Anticomplementary activity and the safety of intravenous immunoglobulin

Quality assurance release levels for anti-complementary (AC) activity of a non-modified intravenous immunoglobulin (IGIV, pH 4.25) were reviewed over a period of one year and nine months in an attempt to correlate the incidence of complement-mediated-type adverse reactions with the AC level. Over 200 lots and ten possible complement-mediated side effects were evaluated. No correlation was found. A similar evaluation was made of a prospective study in which three lots of IGIV, pH 4.25 (one with a low, one with a mid-range, and one with a high AC activity) were used; again no correlation was found. Finally, a comparison was made between the AC activity assay used to release IGIV, pH 4.25 and an alternative AC activity assay designed for a highly modified IGIV preparation. It was demonstrated that the AC activity assay designed for the modified preparation and its assay limits were unsuitable in attempting to define AC activity of the nonmodified preparation.