Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies.
BACKGROUND
Solvent/detergent (S/D) treatment is an established virus inactivation technology that has been applied in the manufacture of medicinal products derived from human plasma for more than 20 years. Data on the inactivation of enveloped viruses by S/D treatment collected from seven Plasma Protein Therapeutics Association member companies demonstrate the robustness, reliability, and efficacy of this virus inactivation method.


METHODS
The results from 308 studies reflecting production conditions as well as technical variables significantly beyond the product release specification were evaluated for virus inactivation, comprising different combinations of solvent and detergent (tri(n-butyl) phosphate [TNBP]/Tween 80, TNBP/Triton X-100, TNBP/Na-cholate) and different products (Factor [F]VIII, F IX, and intravenous and intramuscular immunoglobulins).


RESULTS
Neither product class, process temperature, protein concentration, nor pH value has a significant impact on virus inactivation. A variable that did appear to be critical was the concentration of solvent and detergent.


CONCLUSIONS
The data presented here demonstrate the robustness of virus inactivation by S/D treatment for a broad spectrum of enveloped test viruses and process variables. Our data substantiate the fact that no transmission of viruses such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or of other enveloped viruses was reported for licensed plasma derivatives since the introduction of S/D treatment.
Dichtelmüller
Herbert O
HO
From the Biotest AG, Dreieich, Germany; Octapharma GmbH, Frankfurt, Germany.
Biesert
Lothar
L
Fabbrizzi
Fabrizio
F
Gajardo
Rodrigo
R
Gröner
Albrecht
A
von Hoegen
Ilka
I
Jorquera
Juan I
JI
Kempf
Christoph
C
Kreil
Thomas R
TR
Pifat
Dominique
D
Osheroff
Wendy
W
Poelsler
Gerhard
G
D001798:Blood Proteins / Q000378:metabolism; D002460:Cell Line; D003902:Detergents / Q000494:pharmacology*; D005164:Factor IX / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000378:metabolism; D010949:Plasma / Q000821:virology*; D012997:Solvents / Q000494:pharmacology*; D038301:Virus Inactivation / Q000187:drug effects*
D001798:Blood Proteins; D003902:Detergents; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D012997:Solvents; D005169:Factor VIII; D005164:Factor IX