SHELF LIFE |
Manufacturers A, B, C: 2 years |
ASSAY METHOD |
HPLC method, USP 1990. Three ampoules mixed; measured three times; mean taken. |
ASSAY LIMITS |
90 - 110% (USP) |
SAMPLES OBTAINED |
All Manuf. |
Manuf. A |
Manuf. B |
Manuf. C |
| |
|
|
|
|
|
|
|
|
GMS samples |
no. |
% |
no. |
% |
no. |
% |
no. |
% |
Total |
26 |
100 |
21 |
81 |
4 |
15 |
1 |
4 |
Harare |
13 |
50 |
|
|
|
|
|
|
Bulawayo |
13 |
50 |
|
|
|
|
|
|
Facility samples |
|
|
|
|
|
|
|
|
Total |
67 |
100 |
31 |
46 |
9 |
13 |
27 |
40 |
Age > 50% SLife |
40 |
60 |
|
|
|
|
|
|
Facility type = PCH |
46 |
69 |
|
|
|
|
|
|
Climate = hot |
48 |
72 |
|
|
|
|
|
|
Transport - slow |
40 |
60 |
|
|
|
|
|
|
Unfrig. storage |
8 |
12 |
|
|
|
|
|
|
Longitudinal series |
|
|
|
|
|
|
|
|
Total |
50 |
100 |
28 |
56 |
9 |
18 |
13 |
26 |
SUMMARY ESSAY RESULTS
| |
All Manuf. |
Manuf. A |
Manuf. B |
Manuf. C |
GMS samples |
no. |
% |
|
|
|
|
|
|
Mean age (mths) |
|
3 |
|
1.7 |
|
6.9 |
|
14.5 |
Mean assay |
|
82.4% |
|
85.2% |
|
65.1% |
|
93.9% |
95% CL |
77.7 -87.1% |
80.8 - 89.5% |
57.1 - 73.0% |
|
(93.9%) |
No, and % fail |
17 |
65% |
13 |
62% |
4 |
100% |
0 |
0% |
No. and % low fail |
17 |
65% |
13 |
62% |
4 |
100% |
0 |
0% |
No. and % high fail |
0 |
0% |
0 |
0% |
0 |
0% |
0 |
0% |
Facility samples |
All Manuf. |
Manuf. A |
Manuf. B |
Manuf. C |
Mean age (mths) |
|
13.5 |
|
8.6 |
|
17 |
|
17.8 |
Mean assay |
|
73.6% |
|
66.3% |
|
57.9% |
|
87.2% |
95% CL |
69.2 - 78.0% |
60.0 - 72.0% |
51.5 - 64.4% |
81.8 - 92.6% |
No, and % fail |
48 |
72% |
29 |
94% |
9 |
100% |
10 |
37% |
No. and % low fail |
48 |
72% |
29 |
94% |
9 |
100% |
10 |
37% |
No. and % high fail |
0 |
0% |
0 |
0% |
0 |
0% |
0 |
0% |
Longitudinal series |
at Manuf. |
at GMS |
at facility |
|
|
Mean age (mths) |
|
0 |
|
7.6 |
|
12.5 |
|
|
Mean assay |
|
104.1% |
|
83.8% |
|
68.9% |
|
|
95% CL |
103.4 - 104.8% |
80.4 - 87.1% |
64.6- 73.2% |
|
|
No. and % fail |
0 |
0% |
28 |
53% |
46 |
87% |
|
|
| |
Mean interval (mths) |
4.8 |
| |
Mean loss (-) or gain (+) |
-17.1% |
| |
95% CL for loss/gain |
-21 7 to -12.6% |
Figure 1 - Results of GMS samples
Figure 2 - Results of facility samples
Figure 3 - Difference between GMS/facility pairs
Figure 4 - GMS and facility results: Manufacturer A
Figure 5 - GMS and facility results: Manufacturer B
Figure 6 - GMS and facility results: Manufacturer C
Findings:
a) 12 of 79 facility samples (15%) were expired; these results were excluded.
b) 17 of 26 GMS samples (65%) failed; all failures were below the lower limit (minimum value 58.4%).
c) 48 of 67 facility samples (72%) failed; all failures were below the lower limit (minimum value 20.5%), However, a high value was obtained at 19.8 months for one Sample (Manufacturer C).
d) 50 GMS/facility sample pairs showed a mean loss of potency of -17.1% over a mean interval of 4.8 months.
e) There was a constant initial quality problem for two out of three manufacturers as indicated by the high failure rates (62% for Manufacturer A and 100% for Manufacturer B).
f) The facility samples of these two manufacturers' samples showed a decreased potency reflected by lower mean assays and higher fail rates (Manufacturer A's failures increased to 94% and Manufacturer B's had 100% failures as before).
g) The single GMS sample for Manufacturer C passed (93.9%) even though the age at sampling was 14.5 months.
h) Manufacturer C's facility samples showed a higher potency than those of Manufacturers A and B. However, 37% failed and the mean assay (87.2%) reflected some loss of potency at facility level.
i) The potency loss in GMS/facility pairs was significant (t-test, one tail, p<0.0005). This was the case for each of the manufacturers individually.
j) The conclusion is that all three manufacturers' products were unstable.
k) Manufacturers A and B showed an initial quality problem which worsened at facility level.
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