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STATEMENT OF

AMERICAN ASSOCIATION OF BLOOD BANKS

**AMERICAS BLOOD CENTERS**

**AMERICAN RED CROSS**

**BEFORE THE BLOOD PRODUCTS ADVISORY COMMITTEE**

**December 12, 2002**

# Nucleic Acid Testing of Blood Donors for Human Parvovirus B-19 Virus

**Presented by Kay R. Gregory, MS, MT(ASCP)SBB**

**Director, Regulatory Affairs, AABB**

Parvovirus B19 infection is widespread in the human population.
Transmission generally occurs by the respiratory route. By adulthood,
50% of the population shows antibody evidence of previous infection and
presumably retains immunity to reinfection. Parvovirus B19 infection is
usually either asymptomatic or results in a mild self-limited illness in
immunocompetent individuals. Parvovirus B19 infection can rarely result
in severe, clinically significant outcomes in three patient groups:
transient red cell aplasia with accompanying anemia may occur in
patients with chronic hemolytic anemias, pure red cell aplasia may occur
in immunocompromised patients, and hydrops fetalis with spontaneous
abortion may rarely occur in pregnant women.

Frequent transmission of Parvovirus B19 infection by transfusion of
Factor VIII concentrates prior to the widespread use of viral
inactivation technology has been well documented. Due to the relative
resistance of Parvovirus B19 to viral inactivation and to the high level
of viremia in acutely infected persons, such transmission continued,
though at lower levels, even after the introduction of virally
inactivated concentrates. Data from the transfusion experience with SD
plasma indicate that seroconversion in recipients occurred frequently
when high titer viremia (10^7.5^ to 10^8.5^ copies/ml) was present but
did not occur when viremia was present at \< 10^4^ copies/ml. These
observations have lead most manufacturers of plasma derivatives to
introduce nucleic acid amplification testing (NAT) for high titer
parvovirus B19 viremia performed on relatively large pools of donor
samples. To the best of our knowledge, comprehensive data on the
effectiveness of these procedures in decreasing transmission by factor
concentrates have not been published.

Despite the historically high transmission rates of parvovirus B19 to
recipients of pooled plasma products, very few adverse clinical outcomes
have been reported in patients with hemophilia; a 1999 review article
cites only three cases of erythema infectiosum and one case of
hypoplastic anemia. Similarly, cases of clinical disease associated with
Parvovirus B19 transmission by blood component transfusion in North
America and Europe are rare; we are aware of only 3 published cases. In
each case, the recipient developed anemia; one case was successfully
treated by IVIG, one case spontaneously resolved, and one case did not
report follow-up data. Parvovirus B19 does not appear to be transmitted
by albumin or IVIG.

Because blood centers supply recovered plasma for manufacture of plasma
derivatives, these collectors plan to begin parvovirus B19 minipool NAT
to ensure that plasma sent for fractionation does not contain high
titers of B19. Preliminary data from the American Red Cross using pools
of 512 and an assay that detects 10e^7^ copies/ml per donation shows
donor viremia rates of 1:12,800.

Blood centers intend to perform Parvovirus B19 NAT on minipools as an
in-process manufacturing control, according to previously defined FDA
policies. This can be termed phase 1 of parvovirus testing. Under this
mechanism, Parvovirus B19 testing would not be regarded as donor
screening and there will be no need to resolve the positive minipool to
the level of the individual donation. This would accomplish the aim of
interdicting Parvovirus B19 viremic plasma units prior to pooling for
manufacture.

Given the important and compelling competing safety priorities of
implementing West Nile Virus donor screening and performing bacterial
detection in platelets for the whole blood sector in the next 6 to 9
months, the additional capacity and work that would be required to
perform Parvovirus B19 NAT as a donor screening test cannot be absorbed.
For example, performing Parvovirus B19 as a donor screening assay would
require the addition of another on-line assay requiring completion prior
to all product release, the pulling of samples and further testing to
resolve positive pools, the need for a confirmatory assay, and the
alteration of 510k cleared computer systems to accommodate Parvovirus
B19 results as a release criteria. Furthermore, current FDA policy would
require that donor screening be performed under an IND or IDE which
would be an additional burden for test kit manufacturers who are turning
their efforts to WNV screening test development.

