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Biochemical quality of the pharmaceutically licensed plasma OctaplasLG ® after implementation of a novel prion protein (PrP Sc ) removal technology and reduction of the solvent/detergent (S/D) process time
Author(s) -
Heger A.,
Svae T.E.,
NeisserSvae A.,
Jordan S.,
Behizad M.,
Römisch J.
Publication year - 2009
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/j.1423-0410.2009.01190.x
Subject(s) - chemistry , chromatography , affinity chromatography , ligand (biochemistry) , plasmin , coagulation , fibrinogen , solvent , enzyme , biochemistry , receptor , medicine , psychiatry
Background and Objectives A new chromatographic step for the selective binding of pathological prion proteins (PrP Sc ) to an affinity ligand, developed and optimized for PrP Sc capture and attached to synthetic resin particles (PRDT, USA; ProMetic BioSciences Ltd, Isle of Man, UK) was implemented into the manufacturing process of the solvent/detergent (S/D) treated biopharmaceutical quality plasma Octaplas ® . Materials and Methods Pilot batches of Octaplas ® with the implemented chromatographic step [labelled as OctaplasLG ® (ligand gel)] were manufactured by Octapharma PPGmbH, Vienna, Austria. The biochemical quality was compared directly after manufacturing as well as after 18 months storage. All samples were tested on global coagulation parameters, fibrinogen levels, activities of coagulation factors and protease inhibitors, ADAMTS13 levels, as well as markers of activated coagulation and fibrinolysis. In addition, von Willebrand factor multimeric analysis was performed. Results The incorporation of this novel chromatography into the large‐scale routine manufacturing process was shown to be technically feasible and the performance of the column was assessed to be excellent. The biochemical studies showed that Octaplas ® and OctaplasLG ® produced without and with the new column, respectively, demonstrate an identical biochemical quality. OctaplasLG ® remained stable over a period of 18 months stored frozen. A parallel reduction of the S/D virus inactivation step from 4–4·5 to 1–1·5 h led to significantly higher activities of plasmin inhibitor. Conclusion The studies confirmed that the affinity ligand chromatography under the developed conditions can be introduced into the Octaplas ® manufacturing process, as a mean to reduce potentially present PrP Sc , without hampering the proven quality of this product.