4CPS-100 Quality of intratect: in vitro evaluation of biological activities

Background Human normal immunoglobulin preparations for intravenous application (IVIG) such as Biotest’s Intratect were initially developed as substitution therapy for primary and secondary immunodeficiencies. Over time the clinical use has broadened and now additionally includes treatment for a multitude of hyperinflammatory conditions, typically at higher doses. 1 Recently, chronic inflammatory demyelinating polyradiculo-neuropathy (CIDP) has become a formally approved indication. Purpose Due to this change in use which involves increased doses, and in view of adverse events observed with other IVIG brands, we have re-evaluated quality parameters relevant for product safety and efficacy. Material and methods Since thrombogenicity is a general risk identified for IVIGs, analyses of Intratect with globally-used coagulation tests, such as the thrombin generation Assay, were performed. Additionally, specific tests for the detection of potential impurities (e.g. prekallikrein activator (PKA)) were employed to assess the thrombogenic potential. The tests for anti-A and anti-B hemagglutinins complies with the European Pharmacopoia (2.6.20). Results Intratect was found to be free of procoagulant and other impurities. The content of blood group antibodies, which are associated with the risk of haemolysis, can be controlled by the manufacturing process. In Intratect these antibodies are consistently tightly controlled, and their content is far below the isoagglutinin titer threshold. Pathogen antigen recognition is a prerequisite for the anti-infective activity of immunoglobulins. Intratect was found to contain antibody titers against relevant viruses and bacteria. Quality characteristics of IVIG preparations differ from brand to brand but are typically consistant from batch to batch for a single brand. Conclusion Multiple factors contribute to the quality of the IVIG preparations. Important quality attributes are associated with safety, 2 3 and adequate antimicrobial activity. Different manufacturing processes determine differences in the quality, safety and efficacy of IVIG brands. References and/or acknowledgements 1. Wahn V. From immune substitution to immunomodulation . Semin Hematol2016;53(Suppl. 1):S7–9. Carolin Schmidt and Karina Winterling contributed equally to this work. 2. Bellac CL, et al . The role of isoagglutinins in intravenous immunoglobulin-related hemolysis. Transfusion 2015;55(Suppl 2):S13–22. 3. Etscheid M, et al . Identification of kallikrein and FXIa as impurities in therapeutic immunoglobulins: implications for the safety and control of intravenous blood products. Vox Sang 2012;102:40–6. Conflict of interest Corporate-sponsored research or other substantive relationships: all authors are employees of Biotest AG, Dreieich, Germany.