Even though many proteins may be separated from plasma and commercialized, some of them are more in demand than others. Those generating the highest demand determine the volume of plasma needed for fractionation. By maximizing the volume of plasma fractionated to make each product in adequate quantity, a company can maximize its revenues and profitability. Dubbed “plasma economics”, it leads to the concept of “first liter” and “last liter” (or “marginal liter”) of the plasma fractionated by a company.
The “first liter” of plasma describes a liter of fractionated plasma from which all the plasma proteins are sold by the company. They include all its commercial products, and generate the maximum amount of revenue from each product made from this “first liter” of plasma fractionated. As more plasma is fractionated, the quantities of product which have low demand (due to smaller patient populations) such as factor IX, antithrombin III, etc., are sufficient to meet these demand requirements. However, there is still enough demand for other fractions, such as factor VIII, due to large patient populations. Therefore, the company continues to fractionate enough plasma to make factor VIII until its demand is met. As more plasma is fractionated, one-by-one, all the protein products are made in sufficient quantities to meet heir respective demands. Eventually, only one product remains to justify fractionation. It is the product with the highest demand, requiring the highest volume of fractionated plasma. The point at which a company stops plasma fractionation for obtaining the last remaining products is called its “last liter.” Its needs not be the point where the last protein’s demand is met.
In practice, most companies do not fractionate as much plasma to fulfill the demand for all their products. Instead, their “last liter” is determined by their demand for IgG because it generates high revenues. Albumin is often still in demand at this fractionation level, leading the companies to sell two “last liter” products; IgG and albumin. The option of “two last liters” is caused by the fact that the revenue from selling just one product (albumin or IgG) is insufficient to cover their cost of collecting and fractionating the plasma.
IgG has been the driver of plasma fractionation volumes for the past twenty years. Prior to that, factor VIII was the driving protein for fractionation, but it was lessened by the commercial development and introduction of recombinant factor VIII products in the early 1990’s. At present, IgG and albumin are sold from every liter of plasma fractionated, and factor VIII is sold from nearly all the liters fractionated.
Today, IgG accounts for 40-50% of the global plasma proteins market (approximately $20 billion) although this percentage varies significantly by region. Albumin and plasma-derived factor VIII (pdFVIII) each have a smaller share of the market (10-15% each) again with wide regional variations.