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 liter fractionated.

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., are no longer needed so these products are not purified from the plasma and the proteins are ultimately discarded.

c) Since there is still enough demand for the other proteins, such as factor VIII, due to its larger patient populations and demand, the company still purifies it from the plasma it fractionates after the initial low demand proteins are already discarded. Once the factor VIII demand is met, it is no longer purified from the next liter of plasma and discarded.

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 purified products from the next liter of plasma. Eventually, only one product remains to justify fractionation, which has been IgG for over 20 years. It is the product with the highest demand, requiring the highest volume of fractionated plasma.

As an example, say a fractionation company fractionated 1.0 million liters of plasma every year. The first liter production might include hyperimmune products, rare coagulation products and specialty fractions like AAT, AT-III or fibrinogen. These are high value but low demand products, so not much plasma is needed to produce a entire year’s supply of them. By the time the company has fractionated 0.4 million liters, there is enough production of these low demand products to satisfy the company’s annual demand and so they don’t need to make more until the next year. However, there is still a need for IgG, albumin and factor VIII, so all three of these proteins continue to be purified. After more volume of fractionation, say 0.7 million liters, there is no more demand for factor VIII, so it drops from the purification list and just IgG and albumin are purified. If these to products are purified all the way to the full 1.0 million liter annual throughput, they represent the “last liter” products because they are purified from each liter that was fractionated, unlike the low demand proteins.

In practice, the “last liter” is determined by the demand for IgG by company because it is the product with the most demand relative to production volumes. Albumin is often still in demand at this fractionation level, leading the companies to sell two “last liter” products; IgG and albumin, though the revenue from albumin is much less than the revenue from IgG. 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 or lead to unacceptably low profit levels.

IgG has been the driver of plasma fractionation volumes for over 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. The first “last liter” product was albumin, which was the first product fractionated from plasma going all the way back to World War II. At present, IgG and albumin usually sold from every liter of plasma fractionated, and factor VIII is still sold from many of the liters fractionated. Today, IgG accounts for around 50% of the global plasma proteins market (approximately $12 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. Please Contact Us if you would like the latest figures on plasma protein sales by product, company or country.