Plasma protein fractionation with advanced membrane adsorbents

Area of Science:

• Biochemistry
• Chemical Engineering
• Biotechnology

Background:

• Membrane adsorbents are utilized as stationary phases in chromatography.
• Preparative chromatographic purification of human serum albumin (HSA) is crucial in biopharmaceutical manufacturing.
• Conventional methods using materials like Fast Flow Sepharose have limitations in productivity and scale-up.

Purpose of the Study:

• To evaluate the efficacy of high-capacity membrane adsorbents for HSA purification.
• To compare the performance of membrane adsorbents with conventional chromatography methods.
• To investigate scale-up challenges and identify solutions for membrane adsorption chromatography.

Main Methods:

• A two-step ion exchange fractionation scheme was employed.
• Human plasma was clarified, microfiltrated, and desalted prior to purification.
• Laboratory and pilot scale membrane modules were tested and compared to literature data.

Main Results:

• Albumin purity of 98% was achieved using membrane adsorbents.
• Membrane adsorption chromatography demonstrated increased productivity, reproducibility, and stability.
• Scale-up to pilot scale revealed reduced capacity and productivity due to axial dispersion, with methods to mitigate this identified.

Conclusions:

• Membrane adsorption chromatography is a viable and efficient method for fast protein purification.
• Engineering aspects, such as minimizing axial dispersion, are critical for successful process design and scale-up.
• Membrane adsorbents offer advantages over conventional methods for HSA purification, particularly in productivity and stability.