Distribution of a bovine spongiform encephalopathy‐derived agent over ion‐exchange chromatography used in the preparation of concentrates of fibrinogen and factor VIII

Abstract

Results using a BSE-derived agent suggest that vCJD infectivity would be substantially removed by the ion-exchange process used in the preparation of fibrinogen and factor VIII concentrate. Although 301V infectivity remained bound to the ion-exchange matrix following elution of factor VIII, this appeared to be eliminated by the procedure used for cleaning the ion-exchange media after each use.

Prion‐removal capacity of chromatographic and ethanol precipitation steps used in the production of albumin and immunoglobulins

“…Similar results were reported using murine bioassay of BSE 301 V over Toyopearl DEAE‐650 m [31], in which LRFs of 2·9 and 2·7 were found in eluted fibrinogen and factor VIII, leading to the conclusion that over 99% of BSE infectivity remained bound to the ion‐exchange column. A 2 m NaCl wash removed 5·75% of this infectivity, and infectivity could not be detected in eluates following a 0·1 m NaOH wash.…”

Prion removal capacity of plasma protein manufacturing processes

“…Previously several independent groups have reported intrinsic prion removal capacity during plasma protein purification processes using model prion spiking agents and down‐scale process replicas, methods principally consistent with regulatory recommendations . In spite of the current absence of vCJD prevalence in the general population, the very low prion content potentially present in the plasma of affected individuals, the implemented plasma sourcing control measures, and the absence of factual contamination, PPTA member companies performed extensive studies on their manufacturing processes to evaluate the capacity of removing prions, in the highly unlikely event of a vCJD donor contributing to the plasma pool.…”

Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin Preparation from Human Plasma

“…The regeneration/sanitisation sequence, which includes for both resins a 1 M NaOH treatment, is known to be efficient and robust for virus inactivation [25, 26] and also reduces the prion risk as demonstrated recently by our group [27]. Based on prion removal data in the literature and in-house knowledge of the manufacturing process, three independent process steps with potential capacity to remove prions were identified in the IQYMUNE ® manufacturing process: caprylic acid fractionation [23, 28], ion-exchange chromatography [17, 28, 29] and nanofiltration [28, 29–32]. The overall prion removal capacity was found to be more than 12.9 log 10 , largely in excess of what is needed, according to current risk assessment calculations [32–35].…”