Selective Immunoglobulin Aggregates Removal in Antivenoms by a Simple Chromatographic Step Based on a Monolithic Stationary Phase

Antivenom therapy is a critical intervention for treating the more than 5.000.000 envenomation accidents that occur each year around the world. These immunotherapeutic drugs are mostly produced following techniques developed more than fifty years ago with minor changes. Aggregate content has been described as one of the main causes of early adverse effects after intravenous administration of antivenoms. In this work we propose the introduction of a final polishing step to traditional antivenom manufacturing processes aimed at lowering the aggregate content in the final product. The refinement step proposed in this work is based on the selective capture of immunoglobulin aggregates by a cation exchange monolithic stationary phase. We show that this media can effectively remove aggregates in the final product under isotonic ion-strength and mildly acidic conditions following a negative chromatography strategy, thus making it a useful technique for producing higher quality products.