Diagram of automated plasma collection procedure Source: CSL Behring

Diagram of automated plasma collection procedure
Source: CSL Behring

Plasma Collection:

To obtain enough raw materials to produce plasma products, millions of liters of plasma are needed annually. Some of the plasma is obtained by separating plasma from red blood cells after whole blood donation, for example at a Red Cross Blood Drive. This plasma is called “recovered plasma” because the goal of the blood collection organization it to obtain red cells and platelets, and plasma is a by-product. Another type of plasma for fractionation, called “source plasma,” is generated by dedicated plasma collection centers, which collect plasma from donors through plasmapheresis machines (these machines extract whole blood from the donor, keep the plasma and return the red cells to him/her). In the United States and a few other countries, plasma donors receive a cash compensation for their time and efforts as they may donate frequently, while whole blood donors are encouraged to donate by means of a token non-monetary incentive.

Plasma donation using a plasmapheresis machine Source: Fenwal

Plasma donation using a plasmapheresis machine
Source: Fenwal

It is essential for each company to have access to a sufficient quantity of plasma to meet its production objectives. To this end, the large, multinational plasma companies (the fractionators) own almost all the plasma collection centers in the U.S., where they collect most of the plasma they need. Source plasma is also collected in significant quantities in China, Germany, Austria, Czech Republic and Hungary. Together, the largest three companies (CSL Plasma, Grifols and BioLife (Shire) collect over 80% of the total U.S. source plasma for fractionation.

In recent years, the number of plasma centers has increased significantly in the United States, from less than 500 in 2015 to over 650 in 2017, reflecting that the needs for therapeutic plasma proteins is anticipated to continue to grow in the coming years.

A similar trend has been observed in Europe although the regulations in place in the region generally do not allow as large volumes of plasma to be donated annually or paid as much by an individual donor as in the United States, limiting the growth of plasma collections for fractionation.

Plasma Safety and Viral Inactivation:

Following cases of virus transmission from blood and blood products in the 1980’s, in particular HIV, the plasma industry has implemented strict controls to ensure that only plasma from non-infected donors is used to make plasma products. A variety of measures have been introduced to increase the safety of plasma, some of them introduced by the Plasma Proteins Therapeutics Association (PPTA), the commercial plasma industry group. A set of measures promulgated by PPTA is the “Quality Plasma Program” (QPP) which includes quarantine of donors’ first plasma donation, plasma inventory holds, donor selection and donation screening by nucleic acid testing (NAT) for HIV, Hepatitis B and C.

In addition to selecting donors and testing plasma for specific viruses, the plasma industry has developed several viral inactivation techniques to remove known and unknown viruses and bacteria in the fractionation and purification processes. These techniques include solvent/detergent washes, low pH, heat, nanofiltration, and chromatography. These techniques reduce the risk of any virus transmission from a plasma product by several orders of magnitude. Companies and academic researchers continue to search for new methods of viral inactivation to further improve the safety of plasma-derived products.

 

BioMatCSLPlasmaplasmaCarebiolife

Images of plasma collection centers

 

Plasma Donation using a plasmapheresis machine Source: Fenwal

Plasma Donation using a plasmapheresis machine
Source: Fenwal

Product Pricing and Cost Structure

The plasma industry’s cost structure differs from the traditional pharmaceutical or biotechnology industries. The cost of plasma – the plasma industry’s raw material – is generally higher than the cost of the raw materials used in the traditional pharmaceutical or biotechnology industries. Plasma is expensive because collecting plasma is a complicated and delicate operation, involving a large work force due to the need to collect plasma from thousands of people. Components of this cost include plasmapheresis equipment and highly qualified staff, donors have to donate plasma frequently and many donors are needed by the companies, complex logistics, strict regulations, and donor compensation. As mentioned, it is generally estimated that plasma, the raw material, represents roughly 50% of the total cost to produce plasma-based therapeutic proteins.

For a patient, the annual cost of therapy using a plasma-based product may exceed $200,000, representing an obstacle to their acceptance in many countries although significant progress has been observed in recent years. As healthcare budgets continue to be under increasing pressure, advocacy and awareness are used to ensure that patients in need of these therapies have access to them.