1
DEPARTMENT OF HEALTH AND HUMAN
SERVICES
FOOD AND DRUG
ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION
AND RESEARCH
BLOOD PRODUCTS ADVISORY COMMITTEE
80th Meeting
This
transcript has not been edited or corrected, but appears as received from the
commercial transcribing service:
Accordingly the Food and Drug Administration makes no representation as
to its accuracy.
Thursday, July 22,
2004
8:00 a.m.
Holiday Inn
Gaithersburg
Two Montgomery Village
Avenue
Gaithersburg,
Maryland
2
PARTICIPANTS
James R. Allen, M.D., MPH, Acting Chair
Linda A. Smallwood, Ph.D., Executive
Secretary
MEMBERS
Kenneth Davis, Jr., M.D.
Donna M. DiMichele, M.D.
Samuel H. Doppelt, M.D.
Jonathan C. Goldsmith, M.D.
Harvey G. Klein, M.D.
Suman Laal, Ph.D.
ACTING CONSUMER REPRESENTATIVE
Katherine E. Knowles
NON-VOTING INDUSTRY REPRESENTATIVE
Michael D. Strong, Ph.D.
TEMPORARY VOTING MEMBERS
Liana Harvath, Ph.D.
Matthew J. Kuehnert, M.D.
Susan F. Leitman, M.D.
Keith C. Quirolo, M.D.
George B. Schreiber, Sc.D.
Donna S. Whittaker, Ph.D.
3
C O N T E N T S
PAGE
Welcome, Statement of Conflict of
Interest,
Announcements
Linda Smallwood, Ph.D. 5
James R. Allen, M.D. 11
Committee Updates
FDA Current Thinking on TRALI:
Leslie Holness, M.D. 13
Donor Blood Pressure
Determination:
Alan Williams, Ph.D. 23
Open Public Hearing
TRALI:
Kay Gregory, AABB, ABC 32
Michael Fitzpatrick, Ph.D.,
ABC 40
Donor Blood Pressure Determination:
Kay Gregory, AABB, ABC 50
I. Dating of Irradiated Red
blood Cells
Introduction and Background:
Ping He, M.D. 60
Presentation:
Gary Moroff, Ph.D. 80
Presentation:
Larry Dumont 114
Presentation:
Dean Elfath, M.D. 130
Presentation:
Jessica Kim, Ph.D. 137
Open Public Hearing
Allene Carr-Greer, AABB 159
Michael Fitzpatrick,
Ph.D. 162
Richard Davey, M.D.,
New York Blood Centers 174
4
C O N T E N T S
(Continued)
PAGE
FDA Current Thinking and Questions for
the
Committee:
Jaro Vostal, M.D., Ph.D. 177
Committee Discussions and
Recommendations 184
II. New Standard for Platelet Evaluation
Introduction and Background:
Salim Haddad, M.D. 231
Presentation:
James AuBuchon, M.D. 283
Presentation:
Edward Snyder, M.D. 218
Open Public Hearing
Allene Carr-Greer, AABB 308
Michael Fitzpatrick,
Ph.D. 308
Larry Dumont, Gambro BCT
Inc. 308
FDA Current Thinking and Questions for
the
Committee:
Jaro Vostal, M.D., Ph.D. 310
Committee Discussion and
Recommendations 312
III. Experience with Monitoring
of Bacterial Contamination of
Platelets
Introduction and Background:
Jaro Vostal, M.D., Ph.D. 342
Summary of ACBSA Meeting: Bacterial
Contamination:
Jerry A. Holmberg, Ph.D. 371
Presentation:
Steven Kleinman, M.D. 388
Open Public Hearing
Boris Rotman, Ph.D., BCR
Diagnostics 420
Committee Discussion and
Recommendations 430
5
1 P R O C E E D I N G S
2
Welcome/Statement of Conflict of Interest
3 DR. SMALLWOOD:
Welcome to the 80th
4
meeting of the Blood Products Advisory Committee.
5 I am Linda Smallwood, the Executive
6
Secretary. At this time, I will
read the conflict
7
of interest statement that applies to this meeting.
8
This announcement is part of
the public
9
record for the Blood Products Advisory Committee
10
meeting on July 22nd/23rd, 2004.
11 Pursuant to the authority granted under
12
the Committee Charter, the Director of FDA's Center
13
for Biologics Evaluation and Research has appointed
14
the following individuals as temporary voting
15
members: Drs. Liana Harvath,
Blaine Hollinger,
16
Matthew Kuehnert, Susan Leitman, Keith Quirolo,
17
George Schreiber, Donna Whittaker, Ms. Katherine
18
Knowles.
