Infectious prion protein in the filtrate even after 15 nm filtration.
The evaluation of the removal efficacy during manufacturing is important for the risk assessment of plasma products with respect to possible contamination by infectious prions, as recently reported in several papers on the potential for prion transmission through plasma products. Here, we evaluated a virus removal filter which has 15 nm pores. An antithrombin sample immediately prior to nano-filtration was spiked with prion material prepared in two different ways. The removal (log reduction factor) of prion infectivity using animal bioassays was >or=4.72 and 4.00 in two independent filtrations. However, infectivity was detected in both the pellet and supernatant following ultracentrifugation of the 15 nm filtered samples, indicating difficulty in complete removal. The data supports the conclusion that a certain amount of infectious prion protein is present as a smaller and/or soluble form (less than approximately 15 nm in diameter).
Yunoki
Mikihiro
M
Research & Development Division, Benesis Corporation, Kashima, Yodogawa-ku, Osaka, Japan. Yunoki.Mikihiro@mk.mt-pharma.co.jp
Tanaka
Hiroyuki
H
Urayama
Takeru
T
Kanai
Yuta
Y
Nishida
Aya
A
Yoshikawa
Maki
M
Ohkubo
Yuji
Y
Kawabata
Yoshiyasu
Y
Hagiwara
Katsuro
K
Ikuta
Kazuyoshi
K
D000818:Animals; D001774:Blood Chemical Analysis / Q000662:veterinary; D005591:Chemical Fractionation / Q000379:methods; D006224:Cricetinae; D004340:Drug Contamination; D004868:Equipment Failure; D005374:Filtration / Q000295:instrumentation* / Q000379:methods* / Q000592:standards; D008297:Male; D008647:Mesocricetus; D008851:Micropore Filters / Q000592:standards; D010316:Particle Size; D017096:Prion Diseases / Q000097:blood / Q000517:prevention & control / Q000635:transmission / Q000662:veterinary; D011328:Prions / Q000302:isolation & purification*; D014461:Ultracentrifugation / Q000295:instrumentation / Q000379:methods
D011328:Prions