for the




86th Meeting March 9-10, 2006



The Committee listened to the following briefings and updates. Dr. Jerry Holmberg presented an overview of the January 2006 DHHS Advisory Committee on Blood Safety and Availability. Dr. Pradip Akolkar, FDA, followed with a presentation on current considerations for blood donor screening for West Nile Virus. Ms. Linda Weir provided a briefing on the classification of transfusion recipient ID Systems, followed by Dr. Andrew Daytons summary of the March 8, 2006 workshop on behavior-based donor deferrals in the NAT era. Dr. Steven Kleinman, representing AABB, ABC and ARC, was allowed to make a statement to the committee regarding behavior based donor deferrals.


Topic I


Rapid Tests for Detection of Bacterial Contamination of Platelets


Dr. Jaroslav Vostal introduced the topic and outlined the current evaluation scheme for evaluating bacterial detection devices based on their intended use. The scheme is a three tired approached based on whether the devices will be used for quality control, adjunct to a release test or stand alone release test. His talk was followed by the Open Public Hearing in which 5 manufacturers (Subcinc, Verax, BCR Biotech, Genprime, and Immunetics) gave a short presentation on the systems that they have for rapid detection of bacterial contamination in platelets. Drs. Yomtovian and Jacobs from University Hospitals in Cleveland presented data that they have collected on bacterial contamination and related adverse events following platelet transfusion. Additionally, Dr. Steven Kleinman representing AABB and Celso Bianco representing Americas Blood Centers made a statement regarding this issue. All stated that blood centers are doing 100% quality control screening on platelets when collected. While there is currently no release testing being done on platelets prior to release to patients, many felt that such testing would be problematic and complicated.


The Committee then discussed and voted on the following questions:


  1. Is the proposed 3 tiered regulatory scheme for clearance of rapid bacterial detection tests acceptable? The tiers, with increasing data requirements, include clearance for a Quality Control indication, Adjunct release test indication, and a Release test indication.


The Committee voted on question 1: 9 yes votes, 6 no votes and 0 abstained.

There were many who felt that this scheme was too complicated.



  1. What would be the minimum sensitivity in CFU/mL for detection of a contaminated platelet unit?


The Committee results for question 2: 10 for 10e4 CFU/mL, 1 for 10e5 CFU/mL, 2 for 10e4 10e5 CFU/mL.


  1. Is the kinetic comparison (timed sampling spiking study) an appropriate design of an equivalency demonstration between culture-based and rapid test devices?


There was unanimous agreement that the kinetic comparison is an appropriate design of an equivalency demonstration between culture-based and rapid test devices.



Topic II


Public Comments on Guidance for Industry and FDA Review Staff:

Collection of Platelets by Automated Methods


Dr. Alan Williams introduced the topic and reviewed the public comments received on the Guidance for Industry and FDA Review Staff: Collection of Platelets by Automated Methods. Dr. Jaro Vostal presented the FDAs reasoning for proposing changes to donor deferral due to intake of non-steroidal anti-inflammatory drugs (NSAIDs.) Following their presentations, Dr. Louis Katz, Exceutive Vice President of Medical Affairs at the Mississippi Valley Regional Blood Center presented data from several blood establishments regarding the lack of long term decreases in platelet counts or other observed adverse events and among platelet donors who donate regularly at the volumes permitted for cleared apheresis devices. He also discussed the potential negative impact of the recommendation in the draft guidance on platelet availability in collection facilities.


Questions for the Committee:


1. Do BPAC members agree that the information presented on the duration of effect of platelet function inhibition and half-life of the drug, support limiting collection to 5 days from the last dose of aspirin (ASA) or aspirin containing drugs, and 3 days from the last dose of non-steroidal anti-inflammatory drugs (NSAIDS)?


At the time of the meeting, the question was split into two parts as follows:


1a). Does the BPAC agree with the revised proposed donor deferral criteria for Aspirin (3 days); Motrin group (no deferral); all other COX-1 reversible inhibitors (1 day) except Feldene (3 days) and COX-2 inhibitors (no deferral)?


The Committee voted on question 1: 9 no, 8 yes.


The BPAC discussed the potential effect of these medications on platelets, and the general lack of data concerning adverse events that would warrant additional deferral or extended deferrals for these medications Several Committee members also expressed concern about the complexity of the donor questions and the likelihood that inexperienced donors would have the ability to answer accurately.


1b. Does the Committee recommend to FDA a deferral of five days for Plavix and 10 days for Ticlid?

No formal vote was taken for 1b., but the sense of the committee was that the indications for which these medications were prescribed would normally preclude blood donation, and that eligible donors should re-contact the blood center regarding donation once treatment was complete. Committee members also felt that the same deferral period (i.e. ten days) for these two drugs would be appropriate to help simplify the donor screening questionnaire.



2. Do BPAC members agree that bacterial testing of 500 consecutive collections is appropriate for validation of the aseptic process? If not, what sample size and acceptance criterion does BPAC suggest?


The Committee voted on question 2: 4 yes, 12 no, and one abstention.


The BPAC generally supported the use of a statistical basis for bacterial testing validation, but expressed concerns about the details of the FDA proposal, particularly the inappropriate use of a two-sided confidence interval and encouraged FDA to reconsider the details of the proposal. .. Several Committee members also questioned the need for validation in light of the AABB voluntary industry standard of 100% testing of platelet components for bacterial contamination. FDA clarified that not all blood establishments are necessarily accredited AABB members using bacterial culture for their quality control procedures...



