The physiological PrPC is present in significant amounts in various regions of the body as a monomer with a molecular weight and molecular features
similar to those of gonadotropins. Therefore, low traces of this protein can be found in the final preparation in some purification
processes (9). Even a nanofiltration step, if present into the purification process, cannot efficiently separate gonadotropins
from PrPC. But because infectivity of PrPSc is strictly connected to the formation of high molecular weight aggregates of the same protein the differences in the molecular
dimensions between PrPSc and gonadotropins are sufficient to predict a high level of performance of the nanofiltration step using Viresolve NFP filters
(6, 28). Indeed, in spite of the fact that no evidence exists about the real prion removal mechanism by nanofilters, the aggregation
status and the differences in the molecular weight between gonadotropins and PrPSc could in principle explain the high value of log reduction of infectivity observed in this experimental study and the efficiency
of this nanofiltration step. Together, these observations demonstrate that the nanofiltration technology can significantly
increase the level of prion safety of human-derived biological products.
The authors thank Dr. Adriano Aguzzi, director of the Institute of Neuropathology at the University of Zurich, and his team,
Dr. Harald Seeger and Audrey Marcel, also from the Institute of Neuropathology at the University of Zurich for scientific
and technical collaboration in the study.
Paolo Caccia is director of the biomanufacturing department and Luca Angiolini is head of the protein engineering laboratory, both at the Institut Biochimique SA, Switzerland. Renato Lorenz* is a senior biomanufacturing engineer at Merck Millipore, Italy, and Estelle Zelter is in field marketing in the Europe Virus Safety Solutions group at Merck Millipore, France. *To whom correspondence should
be addressed, email@example.com