QUICK SUMMARY
for the
BLOOD PRODUCTS ADVISORY COMMITTEE
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 Dayton’s 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
The Committee then discussed and voted on the following questions:
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.
The Committee results for question 2: 10 for 10e4 CFU/mL, 1 for 10e5 CFU/mL, 2 for 10e4 – 10e5 CFU/mL.
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 FDA’s 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
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 FDA’s proposed criteria for test performance (analytical and
clinical sensitivity and specificity) for home-use HIV test kits?
BPAC voted unanimously in favor, agreeing with FDA’s
proposed criteria for sensitivity and specificity: 95% as the lower bound of the two-sided 95%
confidence interval, in contrast to 98% that is FDA’s current criterion for
rapid HIV tests.
2.
Does the Committee
concur with FDA’s proposal for the Phase II study?
BPAC voted unanimously in favor, agreeing with FDA’s
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 FDA’s 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 FDA’s 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.