Food and Drug Administration
Center for Biologics Evaluation and Review
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE
March 14, 2013
5630 Fishers Lane, Rockville, MD
|Committee Members||FDA Participants|
|Dr. Linda Detwiler***|
Dr. Brian Appleby
Dr. Ermias Belay
Dr. Patrick Bosque
Dr. Dean Goeldner
Mr. David Huskie
Dr. Monique Turner
Dr. Joseph Parisi
Dr. Philip Schwartz
Dr. Douglas Lee**
Ms. Florence Kranitz*
|Dr. Steven Anderson|
Dr. Luisa Gregori
|Temporary Voting Members |
Dr. Leila Barraj
Dr. Corinne Lasmezas
Dr. Nick Hogan
Dr. Sivan Leviyang
Dr. Suzette Priola
Dr. Peter Bennett
Dr. Noel Gill
Dr. Robert Will
Ms. Sylvia Kreindel
|Designated Federal Official|
Bryan Emery, R.N., LCDR, USPHS
|Committee Management Specialist|
Rosanna L. Harvey
Joanne M. Lipking, M.S.
|* Consumer Representative |
** Industry Representative
*** Acting Chair
|# Did not attend|
These summary minutes for the March 14, 2013, Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee were approved on November 18, 2013.
I certify that I participated in the March 14 2013, Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee and that these minutes accurately reflect what transpired.
|Bryan Emery, R.N., LCDR|
Designated Federal Officer
|Linda Detwiler, D.V.M.|
The Acting Chair, Dr. Linda Detwiler, called the Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee to order at 8:00 a.m. EST on March 14, 2013.
Topic I: Preliminary Results from FDA’s Quantitative Risk Assessment of the vCJD Risks Potentially Associated with the Transfusion of Red Blood Cells in the U.S.
FDA sought the advice of the Committee on the inputs, model structure and interpretation of its draft risk assessment for the risk of variant Creutzfeldt-Jakb (vCJD) from red blood cells in the U.S. Dr. Steven Anderson, from CBER’s Office of Biostatistics and Epidemiology, provided and introduction to the topic and presented an overview of FDA’s risk assessment approaches for potential vCJD risk in red blood cells in the U.S. Next, Professor Robert Will, from the National Creutzfeldt-Jakob Disease Surveillance Unit and the University of Edinburgh, presented an update on the vCJD situation in the United Kingdom (U.K.) and worldwide. He also presented a review of the Transfusion Medicine Epidemiological Review (TMER) study in the U.K. Dr. Sylvia Kreindel then provided an update on the USDA’s BSE Surveillance Program. Professor Noel Gill from the U.K.’s Health Protection Agency presented the results of the second collaborative appendix study assessing the prevalence of abnormal prior protein in the UK. Dr. Peter Bennett, from the Public Health Directorate in the UK, then presented, by phone, the results of an updated risk assessment of vCJD and transfusion of blood components in the U.K.
Following the background presentations, Dr. Steve Anderson presented an introduction to the FDA vCJD risk assessment for red blood cells in the U.S. Then, Dr. Luisa Gregori from the Office of Blood Research and Review, CBER, reviewed the vCJD risk model assumptions and changes since previous risk assessments were presented to the Committee. In the afternoon, Dr. Steven Anderson provided a detailed presentation of the FDA risk assessment model for transfusion-transmitted vCJD risk in the U.S., including a description of the risk model structure, inputs, and results and interpretation of risk. Finally, Dr. Anderson provided a brief summary presentation and presented the questions for the Committee.
