title: Biochemical quality of the pharmaceutically licensed plasma OctaplasLG after implementation of a novel prion protein (PrPSc) removal technology and reduction of the solvent/detergent (S/D) process time.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research and Development Department, Octapharma Pharmazeutika Produktionsges.mbH, Vienna, Austria. andrea.heger@octapharma.com
authors.forename: A
authors.initials: A
authors.lastname: Heger
authors.forename: T-E
authors.initials: TE
authors.lastname: Svae
authors.forename: A
authors.initials: A
authors.lastname: Neisser-Svae
authors.forename: S
authors.initials: S
authors.lastname: Jordan
authors.forename: M
authors.initials: M
authors.lastname: Behizad
authors.forename: J
authors.initials: J
authors.lastname: Römisch
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000071120:ADAMTS13 Protein; D001780:Blood Coagulation Tests; D001793:Blood Preservation; D017848:Blood-Borne Pathogens / Q000302:isolation & purification*; D002846:Chromatography, Affinity / Q000379:methods*; D003902:Detergents / Q000494:pharmacology*; D005240:Feasibility Studies; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D010865:Pilot Projects; D010949:Plasma / Q000187:drug effects*; D018620:PrPSc Proteins / Q000302:isolation & purification*; D011485:Protein Binding; D012117:Resins, Synthetic / Q000494:pharmacology*; D012997:Solvents / Q000494:pharmacology*; D016060:Sorption Detoxification / Q000379:methods*; D013916:Thrombelastography; D013917:Thrombin / Q000096:biosynthesis; D013997:Time Factors; D014841:von Willebrand Factor / Q000032:analysis / Q000737:chemistry
chemical_list: D003902:Detergents; D018620:PrPSc Proteins; D012117:Resins, Synthetic; D012997:Solvents; D014841:von Willebrand Factor; D005340:Fibrinogen; D013917:Thrombin; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human