19 To determine if any conflicts of interest
20
existed, the agency reviewed the agenda and all
21
relevant financial interests reported by the
22
meeting participants.
6
1 For Agenda Topics I, II, III, and V, the
2
Food and Drug Administration has prepared general
3
matter waivers for the special government employees
4
participating in this meeting who required a waiver
5
under Title 18, United States Code 208.
6 Because general topics impact on so many
7
entities, it is not prudent to recite all potential
8
conflicts of interest as they apply to each member.
9
FDA acknowledges that there may be potential
10
conflicts of interest, but because of the general
11
nature of the discussions before the committee,
12
those potential conflicts are mitigated.
13 Based on a review of the agenda, all
14
relevant financial interests reported by the
15
meeting participants, and on the FDA draft guidance
16
on disclosure of conflict of interest for special
17
government employees participating in an FDA
18
product-specific advisory committee meeting, there
19
are no meeting participants who required a waiver
20
under Title 18, United States Code 208 for
21
discussions on hepatitis B virus nucleic acid
22
testing for donors of whole blood.
7
1 We would like to note for the record that
2
Dr. Michael Strong is participating in this meeting
3
as the Non-Voting Industry Representative acting on
4
behalf of regulated industry.
Dr. Strong's
5
appointment is not subject to Title 18, United
6
States Code 208.
7 He is employed by the Puget Sound Blood
8
Center and Program and thus has a financial
9
interest in his employer. He
also is a researcher
10
for two firms that could be affected by the
11
committee discussion. In
addition, in the interest
12
of fairness, FDA is disclosing that his employer
13
Puget Sound Blood Center has associations with
14
regional hospitals and medical centers.
15 With regard to FDA's invited guest
16
speakers, the Agency has determined that the
17
services of these guest speakers are essential.
18
There are interests that are being made public to
19
allow meeting participants to objectively evaluate
20
any presentation and/or comments made by the
21
guests.
22 For the discussions of Topic I related to
8
1
the Dating of Irradiated Blood, Dr. Gary Moroff is
2
employed by the American Red Cross Holland Labs.
3 For the discussions of Topic II on a New
4
Standard for Platelet Evaluation, Dr. Edward Snyder
5
is employed by the Yale-New Haven Hospital Blood
6
Bank. He also has associations
with clinical
7
trials that involve red blood cells.
8 Dr. James AuBuchon has grants and/or
9
contracts with firms that could be affected by the
10
discussions. He is also a
scientific advisor for
11
several affected firms.
12 For the discussion of Topic III on
13
Experiences with Monitoring of Bacterial
14
Contamination of Platelets, Dr. Steven Kleinman
15
receives consulting fees from two firms that could
16 be affected by the committee discussions.
17 Dr. Jerry Holmberg has a financial and
18
professional interest in several firms that could
19
be affected by the committee discussions.
20 In addition, there are regulated industry
21
and other outside organization speakers making
22
presentations. These speakers have financial
9
1
interests associated with their employer and with
2
other regulated firms. They were
not screened for
3
these conflicts of interest.
4 FDA members are aware of the need to
5
exclude themselves from the discussions involving
6
specific products or firms for which they have not
7 been
screened for conflicts of interest.
Their
8
exclusion will be noted for the public record.
9 With respect to all other meeting
10
participants, we ask in the interest of fairness
11
that you state your name, affiliation, and address
12
any current or previous financial involvement with
13
any firm whose products you wish to comment upon.
14
Waivers are available by written request under the
15
Freedom of Information Act.
16 At this time, I am asking if there are any
17
further declarations that have not been mentioned
18
that need before this meeting proceeds.
19 [No response.]
20 DR. SMALLWOOD:
Hearing none, thank you.
21 I would also just like to announce that
22
there is a new procedure and that for each day, and
10
1
also maybe for specific topics, there will be
2
another reading of a conflict of interest
3 statement. That is new, but just to let you know
4
that that is what is taking place.
5 Also, with regard to those speakers that
6
will be speaking in the open public hearing, there
7
will be a statement read by the chairman for each
8
open public hearing to remind you to make the
9
declaration of your name and affiliation and to
10
reveal any association that is pertinent to that
11
discussion.
12 At this time, I would like to make a few
13 announcements.
14 There will be a workshop on plasma
15
standards scheduled August 31st through September
16
the 1st, 2004. It will be held
on the NIH campus,
17
and there is an announcement on the FDA web site.
