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
10
fatalities reported to the FDA and the total
11
fatalities reported to the FDA from 1995 to 2003.
12
There has been a steady increase in total fatality
13
reports to spike in 1998 and also a steady increase
14
in the TRALI fatalities.
15 [Slide.]
16 These are the TRALI fatalities broken out.
17
There is a slowing in 1999 and 2000, but all
18
together there is a steady increase in TRALI
19
fatalities up to 2003.
20 [Slide.]
21 Some of the fatalities are associated with
22
HLA or granulocyte antibodies, and they are sent in
16
1
with the fatality reports.
2 This is a graph of the number of
3
fatalities due to TRALI that were reported to the
4
FDA in these various years, and these are the
5
number of cases where HLA or antigranulocyte
6
antibodies were found. In most
cases, antibodies
7
were found in over 50 percent of the TRALI
8
fatalities.
9 [Slide.]
10 This slide shows the preliminary results
11
of a consensus conference held in Toronto, Canada,
12
in April of this year, 2004. The
conference was
13
sponsored by Canadian Blood Services, Hema-Quebec,
14
and the International Society for Blood
15
Transfusion, ISBT.
16 It was a two-day conference with over 19
17
speakers. There are preliminary
results. More
18
detailed results will be published at the beginning
19
of next year. So, the magnitude
of the TRALI risk
20
is unknown. Depending on the
studies, the
21
estimates are between 1 in 5,000 to 1 in 10,000
22
transfusions.
17
1 There is evidence for two mechanisms for
2
TRALI, and there is insufficient evidence for
3
screening tests and for donor exclusion measures at
4
this time.
5 [Slide.]
6 In April of 2003, the NHLBI convened a
7
working group of TRALI experts to develop a clear
8 definition to be used to clinical
investigation and
9
patient care. The definition
with limitations is
10
as follows:
11 In patients with no acute lung injury
12
prior to transfusion, the diagnosis of TRALI is
13
made if there is new acute lung injury and an onset
14
during or within 6 hours after the end of a
15
transfusion of one or more plasma containing blood
16
products, and there are no other risk factors for
17
acute respiratory distress syndrome.
This
18
definition is still being worked on.
19 [Slide.]
20 These are FDA actions taken in 2001. The
21
issue was presented to the Blood Products Advisory
22
Committee on June 15th of 2001.
We will see the
18
1
results in the next slide.
2 CBER has published a Health Alert in the
3
form of Dear Colleague letter to the blood
4
community in October of 2001. It
was to remind
5
physicians to include TRALI in a differential
6
diagnosis of a patient in respiratory distress
7
during or following a transfusion.
8 Pre-storage leukocyte reduction of blood
9
products was recommended to help prevent formation
10
of leukocyte antibodies in recipients.
11 We recommended voluntary Med Watch
12
reporting of non-fatal TRALI cases, and there were
13
several poster presentations to raise clinician
14
awareness of TRALI.
15
[Slide.]
16 This slide shows the BPAC vote on June 15,
17
2001. The question to the committee was: Should
18
the FDA consider regulatory action at this time to
19
identify donors and donations at increased risk to
20 producing
TRALI in a recipient?
21 The votes were:
1 Yes, 13 No, and there
22
were no abstentions.
19
1 [Slide.]
2 One member thought it was prudent to
3
identify and defer donors implicated in multiple
4
TRALI cases.
5 BPAC agreed that this should be the
6
responsibility of each establishment.
7 The committee also recommended research to
8
define the scope of the syndrome and a prospective
9
epidemiologic study to establish incidence, donor
10
and recipient risks.
11 [Slide.]
12 The further recommendations from the
13
committee.
14 The role of HLA, leukocyte antibodies and
15
other potential causative mechanisms need to be
16
investigated. A careful
evaluation of cases in
17
which the donor can be linked with the reaction.
18 A multi-center study to assess and
19
evaluate acute pulmonary reactions and lung
20
problems in the transfusion setting using a
21
standardized protocol, and the surveillance of
22
recipients of IVIG for TRALI reactions.
20
1 [Slide.]
2 These are possible future regulatory
3
strategies that are being discussed at the FDA at
4
this time.
5 Diversion of plasma from female donors to
6
components other than fresh frozen plasma. This
7
does not involve a new question and fresh frozen
8
plasma is most often involved in TRALI.
