Flebogamma(®) DIF (intravenous immunoglobulin) purification process effectively eliminates procoagulant activities

Area of Science:

• Biochemistry
• Hematology
• Pharmaceutical Manufacturing

Background:

• Studies indicate that activated factor XI (FXIa) in some intravenous immunoglobulin (IVIG) brands may increase thrombotic risk.
• Understanding and mitigating this risk is crucial for patient safety in IVIG therapy.

Purpose of the Study:

• To analyze procoagulant activity during the fractionation of Flebogamma(®) DIF (Grifols' IVIG).
• To assess the efficacy of the manufacturing process in eliminating these procoagulant factors.

Main Methods:

• Fractionation steps included cryoprecipitate supernatant, Fraction I supernatant, and Fraction II + III suspension.
• Purification involved ultrafiltration, acid treatment, and pasteurization.
• Assessed total protein, IgG, and procoagulant activation markers like FXIa, PKA, and NaPTT.

Main Results:

• Fraction II + III showed procoagulant activity markers (PKA, kallikrein-like, NaPTT, TGT, FXIa).
• Post-pasteurization, all procoagulant activity markers were undetectable in the final IVIG concentrate.
• These findings were consistent across different manufacturing batches.

Conclusions:

• The Flebogamma(®) DIF production process effectively removes procoagulant activity.
• Purification steps, particularly pasteurization, are key to ensuring a safe IVIG product free from thrombogenic risks associated with FXIa.