WFH Statements on Product Safety - 2006

December 19, 2006

WFH statement on FDA vCJD Risk Assessment

WFH President Mark Skinner addressed the FDA Transmissible Spongiform Encephalopathies Advisory Committee on December 15, regarding the FDA Factor VIII TSE risk assessment. The following is a summary of his statement.

Patients have a right to be consulted and informed in timely communication which is open and transparent. The WFH appreciates the FDA including us in their process. Clear and comprehensible explanations are essential and it is appropriate to acknowledge areas of uncertainty, thus the WFH supports following a precautionary approach when scientific knowledge is incomplete. However, the WFH is also concerned that unintended health consequences such as patient stigmatization or denial of access to care can result from such exercises.

In the 2004 WFH Guidance on Assessing Product Risk, we wrote, "It is important to avoid the complacency which characterized previous blood borne epidemics in people with hemophilia, while retaining a sense of proportion to this particular issue, and maintain a constant watch on the balance between safety and supply... Structured risk-management processes require a strategy for continuous learning and communication."* The WFH feels that these words still apply. Lack of supply is a very serious safety issue and any actions which might affect supply must be carefully weighed.

Before the introduction of clotting factor preparations, the mean life expectancy of patients with hemophilia was less than 30 years, and patients mostly died of intracranial or other hemorrhages. In patients with severe hemophilia not infected with viruses, mortality is still 40 per cent higher when compared with the general population. This recent study** also found that 27 per cent of the deaths in the cohort of patients not infected with HCV or HIV were because of hemorrhage. Clearly, bleeding is the biggest risk for people with hemophilia today and it is important to keep these different risks in perspective.

The WFH sees the FDA risk assessment as building on global knowledge of vCJD. For example, U.K. health authorities estimated in 2004 that patients who had used U.K. plasma-derived concentrates during a particular time period had a 1 per cent additional risk beyond general population risk of 1:4,225 to 1.8:1,000,000. The FDA risk assessment of 2006 finds that the risk for users of U.S. plasma-derived concentrates is "extremely low but may not be zero" - between 1:105,000 and 1:9,400,000. This lower level of risk from U.S.-sourced plasma in contrast to U.K. plasma was expected by WFH and other experts. The WFH notes that there are a number of uncertainties in the risk assessment models and it is important to continue to follow developments closely as more is learned about issues such as prevalence of vCJD, clearance of prions, or other factors.

The FDA assessment adds to our understanding and provides reassurance for both clinicians and patients when making treatment product selection decisions. The WFH continues to view both recombinant and plasma-derived products as important treatment options for the global bleeding disorders community. The potential remains for adverse events including inhibitor development or unknown pathogen risk, thus continuous learning and communication are required. The WFH will continue to engage with FDA and other stakeholders to remain vigilant concerning the safety of treatment products.

*A. Farrugia – vCJD and Hemophilia – Further Guidance on Assessing the Risk of Plasma-Derived Products for Treating Hemophilia – WFH 2004

** PLUG, I., et. al., Mortality and causes of death in patients with hemophilia, 1992–2001: a prospective cohort study. Journal of Thrombosis and Haemostasis 4 (3), 510-516. doi: 10.1111/j.1538-7836.2006.01808.x

The FDA is expected to publish additional documents for provider and patient groups to use in communicating the risk assessment. We will provide any additional documentation when available.

December 4, 2006

Risk of vCJD transmission by factor concentrates "very low"

The U.S. Food and Drug Administration (FDA) has released preliminary documents on its risk assessment for transmission of variant Creutzfeldt-Jakob disease (vCJD) by plasma-derived products. Results from the FDA plasma-derived factor VIII risk assessment model suggest that the risk of vCJD infection from U.S. licensed plasma derived FVIII appears likely to be very low, but may not be zero.

The FDA documents note that donor deferral criteria in place since 1999 have reduced the risk of donation by exposed persons. As well, manufacturing processes for human plasma derived FVIII products likely reduce the quantity of vCJD agent, if present, but the level of reduction through manufacturing steps is not precisely known. There has been no known case of transmission of vCJD by plasma products including in the U.K. where the risk would be highest.

vCJD is a fatal neurodegenerative disease acquired through infection with the agent that causes bovine spongiform encephalopathy. vCJD has been transmitted by blood transfusion but never by a plasma-derived medicine. The risk assessment looks specifically at factor VIII products currently licensed in the U.S. These products are made with U.S. plasma and manufactured in the U.S. or Europe. Patients around the world with hemophilia A and von Willebrand disease may use these products.

On December 15, the FDA will seek advice from a panel of experts, including members of the hemophilia community, on how to communicate to the public about this risk. The World Federation of Hemophilia will provide more detailed information following the December 15 meeting and will continue to keep you informed on any safety issues related to hemophilia treatment products.

The draft documents relating to the FDA’s risk assessment for plasma derived FVIII products are available online.