Improvement of anticomplementary activity assay for the quality control of immunoglobulin product: an Iranian pilot scale study

Abstract Background and Objectives One of the side effects of immunoglobulin administration is the activation of the complement system related to the high concentration of aggregates/large polymers in the production process. Measuring anticomplementary activity (ACA) is important in pharmaceutical quality control and is a criterion of spontaneous activation of complement system in immunoglobulin products prepared from human plasma. Materials and Methods In this experimental study, ACA was established based on the European Pharmacopoeia (EP) and ACA was measured and compared in two immunoglobulin products obtained by two modified Cohn's methods A or B. The measurement is based on the ability of immunoglobulin for binding to complement and prevent the lysis of sensitized sheep red blood cells (SRBC). Therefore, immunoglobulin was incubated with guinea pig complement and then the remaining complement was titrated by CH50 method and expressed as a percentage. Results ACA values in two products in the two methods of A and B and in two consecutive days and eight times each day were determined to be 0.486 ± 0.08 and 0.466 ± 0.07 CH50/mg protein, respectively; compared to commercial IVIG (Biotest Company) that was 0.486 ± 0.07. ACA activity was measured as less than ≤ 1 CH50 ⁄mg IgG, which was in accordance with the requirements of the pharmacopoeia. Conclusions  Quantitative and qualitative immunoglobulin measurements are as valuable as research and development in plasma purification processes. With the launch of the ACA test, ACA analysis has become possible during the production process as well as in the validation stages of immunoglobulin products.