This is
9
being tried in the UK at this time, but there have
10
been no impressions of the results yet.
11
Our problem is that the
plasma in other
12
components are ignored and that shortages of FFP
13
may occur.
14 [Slide.]
15 Preventive antibody testing and
16
questioning of donors, female donors, on parity,
17 followed by plasma product diversion and red
blood
18
cell loss from donors at risk.
19 The problem here is that samples and
20
testing are not standardized.
All white blood cell
21
antibodies may not be equal in their ability to
22
cause TRALI in recipients.
21
1 [Slide.]
2 Defer donors implicated in a single unit
3
or in more than one multiple unit TRALI case
4
regardless of antibody status.
5 This allows the first case of TRALI to
6
occur which may be fatal, and it depends on
7
accurate case reports and donor tracing.
8 That's it.
With that, I end my
9
presentation.
10 DR. ALLEN: Thank you, Dr. Holness.
11 Questions from the committee members?
12 Obviously, this is very important data,
13
but it is limited in that it is reporting only of
14
fatalities. Do you have other
information in terms
15
of how well the research community has responded to
16
this issue? Are there any
recommendations coming
17
out of the recent meeting that you think should
18
come before the committee at least today or in the
19
near future?
20 DR. HOLNESS: I
think that probably the
21
best thing is to wait until the full report of the
22
committee is out before we make recommendations.
22
1 DR. ALLEN:
Okay. Other questions? Yes.
2 DR. SCHREIBER:
From your graph it looks
3
like we are seeing an increased frequency of TRALI,
4
but it is probably due to more awareness, don't you
5
think, of the reporting, particularly since all of
6
the activities that started around '99?
7 DR. HOLNESS:
That is true.
8 DR. SCHREIBER:
My other question is on
9
one of the slides from the Toronto, you had an
10
incidence, I think it was 1 in 5,000 to 1 in
11
100,000, and that is the incidence of TRALI
12
reactions, TRALI-type reactions, but the mortality
13
rate is somewhere closer to 1 in 750,000, I
14
believe.
15 DR. HOLNESS: I
think you are right on
16
that, yes.
17 DR. SCHREIBER:
Thank you.
18 DR. ALLEN: On
that slide, it said 1 in
19
5,000 and 1 in 100,000, but I think you read 1 in
20
5,000 and 1 in 10,000. Which is
the correct
21
number, the 10,000 or 100,000?
22 DR. HOLNESS: 1
in 100,000. It is my
23
1
mistake, I am sorry.
2 DR. ALLEN:
Thank you very much.
3 We will move on to the second committee
4
update, Donor Blood Pressure Determination
5
presented by Dr. Alan Williams.
6 Donor Blood Pressure Determination
7 Alan Williams, Ph.D.
8 DR. WILLIAMS:
Thank you, Jim, and good
9
morning.
10 As you will note from some of the
11
statements from the blood and plasma community that
12
have been distributed, FDA has been asked to
13
restate and reconsider its position with respect to
14
blood pressure determination as a criterion for
15
blood donation and plasma donation eligibility.
16
That is what I intend to do very briefly this
17
morning.
18 [Slide.]
19 The FDA regulatory position is stated
20
quite clearly in two regulations.
21 CFR
21
640.3(b)(2) requires donor's systolic and diastolic
22
blood pressure are within normal limits, unless a
24
1
physician, after examining the donor, is satisfied
2
that the donor is otherwise qualified.
3 This needs to be considered in conjunction
4
with another regulation, 21 CFR 606.100(b)(2),
5
which states that a blood collection facility
6 include in its Standard Operating Procedures
7
methods of performing donor qualifying tests and
8
measurements, including minimum and maximum values
9
for a test or a procedure when a factor in
10
determining acceptability.
11
[Slide.]
12 When reviewing Standard Operating
13
Procedures presented by licensed blood collection
14
establishments, in fact, we do look for SOPs that
15
define both an upper and a lower range of normal
16
blood pressure, and, in addition, if outside the
17
normal range, a donor must be medically evaluated
18
for donation eligibility.
19 Not only do we do that in current
20
submissions, but we, in fact, did a randomized look
21
at prior approvals of SOPs, and in all of the
22
licensed establishments that we looked at, they had
25
1
both lower and upper limits included.
