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 are compensated for their time to donate, while whole blood donors are not.

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, as it is the raw material to manufacture all the therapeutic proteins. To this end, the large, multinational plasma companies (the “fractionators”) own most of 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, the Czech Republic and Hungary.

 

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.

Plasma Donation using a plasmapheresis machine Source: Fenwal

Plasma Donation using a plasmapheresis machine
Source: Fenwal

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 in order to further improve the safety of plasma-derived products.

 

Effective Use of a Finite Supply:

Plasma-based products can only be produced from plasma, and plasma can only be extracted from human donors. Consequently, plasma is a finite resource that cannot be replicated or mass produced in large industrial processes. Thus, the plasma must be used efficiently by producing as many products as possible from each liter collected. For example, it is more cost-effective to produce IVIG, albumin and plasma-derived factor VIII from a liter of plasma than just the first two products. Furthermore, efficiency is also achieved by improving the yield at which each product is extracted from the plasma, as well as finding new proteins with therapeutic potential in the plasma. Continuing efforts in all these areas are underway to improve the efficiency and profitability of plasma fractionation.

 

BioMatCSLPlasmaplasmaCarebiolife

Images of plasma collection centers

Today, the plasma fractionators collect millions of liters of plasma in the U.S. and elsewhere, generally through their own plasma collection business subsidiaries. They include BPL Plasma (owned by Bio-Products Laboratory), BioLife (owned by Shire), BioMat, PlasmaCare and Grifols Plasma Resources (owned by Grifols), CSL Plasma (owned by CSL Ltd.), Octapharma Plasma (owned by Octapharma), Kedrion Plasma (owned by Kedrion SpA), etc. Together, the largest three companies collect over 75% of the total U.S. plasma. Most of the plasma-collecting companies are based in the U.S. because this country is the main source of plasma worldwide, due to regulations, which permit high donation frequency. Below are some pictures of plasma centers belonging to the largest plasma collection organizations.

 

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 much higher than the cost of raw materials used in the traditional pharmaceutical or biotechnology industry to make therapies. Plasma is expensive because only small quantities of plasma may be collected from donors at a time. Therefore, many donors are needed by the companies, and they have to donate plasma frequently. Furthermore, collecting plasma is a complicated and delicate operation, involving expensive plasmapheresis equipment and highly qualified staff. Consequently, plasma, the raw material, represents roughly 25-50% of the total cost to produce plasma-based therapeutic proteins, and as a result, they are relatively expensive. Furthermore, the fractionation process is complex and expensive.

 

Today the annual cost of therapy using a plasma-based product may exceed $200,000. This comparatively high cost is also caused by the fact that these products are indicated for the treatment of rare diseases. The increasing cost of therapies is a growing concern in many countries, and plasma products are not immune from these concerns. As healthcare budgets continue to be under increasing pressure, advocacy and awareness are used to ensure that deserving patients have access to the therapies they need for better health.

 

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Source: The Marketing Research Bureau, Inc.