Good Blood

The transfusion bag hangs prepped and poised, heavy with the weight of the lifegiving liquid it contains. With the push of a button, the fluid begins to flow, winding silently through the attached tube into the awaiting vein. The infusion itself may take hours, but for the recipient, the time required will be life-sustaining and life-changing — well worth the wait.

Whether the need results from chronic illness, injury or an inherited blood disorder, an estimated 4.9 million people in the U.S.rely on blood transfusions or blood products daily.¹ For these individuals, this gift of life is entirely dependent upon the kindness of strangers who donate blood and plasma. It also is dependent on the vigilance and integrity of an army of regulators, manufacturers and health officials whose oversight for the past three decades has resulted in a blood supply that is safe, trustworthy and stringently screened for blood-borne diseases. According to the Centers for Disease Control and Prevention (CDC), the United States blood supply is currently considered among the safest in the world.² But this achievement did not come without a liberal dose of literal blood, sweat and tears.

Blood Safety in the Age of AIDS

The blood supply industry came under fire three decades ago when a new and deadly virus emerged, infecting thousands of patients, most in the hemophilia community. At the time, acquired immunodeficiency syndrome (AIDS) was an unknown disease, and therefore human immunodeficiency virus (HIV) antibodies were not yet a part of the blood supply screening process.

CDC statistics show that nearly all people infected with HIV through blood transfusions received those transfusions prior to 1985, the year HIV testing began for all donated blood.³ The Public Health Service has since recommended an approach to blood safety in the United States that includes stringent donor selection practices and the use of screening tests. U.S. blood donations have been screened for antibodies to HIV-1 since March 1985 and HIV-2 since June 1992. The p24 antigen test was added in 1996. Blood and blood products that test positive for HIV are safely discarded and are not used. But even with these safeguards in place, questions and concerns still arise.

In fall 2010, a documentary produced by Marilyn Ness titled Bad Blood stirred the blood safety controversy anew by chronicling the circumstances that led to HIV contamination in the nation’s blood supply. Of course, finger-pointing is common in the aftermath of any tragedy, and accusations that more could have been done to prevent the infection of so many may have merit. An analysis of the facts reveals that many factors combined to create this perfect viral storm. For one thing, there was widespread ignorance and fear surrounding HIV and AIDS. AIDS originally was considered a sexually transmitted disease, and initially, no one knew it could be spread by infected blood. In the early 1980s, blood banks were already taxed by diminished supplies, and bad publicity about blood safety had the potential to discourage donations at a time when they were desperately needed. For that reason, blood banks did not immediately rush out with news of the infected blood supplies. Then, there was the political climate. The early ’80s saw a shift toward conservative ideology that promoted the benefits of smaller government and reduced regulation, leaving many health agencies woefully understaffed — and unprepared — for an epidemic of this magnitude.

In the end, it was simply impossible to predict the devastation of the AIDS outbreak; nearly 10,000 people with hemophilia were infected with HIV between 1978 and 1984.⁴ In 1993, the Department of Health and Human Services asked the Institute of Medicine for an analysis of the tragedy.With 20/20 hindsight as an advantage, the study concluded that “a failure of leadership and inadequate decision-making processes” were pivotal. In particular, donor screening was not effective, regulatory action was weak, and hemophiliacs were not well-enough informed about the risks.⁵

In a recent leadership profile in this publication, Victor Grifols, Grifols S.A. president, spoke of the ongoing controversy: “Even 30 years later, we are still learning the lessons from the AIDS outbreak in the 1980s. It is a history that we still have to address.We can say with certainty that the blood and plasma supply chain is much safer today than it was 50 years ago. But, this is an evolving field. We can also say with certainty that the field will be safer 50 years from today. Safety is a never-ending pursuit.”

