
application within the three regions of the EC, Japan, and the United States. It
does not seek necessarily to cover the testing for registration in or export to
other areas of the world. And also include requirement of Canada and Brazil
regulatory requirement for stability to get approval of submitted drug product
submission.
The Document
addresses the information to be submitted in registration applications for new
molecular entities and associated drug products. This document does not
currently seek to cover the information to be submitted for abbreviated or abridged
applications, variations, clinical trial applications, etc.
The purpose of
stability study is to provide evidence on how the quality of a drug substance
or drug product varies with time under the influence of a variety of environmental
factors such as temperature, humidity, and light, and to establish a re-test
period for the drug substance or a shelf life for the drug product and
recommended storage conditions.
The mean
kinetic temperature in any part of the world can be derived from climatic data,
and the world can be divided into four climatic zones, I-IV.
Stress testing
of the drug substance can help identify the likely degradation products. The
nature of the stress testing will depend on the individual drug substance and
the type of drug product involved.
Stress testing
is likely to be carried out on a single batch of the drug substance. It should include the effect of temperatures
(in 10°C increments (e.g., 50°C, 60°C, etc.) above that for accelerated
testing), humidity (e.g., 75% RH or greater) where appropriate, oxidation, and
photolysis on the drug substance. The
testing should also evaluate the susceptibility of the drug substance to
hydrolysis across a wide range of pH values when in solution or suspension.
General case
Study
|
Storage condition
|
Minimum time period covered by data at submission
|
Long term$
|
25°C ± 2°C/60% RH ± 5% RH or
30°C ± 2°C/65% RH ± 5% RH |
12 months
|
Intermediate##
|
30°C ± 2°C/65% RH ± 5% RH
|
6 months
|
Accelerated
|
40°C ± 2°C/75% RH ± 5% RH
|
6 months
|
$It is up to
the applicant to decide whether long term stability studies are performed at 25
±
2°C/60% RH ± 5%
RH or 30°C ±
2°C/65% RH ± 5%
RH.
##If 30°C ± 2°C/65% RH
± 5%
RH is the long-term condition, there is no intermediate condition.
New drug substances intended for storage in a
refrigerator
Study
|
Storage condition
|
Minimum time period covered by data at submission
|
Long term
|
5°C ± 3°C
|
12 months
|
Accelerated
|
25°C ± 2°C/60% RH ± 5% RH
|
6 months
|
New drug substances intended for storage in a freezer
Study
|
Storage condition
|
Minimum time period covered by data at submission
|
Long term
|
- 20°C ± 5°C
|
12 months
|
The purpose of
the stability study is to establish, based on testing a minimum of three
batches of the drug substance and evaluating the stability information
(including, as appropriate, results of the physical, chemical, biological, and
microbiological tests), a re-test period applicable to all future batches of
the drug substance manufactured under similar circumstances. The degree of
variability of individual batches affects the confidence that a future
production batch will remain within specification throughout the assigned
re-test period.
The data may
show so little degradation and so little variability that it is apparent from
looking at the data that the requested re-test period will be granted. Under
these circumstances, it is normally unnecessary to go through the formal
statistical analysis; providing a justification for the omission should be
sufficient
General case
Study
|
Storage condition
|
Minimum time period covered by data at submission
|
Long term$
|
25°C ± 2°C/60% RH ± 5% RH
or 30°C ± 2°C/65% RH ± 5% RH |
12 months
|
Intermediate##
|
30°C ± 2°C/65% RH ± 5% RH
|
6 months
|
Accelerated
|
40°C ± 2°C/75% RH ± 5% RH
|
6 months
|
$It is up to
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% RH ± 5%
RH.
##If 30°C ± 2°C/65% RH ± 5% RH is the
long-term condition, there is no intermediate condition.
Other comparable approaches can be developed and
reported for non-aqueous, solvent-based products.
Study
|
Storage condition
|
Minimum time period covered by data at submission
|
Long term*
|
25°C ± 2°C/40% RH ± 5% RH
or 30°C ± 2°C/35% RH ± 5% RH |
12 months
|
Intermediate**
|
30°C ± 2°C/65% RH ± 5% RH
|
6 months
|
Accelerated
|
40°C ± 2°C/not more than (NMT) 25% RH
|
6 months
|
Other comparable approaches can be developed and
reported for non-aqueous, solvent-based products.
Study
|
Storage condition
|
Minimum time period covered by data at submission
|
Long term*
|
25°C ± 2°C/40% RH ± 5% RH
or 30°C ± 2°C/35% RH ± 5% RH |
12 months
|
Intermediate**
|
30°C ± 2°C/65% RH ± 5% RH
|
6 months
|
Accelerated
|
40°C ± 2°C/not more than (NMT) 25% RH
|
6 months
|
*It
is up to the applicant to decide whether long term stability studies are
performed at 25 ±
2°C/40% RH ±
5% RH or 30°C ±
2°C/35% RH ±
5% RH.
**If
30°C ±
2°C/35% RH ±
5% RH is the long-term condition, there is no intermediate condition.
Drug products intended for storage in a refrigerator
Study
|
Storage condition
|
Minimum time period covered by data at submission
|
Long term
|
5°C ± 3°C
|
12 months
|
Accelerated
|
25°C ± 2°C/60% RH ± 5% RH
|
6 months
|
Drug products intended for storage in a freezer
Study
|
Storage
condition
|
Minimum time period covered by data at submission
|
Long term
|
- 20°C ± 5°C
|
12 months
|
