Sunday, 16 October 2016
Sunday, 3 July 2016
Bracketing
As defined in the
glossary to the parent guideline, bracketing is the design of a stability
schedule such that only samples on the extremes of certain design factors
(e.g., strength, container size and/or fill) are tested at all time points as
in a full design. The design assumes that the stability of any intermediate
levels is represented by the stability of the extremes tested.
The use of a bracketing
design would not be considered appropriate if it cannot be demonstrated that
the strengths or container sizes and/or fills selected for testing are indeed
the extremes.
Table 1: Example of a
Bracketing Design
Strength
|
50
mg
|
75
mg
|
100
mg
|
|||||||
Batch
|
1
|
2
|
3
|
1
|
2
|
3
|
1
|
2
|
3
|
|
Container
size
|
15
ml
|
T
|
T
|
T
|
T
|
T
|
T
|
|||
100
ml
|
||||||||||
500
ml
|
T
|
T
|
T
|
T
|
T
|
T
|
||||
Key: T = Sample tested
Matrixing
As defined in the
glossary of the parent guideline, matrixing is 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 a specified time point. At a
subsequent time point, another subset of samples for all factor combinations
would be tested. The design assumes that the stability of each subset of
samples tested represents the stability of all samples at a given time point.
The differences in the samples for the same drug product should be identified
as, for example, covering different batches, different strengths, different
sizes of the same container closure system, and possibly, in some cases,
different container closure systems.
“One-Half
Reduction”
Time point (months)
|
0
|
3
|
6
|
9
|
12
|
18
|
24
|
36
|
||
S
t
r
e
n
g
t
h
|
S1
|
Batch 1
|
T
|
T
|
T
|
T
|
T
|
T
|
||
Batch 2
|
T
|
T
|
T
|
T
|
T
|
T
|
||||
Batch 3
|
T
|
T
|
T
|
T
|
T
|
|||||
S2
|
Batch 1
|
T
|
T
|
T
|
T
|
T
|
||||
Batch 2
|
T
|
T
|
T
|
T
|
T
|
T
|
||||
Batch 3
|
T
|
T
|
T
|
T
|
T
|
|||||
Key:
T = Sample tested
“One-Third
Reduction”
Time point (months)
|
0
|
3
|
6
|
9
|
12
|
18
|
24
|
36
|
||
S
t
r
e
n
g
t
h
|
S1
|
Batch 1
|
T
|
T
|
T
|
T
|
T
|
T
|
||
Batch 2
|
T
|
T
|
T
|
T
|
T
|
T
|
||||
Batch 3
|
T
|
T
|
T
|
T
|
T
|
T
|
T
|
|||
S2
|
Batch 1
|
T
|
T
|
T
|
T
|
T
|
T
|
T
|
||
Batch 2
|
T
|
T
|
T
|
T
|
T
|
T
|
||||
Batch 3
|
T
|
T
|
T
|
T
|
T
|
T
|
||||
Key: T = Sample tested
Matrixing Designs for a Product with Three Strengths and Three
Container Sizes
3a Matrixing on Time Points
Strength
|
S1
|
S2
|
S3
|
||||||
Container size
|
A
|
B
|
C
|
A
|
B
|
C
|
A
|
B
|
C
|
Batch 1
|
T1
|
T2
|
T3
|
T2
|
T3
|
T1
|
T3
|
T1
|
T2
|
Batch 2
|
T2
|
T3
|
T1
|
T3
|
T1
|
T2
|
T1
|
T2
|
T3
|
Batch 3
|
T3
|
T1
|
T2
|
T1
|
T2
|
T3
|
T2
|
T3
|
T1
|
3b
Matrixing on Time Points and Factors
Strength
|
S1
|
S2
|
S3
|
||||||
Container size
|
A
|
B
|
C
|
A
|
B
|
C
|
A
|
B
|
C
|
Batch 1
|
T1
|
T2
|
T2
|
T1
|
T1
|
T2
|
|||
Batch 2
|
T3
|
T1
|
T3
|
T1
|
T1
|
T3
|
|||
Batch 3
|
T3
|
T2
|
T2
|
T3
|
T2
|
T3
|
|||
Key:
Time-point (months)
|
0
|
3
|
6
|
9
|
12
|
18
|
24
|
36
|
T1
|
T
|
T
|
T
|
T
|
T
|
T
|
T
|
|
T2
|
T
|
T
|
T
|
T
|
T
|
T
|
||
T3
|
T
|
T
|
T
|
T
|
T
|
T
|
S1, S2, and S3 are different strengths. A, B, and C are different container sizes.
T = Sample tested
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