Ironically, the AIDS epidemic exposed how vulnerable the blood supply can be to new diseases. Yet it also served as a catalyst for industry improvement and reform. Doctors began making more informed choices about recommending transfusions. Scientists began devising improved methods for disease testing and virus inactivation. Manufacturers, too, developed better testing and screening protocols. Positive changes emerged on the heels of disaster.

Of course, the fact that HIV and other viral contaminants appear to be under control doesn’t mean that manufacturers, healthcare providers or consumers can relax and disregard old safety concerns. As the focus on safety continues to evolve, everyone involved in the process is tasked with proactively expanding safety guidelines to keep history from repeating itself and protect the blood supply from new threats.

Safety at the Manufacturing Level

Patients who need blood transfusions or infusions of blood plasma products often have few options when it comes to being selective about the product they receive, typically leaving such decisions in the hands of their healthcare providers. Still, it is the ultimate act of faith to merge someone else’s life blood with your own, with no knowledge of the donor’s personal habits, health history or background. As a patient, you simply trust that the products have been adequately screened and processed prior to being administered. And few patients are aware of just how lengthy and involved that screening process is.

“Over the last 25 years, pharmaceutical manufacturers have implemented extensive safety protocols in collecting and producing plasma products,” says Christopher Healey, vice president, government and public affairs, Grifols Inc. “No longer is plasma collected from high-risk populations — all donors are carefully screened, all donations are tested, and all plasma-derived products are virally inactivated.”

Healey goes on to explain that donor screening and testing are only the first steps in the complex manufacturing process for blood and plasma products. Although manufacturers use plasma only from donors who have been screened and test negative for the presence of common viral pathogens, each individual plasma product is subjected to multiple purification viral inactivation and removal processes. The type of viral inactivation and removal methods used depend on the plasma product, but common viral inactivation methods include:

• Solvent detergent treatment that consists of adding a soaplike chemical to the plasma that breaks down and destroys the fatty coating surrounding lipid-enveloped viruses. By destroying this fatty coating, the viruses are also destroyed.
• Heat treatment that involves heating each product vial to 80 degrees Centigrade for 72 hours. The temperature is carefully controlled to maintain it at a level that is effective against pathogens but not damaging to the therapeutic proteins.
• Nanofiltration that allows the wanted therapeutic proteins to pass through a specially designed membrane with a reduced pore size, while other particles or pathogens are trapped and discarded.

These are validated procedures that have proven to be effective at eliminating a wide array of potential contaminants such as bacteria and viruses, including hepatitis, HIV and many others. It’s notable that there have been no cases of HIV or hepatitis transmission via plasma medicines since the implementation of such validated viral inactivation methods in the early 1990s. An important distinction is that plasma products can be virally inactivated while blood cannot, and it relies wholly on donor screening and testing. Additionally, the Internal Quality Plasma Program (IQPP), which was adopted by U.S. plasma companies, exceeds the Food and Drug Administration’s (FDA) screening requirements. IQPP guidelines include the exclusive use of repeat donors, 60-day inventory holds and nucleic acid testing (NAT) for each donation. Procedures such as these have been incorporated industry-wide in an effort to maximize plasma product supply chain safety.

In its 2010 Corporate Responsibilities Report, global specialty biopharmaceutical company CSL Behring notes that for plasmaderived therapies, the most important safety issue is the potential for contamination with pathogens that originate from the plasma itself. The company adds that while the theoretical risk of pathogen transmission can never be zero, it consistently utilizes multiple and overlapping safety measures to reduce contamination risk to as low as is technically feasible.

“CSL Behring and its subsidiary, CSL Plasma, maintain an unwavering focus on safety that is driven by an integrated system of safety across four critical areas of operation: selection of plasma, manufacturing of plasma-derived products, quality control and monitoring,” says Albrecht Gröner, PhD, CSL Behring’s director of preclinical R&D–pathogen safety. “In the event that pathogens enter the manufacturing pools from quality controlled plasma, which is a very low probability, we have effective and robust pathogen inactivation and removal steps in place, including pasteurization and nanofiltration. These processes ensure a final product with a strong margin of safety.”