2 FDA has not historically specified the
3
cutoff values to be used for a lower limit. This
4
is, in fact, controversial as to what the
5
predictive value of the lower limit is and what the
6
lower limit of normal, in fact, should be,
7
certainly a subject for future discussion.
8 But I will note that while there are some
9
studies which have been cited by some of the
10
position statements, what probably is lesser known
11
is that FDA has received some isolated reports of
12
severe vasovagal reactions in donors who were
13
found, upon review of the record, to have had
14
abnormally low blood pressures at the time of
15
donation.
16 [Slide.]
17 To summarize, I think what the basis is of
18
the industry request for policy clarification, on
19
the fact that the predictive value of a single low
20
blood pressure determination has not been finally
21
established, I think you can see a range in the
22
literature, and in some of the cases, particularly
26
1
the case-controlled studies, you can see that blood
2
pressure on a univariate analysis emerges as a
3
factor, but may not stand up to a multivariate
4
analysis.
5 This is evidence that it may not be an
6
independent factor, but, in fact, may be tied up in
7
interaction with demographic or other variables.
8
So, analyses of some of these studies require both
9
large studies and rather complex multivariate
10
analysis to determine what the interaction effects
11
and other potential impact might be.
12 The European community, particularly the
13
UK, in their blood collection procedures do not
14
determine a blood pressure value at all, although
15
if the donor has a history of reactions or of
16
hypertension, they maintain the equipment available
17
to make the determination, but, in short, in the
18
UK, the blood pressure is not determined.
19 The 2004 EU directive does not include a
20
blood pressure determination requirement, and the
21
current Council of Europe guide includes only an
22
upper blood pressure limit.
27
1 [Slide.]
2 And though not necessarily scientifically
3
based, the observation has been made that the
4
voluntary industry standards for blood collection,
5
which originally required both an upper and lower
6
blood pressure value, were modified to remove the
7
lower level requirement some time ago, in 1987, and
8
that some blood establishment SOPs may current
9
omit, or may have historically omitted, a lower
10
blood pressure cutoff value.
11 As I stated, licensed establishments are
12
reviewed for having an SOP that includes this
13
requirement, it is possible that some of the sites
14
that don't may be registered facilities which
15
should be following the regulation, but whose SOPs
16
are not reviewed by FDA.
17 [Slide.]
18 So, in summary, FDA strictly adheres to
19
the existing regulations, but FDA does not
20
recognize the need for scientific consensus on the
21
value of donor blood pressure determinations and
22
considers its regulations to require that they be
28
1
scientifically based.
2
So, I think some of the
uncertainties that
3
may be there in the published literature should be
4
looked at further.
5 Under the HHS Blood Action Plan, FDA
6
intends to propose rulemaking that will
7
comprehensively address donor eligibility
8
requirements including blood pressure, and as part
9
of this process, there will be an opportunity for
10
data presentation and comment to any proposed rule
11
that might emerge.
12 Thank you.
13 DR. ALLEN:
Thank you, Dr. Williams.
14 Questions or comments from the committee?
15
Yes.
16 DR. GOLDSMITH:
What were the blood
17
pressures in the FDA reports for the severe
18
reactions, how low were they really?
19 DR. WILLIAMS:
I do not remember the
20
actual values, but they were lower than what the
21
original industry standard was, which I believe the
22
lower limits were 90 and 50 for the systolic and
29
1
diastolic.
2 DR. KLEIN:
Alan, I am sure you are aware
3
that there may be a little bit of a reporting bias
4
in those reports you have. There
has been an
5
extensive literature on vasovagal reactions and
6
donor vital signs, and to the best of my knowledge,
7
there has never been any correlation between blood
8
pressure and vasovagal reactions, and knowing how
9
vasovagal reactions generally occur, I am not sure
10
that there should be.
11 DR. LEITMAN:
You quote a study, which is
12
an excellent one, a multi-center study published in
13
Transfusion in '99, where Trend and colleagues
14
looked at the effect of blood pressure and other
15
factors pre-donation on the incidence of vasovagal
16
during donation, and in a univariate analysis, low
17
blood pressure was associated with vasovagal
18
reactions, but in a regression analysis, which is
19
very important, when you put in the variables of
20
age, weight, and donor status prior donations, that
21
fell out.
