Dennis Williams, MD Kentucky Blood Center University of Kentucky Dept. Path and Lab Med

Transcription

1 Dennis Williams, MD Kentucky Blood Center University of Kentucky Dept. Path and Lab Med

2 None Disclosures

3 Objectives 1) Describe the FDA Draft Guidance Background and Requirements 2) Review the responsibilities and challenges posed by the options given 3) Outline possible models to comply 4) Review supporting data for potential changes to 2018 draft

4 Background Why? March 2016 replaced draft guidance Dec 2014 Goal Improve safety of platelets Bacterial contamination risk sepsis Multiple steps introduced since 2004 to decrease risk Skin cleansing Diversion pouch Bacterial screening Decreased risk of sepsis by 2/3 Risk of septic fatalities remains Most septic reactions and all fatalities day 4 and 5 However, most platelet transfusions are on day 4 and 5

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6 Background New rules for 5 day platelets Extension to 7 days Pathogen Reduction vs Bacterial detection Primary Testing Secondary Testing Secondary testing for 5 days platelets Secondary testing to extend 7 days Test must be labeled as safety measure

7 FDA recommendations to blood collection establishments AP Pathogen reduction Culture based testing method (primary testing) No sooner than 24hours after collection Use upper limit volume per manufacturer and at least aerobic bottle If use more volume then use more bottles Release using minimum time recommended by manufacture if no minimum time then make sure you have the ability to notify hospital quickly

8 FDA recommendations to blood collection establishments Pre-storage pooled platelets Pathogen reduction when FDA approved Culture based testing method (primary testing) same as for AP except use freshest unit in the pool as your time cutoff Single units of WBD platelets Culture based use largest sample possible Rapid test when available can use Pathogen reduction when available can use

9 FDA recommendations to Transfusion Services 5 days Pathogen-reduced APs no further measures Culture Based Primary test - AP and pre-storage pooled platelets Rapid test on day of transfusion day 4 or 5 done within 24hrs Culture day 4 and release as follows As directed by instructions for use of the bacterial detection device if minimum is specified 12 hours if no minimum establishment must have measures in place to notify hospital if positive test If release directly after culture recommend using rapid test

10 FDA recommendations to Transfusion Services 5 days Post storage pooled platelets rapid test within 4 hrs of transfusion if single units not individually tested Single WBD units not pooled Culture largest practical volume Rapid test not cleared for use with single WBD units yet

11 FDA recommendations Extending to 7 days Recommendations to Transfusion Services perform secondary testing on APs previously cultured or PRT-treated (PRT not FDA approved yet for 7 days) or on single units of WBD platelets (rapid test not available) must register with FDA as a blood establishment Rapid test within 24hrs prior to transfusion safety measure Culture day 4 extend 48 hrs (through day 6) following negative results 24hrs after sampling (no culture based method listed as safety measure yet) Culture day 5 extend 48 hrs (through day 7).as above. Can send back to Blood Center to do it?

12 Verax PGD Detects lipoteichoic acid (LTA) and lipopolysaccharide (LPS) found on cell walls aerobic and anaerobic GP and GN bacteria, respectively Utilizes antibody binding agents immobilized on colloidal gold and nitrocellulose

13 Verax PGD Approved for testing: Apheresis platelets (PAS-C or 100% plasma) no 7 Day PAS products Pre-storage pools of up to 6 products (Acrodose ) Post storage pools of up to 6 whole blood derived platelets pooled within 4 hours of transfusion Single whole blood derived platelets within 4 hours of transfusion Moderate complexity test Requires Medical Technologist test.asp

14 Verax PGD Procedure overview Mix 500ul sample with reagent 1, mix, centrifuge 5 minutes, decant plasma, add reagent 2, add reagent 3, vortex place into sample well Incubate for 20 minutes Check every 10 minutes thereafter for up to 60 minutes for control color change Record results

15 Verax PGD What to do with a positive? Repeat test twice with new sample If both repeats negative interpret negative If at least repeat positive interpret as repeat reactive What to do with negative Interpret as negative Change out date to 24 hours from testing False negative rate: precise FN rate cannot be estimated Observed in Jacobs, :5212 = ~0.02% False positive rate: 1:194 = ~0.51% BacT Alert quoted in literature as up to 0.9% but not that high in practical experience (BCA Medical Director discussion and Hundhausen T, 2005)

16 Pathogen Reduction Technology Currently only one technology available INTERCEPT by Cerus Approved for apheresis platelets only 100% plasma by Trima and PAS by Amicus

17 Pathogen Reduction Technology

18 Pathogen Reduction Technology The Good Inactivates a broad spectrum of bacteria, viruses, spirochetes, parasites, and even T-cells Helps with emerging infections that we don t test for Eliminates requirement for Zika testing Not great against non-enveloped viruses like Parvo B19, Hepatitis A and Hepatitis E Eliminates window period transmissions Replaces irradiation No additional testing of platelets required on Days 4 and 5

19 Pathogen Reduction Technology Expensive The Bad Adds at least $100 to platelet product cost (more on cost analysis later) Currently the only technology in the US market no competition

20 Pathogen Reduction Technology The Bad Platelets are activiated Decreased response to agonists? More transfusions are required Decreased 1 hour CCI Decreased time to next transfusion More transfusion events BUT probably no increased risk of bleeding, all grades

21 Pathogen Reduction Technology The Bad Current technology isn t feasible for blood centers No triple collection sets currently approved One week of representative data 88 lost products from 583 collections Narrow band of acceptable products for processing Currently ~15% of our products would be eligible With significant changes a prominent fellow NBC member center could only get to 70%

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23 Only 3-5% of collections currently met configuration At best with optimizing collections to IBS guardbands Only 32% of inventory could be pathogen reduced Lose 12-15% of total collections

24 4 years experience ( ) in the British National Health Service Utilize 7-day platelet product expiration At hours inoculate 8 ml to aerobic and anaerobic bottles (16mL total) Product held for 6 hours before release to hospital Using BacT/ALERT system 1,239,029 platelet products 960,470 apheresis platelets 278,559 pooled platelet products

25 0.8/1,000,000 (95% CI ) septic transfusion reactions for 7 day products compare to 73/1,000,000 with verax 4 false negative results (0.0003%) 3 detected on visual inspection, 1 transfused with patient morbidity 0.19% false positive Compared to 0.51% for Verax PGD 90% reduction in clinically adverse transfusion transmissions DelageG et al. Transfusion 2016;56:58A Héma-Québec

26 Questions