Pathogen safety of a pasteurized four-factor human prothrombin complex concentrate preparation using serial 20N virus...

Area of Science:

• Biochemistry
• Virology
• Process Engineering

Background:

• Beriplex P/N (Kcentra, Coaplex, Confidex) is a four-factor human prothrombin complex concentrate (PCC).
• An improved manufacturing process was developed to enhance the virus safety of Beriplex P/N.

Purpose of the Study:

• To evaluate the pathogen safety profile of an improved manufacturing process for Beriplex P/N.
• To characterize the biochemical properties of the enhanced PCC manufacturing process.

Main Methods:

• Product intermediates were spiked with viruses and prions to assess pathogen inactivation and removal under scaled-down commercial manufacturing conditions.
• Clotting factor activities (FII, FVII, FIX, FX), protein C, protein S, heparin, and antithrombin III levels were determined in nine product lots.

Main Results:

• The manufacturing process demonstrated high virus reduction capacity (≥15.5 to ≥18.4 log for enveloped viruses, 11.5 to ≥11.9 log for nonenveloped viruses).
• Virus reduction was achieved through pasteurization, 20N virus filtration, and purification steps (ammonium sulfate precipitation, calcium phosphate adsorption).
• Prion removal was effective, and clotting factor levels in the final product were well-balanced.

Conclusions:

• The improved manufacturing process for Beriplex P/N significantly enhances pathogen safety.
• The process effectively removes and inactivates a wide range of viruses and prions, improving the overall safety margin.