Tags

Type your tag names separated by a space and hit enter

Assessment of the ability of the Privigen® purification process to deplete thrombogenic factor XIa from plasma.
Vox Sang. 2014 Jul; 107(1):26-36.VS

Abstract

BACKGROUND AND OBJECTIVES

Activated clotting factor FXI (FXIa) has been postulated to play a significant role in thromboembolic events potentially associated with the administration of intravenous immunoglobulin. The purpose of this study was to demonstrate that thrombogenic agents, in particular FXIa and FXI, are depleted or inactivated in Privigen(®) .

MATERIALS AND METHODS

The ability of the purification process to deplete FXIa from plasma was studied. All steps of the Privigen(®) production were investigated for potential activation of FXI to FXIa with spiking experiments.

RESULTS

Privigen(®) contains no procoagulant activity as determined by FXIa chromogenic assay, non-activated partial thromboplastin time (NaPTT) and thrombin generation assays (TGA, FXIa-like activity). The coagulation times were >200 s in the NaPTT test. FXIa was below the detection limit of 0·14 ng/ml (chromogenic assay) and below the quantification limit of 0·2 ng/ml (TGA). FXIa spiking experiments showed that the analytical methods used can detect traces of procoagulant activity in immunoglobulin samples. FXIa spiking and kinetic experiments during the octanoic acid fractionation step showed that a substantial reduction in FXIa specific activity (by ≥99·9% within 40 min of octanoic acid incubation) was reached already at an early stage of the manufacturing process. These results were confirmed in vivo: in a modified Wessler test, no thrombus was reported.

CONCLUSION

The Privigen(®) manufacturing process has the capability to remove thrombogenic factors: octanoic acid precipitation, designed to remove a variety of contaminants during immunoglobulin purification, also removes almost all FXIa from plasma and further purification steps do not activate FXI.

Authors+Show Affiliations

Research and Development, CSL Behring AG, Bern, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24329163

Citation

Komenda, M, et al. "Assessment of the Ability of the Privigen® Purification Process to Deplete Thrombogenic Factor XIa From Plasma." Vox Sanguinis, vol. 107, no. 1, 2014, pp. 26-36.
Komenda M, Stadler D, Malinas T, et al. Assessment of the ability of the Privigen® purification process to deplete thrombogenic factor XIa from plasma. Vox Sang. 2014;107(1):26-36.
Komenda, M., Stadler, D., Malinas, T., Moses, M., Pragst, I., Herzog, E., Schmutz, P., Minnig, K., & El Menyawi, I. (2014). Assessment of the ability of the Privigen® purification process to deplete thrombogenic factor XIa from plasma. Vox Sanguinis, 107(1), 26-36. https://doi.org/10.1111/vox.12119
Komenda M, et al. Assessment of the Ability of the Privigen® Purification Process to Deplete Thrombogenic Factor XIa From Plasma. Vox Sang. 2014;107(1):26-36. PubMed PMID: 24329163.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of the ability of the Privigen® purification process to deplete thrombogenic factor XIa from plasma. AU - Komenda,M, AU - Stadler,D, AU - Malinas,T, AU - Moses,M, AU - Pragst,I, AU - Herzog,E, AU - Schmutz,P, AU - Minnig,K, AU - El Menyawi,I, Y1 - 2013/12/13/ PY - 2013/07/18/received PY - 2013/11/04/revised PY - 2013/11/07/accepted PY - 2013/12/17/entrez PY - 2013/12/18/pubmed PY - 2014/12/15/medline KW - Factor XIa KW - Privigen® KW - intravenous immunoglobulin KW - procoagulant activity KW - thromboembolic events SP - 26 EP - 36 JF - Vox sanguinis JO - Vox Sang VL - 107 IS - 1 N2 - BACKGROUND AND OBJECTIVES: Activated clotting factor FXI (FXIa) has been postulated to play a significant role in thromboembolic events potentially associated with the administration of intravenous immunoglobulin. The purpose of this study was to demonstrate that thrombogenic agents, in particular FXIa and FXI, are depleted or inactivated in Privigen(®) . MATERIALS AND METHODS: The ability of the purification process to deplete FXIa from plasma was studied. All steps of the Privigen(®) production were investigated for potential activation of FXI to FXIa with spiking experiments. RESULTS: Privigen(®) contains no procoagulant activity as determined by FXIa chromogenic assay, non-activated partial thromboplastin time (NaPTT) and thrombin generation assays (TGA, FXIa-like activity). The coagulation times were >200 s in the NaPTT test. FXIa was below the detection limit of 0·14 ng/ml (chromogenic assay) and below the quantification limit of 0·2 ng/ml (TGA). FXIa spiking experiments showed that the analytical methods used can detect traces of procoagulant activity in immunoglobulin samples. FXIa spiking and kinetic experiments during the octanoic acid fractionation step showed that a substantial reduction in FXIa specific activity (by ≥99·9% within 40 min of octanoic acid incubation) was reached already at an early stage of the manufacturing process. These results were confirmed in vivo: in a modified Wessler test, no thrombus was reported. CONCLUSION: The Privigen(®) manufacturing process has the capability to remove thrombogenic factors: octanoic acid precipitation, designed to remove a variety of contaminants during immunoglobulin purification, also removes almost all FXIa from plasma and further purification steps do not activate FXI. SN - 1423-0410 UR - https://www.unboundmedicine.com/medline/citation/24329163/Assessment_of_the_ability_of_the_Privigen®_purification_process_to_deplete_thrombogenic_factor_XIa_from_plasma_ L2 - https://doi.org/10.1111/vox.12119 DB - PRIME DP - Unbound Medicine ER -