We believe this practical solution of performing Parvovirus B19 testing
as an in process control at this time is supported by the available
scientific and medical data on the clinical significance of Parvovirus
B19 infection.

-   Parvovirus B19 infection in a blood donor is of no consequence to
    the donor\'s health and secondary transmission of the infectious
    agent does not occur by preventable parenteral routes.
    Realistically, donor notification for any agent cannot be
    accomplished until 7 to 14 days after donation. By this time, a
    donor with a previously high viremia would likely have resolved the
    viremia and/or developed antibody and would be very unlikely to
    still be infectious. Furthermore, notification of contacts of the
    donor to alert them to the possibility of recent exposure would have
    no value in preventing virus transmission or in helping either the
    donor or the contacts to receive treatment or undergo diagnostic
    laboratory testing. The most likely effect of donor notification
    would be a high degree of donor confusion and/or anxiety as has been
    demonstrated with other agents.

-   Identifying and deferring the individual donor with high viremia
    would not significantly enhance safety for recipients of blood
    components. Since such infections spontaneously resolve rapidly,
    donors would be safe at the time they became eligible for their next
    whole blood donation.

-   As a consequence of not identifying the individual donor, it will
    not be possible to prevent the transfusion of the red cells and
    platelet units from that positive donation. Although it might be
    desirable to do so, the data indicate that the enhancement of safety
    that would be provided by such component removal is likely to be
    minimal. Continued transfusion of such components, as occurs
    currently, very rarely results in reported clinical disease.

At the present time, blood centers must prioritize their efforts and
implement procedures that deal with the highest level risks to
transfusion recipients. At a later date, it is possible that Parvovirus
B19 testing can move into a phase 2 in which positive results are linked
to an individual donation and all components of that donation are
removed from inventory. The policy issues associated with such phase 2
testing (in which Parvovirus B19 is performed as a screening test) and
the logistics of implementing such a policy will need further
discussion.

In conclusion, the issue of prioritization of blood safety initiatives
and the capacity of the system to absorb multiple changes simultaneously
is a reality that must be recognized.

America's Blood Centers (ABC) is an international network of
community-based blood centers that collects nearly half of the U.S.
blood supply and about 25% of the Canadian blood supply. The largest
provider of blood components and services, America's Blood Centers\'
members are located in 45 states, serving more than 125 million people
at 450 blood donation sites. For 40 years, America's Blood Centers\'
members have been committed to serving the needs of their local
communities by saving lives through volunteer blood donation.

The American Red Cross (ARC) is an independent, non-profit organization
dedicated to saving lives, easing suffering and restoring hope at home
and around the world. The Red Cross, through its 36 Blood Services
regions, supplies approximately half of the nation's blood for
transfusion needs. Its primary focus is providing high quality blood and
blood products to the patients who need them, but ARC is also a large
supplier of human allograft tissue including heart valves, skin, bone
and associated connective tissues. Additionally, the Red Cross is
engaged in research and other efforts to support donation and processing
of such human derived products as umbilical cord blood and bone marrow
for use in treatment of malignancies and other serious diseases.

The American Association of Blood Banks (AABB) is the professional
society for over 8,000 individuals involved in blood banking and
transfusion medicine and represents approximately 2,000 institutional
members, including blood collection centers, hospital-based blood banks,
and transfusion services as they collect, process, distribute, and
transfuse blood and blood components and hematopoietic stem cells. Our
members are responsible for virtually all of the blood collected and
more than 80 percent of the blood transfused in this country. For over
50 years, the AABB\'s highest priority has been to maintain and enhance
the safety and availability of the nation\'s blood supply.