22 So, you really have to go with the best
30
1
scientific data you have, I think, in a complex
2
analysis like this, and that is very helpful for me
3
to look at this data.
4 DR. WILLIAMS:
Yes, I agree. There was
5
probably a most sophisticated analysis to address
6 this
particular subject, but, you know, one could
7
argue was that study large enough to pick up a
8
potential interaction effect between the
9
demographic variables and blood pressure.
10 In fact, on univariate analysis, there was
11
quite a difference, 3 percent incidence of
12
reactions with the lower blood pressures versus 1
13
percent of the control group, so I think it just
14
bears a further look with more sophisticated
15
analysis.
16 DR. ALLEN:
Other questions or comments?
17
Okay. Thank you very much.
18 At this point, we will move on the open
19
hearing, to the public hearing.
20 Before we get started on that, I need to
21
read an open public hearing announcement for
22
general matters meetings.
31
1 Both the Food and Drug Administration and
2
the public believe in a transparent process for
3
information gathering and decisionmaking. To
4
ensure such transparency at the open public hearing
5
session of the Advisory Committee meeting, FDA
6
believes that it is important to understand the
7
context of an individual's presentation.
8 For this reason, FDA encourages you, the
9
open public hearing speaker, at the beginning of
10
your written or oral statement to advise the
11
committee of any financial relationship that you
12
may have with any company or any group that is
13
likely to be impacted by the topic of this meeting.
14
For example, the financial information may include
15 a
company's or a group's payment of your travel,
16
lodging, or other expenses in connection with your
17 attendance
at the meeting.
18 Likewise, FDA encourages you at the
19
beginning of your statement to advise the committee
20
if you do not have any such financial
21
relationships. If you choose not
to address this
22
issue of financial relationships at the beginning
32
1
of your statement, it will not preclude you from
2
speaking.
3 Open Public Hearing
4 DR. ALLEN:
Let's go ahead with the public
5
statements on TRALI. I have a
request from the
6
American Association of Blood Banks.
7 MS. GREGORY:
Thank you. My name is Kay
8
Gregory and I am the Director of Regulatory Affairs
9 for the AABB, and I have only financial
10
arrangements with them and no other companies.
11 AABB is an international association
12
dedicated to advancing transfusion and cellular
13
therapies worldwide. Our members
include more than
14
1,800 hospital and community blood centers and
15
transfusion and transplantation services as well as
16
approximately 8,000 individuals involved in
17
activities related to transfusion, cellular
18
therapies, and transplantation medicine.
19 For over 50 years, AABB has established
20
voluntary standards for, and accredited
21
institutions involved in, these activities. AABB
22
is focused on improving health through the
33
1
advancement of science and the practice of
2
transfusion medicine and related biological
3
therapies, developing and delivering programs and
4
services to optimize patient and donor care and
5
safety.
6 The AABB believes that TRALI is a
7
significant transfusion safety concern that merits
8
increased awareness and research.
In an effort to
9
educate our members about the clinical and
10
laboratory features of TRALI, AABB has issued
11
guidelines for the management of TRALI, and our
12
association considers this a priority transfusion
13
safety matter.
14 We commend the FDA for alerting physicians
15
to the risk of TRALI from transfusion of
16
plasma-containing blood products in 2001, however,
17
we are disappointed that the Federal Government has
18
not done more to advance needed research regarding
19
this important transfusion safety issue since the
20
Blood Products Advisory Committee last addressed
21
TRALI in 2001.
22 In order to allow for the most effective
34
1
and meaningful research and clinical understanding
2
of this condition, the AABB proposed that a
3
standard uniform definition of TRALI be established
4
and adopted by the medical community and
5
policymakers, including the FDA.
6 Earlier this year, Canadian Blood Services
7 and Hema-Quebec hosted
a valuable consensus
8
conference, bringing together the leading experts
9
to discuss the current state of knowledge regarding
10
TRALI.
11 At the end of this conference, the group
12
recommended definitions of TRALI and "possible
13
TRALI," and we have attached to our written
14
statement our current understanding of those
15
definitions.
16 In general, the group recommended that
17
TRALI should be diagnosed in patients with no acute
18
lung injury prior to transfusion who, during or
19
within six hours after transfusion, experienced
20
certain specific criteria. They
distinguished
21
"possible TRALI" cases, which would involve
22
patients with the same criteria who also had one or
35
1
more temporally associated ALI risk factors.
