[First results in the prevaluation of the human whole blood assay for pyrogens in biological pharmaceuticals] [Article in German]

Abstract

When establishing the whole blood assay for pyrogens in our laboratory we did several investigations on the standard pyrogen to be used. Because of the hydrophobicity of the lipopolysaccharid (LPS) it is difficult to get a homogeneous solution. Therefore we used ultrasonic and biphenyl hydroxyl amine chloride for a better dispergation.
Surprisingly the reactivity of the LPS in the whole blood assay for pyrogens dropped the more the LPS was dispergated. That's right inverse to the situation in the LAL.
There are first experiences in the whole blood assay for pyrogens with biological pharmaceuticals. This includes immunoglobulins, vaccines and coagulation factors.
Except of the vaccines and albumin the rabbit assay is the only way to test these pharmaceuticals for pyrogens.
The albumins show a little amplification of the reactivity of LPS in the whole blood assay for pyrogens. The testing of albumin in the whole blood assay for pyrogens showed highly reproproducible results and a detection limit under 50 pg/ml LPS.
The immunoglobulins show an amplifying effect as well. Immunoglobulins spiked with LPS were detected as pyrogenic in all cases.
Some vaccines show a slight pyrogenity in the whole blood assay which gets visible when diluting the sample. Undiluted vaccines may cover a LPS contamination in the whole blood assay for pyrogens.