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

Abstract

Using rodent-adapted scrapie as a model, the studies indicated that ion exchange chromatography, as well as Cohn immunoglobulin fractionation have the potential to effectively reduce the load of TSE agents should they be present in plasma pools.

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

“…This article describes the virus and prion clearance evaluation for four steps of the manufacturing process of IQYMUNE ® . The process includes two orthogonal-specific virus inactivation/removal steps—S/D treatment and 20 nm nanofiltration—as well as two steps with inherent virus/prion reduction capacity [13–17]—caprylic acid fractionation and anion-exchange chromatography.…”

“…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].…”

Investigation of prion removal/inactivation from chromatographic gel

“…Similarly a 3 log reduction in scrapie 263K infectivity from a microsomal spike over DEAE Sepharose was determined by Western blot [4], and it was hypothesized that PrP sc remained bound to the chromatography column. A previous Western blot study by our laboratory of all eluates from a DEAE Sepharose column used to purify albumin and IgG found substantial removal of scrapie 263K PrP sc from product streams [6]. The recovery of < 0·4% of added infectivity in the column washes and eluates indicated that a substantial portion of infectivity was bound to the column prior to gel regeneration and cleaning.…”