JOURNAL ARTICLE

Implementation of a 20-nm pore-size filter in the plasma-derived factor VIII manufacturing process

Kenji Furuya, Katsushi Murai, Takeshi Yokoyama, Hideki Maeno, Yoshio Takeda, Takashi Murozuka, Akemi Wakisaka, Masaaki Tanifuji, Tsugikazu Tomono
Vox Sanguinis 2006, 91 (2): 119-25
16907872

BACKGROUND AND OBJECTIVES: Virus inactivation and removal are important prerequisites to ensure the safety of plasma derivatives. For virus inactivation and removal in our coagulation factor VIII (FVIII) product, CROSS EIGHT M, the production process consists of solvent-detergent (S/D) treatment, two chromatography steps and virus filtration with a 35-nm pore-size filter. However, the clearance of non-enveloped viruses was not as good as that of enveloped viruses because non-enveloped viruses are resistant to S/D treatment and are too small to be removed by the filter. In this study, in order to improve the viral safety of the FVIII products, we attempted to replace the 35-nm pore-size virus filter with a 20-nm filter.

MATERIALS AND METHODS: The virus-filtration process was validated for the removal of enveloped and non-enveloped model viruses. Several factors that might affect the FVIII yield on filtration were investigated to obtain a higher recovery. The biochemical properties of the FVIII products produced with the 20-nm pore-size filter were compared with those produced by the 35-nm filter.

RESULTS: Virus filters of 20-nm pore size effectively removed the small non-enveloped viruses when compared with the 35-nm pore-size virus filter. The permeability of FVIII through the 20-nm pore-size filter was inversely proportional to the concentration of FVIII at filtration, and directly proportional to the amount of postfiltration solution. No differences were observed in the biochemical properties of both FVIII products, such as the structure and stability of the FVIII, the contents and multimeric structure of von Willebrand factor (vWF), and FVIII activation by thrombin.

CONCLUSIONS: The virus-clearance efficiency of the FVIII product, CROSS EIGHT M, was markedly increased, in particular against small non-enveloped viruses, by changing the virus filter pore size from 35 nm to 20 nm. It was possible to implement the 20-nm pore-size filter without variation of the biochemical properties or a serious loss of FVIII.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
16907872
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"