2 The AABB endorses the definitions set
3
forth during the consensus conference and urges the
4
FDA to adopt these definitions as well.
Emerging
5
data and research regarding TRALI should be
6
carefully monitored to determine if refinements to
7
these definitions are necessary over time.
8 Using the uniform definitions, AABB
9
recommends that additional research be conducted to
10
define the scope of the problem and its mechanisms
11
or pathophysiology. As we
proposed to BPAC in
12
2001, AABB continues to advocate a prospective
13
epidemiologic study to establish the incidence of
14
TRALI. For example, we propose a
multi-center
15
study of acute lung problems in the transfusion
16
setting to assess, evaluate, and analyze all
17
pulmonary reactions using a standardized protocol.
18 The AABB also continues to recommend that
19
the NHLBI establish a multi-center study to lead to
20 a
better understanding of the mechanisms that cause
21
TRALI. Once the mechanisms of
TRALI are better
22 understood,
the risk factors in donors and
36
1
recipients may become apparent.
2 The AABB continues to believe that more
3
data are needed before establishing donor deferral
4
criteria or other regulatory strategies for TRALI.
5
When a severe clinical reaction has occurred, an
6
antibody has been identified in the donor and the
7
recipient has the corresponding antigen, the
8
preventive measure is relatively clear.
9 In such cases, it is generally agreed that
10
blood from that donor should never again be
11
transfused to the same recipient.
However, it is
12
not so clear that such a donor should be
13
permanently deferred from donating any blood
14
component.
15 The appropriate preventive measures for
16
TRALI are even less obvious for the majority of
17
pulmonary reactions that occur in the transfusion
18
setting.
19
It is also important to
understand what
20
proportion of the donor population would be
21
affected by proposed deferral criteria or other
22
regulatory strategies, so that the potential impact
37
1
on the blood supply can be evaluated. These data
2
are especially critical, as we already too
3
frequently face blood shortages in regions across
4
the country.
5 A careful and thorough analysis of the
6
risks and benefits of any donor deferrals or any
7
other regulatory strategy must be completed before
8
taking steps that could unnecessarily hinder
9
patient access to life-saving blood components.
10 Thank you.
11 DR. ALLEN:
Thank you very much.
12 Questions or comments from the committee
13
in response? Yes.
14 DR. KLEIN: We
have heard on a couple of
15
occasions now about the Canadian Consensus
16
Conference and clearly it's an important one, but
17
the results haven't been published yet, and I would
18
certainly caution the FDA about the definition that
19
has been proposed. It's a
preliminary definition.
20 Many of the patients that we take care of
21
are in intensive care units, they are on
22
respirators, they do have some kind of underlying
38
1
lung disease, and they get a lot of blood
2
transfusions. By the definition
that has been
3
proposed, should any of them have what looks like
4
TRALI, they would be excluded under the proposed
5
definition.
6 I am not sure that is the permanent
7
definition. I think we ought to
wait before
8
adopting anything to see what the publication says.
9 DR. ALLEN:
Thank you. I think that is
10
very good advice.
11 Other questions or comments? Yes.
12 DR. HARVATH: I
would like to just address
13 a
couple of points about the recommendation for
14
supportive research from the NHLBI perspective.
15
There have been a number of ways we have been
16
trying to stimulate this during the past several
17
years.
18 One of the ways that we are going about
19
doing this is through the transfusion medicine
20
hemostasis clinical trial network, which is a
21
multi-center, 17 clinical centers throughout the
22
United States.
39
1 We have discussed with that committee
2
looking at prospectively any study which involved
3
the transfusion of components, and almost every
4
study does, looking prospectively to find any
5
evidence of TRALI in the patients in those studies,
6
so it will be the opportunity to look at both a
7
platelet transfusion study, which is our first
8
study, and possibly a second study that would
9
potentially involve FFP, and these would be
10
randomized studies, and the work would be done
11
prospectively.
12 The second point is that the NHLBI also
13
funds a multi-center acute respiratory distress
14
network, which involves the pulmonary specialists,
15
and they have become interested in this area, so
16
there are investigators who are also interested in
17
looking in that patient population.
