###### Issue Summary

Transmissible Spongiform Encephalopathies

Advisory Committee Meeting

February 8, 2005

Silver Spring, MD

Topic 3: Deferral of Blood and Plasma Donors for History of Transfusion
in European Countries

###### Issue:

In January 2002, FDA recommended deferral of blood and plasma donors who
received blood transfusions in the U.K. since 1980 as an additional
safeguard against potential transmission of vCJD by blood products. FDA
seeks the advice of the Committee whether this deferral now should be
expanded to include history of transfusion in other European countries.

###### Background

At the October 14, 2004 meeting of the TSE Advisory Committee, FDA asked
the Committee to consider whether any modifications of protective
measures for the US blood supply were indicated. These discussions were
prompted by the recent observation of two cases of vCJD in individuals
who received transfusions derived from asymptomatic blood donors who
later developed vCJD. One of these cases was heterozygous for met/val at
codon 129 and neurologically asymptomatic at the time of death, but
exhibited prion protein in the lymphoid tissues. This scenario
potentially reflects longer-incubation vCJD infection in met/val
heterozygous individuals who may have been exposed to the vCJD agent.
The committee did not recommend additional donor deferral actions at the
October, 2004 meeting. However, there was discussion in two areas: a)
the predictive value of the donor travel/residence eligibility
questions, and b) the possibility that deferral for transfusion in other
European countries outside of the UK may be worthy of additional
consideration.

French Health authorities recommended deferral of donors that had
previously been transfused in 1998. In December 2004 the Dutch Health
Ministry announced that individuals who had received any blood
transfusion since 1980 would no longer be eligible as blood donors. This
policy resulted in an estimated 8% loss of the Dutch donor base.

###### Discussion

Few data are available to assess the potential for secondary
transmission of vCJD in the US from a donor with prior parenteral
exposure to vCJD by transfusion or other means. FDA current donor
deferral recommendations are based on a dietary risk (and approximate
vCJD case ratio) for France that is 5% of the UK risk and, for the rest
of Europe, is 1.5 % of the UK risk. These risks are based upon observed
BSE incidence. At the October 2004 TSEAC meeting, FDA presented
estimates that additional blood donor loss from deferrals for
transfusion in a broader geographic area of BSE endemicity would be 1.4
per 10,000 for prior transfusion in France, and 3 per 10,000 for prior
transfusion elsewhere in non-UK Europe. Deferral for any history of
transfusion since 1980 among US donors would result in the approximate
loss of 5% of the US donated blood supply. Corresponding loss estimates
for Source Plasma donors are not available, but (due to age-specific
increases in prevalence) are likely to be lower based upon the younger
mean age of the donor base.

The negative predictive value of geographically based donor eligibility
criteria is also difficult to estimate due to the inherent difficulties
in validation. Donor survey research conducted in the early to mid
1990's indicated that false negative donor responses to medical and
behavioral questions as assessed by a subsequent anonymous survey tool,
may occur in 2-3% of donations. Post-donation information related to
geographic exposures continues to comprise a high proportion of
biological product deviation reports submitted to FDA, indicating that
improvements in current donor eligibility determinations are still
needed. A major effort to improve and standardize the donor interview
process has been underway by the blood community in collaboration with
FDA and other Agencies. This effort includes the cognitive evaluation of
all donor questions in an effort to maximize understanding by the
broadest segment of donors.

Relevant to any further consideration of a deferral for donors
transfused in Europe is the observation that for many years a large
proportion of the New York metropolitan area red blood cell supply was
imported from US-licensed collection facilities in Germany, Switzerland
and the Netherlands. The blood from these facilities (Euroblood) was
provided for more than thirty years beginning in the early 1970's and
constituted the only licensed blood components imported into the US. The
following are some key observations about Euroblood:

-   The Euroblood program began in the early 1970's to address chronic
    RBC shortages in NY area (due the presence of numerous tertiary care
    facilities)

-   During its peak period, the Euroblood program represented one third
    of the New York area RBC supply and approximately 2.0 % of the total
    US RBC supply

-   200 New York Metropolitan-area hospitals were supplied with
    Euroblood over the 30 year period of importation providing
    transfusions to an estimated \>4 million recipients

-   In the absence of a massive lookback effort, Euroblood recipients
    currently living in the US are largely untraceable.

-   The Euroblood program ended in the months prior to 10/31/02, when
    the FDA recommendations resulted in deferral of whole blood donors
    for \> 5 years travel/residence in Europe.

While a policy to defer any individuals transfused in Europe would
result in marginal donor loss, such a policy would not address the US
recipients of Euroblood since 1980.

Recent epidemiologic observations about vCJD in France and elsewhere,
including current estimates of the potential for
transfusion-transmission will be presented during the session to assist
the Committee's deliberations.

[Questions for the Committee]{.underline}

1\. Based upon the available scientific information, does the committee
recommend deferral of blood donors transfused since 1980

a.  In France?

b.  In other countries of Europe?

2\. Based upon the available scientific information, does the committee
recommend deferral of Source Plasma donors transfused since 1980

c.  In France?

d.  In other countries of Europe?