Yes. With some exceptions (see below), finished drug product units may be pooled into a composite sample and assayed for bacterial endotoxins. The composite sample may be represented by the entire unit or partial aliquots (equal volumes) of finished product containers from one manufactured lot of aqueous-based pharmaceuticals. Pooling would generally be accepted for small-volume parenterals (those with volumes of 100 mL or less) as long as the MVD is adjusted to a proportional, lower value because of the potential for diluting a unit containing harmful levels of endotoxins with other units containing lower, less harmful, levels of endotoxins. This “adjusted MVD” is obtained by dividing the MVD computed for an individual sample by the total number of samples to be pooled. FDA suggests pooling no more than three units per composite in keeping with the concept of testing representative beginning, middle, and end finished product containers. If this reduction in MVD results in an inability to overcome product-related assay interference because of an insufficient dilution, then the samples should be tested individually.
Finished medical devices may also be pooled into a composite sample and assayed for bacterial endotoxins. Testing for medical devices should be conducted using rinsing/eluting and sampling techniques as described in ISO 10993-1[14] and ISO 10993-12, as also used for inhibition/enhancement. Sampling can be adjusted for special situations. After a suitable eluate/extract pool is obtained from a finished production lot, this pooled extract should be kept under conditions appropriate for stability until it is tested in duplicate.
FDA recommends that pooled samples be a composite of aseptically removed aliquots (after at least 30 seconds of vigorous mixing) from each of the product containers. In this way, the original, individual containers will be available for possible retesting in the event the pooled sample displays an OOS result.
Some product types should not be pooled. Two examples are drug products that have an initial low MVD (see discussion above of “adjusted MVD”) and products that are manufactured as a suspension, because sample aliquot homogeneity may present significant interference issues. FDA also does not recommend pooling in-process samples from different in-process stages of the manufacturing process because it may be difficult to ensure the homogeneity of these materials.
