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Flebogamma(®) DIF (intravenous immunoglobulin) purification process effectively eliminates procoagulant activities.
Biologicals. 2013 Nov; 41(6):393-9.B

Abstract

BACKGROUND

Studies have demonstrated that traces of activated factor XI (FXIa) present in specific brands of intravenous immunoglobulin (IVIG) concentrates may pose a thrombogenic risk.

AIM

To characterize procoagulant activity during fractionation and the elimination capacity of the Flebogamma(®) DIF (Grifols' IVIG) manufacturing process.

METHODS

Flebogamma(®) DIF fractionation steps included cryoprecipitate supernatant (Cryo/S), Fraction (Fr) I supernatant, and Fr II + III suspension. Purification steps included ultrafiltrate I, acid treatment, and pasteurization. Samples were assessed for total protein, IgG, and procoagulant activation markers.

RESULTS

Cryo/S showed no procoagulant activity for prekallikrein activator (PKA), kallikrein-like, and non-activated partial thromboplastin time (NaPTT) with normal (-PPP) or FXI-deficient (-FXI) platelet poor plasma. Thrombin generation test (TGT)-PPP and TGT-FXI were <83-148 and <53-197 nM thrombin, respectively. Shortened NaPTTs (100-296 s), high PKA (51-119 IU/mL), kallikrein-like activities (0.043-0.075 ΔAU/min), positive TGTs (98-298 nM), and FXIa (9.5-14.0 ng/mL) were detected in Fr II + III. After pasteurization, no residual evidence of any procoagulant activity marker was observed, including the final IVIG concentrate at 5% or 10% protein. Results were similar in Fr II + III from different IVIG manufacturing facilities.

CONCLUSIONS

The Flebogamma(®) DIF production process is capable of eliminating procoagulant activity because of its purification steps.

Authors+Show Affiliations

Instituto Grifols S.A., Research and Development Area, Polígon Llevant, Can Guasch, 2, 08150 Parets del Vallès, Barcelona, Spain. Electronic address: marta.jose@grifols.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24051302

Citation

José, Marta, et al. "Flebogamma(®) DIF (intravenous Immunoglobulin) Purification Process Effectively Eliminates Procoagulant Activities." Biologicals : Journal of the International Association of Biological Standardization, vol. 41, no. 6, 2013, pp. 393-9.
José M, Marzo N, Pons B, et al. Flebogamma(®) DIF (intravenous immunoglobulin) purification process effectively eliminates procoagulant activities. Biologicals. 2013;41(6):393-9.
José, M., Marzo, N., Pons, B., Herrerias, A., López, L., Faro, M., López, M., & Jorquera, J. I. (2013). Flebogamma(®) DIF (intravenous immunoglobulin) purification process effectively eliminates procoagulant activities. Biologicals : Journal of the International Association of Biological Standardization, 41(6), 393-9. https://doi.org/10.1016/j.biologicals.2013.08.002
José M, et al. Flebogamma(®) DIF (intravenous Immunoglobulin) Purification Process Effectively Eliminates Procoagulant Activities. Biologicals. 2013;41(6):393-9. PubMed PMID: 24051302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Flebogamma(®) DIF (intravenous immunoglobulin) purification process effectively eliminates procoagulant activities. AU - José,Marta, AU - Marzo,Núria, AU - Pons,Berta, AU - Herrerias,Aida, AU - López,Laura, AU - Faro,Merche, AU - López,Maite, AU - Jorquera,Juan I, Y1 - 2013/09/17/ PY - 2013/03/25/received PY - 2013/07/22/revised PY - 2013/08/11/accepted PY - 2013/9/21/entrez PY - 2013/9/21/pubmed PY - 2014/7/26/medline KW - Activated coagulation factor XI KW - Flebogamma(®) DIF KW - Intravenous immunoglobulin KW - Procoagulant activity KW - Purification process KW - Thrombotic risk SP - 393 EP - 9 JF - Biologicals : journal of the International Association of Biological Standardization JO - Biologicals VL - 41 IS - 6 N2 - BACKGROUND: Studies have demonstrated that traces of activated factor XI (FXIa) present in specific brands of intravenous immunoglobulin (IVIG) concentrates may pose a thrombogenic risk. AIM: To characterize procoagulant activity during fractionation and the elimination capacity of the Flebogamma(®) DIF (Grifols' IVIG) manufacturing process. METHODS: Flebogamma(®) DIF fractionation steps included cryoprecipitate supernatant (Cryo/S), Fraction (Fr) I supernatant, and Fr II + III suspension. Purification steps included ultrafiltrate I, acid treatment, and pasteurization. Samples were assessed for total protein, IgG, and procoagulant activation markers. RESULTS: Cryo/S showed no procoagulant activity for prekallikrein activator (PKA), kallikrein-like, and non-activated partial thromboplastin time (NaPTT) with normal (-PPP) or FXI-deficient (-FXI) platelet poor plasma. Thrombin generation test (TGT)-PPP and TGT-FXI were <83-148 and <53-197 nM thrombin, respectively. Shortened NaPTTs (100-296 s), high PKA (51-119 IU/mL), kallikrein-like activities (0.043-0.075 ΔAU/min), positive TGTs (98-298 nM), and FXIa (9.5-14.0 ng/mL) were detected in Fr II + III. After pasteurization, no residual evidence of any procoagulant activity marker was observed, including the final IVIG concentrate at 5% or 10% protein. Results were similar in Fr II + III from different IVIG manufacturing facilities. CONCLUSIONS: The Flebogamma(®) DIF production process is capable of eliminating procoagulant activity because of its purification steps. SN - 1095-8320 UR - https://www.unboundmedicine.com/medline/citation/24051302/Flebogamma_®__DIF__intravenous_immunoglobulin__purification_process_effectively_eliminates_procoagulant_activities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1045-1056(13)00103-6 DB - PRIME DP - Unbound Medicine ER -