Prion removal capacity of plasma protein manufacturing processes

Abstract

The results support the intrinsic ability of certain plasma protein manufacturing steps to remove prions in case of an unlikely contamination, providing a safeguard to products.

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].…”

Plasma products and prion removal: “Is you is or is you ain't …?”

“…A third question concerns prion removal over a multistep process and whether or not prion reduction values measured at individual process steps can be considered to be additive. It is perhaps here that the paper of Cai and coworkers is most helpful, providing convincing evidence that different steps can complement one another where the principles of protein separation are different at each step.…”

“…The first study of this type was published in TRANSFUSION in 1998; now, two articles in this issue of TRANSFUSION encapsulate progress over this 15‐year period. The first, by Cai and coworkers, deals with the manufacture of plasma derivatives, while the second, by Jilma‐Stohlawetz and coworkers concerns plasma for transfusion.…”

“…This approach is described in the paper by Cai and coworkers which summarizes data from five major commercial manufacturers obtained from 218 studies, covering eight types of protein separation technology used in the manufacture of a dozen different types of plasma derivative. Prion determination was undertaken using biochemical assays and bioassays.…”

“…It is therefore necessary to question whether or not prion contamination would be removed completely by the processes examined. In the studies of Cai and coworkers prion was sometimes detected in a product stream after completion of the process step under investigation. Was this because the capacity for prion removal was exceeded experimentally or could there have been a subfraction of prion with properties that caused it to distributed into the product stream such as a subfraction, which remained soluble after precipitation, or a subfraction remaining after chromatographic purification because it was nonadsorbent with respect to the matrix used?…”