Application note Reduce isoagglutinin risk while protecting yield with IsoClear® XT Robust isoagglutinin reduction with high IgG recovery across relevant process conditions.
Overview
Introduction
Isoagglutinins in IVIG are a recognized contributor to hemolysis risk and must be reduced without compromising plasma utilization, IgG recovery or process efficiency. Traditional approaches such as donor screening can restrict plasma availability while delivering only modest reductions in isoagglutinin levels. IsoClear® XT is an immunoaffinity chromatography solution designed to remove isoagglutinins while maintaining high IgG recovery.
IsoClear® A XT and IsoClear® B XT adsorbents are designed to remove isoagglutinins by immunoaffinity chromatography while maintaining high recovery of total IgG. For IVIG manufacturers, this addresses a critical challenge: reducing hemolysis risk without unnecessary compromise to plasma utilization, yield, or process efficiency 1,2.
This application note evaluates IsoClear® XT under processrelevant conditions to assess three questions that matter most to IVIG manufacturers: can isoagglutinin removal be achieved reliably, can high IgG recovery be maintained, and can the step integrate into manufacturing without creating unnecessary process burden? Across the conditions tested, IsoClear® XT delivered robust isoagglutinin reduction together with strong recovery, broad operating flexibility, and favorable processability, supporting its use as a practical polishing solution for IVIG manufacturing.
Key findings: • Achieved 2–3 titer-step isoagglutinin reduction across relevant operating conditions - Maintained high IgG recovery, averaging 96% at pH 5–5.5 and 1-minute residence time - Performed consistently across pH 4–7 and conductivity up to 30 mS/cm - Maintained effective clearance at 1-minute residence time, with additional binding margin at 5 minutes • No loss of performance after extended 0.5 M NaOH exposure • Showed robust performance across variable feedstock titers - Generated lower running pressure than a commercial comparator
Isoagglutinin reduction remains an important consideration because IVIG-associated hemolysis, although infrequent, may lead to serious clinical consequences 3-6. Regulatory expectations are also increasing, with current pharmacopeial limits criticized for not fully addressing hemolysis risk in high-dose immunomodulatory use and the EMA revising its IVIG clinical investigation guideline in 2022 to strengthen hemolysis monitoring requirements7. At the same time, plasma supply remains a major constraint for IVIG manufacturers. Donor exclusion strategies can further tighten supply while delivering only modest reductions in isoagglutinin levels, whereas immunoaffinity chromatography offers a more direct and effective route to reduction without excluding plasma donations. In practice, manufacturers need more than effective clearance alone. Any isoagglutinin reduction step must also support high IgG recovery, practical throughput, cleaning compatibility, and straightforward integration into existing downstream workflows. IsoClear® XT is designed to meet these requirements by combining robust isoagglutinin removal with strong IgG recovery and process-friendly operating characteristics. The commercial implications may also be substantial. For a large-scale fractionator processing 10 million liters of plasma per year, recovering the additional 5% of plasma typically excluded through donor screening may represent up to £120 M in additional annual product value*, before considering the added benefit of improved process recovery. In the same context, a 1% change in IVIG recovery may represent up to