Verax Biomedical

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Verax Biomedical Platelet PGD Test
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Verax Biomedical Platelet PGD Test

• Designed for use with LR or non-LR RDPs,
  Pooled RDPs SDPs

• Results in approximately 30 minutes

• 2 to 3 minutes attended labor per test

• Analytical sensitivity 103 104 CFU/mL

• 510(k) lots produced, prepared to enter
  clinical trials

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Medical Advisory Board
James AuBuchon, M.D.
Dartmouth-Hitchcock Medical Center
Leslie Silberstein, M.D.
Harvard School of Medicine
Mark Brecher, M.D.
University of North Carolina
Roslyn Yomtovian, M.D.
Case Western Reserve University
Ira Shulman, M.D.
University of Southern California
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Patented PGD technology
Pan Genera Detection
Detects conserved antigens on bacteria

• LTA on all Gram-positive

• LPS on all Gram-negative

Expressed on surface of bacteria
gt 200,000 copies per cell
Therapeutic antibody targets
Antigen detection via immunoassay
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PGD Immunoassay Format two tests run
simultaneously
Gram positive Sandwich Immunoassay
Gram negative Sandwich Immunoassay
LPS capture antibodies
LTA capture antibodies
GN bacterial capture
GP bacterial capture
Labeling by LPS conjugate antibodies
Labeling by LTA conjugate antibodies
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Verax Biomedical Platelet PGD Test procedure
Centrifugation
Resuspension
Reading
A.
B.
C.
Transfer to well and Wait for results
Add 8 drops of Reagent
Add 8 drops of Reagent to 500uL Platelet
Sample - Solution Turns Green
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1
and Resuspend Pellet Solution Turns BLUE
Interpret results
Negative
GP
GN
Positive
C
C
Add 4 drops of Reagent Solution Turns yellow
GP
GN
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Invalid
Spin for 5 Minutes Decant
C
C




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Test Results and Interpretation
Unused test cartridge
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Test Results and Interpretation
Valid non-reactive result
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Test Results and Interpretation
Valid reactive result
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Test Results and Interpretation
Invalid result
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Current early sampling techniques risk false
negatives
Pre-Storage Testing
Sampling early in life limits
Clinical sensitivity
High Titer False Negatives
Not all units bloom within 24 hours
May be too few bacteria to sample
Results in False Negatives
Culture sample _at_ 24 hours
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Breakthrough cases False Negatives associated
with current testing
Reported by CDC at January 2005 DHHS Blood Safety
Availability Meeting

• FATALITY - Culture false negative

Premature newborn received two doses from an
apheresis platelet unit. Unit tested negative by
24 hour sample plate culture and normal pH (7.3).
Unit contaminated with Serratia marcescens.
Child died 27 hours later. Second culture on
original sample also negative.

• FATALITY - Culture false negative

79 year old coronary-artery bypass patient
transfused apheresis unit that tested
negative for bacteria by BacT Alert on a 24 hour
sample. Unit contaminated with Staphylococcus
lugdunensis. Patient died 27 hours later.
Original BacT culture still negative after 10
days.

• FATALITY - pH false negative

74 year old patient with leukemia receiving a
routine platelet transfusion.  Received a 5
unit irradiated platelet pool tested normal by pH
(gt6.4). Pool contaminated with Staph aureus.
Patient died after a 21 day hospital stay.
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Testing near time of transfusion offers a
potential benefit
Testing at Release
Testing close to transfusion
maximizes clinical sensitivity
Minimizes False Negatives Their Titer
Reduce false negatives
Simple pre-transfusion test
Avoid call-backs
Run our test at time of issue
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Considerations for the establishment of a
regulatory pathway for rapid tests for
bacterial contamination.
Kinetic studies for QC claim equivalence
This approach is the one most likely to
demonstrate equivalence for QC purposes

• Allows for the widely differing time of sampling
  for culture methods and
• rapid tests intended to be used near the time
  of release

• Allows for the differing analytical
  sensitivities of the two methods

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Considerations for the establishment of a
regulatory pathway for rapid tests for
bacterial contamination.
Analytical sensitivity targets
We must be careful in establishing a priori
analytical sensitivity targets now for tests
intended for use near the time of transfusion

• Time of testing is likely to be a more
  significant driver of clinical performance
• than analytical sensitivity

• The more important question is how many
  contaminated units
• do we avoid transfusing? best answered with
  populations studies

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Calculated Impact of Analytical Sensitivity
Testing Close to Transfusion
Assuming 12,000 Underlying Incidence Rate
Testing Within 4 Hours of Transfusion
Residual Risk of Testing With a Rapid Test With
a Sensitivity of



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Calculated Impact of Analytical Sensitivity
Testing Close to Transfusion
Approximates 110,000 FDA Hurdle for Culture
Release Indication
Typical Platelet PGD Analytical Sensitivity
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Considerations for the establishment of a
regulatory pathway for rapid tests for
bacterial contamination.
Three tiers of data required for a release test
indication
Given the need for tests with release
indications, we are concerned that FDAs
proposal may not be the least burdensome route to
a release test

• the requirement for a QC equivalence claim, plus

• a 450,000 unit post market surveillance data
  set, plus

• a post market study of unknown size testing
  culture positives, plus

• an additional 100,000 unit post market study
  comparing with culture _at_ outdate
• (how is this possible when units have been
  transfused?)

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Considerations for the establishment of a
regulatory pathway for rapid tests for
bacterial contamination.
Three tiers of data required for a release test
indication
For example

• the 3 post market data sets would appear to
  gather overlapping data
• some data (culture confirmation at outdate for
  rapid test-negatives) could not be
  obtained as the platelets would have been
  transfused

• this pathway would likely delay a release
  indication by 3 to 4 years

• this pathway would take longer to answer the
  question of the actual clinical
• sensitivity of the method than simply
  performing a classic virus screening trial

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Considerations for the establishment of a
regulatory pathway for rapid tests for
bacterial contamination.
Three tiers of data required for a release test
indication
We recommend that FDA consider a streamlined,
two-step regulatory strategy for a release claim
- Step 1 510(k) for Quality Control

• Step 2 Screening for release
  (well-controlled, structured trial comparing
• to culture at time of transfusion on 50,000 to
  100,000 units)

• Supplemented by ongoing post market
  surveillance of observed
• incidence data from end-users