3. Do the BPAC members agree that the proposed recommendations on donation frequency, interval between donations, and number of components collected per year are appropriate to protect the safety of the donor pending the availability of additional safety data on larger annual volumes of collection? If not, please comment on limits that would be more appropriate.


The proposed recommendations included:

a.       A predonation platelet count of 150,000 (either actual, a mean of pre-donation counts, or a facility mean)

b.      A minimum targeted platelet count of 100,000

c.       24 components per year

d.      A maximum double unit collection for new donors who lack a pre-donation platelet count

e.       A seven day deferral for collections that are larger than a single

f.       Solicitation of additional safety data, for instance related to loss of plasma proteins over time

g.      Elimination of recommendation for collection of a post-donation platelet count.


Due to an absence of adverse event observations, BPAC expressed concern about recommendations that would limit apheresis collections to 24 per year (vs 24 single, double, or triple components per year). This portion of the question (c.) was deleted based upon the sense of the Committee that FDA should continue to seek relevant data, but not propose changes to current practice without supporting evidence.


Additionally the other proposed criteria as safety mechanisms were discussed.


Following discussion of the remaining recommendations, the Committee voted 12 yes, 2 no and 1 abstention for the remaining portion of question 3...




Topic III


Proposed Studies to Support the Approval of Over the Counter Home-Use HIV Kits


Dr. Elliot Cowan introduced the topic and reviewed the proposed studies to support approval of over-the-counter home-use HIV test kits. Dr. Bernard Branson from the Centers for Disease Control and Prevention presented an overview of clinical experience with approved rapid HIV tests.


There was considerable discussion on who will utilize home use HIV test kits, and concern was expressed that particular groups of end-users will be left out of clinical trials if the sponsor is left to decide. Therefore, FDA should have a role in specifying the makeup of clinical trial participants. Taken into consideration should be low income, gender, minorities.


Questions for the Committee:


1.      Does the Committee concur with FDAs proposed criteria for test performance (analytical and clinical sensitivity and specificity) for home-use HIV test kits?


BPAC voted unanimously in favor, agreeing with FDAs proposed criteria for sensitivity and specificity: 95% as the lower bound of the two-sided 95% confidence interval, in contrast to 98% that is FDAs current criterion for rapid HIV tests.


2.      Does the Committee concur with FDAs proposal for the Phase II study?


BPAC voted unanimously in favor, agreeing with FDAs proposal for Phase II studies, the goal of which is to evaluate, in a controlled setting, (a) the effectiveness and safety of sample collection by untrained potential users; (b) the ability of untrained potential users to perform the test properly; (c) the ability of untrained potential users to read and interpret test results; (d) the performance of the test (sensitivity and specificity) in the hands of untrained potential users; and (e) reactions to test results by untrained potential users.


3.      For Phase III studies, which of the options presented do the committee recommend?


There was considerable discussion on the 3 options for Phase III studies (option 1: to include both determination of performance and validation of the ability of the informational materials to substitute for live counseling, option 2: to include only the latter; and option 3: to not be required at all). Discussion points included:

o       Give the manufacturer the option. If the Phase II studies are designed appropriately, then Phase III studies may not be necessary.

o       If the sponsor puts elements of Phase III into Phase II, then this would be closer to actual use. (Phase IIA and IIB)

o       Phase III more closely resembles real world use and is uniquely positioned to provide information that Phase II cannot.

o       The goals of Phase III studies could be met with post-market studies.

o       Ultimately, we are asking what would be learned in Phase III that cannot be learned in Phase II? What is the value of the additional information gained in a real field environment?

Voting on Phase III studies:

Option 1: 10 in favor

Option 2: 4 in favor

Option 3: 1 in favor


4.      Does the Committee concur with FDAs proposed content for informational materials provided with home-use HIV test kits and the steps that should be taken to validate the adequacy of those informational materials to communicate or provide pathways to adequately address issues including:


a. Accuracy of testing

b. Correct test interpretation

c. The importance of supplemental testing for confirmation of positive results

d. Management of psychological and social issues

e. Medical referral


There was unanimous agreement with FDAs proposal for content of informational materials, including the following recommendations:


o       Labeling must clearly communicate the need to read the informational materials prior to conducting the test.

o       The reading level of the informational materials should be easy to comprehend by potential users of the test.

o       The informational materials must clearly communicate the expected performance of the test kit based on the clinical studies, including the number of false positive and false negative results observed.

o       The informational materials must clearly communicate the limitations of window period testing.

o       The test manufacturer should be prepared to offer users advice and referral mechanisms to obtain proper medical follow-up of test results.

o       The informational materials must clearly communicate the actions to be taken in the event of a reactive test result.

o       Clear and convenient methods for follow-up testing and referral must be established and communicated in the informational materials.

o       Counseling must be accessible by means appropriate to potential desired users and be available at any time. This information must be clearly communicated in the informational materials.


5.      If the Committee does not concur with any of the proposals in Questions 1-4, what additional information/modification would be needed to support approval of a home-use HIV test kit?


Given the answers to the previous questions, this question was not necessary.



Topic IV


Summary of the Office of Blood Research and Review Office Site Visit (July 22, 2005)


An overview of the OBRR Office Site Visit was given in open session and in closed session the report was discussed.


Topic V


Review of Research Program Site Visit of the Division of Hematology Laboratories, OBRR, CBER (Oct 6, 2005)


An overview of the Division of Hematology Laboratories Site Visit was given in open session and in closed session the report was discussed.