18 So, these are existing clinical trial
19
networks where this would be possible to integrate
20
this type of research, and also to add that NHLBI
21
welcomes any investigator-initiated studies to come
22
forward to the institute and to let us know what
40
1
kinds of research investigators or groups of
2
investigators would like to pursue.
So, we are
3
very open to that.
4 DR. ALLEN:
Thank you. It is certainly
5
helpful to have both lung and blood in the same
6
institute from that perspective, I am sure.
7 Other questions or comments?
8 Okay. We will
move on to the next
9
statement on blood pressure lower limits by the
10
AABB. I am sorry, excuse me, we
do have one
11
additional statement on TRALI, Dr. Fitzpatrick from
12
the America's Blood Centers.
13 DR. FITZPATRICK:
Mike Fitzpatrick, Chief
14
Policy Officer for America's Blood Centers, and I
15
am employed by them.
16 America's Blood Centers, or ABC, is
an
17
association of 76 not-for-profit, community-based
18
blood centers that collect nearly half of the U.S.
19
blood supply from volunteer donors.
ABC thanks
20
FDA's Center for Biologics Evaluation and Research
21
for the opportunity to make public comments before
22
the Blood Products Advisory Committee.
41
1 Our members share FDA's concerns about
2 transfusion related acute lung injury. While rare,
3
this is a serious and sometimes fatal
4
transfusion-associated event. We
know that TRALI
5
is a complex phenomenon, and there is no agreement
6
in the published literature about the major
7
mechanisms of disease.
8 This was clearly documented at the
9
Canadian Consensus Conference that we have heard
10
about.
11 At least two mechanisms appear to play a
12
role, one involving antibodies to leukocytes, the
13
other involving biologically active mediators.
14
Interestingly enough, in the paper published by
15
Silliman--I won't quote the source here, but you
16
have got that--most of the TRALI events appear to
17
be related to biologically active mediators and
18
only one of the 90 reactions studied involved a
19
plasma unit.
20 Most reactions, 74, involved whole blood
21
derived and apheresis platelets.
Kopko has
22
indicated that many units implicated in TRALI
42
1
reactions carry antibodies to white blood cells.
2
However, she concluded from her studies that HLA
3
antibodies in a donor corresponding to HLA antigens
4
in a recipient are not sufficient to cause TRALI in
5
all recipients.
6 She also noted that based on lookback
7
studies, donors implicated in TRALI reactions can
8
cause TRALI in other recipients, regardless of
9
antigen-antibody correlations.
While presentations
10
also indicated a higher rate of female plasma
11
donors who have been pregnant carry anti-HLA
12
antibodies, data is lacking that would establish a
13
definitive link between gender and/or anti-HLA
14
antibodies and TRALI.
15 Dr. Holness from FDA presented the FDA
16
fatality data at that conference and a summary of
17
the data today here. He showed
an apparent
18
increase in TRALI associated fatalities in recent
19
years. He also indicated that
the majority of the
20
49 fatalities that occurred between 2001 and 2003
21
were associated with plasma transfusions. The
22
number or percent was not indicated.
43
1 The donor data presented did not include
2
donor gender or prevalence of antibodies to
3
leukocytes, so we cannot estimate the impact of the
4
three preventive strategies enumerated by FDA:
5
only transfuse plasma containing components from
6
male donors, perform preventive antibody testing,
7
defer donors implicated in TRALI cases.
8 We agree that FDA should review and
9
consider interventions to address the issue of
10
TRALI. The impacts of such
strategies must also be
11
considered by asking the following questions:
12 How many TRALI associated fatalities will
13
be prevented by the implementation of each
14
strategy? What blood components
should be included
15
in the strategy? TRALI has been
associated with
16
all blood components, including red blood cells,
17
apheresis platelet units, which contain as much or
18
more plasma than a unit of fresh frozen plasma.
19 What impact will this have on the
20
availability of components? Are
there other
21
strategies that could be considered?
22 The data presented by FDA, the current
44
1
literature, the recommendations made by BPAC in
2
2001 and the conclusions of the Canadian Consensus
3
Conference, while not yet published, that were
4
summarized at the meeting, do not provide a clear
5 basis for any of the regulatory strategies listed.
6
Whole blood, whole blood derived platelets,
7
apheresis platelets, and plasma have all been
8
implicated in TRALI. Why
restrict the approach the
9
plasma, what about apheresis platelets?
