BAY 81-8973, a full-length recombinant factor VIII: manufacturing processes and product characteristics

Area of Science:

• Biotechnology
• Hematology
• Biopharmaceutical Manufacturing

Background:

• Hemophilia A is a genetic bleeding disorder caused by deficiency in coagulation factor VIII (FVIII).
• Recombinant FVIII (rFVIII) products are crucial for managing hemophilia A, with ongoing advancements in manufacturing processes.
• BAY 81-8973 (Kovaltry®) is an unmodified, full-length rFVIII approved for hemophilia A treatment.

Purpose of the Study:

• To describe the manufacturing process of BAY 81-8973 (Kovaltry®).
• To highlight the enhancements in production efficiency, pathogen safety, and raw material sourcing.
• To detail the resulting product characteristics and their implications for hemophilia A treatment.

Main Methods:

• Modification of the baby hamster kidney cell line used for rFVIII-FS production by introducing the human heat shock protein 70 gene.
• Implementation of a 20-nm filtration step for enhanced pathogen safety.
• Elimination of animal- and human-derived raw materials throughout the production process.

Main Results:

• Improved cell line robustness and productivity.
• Enhanced removal of viruses, transmissible spongiform encephalopathy agents, and protein aggregates.
• Production of a highly pure rFVIII product with consistent, high sialylation of N-linked glycans.

Conclusions:

• The innovative manufacturing process for BAY 81-8973 yields an effective rFVIII product.
• The process ensures enhanced purity and a favorable safety profile for hemophilia A treatment.
• BAY 81-8973 represents an advancement in the production of biopharmaceuticals for rare diseases.