Dedicated removal of immunoglobulin ( Ig ) A , IgM , and F actor ( F ) XI /activated FXI from human plasma IgG

Background Adverse events can be associated with treating critically ill patients with immunoglobulin ( Ig ) G . Some adverse events are due to contaminants like IgA and activated F actor ( F ) XI . Therefore, new purification strategies are needed for dedicated removal of these contaminants without impairing IgG recovery. Study Design and Methods An immunoglobulin fraction containing IgG , IgM , and IgA was prepared by caprylic acid precipitation of cryoprecipitate‐poor plasma. The capacities of the cation exchangers ( S H yper C el and CM C eramic HyperD F ) and anion exchangers ( H yper C el STAR AX and Q H yper C el) to remove IgA , IgM , and spiked FXI were tested following a design of experiment approach using microplates and chromatographic column scale‐up. FXI removal was also evaluated using M ustang S chromatographic membranes. IgG / IgG subclasses, IgA , IgM , and FXI were assessed by enzyme‐linked immunosorbent assay, and caprylic acid, by gas chromatography. Results Extensive removal of IgA and IgM , but not FXI , was achieved by a two‐step chromatographic process combining S H yper C el used in the IgG binding and elution mode and H yper C el STAR AX used in the IgG flow‐through mode, providing high IgG and IgG subclass recovery (>85%), high purity (>99.5%), and efficient removal of IgA (<0.5%) and IgM (undetectable). Twenty‐six‐fold FXI removal was achieved by processing the resulting purified IgG fraction through M ustang S cation‐exchanger membranes at pH  6.0 and 12.7  mS /cm. Caprylic acid was removed by S H yper C el. Conclusions Combining S H yper C el and H yper C el STAR AX extensively removed IgA and IgM , with good IgG recovery. Mustang® S membranes can be used for dedicated removal of FXI .