No. It is not acceptable to take the average among the LVP units tested in each batch/lot when following this method because the purpose of this method is to measure and limit intra-batch variability.
Particulate matter refers to small, subvisible particles. General Chapter <788> provides two tests for detecting such particulates—light obscuration and microscopic assay. Both are generally accepted for use in testing LVPs and small volume parenterals (SVP) for the determination of subvisible particulate matter. Normally, samples are first tested by the light obscuration method; if the sample fails the specified limits, the microscopic assay method can then be used. However, the microscopic method can be the sole test if there is a documented technical reason or interference the product under test that would make the light obscuration method unsuitable or the results invalid.
Confusion about when averaging data is and is not acceptable is probably due to the sample preparation method for the light obscuration test (General Chapter <788>). At least 2, 5-mL aliquots each sampled unit or the pooled sample (see below) are to be used in the particulate determination, and the results these aliquots are to be averaged for comparison with the specification. Note that the average is of the results examining each aliquot and not between units. (The results of the first aliquot examined by light obscuration are to be discarded, and the subsequent aliquots—2 or more—are retained.) Pooling units prior to analysis is permitted only if the volume in each unit is less than 25 mL, in which case 10 or more units may be pooled. If the volume in the SVP or LVP is 25 mL or more per unit, single units are to be examined by this method (General Chapter <788>).
Results among the test units cannot be averaged because particulate matter is assumed to be non-uniformly dispersed throughout the lot. The intent of assessing results each individual unit is to ensure adequate representation of the lot and to detect potential variation within a lot.
As to the number of individual units to be tested for LVP and SVP units having a volume of 25mL or more, the USP states that the number of units tested depends on "statistically sound sampling plans," and "sampling plans should be based on consideration of product volume, numbers of particles historically found to be present in comparison to limits, particle size distribution of particles present, and variability of particle s between units." The USP also suggests that the total number of units tested for any given batch may be less than 10 units (for LVP and pooled SVPs) with proper justification. This is consistent with the CGMP requirement for statistical sampling plans (see 21 CFR 211.165).
