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Specific Anti_A/B Immunoaffinity Chromatography Step Reduces Isoagglutinin Levels in an Intravenous Immunoglobulin Product
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Alphonse P. Hubsch, Annette Gaida, Ibrahim El Menyawi, Sandra Wymann, Adriano Marques A., Nicole Spiegl, Thomas Roten, Eleonora Widmer
Rationale: Titers of anti-A and anti-B antibodies (isoagglutinins) in intravenous immunoglobulin (IVIG) products correlate with the risk of hemolysis. Therefore, it is hypothesized that reduction of anti-A/B may reduce this risk.

Methods: We tested the effect of a specific immunoaffinity chromatography (IAC) step, using a blood group A and B trisaccharides-coupled resin, added to the manufacturing process of an IVIG (Privigen®, CSL Behring). Anti-A/B in the final product was measured by the direct agglutination test (DAT). Historical Privigen® lots produced without the IAC step or other measures of isoagglutinin reduction (donor screening) were used as comparators. A fluorescence-activated cell sorting (FACS)-based anti-A/B binding assay was used to compare intermediate products before and after the IAC step.

Results: The most frequent titer in 44 IAC lots was 1:8 (range 1:8 to 1:16) for anti-A, and 1:4 (1:4 to 1:8) for anti-B. In 294 historical lots, the most frequent titer was 1:32 (1:8 to 1:64) for anti-A, and 1:16 (1:4 to 1:32) for anti-B. FACS analyses showed a reduction of 87% (81% to 91%) for anti-A, and 87% (82% to 93%) for anti-B as a result of the IAC step.

Conclusions: We have shown that, with the introduction of an IAC step in a production-scale IVIG (Privigen®) manufacturing process, a reduction of anti-A/B by 2 to 3 titer steps (equivalent to 75.0% to 87.5%) is feasible. The impact of this isoagglutinin reduction on the risk of hemolysis is currently under investigation.