The Complex Relationship Between Patients and Donors

Blood donation and plasma donation meet very different and essential needs, and both are vital to the healthcare system. Blood and plasma donors come from all walks of life and donate for many reasons.All are paid for their services, but not all donors are motivated by monetary gain.

Coni Dutka, a retired educator and longtime blood donor, recently began donating plasma after learning there was a great need for the colorless watery fluid that is the key ingredient for many products crucial to treating the chronically ill. Patients suffering from a host of life-threatening conditions, including hemophilia, shock or trauma, immune deficiencies and other blood disorders, benefit from plasma.

After undergoing the intensive plasma donor screening process, Dutka, 62, became curious and began researching what happened to her plasma once the donation was completed. What she learned was eye-opening. “I had the opportunity to visit a well-known fractionation plant and watch the detailed process up close,” says Dutka. “Observing how many safety steps were involved was very impressive. I also had the chance to meet some of the patients who benefit from my donations. That’s when I realized that donating plasma is similar to donating an organ because something from my body is going into someone else’s body and giving them life.”

Kris McFalls, the mother of two children who have depended on plasma-derived intravenous immune globulin (IVIG) for the past 20 years, says that the goodness and generosity of plasma donors and the vigilance of blood product manufacturers is something she never takes for granted. “Safety is always a concern for us. No amount of contamination is acceptable when lives are at risk,” says McFalls. “I have seen the manufacturing process with my own eyes. I know each and every employee takes their job very seriously. Nothing is left to chance, and higher-than-required standards are used. I feel quite confident my kids’ safety is taken into account with each and every step of the donation and manufacturing process.”

In 2009, McFalls toured the Talecris Biotherapeutics manufacturing plant in Clayton, N.C. The company hosts its “Up Close and Personal Patient Open House” event annually, and patients are invited to observe various aspects of the complex manufacturing process. Talecris, like other plasma and blood product manufacturers, is held to universally stringent FDA guidelines for sterility and safety — standards that afford patients and caregivers of those with chronic illness muchneeded peace of mind. “Taking that tour gave me comfort because I saw firsthand the care and pride put into manufacturing life-saving medications like immune globulin,” McFalls says.

The FDA’s Role in Blood Product Safety

Over a period of years, the FDA has progressively strengthened the overlapping safeguards that protect patients from unsuitable blood and blood products. For one thing, blood donors are now asked specific and very direct questions about risk factors that could indicate possible infection with a transmissible disease. This “upfront” screening eliminates approximately 90 percent of unsuitable donors, and is a marked departure from screening processes in the ’80s, when it was considered inappropriate to ask about a donor’s sexual preference or drug habits. In addition, the FDA requires blood centers to maintain lists of unsuitable donors to prevent the use of collections from them. Last, all blood donations are routinely tested for seven different infectious agents.⁶

In addition to more stringent screening guidelines, the FDA has significantly increased its oversight of the blood industry as a whole. FDA inspects all blood facilities at least every two years, and “problem” facilities are inspected more often. And, blood establishments are now held to quality standards comparable to those expected of pharmaceutical manufacturers.

With so many safeguards in place, is it safe to say the nation’s blood supply is 100 percent infection-free? Unfortunately, as biological products, blood and blood products are likely always to carry an inherent risk of infectious agents, which means zero risk may be unattainable. Still, statistics show that in 1995, the risk in the U.S. of HIV-1 transmission per blood unit transfused was estimated to be between one in 450,000 and one in 660,000. By 2003, this estimated risk had decreased to between one in 1.4 million and one in 1.8 million units, with new and improved safety and screening methods continually on the horizon.

While a blood supply with zero risk of transmitting infectious disease may not be possible, the blood supply today is safer than it has ever been. The role of regulatory agencies, blood banks and blood product manufacturers remains to drive that risk to the lowest levels achievable without unduly decreasing the availability of this life-saving and life-giving resource.