SUMMARY ASSAY RESULTS

Figure 1 - Results of GMS samples

Figure 2 - Results of facility samples

Findings:

a) No expired samples were found.

b) The number of GMS samples is small but represents all batches over one year,

c) Five out of five GMS samples (100%) failed; all failures were below the lower limits (59.7, 68.5, 71.6, 74.6, 63.4%).

d) The manufacturer's assay (on batch certificate) was below the lower limit for one batch (92.8%).

e) 46 of 51 facility samples (90%) failed; all failures were below the lower limit. The mean facility assay was 73.5%, but the range was wide (40.2 - 116.7%).

f) No consistent loss of potency was found in 30 GMS/facility sample pairs; large individual values for gain (+44.9, +95.5%) indicate gross measurement error.

g) There was a consistent problem of low potency in GMS samples (mean 67.6%).

h) The problem of initial low potency was reflected in the facility samples (mean 73.5%); the two manufacturers showed a similar low potency (means 72.3 and 73.7%),

i) Although the manufacturers' certificates indicate the required level of active ingredient (with one exception), there is no indication of loss of potency with time, so the conclusion is that this is an initial quality problem. The difference is rather large to be explained by a difference in assay methods/laboratory (manufacturer versus ZRDCL/external laboratory).

j) No clear sign of instability, but outliers and wide confidence limits make interpretation difficult.

k) Three outlier results were replaced by the assay result obtained during validation.