Natural human antibodies have been identified that cause pyrogenic responses during USP pyrogen tests. Some human donors naturally produce these “atypical antibodies,” perhaps resulting from exposure to rabbits, rodents, or paracitic insects preying upon such host animals (i.e., fleas). The atypical antibodies are anomalous and uncommon, but are not harmful to humans. Atypical antibodies can cross-react with rabbit white blood cell antigens and cause a pyrogenic response during rabbit pyrogen tests. The pyrogenic response is, however, a “false positive” result because other methods, such as the limulus amoebocyte lysate assays (LAL), showed that suspect plasma samples giving pyrogenic responses in the rabbit assay do not contain endotoxins. In addition, the results of in vitro pyrogen tests (aka monocyte activation tests) indicate the absence of non-endotoxin pyrogens. Accordingly, atypical antibodies in human blood or plasma cause erroneous rabbit pyrogen test results and may result in the disposal of individual or pooled blood or plasma that falsely tests positive as “pyrogenic.”
The methods described herein permit the identification of blood or plasma samples containing atypical antibodies that result in false positives in pyrogen assays. This method is advantageous because atypical antibody-containing samples can be eliminated before pooling with other blood or plasma and contaminating the pool. Accordingly, the method reduces manufacturing cost by preventing the unnecessary contamination of blood or plasma pools with samples that appear “pyrogenic” owing to the presence of atypical antibodies. High throughput testing methods described herein permit identification of suspect falsely positive samples. Such samples can be discarded prior to pooling with other samples and prevent tainting the pool with atypical antibodies.