Dr. Robert Rohwer, Director of the Molecular Neurovirology Laboratory at the Baltimore Veteran’s Affairs Medical Center and the University of Maryland presented during the Open Public Hearing. He emphasized the importance not to discredit the appendix survey and called attention to the possibility that a significant number of clinical and subclinical cases of vCJD could easily be missed, especially with the low rate of autopsies in the US. He also noted that the ascertainment rate of the appendix tissue survey cannot be 100%; therefore, those estimates represent the minimum number of individuals with positive appendix and the real number most likely is higher. He further commented that the PMCA assay for prion detection has 10,000 times the sensitivity of bioassay and could be adapted to donor screening. He cautioned against any change in the deferral policy pending scientific advancements that are on the horizon.
An Open Public Hearing was announced and one public comment was offered.
The Committee addressed the following questions:
- Does the Committee agree that the FDA Risk Assessment Model is structured appropriately?
Please comment on any specific modifications to the model structure that FDA should consider.
The Committee agreed with the basic structure of the model and did not suggest specific modifications to the model structure.
- Does the Committee agree with the inputs and assumptions used in the FDA Risk Assessment Model?
Please comment on any specific inputs or assumptions that FDA should consider modifying or adding.
Overall, the Committee agreed with the inputs and assumptions used in the FDA risk assessment model provided that it is made clear that the model represents the risk of transfusion-transmitted clinical vCJD and not the risk of vCJD infection. Additional comments provided by the Committee are as follows:
The Committee provided the following comments:
- Several committee members commented that the assumptions in the model of U.K. vCJD prevalence based on epidemiological modeling and the most recent appendix survey estimate two different parameters and this affects how they should be used to make model projections.
- The members recommended that FDA use modified terminology to distinguish between the estimate of preclinical cases in the UK (based on epidemiological modeling) and the estimate of vCJD infections in the UK (derived from the second appendix survey).
- Regarding the second appendix survey, the Committee members commented on the absence of a control group as a major limitation of the study and asked about the feasibility of such a study being conducted in the U.S.
- The Committee discussed possible reasons for the discrepancy in the number of infections demonstrated by abnormal prion protein in the appendix studies and the actual number of cases seen in the U.K., including reduced susceptibility to vCJD in the population or a shift in transmission of a less virulent agent. However, Committee members cautioned that infectivity in the blood of those with abnormal prion protein in the appendix should not be ruled out.
- Several members commented on potential BSE risk from travel to Western Canada. The number of BSE cases in Canada was discussed in comparison to the BSE cases reported in the in U.S.
- One member commented that the model should reflect the significant percentage of blood components that are leukoreduced in the U.S. The member suggested that the addition of this input to the model could reduce risk estimates.
- Members commented on the estimated efficiency of donor screening, noting that it is the second most important driver of risk in the model. One member commented that the risk remaining after the implementation of current donor deferral policies (for example, the risk remaining from donors who spent less than 3 months cumulatively in the U.K.) may be overestimated in the model.
- Does the Committee agree that the validation exercises (predictions of primary vCJD case in the U.S. and TTvCJD cases in the U.K. and France) support FDA’s conclusion that outputs of the FDA risk model based upon the low prevalence estimate of vCJD in the U.K. is likely to be more reliable for predicting clinical transfusion-transmitted vCJD in the U.S. than those based on the appendix survey?
Vote: 10 yes, 2 no, 1 abstain
- Does the Committee agree with FDA's interpretation that the risk of clinical TTvCJD in the U.S., while highly uncertain, is likely to be very small, based upon the results of the Risk Assessment Model in the context of other available evidence?
Vote: 12 yes, 1 no
The Committee provided the following comments:
- The Committee recommended that FDA should not reject the high prevalence estimate of risk, but instead should use it to estimate the number of vCJD infections in the U.S. and U.S. donor population.
- One Committee member urged FDA to consider policy changes if the risk estimates based on the high UK vCJD prevalence estimates are believable.
Following is a summary of the discussion. Additional information and specific details may be obtained from the transcript of the meeting. The transcript may be viewed on the World Wide Web at the 2013 Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript page.
Proceedings were adjourned at approximately 4:00 pm on March 14, 2013
Please read the official transcript for a detailed account of the meeting.