Source: Grifols

Source: Grifols


Unlike the traditional pharmaceutical industry, the plasma industry uses living cells – human blood plasma –  as its raw material to manufacture life-saving drugs. The production of these drugs depends on a supply of raw material which is not in infinite supply, and which is generally significantly more expensive and complicated to obtain than non-living molecules and even biologics grown in biotechnology facilities. It is roughly estimated that the cost of the raw material exceeds 50% of the finished product’s cost, compared with less than 5% in the traditional pharmaceutical industry. The supply of plasma for fractionation, due to its human origin needs to be carefully planned and managed. Therefore, there is a close link between plasma fractionation volumes, or plant throughput, and the demand for the various therapeutic proteins. Plasma economics illustrate this relationship.

Even though many proteins can 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.

a) The “first liter” of plasma describes a liter of fractionated plasma from which all the plasma proteins are sold by the company. Since it includes all the company’s commercial products, this first liter of plasma fractionated generates the maximum amount of revenues from each product.

b) As more plasma is fractionated, the quantities of proteins (or products), which have low demand, due to smaller patient populations such as factor IX, antithrombin III, etc., disappear from the list of products made from the next liter of plasma.

c) Since there is still enough demand for the other proteins, such as factor VIII, due to its large patient populations, the company fractionates plasma from the next liter to meet its demand, until it is fully met. Once the factor VIII demand is met, it is removed from the list of products made from the next liter of plasma.

d) As more plasma is fractionated, one-by-one, each protein product is manufactured in sufficient quantities to meet its respective demand and it is removed from the list of manufactured products from the next liter of plasma. 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 to manufacture the last product remaining on the list is its “last liter

In practice, most companies do not fractionate as much plasma as to fulfill the demand for all their products. Instead, their “last liter” is determined by their demand for IgG because it generates the highest revenues among all the plasma products. Albumin is often still in demand at this fractionation level, leading the companies to sell two “last liter” products; IgG and albumin. Many companies opt for  the “two last liters” strategy because the revenues from only one product (albumin or IgG)  do not suffice to cover their cost of collecting and fractionating 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 gradually ended when recombinant factor VIII products were introduced in the early 1990’s and cannibalized plasma-derived factor VIII. At present, IgG and albumin are sold from every liter of plasma fractionated, and factor VIII is still 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.