10 We carried out a survey to assess the
11
impact of using only male plasma and platelet
12
apheresis products among ABC members.
Forty-two
13
centers collecting a total of almost 4 million
14
whole blood and apheresis units a year responded.
15 Based on the gender distribution of ABC
16
donors, we estimate that a ban on female plasma and
17
apheresis platelets would lead to the loss of
18
113,000 donors and 275,000 donations in one year.
19
If we double this estimate to include collections
20
by the American Red Cross, 550,000 donations would
21
be lost in the U.S.
22 Females represent about 44 percent of all
45
1
apheresis donors. Our members indicated that they
2
could not effect these changes without seriously
3
impairing product availability.
When our members
4
were asked whether they could provide male plasma
5
only to their hospitals, 55 percent responded yes.
6 However, they indicated that it would take
7
them between 18 and 24 months to implement the
8
changes, including software modifications, and that
9
the change would create serious shortages of type
10
specific plasma, particularly type AB.
11 ABC members disagree with FDA's point of
12
view that strategy number 3, deferral of donors
13
implicated in TRALI incidents, is inadequate
14
because it allows for the first incident to occur
15
before donor deferral is instituted and does not
16
eliminate TRALI.
17 Unfortunately, all the proposed strategies
18
suffer from this deficiency because of the myriad
19
causes of TRALI. Strategy 1
addresses an
20
undetermined fraction of TRALI cases and has more
21
serious consequences for blood availability.
22 At the present time and with the present
46
1
knowledge, regulatory action should be restricted
2
to donors implicated in TRALI episodes, as stated
3
in the third strategy.
4 FDA also needs to support effective
5
training of physicians and other hospital personnel
6
for early recognition of TRALI, based on the case
7
definition being considered by an NHLBI task force,
8
which was not discussed this morning, under the
9
leadership of Dr. Pearl Toy.
This may be more
10
efficient in the prevention of fatalities than any
11
of the proposed strategies.
12 The implementation of a global strategy
13
such as the deferral of male donors may have other
14
adverse consequences. It may
convey to the medical
15
community and to the public the erroneous
16
impression that the problem of TRALI has been
17
addressed and resolved, leading physicians to
18
consider other diagnoses and prescribe
19
inappropriate therapy.
20 Finally, we will have to deal with the
21
frustration of female donors when they learn that
22
their donations are not good for transfusion.
47
1 ABC members thank FDA and the BPAC for the
2 opportunity
to comment.
3 Thank you.
4 DR. ALLEN:
Thank you very much.
5 Questions or comments with regard to Dr.
6
Fitzpatrick's presentation? Jay.
7 DR. EPSTEIN: I
just want to comment that
8
this was an informational update, and the intent
9
was more to get the issue on everybody's radar
10
screen than to propose action at this point in
11
time. I think that Dr. Holness'
presentation made
12
clear that we are aware of all the uncertainties
13
and the ambiguities.
14 It is also true that the UK, faced with
15
the same uncertainties and ambiguities, felt that
16
action should be taken and it has its pros and
17
cons, so this is not rush to judgment and I
18
appreciate all the cautionary notes that have been
19
sounded, but I think that, you know, we have been
20
living with awareness of TRALI without effective
21
intervention for some time, and the idea here is to
22
provoke ourselves to think about could we be doing
48
1
more and what should that be.
So, this is just an
2
early stage of thinking.
3 DR. FITZPATRICK:
We understand, Jay, and
4
we just appreciated the opportunity to make some
5
comments and present some questions.
6 DR. ALLEN:
Other questions or comments
7
from the committee members?
8 Dr. Davis.
9 DR. DAVIS: I
would like to speak as
10
somebody that treats a lot of people with acute
11
lung injury. TRALI is not
something that is on
12
most of our radar screens. Most
of the people that
13
have acute lung injury, if you look at the list of
14
risk factors, most of those people, as Dr. Klein
15
alluded, get multiple transfusions for a lot of
16
other reasons.
17 The other thing that I really haven't
18
heard, and I don't know if there is an answer to
19
the question, is what is the survival rate. I mean
20
we have heard what the fatality is, but how many
21
people get TRALI and actually survive.
22 I think it is going to be hard to isolate
49
1
those kinds of isolated transfusion-related
2
injuries. I am not sure how many
clinicians are
3
actually aware of TRALI.