18
Additionally, the next meeting
of the
19
Blood Product Advisory Committee is tentatively
20
scheduled for October 21st/22nd, 2004 at this
21
hotel. There will be further
announcements.
22 At this time, I will introduce to you the
11
1
members of the Blood Products Advisory Committee.
2 Today, Dr. James Allen will be the Acting
3
Chairman in the absence of Dr. Kenrad Nelson, who
4
is expected to join us tomorrow.
Dr. Allen, would
5
you please raise your hand. Thank you.
6 As I call your names, would you please
7
raise your hand.
8 Dr. Kuehnert.
Dr. Harvath. Dr. Klein.
9
Dr. Goldsmith. Dr. Leitman. Dr. Doppelt. Dr.
10
DiMichele. Dr. Davis. Dr. Laal.
Dr. Quirolo.
11
Dr. Whittaker. Dr.
Schreiber. Ms. Knowles. Dr.
12
Strong.
13 Thank you.
14 As indicated on the agenda, we do have
15
times indicated for the speakers.
We would ask
16
that you would adhere to that.
Our Acting Chairman
17
says he will enforce that and we have a timer.
18 At this time, I would like to turn over
19
the proceedings of this meeting to the Acting
20
Chairman, Dr. James Allen.
21 DR. ALLE N: Thank you, Dr.
Smallwood.
22 Good morning and welcome to the meeting.
12
1
We have a very full agenda with a lot of important
2
items. I don't think in my
experience on the
3
committee I have ever seen so many questions being
4
asked in one meeting, so it is important that we
5
get the information before us from the speakers as
6
succinctly as possible, that we maximize the time
7
that we have for committee discussion and questions
8
of the speakers, and discussion among ourselves
9
before deciding to vote. So, I
really would like
10
to ask people, please, to keep your presentations
11
to the point and move along properly.
12 We have got two committee updates
13
initially and then we will follow that by an open
14
public hearing. There are
comments during the open
15
public hearing that will be addressing both of the
16
updates, but we will have both updates first with
17
time for questions of the speakers.
18 At this point, let's move into the first
19
committee update, Dr. Leslie Holness from the Food
20
and Drug Administration will give an update on
21
Transfusion Related Acute Lung Injury (TRALI).
22 Committee Updates
13
1 FDA Current Thinking on TRALI
2 Leslie Holness, M.D.
3 DR. HOLNESS:
Thank you, Dr. Allen.
4 Good morning.
5 [Slide.]
6 The FDA Fatality Program receives reports
7
of fatalities that occur as a complication of
8
transfusion or donation. We have
seen a steady
9
rise in fatalities due to TRALI since the first FDA
10
report in 1992.
11 [Slide.]
12 This slide covers reported fatalities for
13
three fiscal years. Between 2001
and 2003, the
14
three principal causes reported in terms of numbers
15
are TRALI, ABO hemolytic reactions primarily caused
16
by clerical errors, and bacterial contamination.
17 In Fiscal 2001 and 2003 TRALI led in the
18
number of fatality reports received.
In Fiscal
19
2002, reports of fatalities from bacterial
20
contamination of products were most numerous.
21
Other transfusion related fatality causes were
22
non-ABO, antibodies, and mishandling of products.
14
1
In this category, the transfusion may or may not
2
have contributed to the recipient's death.
3 In this category, the fatalities were not
4
transfusion related, and there are donor fatalities
5
and the total fatalities at the bottom of the
6
slide.
7 [Slide.]
8 If we look at the average of the key
9
causes for the last three years, TRALI leads with
10
16.3 percent followed by ABO hemolytic transfusion
11
reactions at 14.3 percent, and bacterial
12
contamination at 14.1 percent.
13 [Slide.]
14 So, the FDA Fatality Program reports that
15
TRALI was implicated in 16 to 22 percent of total
16
fatalities reported in each of the last three
17
years, and it was the most common cause of
18
transfusion related fatalities reported to the FDA
19
in 2003.
20 The majority of deaths were associated
21
with fresh frozen plasma followed by red blood
22
cells and apheresis platelets.
15
1 [Slide.]
2 Dr. Kathleen Sazama, of M.D. Anderson
3
Cancer Center at the University of Texas, looked at
4
20 years of FDA fatality reports from 1976 to 1995,
5
and found respiratory deaths as a percentage of
6
total reported deaths to be 15 percent, and many of
7
these are probably due to TRALI.
8 [Slide.]
9 This slide is a bar graph of TRALI