rHu Albumin: A Recombinant Human Serum Albumin Developed for Clinical Uses

rHu Albumin

Serum albumin is the most abundant protein found in human blood plasma. It acts as a carrier protein for various components like hormones, fatty acids, and minerals throughout the body. Albumin helps maintain blood volume and pH, plays a role in nutrient exchange and waste removal. Albumin is produced in the liver and has a half-life of approximately 21 days in healthy people. The normal albumin concentration range is 3.5-5 g/dL.

The Need for an Alternative Albumin Supply

Human serum albumin has long been used clinically as a volume expander during surgery, trauma care, burns and other conditions where large amounts of fluid are lost. It is also used to treat various liver diseases that result in low albumin levels. The major supplier of albumin has traditionally been human plasma fractionation facilities. However, the limited availability of donated human plasma constrains supply. This led researchers to develop rHu Albumin using biotechnology methods.

Development of rHu Albumin

Recombinant DNA technology allows for the insertion of the gene encoding human serum albumin into cultured cells like yeast. The cells are then able to produce albumin identical to the native human version. Dutch biotech company Albumin Therapeutics N.V. worked to develop a process for large-scale commercial production of rHu Albumin using yeast cells. They optimized fermentation, purification and formulation methods to produce a product comparable to plasma-derived albumin. Various preclinical and clinical trials demonstrated human albumin to be as safe and effective as plasma-derived albumin for various indications. In 1998, It received marketing approval in Europe under the trade name Albumex.

Manufacturing Process for rHu Albumin

The production process begins by cloning the gene for human serum albumin into yeast expression vectors. The gene is then transformed into a strain of Saccharomyces cerevisiae yeast cells through introduction of the vector. The cells are fermented in specialized bioreactors, where they multiply and secrete albumin into the growth media. Once fermentation is complete, the yeast cells and debris are removed through centrifugation and microfiltration. The albumin in the supernatant is further purified using various chromatography steps. The purified albumin is then sterilized filtered and undergoes formulation with stabilizers before final filling into vials under aseptic conditions. The entire process is carefully controlled and monitored to ensure consistency and quality of the final product.

Properties and Formulation of rHu Albumin

It has an identical amino acid sequence and biological properties compared to plasma-derived albumin. Its main function is to maintain colloid osmotic pressure in the vascular system. It has a half-life similar to endogenous albumin and distributes efficiently in the extracellular fluid compartment after intravenous infusion. It is purified to a high degree with a purity of over 98%. The formulation contains albumin in a pH 7.4 solution along with stabilizers like N-acetyltryptophanate and sodium caprylate to maintain stability and prevent aggregation during storage. The sterile formulation is filled into single-use glass vials and has a shelf life of 3 years when stored under refrigeration.

Clinical Uses of rHu Albumin

Being functionally equivalent to plasma-derived albumin, It has been approved for all the major clinical indications where albumin therapy is used:

- Volume expansion - It is indicated for restoration and maintenance of circulating blood volume in surgery, burns, trauma, etc. where large fluid shifts occur.

- Liver disease - It helps manage ascites and edema in conditions like cirrhosis that cause hypoalbuminemia.

- Hyperbilirubinemia - It displaces bilirubin from albumin-binding sites, increasing bilirubin excretion in neonates with jaundice.

- Hemofiltration and hemodialysis - It improves hemodynamic stability in these renal replacement therapies.

- Protein supplementation - For patients with protein calorie malnutrition or atelectasis that arises due to low oncotic pressure.

Clinical trials comparing human albumin to plasma-derived albumin demonstrated equivalent efficacy, safety, tolerability and pharmacokinetic profiles.

Advantages of human albumin

The major advantages of rHu Albumin over plasma-derived albumin include:

- Unlimited supply - It avoids limitations of plasma collection and ensures consistent availability.

- Purity and consistency - Produced under cGMP following a well-defined process with strict quality controls.

- Eliminates impurities - Free from any infectious agents or prions that may be present in plasma.

- Cost-effectiveness - Lower production costs make it more affordable than imported plasma albumin.

- Ethical production - Avoids issues regarding human donation and does not deplete plasma reserves.

Human albumin provides a safe and effective alternative to plasma-derived albumin, addressing key limitations in supply and ensuring availability of this essential therapeutic protein.

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