Manufacturing of a prothrombin complex concentrate aiming at low thrombogenicity

Area of Science:

• Biochemistry
• Hematology
• Biotechnology

Background:

• Prothrombin complex concentrates (PCCs) are crucial for managing vitamin K-dependent clotting factor deficiencies.
• Existing PCCs require optimization for enhanced virus safety and balanced factor content.

Purpose of the Study:

• To develop and characterize a novel prothrombin complex concentrate (PCC) with improved virus safety and balanced vitamin K-dependent clotting factors.
• To evaluate the safety and efficacy of the new PCC in clinical settings.

Main Methods:

• Optimized anion exchange chromatography and solid-phase extraction for PCC production.
• Incorporation of nanofiltration alongside solvent/detergent treatment for enhanced virus inactivation.
• Assessment of clotting factor activities (II, VII, IX, X), inhibitors (Protein C, S, Z), and thrombogenicity (in vitro and in vivo).

Main Results:

• The developed PCC exhibits high virus safety and a balanced 1:1:1:1 ratio of factors II, VII, IX, and X.
• Therapeutically effective concentrations of Protein C, Protein S, and Protein Z were confirmed.
• The PCC demonstrated no thrombogenicity in preclinical models.
• Clinical studies confirmed the PCC's safety and efficacy in treating factor IX (FIX) and factor VII (FVII) deficiencies, with successful bleeding control and surgical procedures.

Conclusions:

• The novel PCC production process yields a product with superior virus safety and balanced hemostatic components.
• The concentrate is a safe and effective therapeutic option for patients with vitamin K-dependent clotting factor deficiencies.
• The optimized production method significantly reduces manufacturing time.