Rapid Tests for
Detection of Bacterial Contamination of Platelets
Blood Products Advisory
Committee, March 9, 2006
Steven Kleinman, MD
Senior
Medical Advisor, AABB and
AABB Interorganizational
Task Force on Bacterial Contamination of Platelets
AABB strongly supports
development of rapid, sensitive and specific non-culture assays to detect
bacterial contamination of platelets, using an approval scheme that does not
unduly delay their licensure. Our most
urgent need is for technology(ies) to replace the insensitive, non-specific and
unregulated surrogate methods such as pH and glucose dipsticks, being used to
test platelets from whole blood. Second, we must agree on an estimate of the
sensitivity required to prevent or substantially reduce residual episodes of
clinical sepsis and infection that continue to occur even after implementation
of the AABB Standard requiring methods to detect and prevent bacterial
contamination.
There is no agreed
upon sensitivity standard for rapid tests performed shortly before platelets
are issued for transfusion, but there is informed opinion that, when used as a
pretransfusion test in the hospital blood bank for the goal of preventing
clinical sepsis, the benchmark should be in the range of 103–104
CFU/mL.
There is broad understanding
that rapid tests now in development will not have analytic sensitivity
equivalent to culture-based tests if the new assays are used early during
storage before time for bacterial proliferation sufficient for detection. When used later, especially in the
transfusion service at the time of distribution for transfusion, rapid tests
should be able to identify units in the target range and prevent adverse
clinical events.
The FDA must find a
regulatory scheme that is not unreasonably constrained by consideration of the
current culture-based tests as “predicate devices.” It is known that some bacterially
contaminated platelet units may be culture negative (i.e. false negative)
using approved quality control devices; some estimates suggest
that such negative culture results may occur in up to 25% of
bacterially contaminated units. The
initial utility of rapid tests will be for use just prior to transfusion to
detect units falsely negative or untested by culture. Furthermore, as surrogate testing methods may
detect only a minority of contaminated units (perhaps as few as one-third: Transfusion 2005;45:1133-7.) licensure
of rapid tests for use immediately before transfusion will improve transfusion
safety in comparison to current insensitive and nonspecific approaches to
testing platelet pools derived from whole blood. Reasonable sensitivity and the expected
specificity of rapid
tests would, we suspect, represent a marked improvement for prevention of
clinical events.
A kinetic approach as outlined by FDA can be
reasonable if a developer seeks approval for a QC indication similar to the
current culture based systems, but emphatically not for an indication as an
adjunct to culture to be used near the time of issue for transfusion. The suggested approach seems likely to hamper
development of the latter approach, resulting, for example, in unneeded delay
in implementation of methods to test platelets from whole blood. We recommend that the FDA seek an alternate
route to labeling rapid tests for this specific indication. A possible approach can be to establish the
performance characteristics of a rapid test based on serial dilutions of a
spiked unit.
For the standard quality control indication,
demonstration in a parallel clinical study that the applicant test(s) can
detect contaminated or spiked units that are identified by currently licensed
systems at a given time point seems a reasonable criterion. For example, if a unit is spiked with 1 CFU/mL
at collection, stored for 24 hours, inoculated into the predicate and applicant
systems and detected after 24 hours in both systems, they might be considered
equivalent.
In summary, the most urgent uses for the kind of
assays under consideration are to replace current surrogate approaches widely
used for testing platelets derived from whole blood and known to be both
insensitive and nonspecific. Approval of
rapid tests offers the opportunity for pretransfusion testing of platelets from
whole blood to prevent a proportion of residual platelet associated sepsis. Accordingly the approval criteria should not
require equivalence of the new approaches to culture based testing, but rather
should be based on an agreed upon sensitivity that will accomplish the clinical
goal. Approval for a more standard
quality control indication should likewise demonstrate focus on the prevention
of clinical sepsis without necessarily insisting on a single approach.
AABB is an international association dedicated to advancing transfusion
and cellular therapies worldwide. Our members include 1800 hospital and community blood centers,
transfusion and transplantation services and 8000 individuals involved in
activities related to transfusion and transplantation medicine. For over 50 years, AABB has established
voluntary standards and inspected and accredited institutions. Our members are responsible for virtually all
of the blood collected and more than 80 percent of the blood transfused in this
country. AABB’s highest priority is to maintain and enhance the safety and
availability of the nation's blood supply.
The AABB Interorganizational Task Force on
Bacterial Contamination of Platelets is composed of experts representing both
transfusion services and donor collection facilities from AABB,