September 18 & 19, 2006

Gaithersburg, MD


This quick summary is provided as an unofficial overview of the September 18 & 19, 2006 TSEAC meeting until the official transcripts become available.


Topic II

Potential screening assays to detect blood and plasma donors infected with agents of transmissible spongiform encephalopathies (TSE agents or prions)

Possible FDA review criteria and related issues

FDA sought the advice of the TSEAC regarding potential approaches and issues to consider when validating candidate screening tests for vCJD and other TSE infections in donors of blood, plasma and human cells, tissues and cellular and tissue-based products.

Dr. Pedro Piccardo introduced the topic and discussed donor TSE screening test issues of concern to FDA including test sensitivity, specificity, and confirmatory testing. Next, Dr. Marc Turner, University of Edinburgh, presented an algorithm for eventual approval of human TSE blood donor screening tests in Europe. Dr. Philip Minor, NIBSC, presented a review of TSE reference materials available through the WHO and UK authorities to assist in development and validation of TSE screening tests. The Committee then received research updates on the current status of test development from the following speakers:

         Alex Raeber, Ph.D., Prionics AG

         Claudio Soto, Ph.D., University of Texas

         Stuart Wilson, Ph.D., Microsens Biotechnologies

         Peter van Driessche, BioMerieux

         Kent Lohman, Ph.D., Adlyfe

         David Peretz, MSc., DSc., Chiron

         Jiri Safar, M.D., University of California San Francisco


During the Open Public Hearing session, Allene Carr-Greer of the American Association of Blood Banks encouraged FDA to use tools available through the Critical Path Initiative to consider several issues, e.g., (i) prognostic significance of repeatedly reactive TSE screening test results in a low risk population, (ii) information provided to individuals with a repeatedly reactive screening test results, and (iii) the need for a confirmatory test.

Questions for the Committee

1)      Please comment on pre-clinical analytical studies needed to evaluate candidate donor screening tests for vCJD and other TSEs.

2)      Please comment on clinical studies needed to evaluate candidate donor screening tests for vCJD and other TSEs.

3)      Please discuss the relative merits of technical options that might be feasible to confirm screening test results for vCJD and other TSEs, e.g., bioassays, alternate immunoassays, prion protein amplification, etc.

Committee members offered individual comments regarding the above three questions. No votes were taken or consensus attempted. Some of the more important comments were the following:

Caution must be used when using data from tests with animal samples to predict infectivity of various tissues and body fluids from humans with TSEs. However, due to the shortage of samples of infected human blood, early development of tests should begin using animal models. A recommendation was made that animal models used should include mouse-adapted vCJD or BSE models.

To evaluate candidate TSE tests, developers must establish both analytical sensitivity and clinical diagnostic sensitivity. In order to do that, Committee Members encouraged the identification, and follow-up of high-risk populations, such as individuals receiving blood transfusion from donors who later developed vCJD and to obtain adequate blood samples from such blood recipients when possible.

Due to the shortage of suitable blood samples from living subjects, the Committee discussed a suggestion to use cadaveric blood from autopsies of persons dying with vCJD. However, members suggested caution in using such samples, due to the multiple differences between blood samples collected ante mortem and post mortem.

The Committee agreed that supplementary test should be developed to confirm results of screening tests, because large numbers of false-positive results are expected when screening a low-risk population and would probably be unacceptable in the setting of blood programs. The Committee noted that, although bioassay (transmission of disease to animals) remains the “gold standard” to assess the presence of infectivity in biological materials, for practical reasons, bioassays will probably be used mainly to compare the performance of various tests. In addition, the Committee indicated that characterization of TSE reference materials should include estimates of infectivity by bioassays.