Blood Plasma Fractionation

Immunoglobulin

Polyclonal immunoglobulin G (IgG) is the primary high-value product for all plasma manufacturers. Today, immunoglobulin is administered in higher concentration dosages; this requires formulations which are well-tolerated by the patient. Key parameters for tolerability include:

• High purity
• Low immunoglobulin A and M (igA, IgM) content
• Low prekallikrein activator (PKA) content
• Low anticardiolipin antibody (ACA) content
• Low isoagglutinin content

The clinical efficacy of IgG is determined by the process and the quality of manufacture. Key features include an intact molecule, physiological sub-class distribution, pH of administration, absence of pyrogens, and low toxic residue content. IgG is currently used to treat primary immunodeficiency (PID), neurological conditions, hematology, and other infectious diseases.

Albumin

Albumin, often referred to as HSA (human serum albumen), is a stable protein with a molecular weight of 67 kD. It is sometimes added as a stabilizer for other plasma products, though its therapeutic use is as a fluid replacement treatment to expand blood volume in patients typically traumatized by burns or surgery. Albumin is manufactured in large quantities and is produced by all plasma manufacturers. Frequently, three to five batches per week may be manufactured in both low and high concentrations.

While raw plasma contains around 35–50 g of albumin per liter, 25–40% of that volume is lost during the actual fractionation process. This can lead fractionators to consider a chromatography method instead of Cohn fractionation, as chromatography has more favorable loss percentages of around 15–20%.

Factor VIII

Improving purity while maintaining specific activity is important in production of Factor VIII (FVIII), an essential blood-clotting protein. Clinical requirements of administration to a patient include low immunogenicity and high purity, which translates to low isoagglutinins and accompanying protein count, no foreign proteins or DNA, and low amounts of chemical residues. The purification process is designed to achieve these requirements:

• Increasing process efficiency and product recovery
• Achieving higher product yield
• Ensuring process safety and reproducibility of multi-strain products