Plasma is the portion of blood that remains after red cells, leukocytes and platelets are removed. Plasma consists of water, salts, enzymes, antibodies and other proteins. Plasma proteins perform a variety of roles, including clotting blood, fighting diseases and other critical functions. They are the starting material for a wide range of lifesaving medicines. Other therapies use recombinant DNA technology. With this technology, protein is synthesized in genetically engineered cell lines instead of being extracted from blood.
Producing plasma-derived products is a unique process where several therapies are created from a single starting material - human plasma. The biological nature of human plasma provides particular challenges to obtaining safe starting material and manufacturing safe and high-quality therapies.
Our therapies are indicated for the treatment of rare diseases such as hemophilia and other bleeding disorders, primary immune deficiency disorders and inherited respiratory disease. Plasma-derived therapeutics can also prevent Rh factor problems in newborns, speed recovery from heart surgery, and help victims of shock and burns recover faster.
Plasma-derived proteins replace missing components in the blood to allow individuals with these chronic conditions to survive and lead healthier lives.
From Plasma Donation to Final Product
Manufacturing plasma therapeutics is a complex, highly sophisticated process that takes about seven months from plasma donation to completion of the finished product. Throughout the manufacturing process, safety and quality are our highest priorities.
CSL Behring has more than 70 plasma collection centers, eight in Germany and the rest in the United States, all operated by our subsidiary, ZLB Plasma. We are always reaching out to qualified plasma donors.
Once donors are qualified, their plasma is collected through a procedure called plasmapheresis. The donor’s blood is drawn through a needle in the arm into a machine that separates blood cells from the plasma. At the end of the donation, the cells are returned to the donor through the same needle. During this process many donors read, watch a movie or relax.
The first donation is tested to ensure safety and quality and isn’t released for processing until after a second donation is made by the same donor and found to be safe.
Serum samples from each unit of plasma are shipped to one of our state-of-the-art testing laboratories in Knoxville, Tenn., and Göttingen, Germany. Although our donors are carefully screened, we use many additional precautions and procedures before we approve the plasma for manufacturing. All plasma samples are tested for HIV, Hepatitis B, Hepatitis C, and other pathogens. Any units that test positive for a virus are discarded.
Frozen plasma is stored in one of our Plasma Logistics Centers (PLCs). While the plasma samples are being tested, the rest of the unit is held in inventory, and all units are carefully tracked. If any problems are found, the plasma is rejected. The PLCs make sure that only units that pass sensitive testing are sent to the manufacturing sites.
CSL Behring operates three manufacturing sites in Bern, Switzerland; Marburg, Germany; and Kankakee, Illinois. At each site, thousands of units of plasma are combined into a plasma "pool" and tested again. Our therapeutics are made using a process called fractionation. Fractionation uses purification methods-including precipitation, centrifugation and column chromatography-to break down plasma into its various proteins, separating out specific proteins for our various therapies. Different products require different means of separation.
Finally, we package finished therapies for distribution. Regulatory authorities check each lot before approving it for release.
Economics of Plasma Therapies
Plasma therapeutics are different from traditional pharmaceuticals in important ways. The starting material is human plasma, not a chemical compound. The cost associated with collecting, testing, storing and transporting this lifesaving starting material is significant. With pharmaceutical chemical compounds, the cost of raw materials typically represents a proportionally smaller portion of the cost of the products. Plasma therapeutics treat small patient populations, while many pharmaceuticals treat millions of patients worldwide. This means that the cost of our therapies are spread over a much smaller base of patients. Further, plasma protein therapies have long planning and production times, often well over 200 days from collection of raw material to finished products for sale reaching the patients.
To be economically healthy, a company must produce several therapies from each unit of plasma. Revenues from all therapies are needed to cover costs incurred producing them. While companies strive to meet requirements for each plasma therapy, unsold inventory can result in losses.
Improvements in two key areas can benefit the economic viability of the industry and ensure continued patient access to and choice of therapies.
First, global harmonization of the stringent regulatory requirements for plasma-derived therapies can lead to more consistency at lower cost of production. Second, reimbursement fees should reflect the unique nature of plasma protein therapeutics and the costs involved in manufacturing safe, effective, life-saving therapies.