SHELF LIFE |
Manufacturer A: |
2 years |
| |
Manufacturer B: |
3 years |
ASSAY METHOD |
Titration method, BP 1988, p.946. |
| |
Contents of 20 capsules mixed; measured three times; mean taken. BP 1988 Disintegration test on six tablets. |
ASSAY LIMITS |
95 - 105% (BP) |
SAMPLES OBTAINED |
All Manuf. |
Manuf. A |
Manuf. B |
| |
|
|
|
|
|
|
GMS samples |
no. |
% |
no. |
% |
no. |
% |
Total |
23 |
100 |
14 |
61 |
9 |
39 |
Harare |
9 |
39 |
|
|
|
|
Bulawayo |
14 |
61 |
|
|
|
|
Facility samples |
|
|
|
|
|
|
Total |
76 |
100 |
54 |
71 |
19 |
25 |
Age > 50% SLife |
42 |
55 |
|
|
|
|
Facility type = PCH |
58 |
76 |
|
|
|
|
Climate = hot |
57 |
75 |
|
|
|
|
Transport = slow |
52 |
68 |
|
|
|
|
Longitudinal series |
|
|
|
|
|
|
Total |
24 |
100 |
17 |
71 |
7 |
29 |
SUMMARY ASSAY RESULTS
| |
All Manuf. |
Manuf. A |
Manuf. B |
GMS samples |
no. |
% |
no. |
% |
no. |
% |
Mean age (mths) |
|
7.0 |
|
8.9 |
|
4.0 |
Mean assay |
|
100.6% |
|
101.4% |
|
99.4% |
95% CL |
98.9 - 102.3% |
99.2- 103.5% |
96.8 - 101.9% |
No, and % fail |
5 |
22% |
3 |
21% |
2 |
22% |
No, and % low fail |
2 |
9% |
1 |
7% |
1 |
11% |
No, and % high fail |
3 |
13% |
2 |
14% |
1 |
11% |
Facility samples |
All Manuf. |
Manuf. A |
Manuf. B |
| |
|
|
|
|
|
|
Mean age (mths) |
|
14.5 |
|
14.8 |
|
13.6 |
Mean assay |
|
103.5% |
|
105.2% |
|
98.3% |
95% CL |
102.3 -104.6% |
104.0 -106.4% |
97.1 - 99.5% |
No, and % fail |
31 |
41% |
29 |
54% |
2 |
11% |
No, and % low fail |
2 |
3% |
0 |
0% |
2 |
11% |
No. and % high fail |
29 |
38% |
29 |
54% |
0 |
0% |
Longitudinal series |
All Manuf. |
at GMS |
at facility |
Mean age (mths) |
|
0 |
|
7.2 |
|
14.1 |
Mean assay |
|
100.2% |
|
101.6% |
|
101.6% |
95% CL |
99.1 -101.5% |
98.6 - 101.9% |
99.8 - 103.3% |
No, and % fail |
0 |
0% |
5 |
21% |
6 |
25% |
| |
Mean interval (mths) |
6.9 |
| |
Mean loss (-) or gain (+) |
+1.5% |
| |
95% CL for loss/gain |
-0.7 to +3.6% |
Figure 1 - Results of GMS samples
Figure 2 - Results of facility samples
Findings:
a) Two of 78 facility samples (3%) were expired; these results were excluded,
b) Five of 23 GMS samples (22%) failed; two failures were below the lower limit (93.7, 94.7%), three failures were above the upper limit (105.1, 105.4, 110.0%).
c) 31 of 76 facility samples (41%) failed; two failures was below the lower limit (91.9, 92.5%); 29 failures were above the limit (highest value 112.4%).
d) For Manufacturer A, 29 of 54 of facility samples (54%) failed, and all the failures were high. The confidence limit of the mean extends above the upper limit of the BP specification.
e) For Manufacturer B, two of 19 facility samples failed, and both failures were low.
f) No consistent loss of potency was found in 24 GMS/facility sample pairs,
g) The failure to meet assay specifications is possibly due to narrow BP limits (95-105%).
h) Only four samples were low (91.9-94.7%); most failures were high (105.2-112.4%).
i) This low/high content does not have any therapeutic significance.
j) No sign of instability, even in the late part of shelf-life.
k) Approximately 50% of samples failed the disintegration test carried out in some samples.
l) Reduced bioavailability indicated by poor disintegration may lead to therapeutic failure.
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