1 Verax Biomedical Platelet PGD ® Test. 2 Verax Biomedical Platelet PGD ® Test Results in approximately 30 minutes Designed for use with LR or non-LR:

V BERAXIOMEDICAL I N C O R P O R A T E D

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Verax BiomedicalPlatelet PGD® Test


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Verax Biomedical Platelet PGD® Test

• Results in approximately 30 minutes

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

• 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

Ira Shulman, M.D.University of Southern California

Roslyn Yomtovian, M.D.Case Western Reserve University

Mark Brecher, M.D.University of North Carolina


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Patented PGD® technology

Detects conserved antigens on bacteria

Expressed on surface of bacteria

> 200,000 copies per cell

Therapeutic antibody targets

Antigen detection via immunoassay

• LPS on all Gram-negative

• LTA on all Gram-positive

Pan Genera Detection


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Labeling by LTA conjugateantibodies

Gram positiveSandwich Immunoassay

LTA captureantibodies

GP bacterial capture

Labeling by LPSconjugateantibodies

Gram negativeSandwich Immunoassay

LPS captureantibodies

GN bacterial capture

PGD Immunoassay Format – two tests run simultaneously


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1

Add 8 drops ofReagent

to 500uL Platelet Sample

-Solution Turns

Green

A.

Spin for 5 Minutes& Decant

Verax Biomedical Platelet PGD® Test procedure

Add 8 drops of Reagent

2

B. C.

Add 4 drops ofReagent

Solution Turns yellow

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GP GN

CC

GP GN

CC

GP GN

CC

Transfer to well and

Wait for results

Negative

Positive

Invalid

Interpret results

Centrifugation Resuspension Reading

- or -

and Resuspend PelletSolution Turns

BLUE


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Unused test cartridge

Test Results and Interpretation


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Valid non-reactive result



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Valid reactive result



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Invalid result



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May be too few bacteria to sample

Results in False Negatives

Clinical sensitivity

Sampling early in life limits

Pre-Storage Testing

Not all units “bloom” within 24 hours

Culture sample @ 24 hours

High TiterFalse

Negatives

Current early sampling techniques risk false negatives


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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

• FATALITY - Culture false negative

• FATALITY - pH false negative 74 year old patient with leukemia receiving a routine platelet transfusion. Received a 5 unitirradiated platelet pool tested normal by pH (>6.4). Pool contaminated with Staph aureus. Patient died after a 21 day hospital stay.

79 year old coronary-artery bypass patient transfused apheresis unit that tested negativefor 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.

Premature newborn received two doses from an apheresis platelet unit. Unit tested negativeby 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.


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Testing near time of transfusion offers a potential benefit

maximizes clinical sensitivity

Testing close to transfusion

Testing at Release

Simple pre-transfusion test

Avoid call-backs

Reduce false negatives

Run our test at time of issue

MinimizesFalse

Negatives& Their Titer


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This approach is the one most likely to demonstrate equivalence for QC purposes:

Considerations for the establishment of a regulatory pathway for rapid tests for bacterial contamination….

- Allows for the differing analytical sensitivities of the two methods

Kinetic studies for QC claim equivalence

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


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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 performancethan analytical sensitivity

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

Analytical sensitivity targets


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Residual Risk of Testing With a Rapid Test With a

Sensitivity of:

Species Causing98% + of

Contamination

Staph

Bacillus

Strep

E coli

Klebsiella

Salmonella

Pseudomonas

Serratia

Enterobacter

Enterococcus

Corynebacter

Proteus

60%

15%

10%

5%

3%

1%

1%

1%

1%

1%

1%

1%

+

Time RequiredTo GrowOne Log

8.3 Hours

3.6 Hours

5.5 Hours

5.3 Hours

8.5 Hours

7.9 Hours

12.8 Hours

4.4 Hours

12.3 Hours

12.8 Hours

12.8 Hours

12.8 Hours

+

DistributionOf Platelet

Transfusions

Day 2 12%

Day 3 29%

Day 4 26%

Day 5 33%

=

Assuming: 1:2,000 Underlying Incidence Rate & Testing Within 4 Hours of Transfusion

Calculated Impact of Analytical Sensitivity Testing Close to Transfusion

1 : 6,225

1 : 8,220

1 : 11,899

1 : 18,333

1 : 31,052

1 : 67,957

1 : 188,311

1 : 662,268

1 : 2,494,651

1 : 5,038

109 CFU/mL

108 CFU/mL

107 CFU/mL

106 CFU/mL

105 CFU/mL

104 CFU/mL

103 CFU/mL

102 CFU/mL

101 CFU/mL

1010 CFU/mL


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Calculated Impact of Analytical Sensitivity Testing Close to Transfusion

Approximates1:10,000

FDA Hurdle forCulture Release

Indication

Residual RiskOf Contamination

1 in 6,225

1 in 8,220

1 in 11,899 1 in 18,333

1 in 31,052

1 in 67,957

1 in 188,311 1 in 662,268

1 in 2,494,651

1 in 5,038

Average SensitivityLevel of Test

109 CFU/mL

108 CFU/mL

107 CFU/mL

106 CFU/mL

105 CFU/mL

104 CFU/mL

103 CFU/mL

102 CFU/mL

101 CFU/mL

1010 CFU/mL

TypicalPlatelet PGD®

Analytical Sensitivity


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Given the need for tests with release indications, we are concerned that FDA’s proposal may not be the least burdensome route to a release test:


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

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

Three tiers of data required fora release test indication

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

- the requirement for a QC equivalence claim, plus


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For example:


- 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

- 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


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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

Documents

1 Verax Biomedical Platelet PGD ® Test. 2 Verax Biomedical Platelet PGD ® Test Results in approximately 30 minutes Designed for use with LR or non-LR: