II for more information on testing procedures.) Risk of Infectious Units Entering Plasma Pools Is Somewhat Higher for Paid Plasma Donors Than for Volunteer Donors

We calculated the risk of incorporating an infectious unit of plasma into a plasma pool for HIV, HBV, and HCV for both volunteer and paid plasma donors. However, a number of safety initiatives have been instituted by paid plasma centers that greatly reduce the likelihood of infectious units being pooled for manufacturing. We also compared the residual risk of a potentially infectious plasma donation by a volunteer versus paid plasma donor actually entering a plasma pool by examining the effect of the length of the window period as well as the use of only “qualified donors” and the 60-day inventory hold program instituted by the paid plasma industry. Overall Comparison of Risks of Pooling Infectious Units

When comparing the overall residual risk of incorporating an infectious window period unit into a plasma pool for each of the three viruses examined in this study, the rates for HIV for volunteer and paid plasma donors are virtually identical (1 in 689,655 and 1 in 680,272, respectively); the rates for HCV are also similar (1 in 29,850 to 1 in 27,824). In response to these concerns, manufacturers have recently taken steps to reduce the size of the plasma pools they use for producing plasma derivatives. Modeling techniques indicate that this effort can have an impact on infrequent users by minimizing their exposure to a certain number of donors. However, for frequent users of plasma products, such as hemophilia patients, this limit has a negligible impact due to the large number of different pools to which they are exposed throughout their lifetime. As a policy, the American Red Cross has a 60,000-donor limit for plasma products that are further manufactured by Baxter Healthcare. For example, the recent transmission of HCV by a plasma derivative that had not undergone viral inactivation procedures showed that the risk of seroconversion of recipients of this product increased with the number of positive HCV lots infused and the quantity of HCV viral material infused. Risk of Infection Reduced Through Viral Inactivation and Removal Techniques

Since it is possible that certain infectious units could make it through the donor screening, deferral, and testing process, manufacturers have introduced additional steps in the fractionation process to inactivate or remove viruses and bacteria that may have made their way into plasma pools. These techniques virtually eliminate enveloped viruses, such as HIV, HBV, and HCV. It is based on the amount of virus that is killed or removed and, therefore, the extent to which these processes eliminate viruses through manufacturing. III for a more complete discussion of viral clearance.) Recent Noncompliance With Current Good Manufacturing Practices Could Jeopardize the Safety of Plasma Products

Although viral inactivation and removal techniques have been shown to be highly effective, they are only useful if the steps in the manufacturing process are carried out properly. Without strict adherence to these practices, the safety of plasma products could be compromised. If properly implemented, these actions by plasma manufacturers and FDA should help alleviate the problems related to adherence to current good manufacturing practices and quality assurance.
Why GAO Did This Study

Pursuant to a congressional request, GAO provided information on blood plasma safety, focusing on: (1) comparing the risk of incorporating an infectious unit of plasma into further manufacturing from volunteer versus paid plasma donors for human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV); (2) examining the impacts on frequent and infrequent plasma users when pooling large numbers of plasma donations into manufactured plasma products; (3) assessing the safety of end products from plasma after they have undergone further manufacturing and inactivation steps to kill or remove viruses; and (4) examining the recent regulatory compliance history of plasma manufacturers.

What GAO Found

GAO noted that: (1) viral clearance techniques have made the risks of receiving an infected plasma product extremely low when manufacturers follow all the procedures in place to ensure safety; (2) while paid plasma donors are over one and a half times more likely to donate potentially infectious units (1 in every 3,834 units), a number of recent initiatives by the source plasma industry greatly reduce the chances of these units being pooled for manufacturing (to 1 in every 10,959 units); (3) even with these initiatives in place, the risks are still somewhat higher from plasma units donated by paid donors than from volunteer donors; (4) limiting the number of donors whose plasma is pooled for production into plasma products helps to reduce the risks of viral transmission for those receiving these products; (5) presently, a 60,000-donor limit has been established for each individual plasma product; (6) this effort has an impact on infrequent users by minimizing their exposure to a certain number of donors for the few times they would be infused with a plasma product; (7) for frequent users of plasma products, this donor limit has a negligible impact because of the large number of infusions that they receive and, thus, the large number of pools that they would be exposed to in the course of their lifetime; (8) a more significant step in reducing risk of infection occurs in manufacturing--where all plasma products for intravenous use undergo viral removal, inactivation procedures, or both--which virtually eliminates enveloped viruses such as HIV, HBV, and HCV; (9) this is supported by epidemiological data on the transmission of viruses through plasma products since the introduction of adequate viral removal and inactivation procedures in the late 1980s as well as laboratory data that characterize the effectiveness of viral clearance through these procedures; (10) certain advances are only effective if the processes used to produce finished plasma products adhere to current good manufacturing practices; (11) this, however, has not been the case with all of the major manufacturing companies that produce plasma products; and (12) without strict adherence to current good manufacturing practices related to the efficacy of viral removal and inactivation procedures, the safety of these plasma products could be compromised.