4 DR. ALLEN: I
think those are very good
5
points and certainly go right along with what Dr.
6
Harvath was saying about the need for prospective
7
multi-center studies.
8 The comment was made earlier today also
9
about the definition of TRALI, and it sounds to me,
10
with two proposed mechanisms in place, that we may
11
actually be dealing with multiple different
12
clinical events that need to be teased apart and
13
separated, and it sounds to me as though there is a
14
lot of research that needs to be done.
15 It is an important issue given the
16
relative incidence in terms of serious events
17
related to transfusion. I am sure that we are not
18
ready for any regulatory consideration at this
19
point.
20 We will look forward to additional updates
21
and research findings.
22 Other questions or comments?
50
1 [No response.]
2 DR. ALLEN:
Okay. Thank you.
3 We will move on the statements with regard
4
to blood pressure lower limits.
AABB.
5 Could I ask you not to read the first
6
paragraph, please, and just to move on with the
7
statement itself. Thank you.
8 MS. GREGORY:
Thank you. I had every
9
intention of doing that.
10 I also wanted to make the committee aware
11
that I am speaking, not only on behalf of the AABB,
12
but I am also speaking on behalf of America's Blood
13
Centers. Your written statements
don't reflect
14
that simply because of the need to get it in
15
quickly, so that you could have it ahead of time,
16
but I am speaking for both organizations.
17 Neither the AABB nor ABC supports the need
18
for a lower limit for blood pressure for blood
19
donors. Blood collection
facilities have had only
20
upper limits for blood pressure in place for many
21
years.
22 The AABB Standards for Blood Banks and
51
1
Transfusion Services requires that the blood
2
pressure be 180 systolic and 100 diastolic. These
3
levels have been the requirement since 1987. This
4
particular standard was reviewed again in 2002 and
5
again in 2003, and the Blood Banks and Transfusion
6
Services Standards Program Unit found no scientific
7
evidence to warrant changing the standard.
8 I also want to explain the difference
9 between
the AABB standards and the AABB technical
10
manual because the written materials that you
11
received talked about statements that are in the
12
technical manual.
13 The AABB standards are where the
14
requirements are stated, and they include
15
requirements for both quality management and
16
technical requirements. The
technical manual is
17
published to provide background material, some
18
guidance, and methods and procedures, but does not
19
include requirements.
20 The technical manual may provide practices
21
that will assist facilities in implementing
22
standards, but the standards is the definitive
52
1 document.
2 Another reason why we do not see a need
3
for a lower limit for blood pressure is that we
4
know that blood pressure is not a requirement for
5
donor qualification in the latest European Union
6
Commission directive.
7 The Council of Europe Guide states: If
8
pulse and blood pressure is tested, then the pulse
9
should be regular and between 50 and 100 beats per
10
minute. It is recognized that
recording the blood
11
pressure may be subject to several variables, but
12
as a guide, the systolic blood pressure should not
13
exceed 180 millimeters of mercury and the diastolic
14
pressure 100 millimeters.
15 A review of medical textbooks revealed
16 that there is no consistency about what is
17
considered to be hypertension in asymptomatic
18
individuals, and that a low blood pressure is not a
19
matter of great concern or interest outside of the
20
emergency room or intensive care settings.
21 A number of researchers have published
22
articles in peer-reviewed journals showing a lack
53
1
of correlation between low pre-donation systolic or
2 diastolic blood pressure and adverse donor
3
reactions.
4 A 2002 study of 72,059 whole blood
5
donations at the American Red Cross showed no
6
statistical association between low pre-donation
7
systolic or diastolic blood pressure and adverse
8
reactions.
9 In addition, the American Red Cross
10
reviewed pre-donation blood pressure on all donors
11
with adverse reactions that resulted in
12
hospitalization from January of 1999 to December of
13
2002. This review showed no
over-representation of
14
low blood pressure in those donors.
15 Finally, a review of donor fatality
16
reports obtained under the Freedom of Information
17
Act showed no low pre-donation blood pressure
18
either.
19 There are two Code of Federal Regulation
20
requirements that FDA has quoted as the rationale
21
for adding a lower limit for blood pressure. 21
22
CFR 640.3(b)(2), which states that systolic and
54
1
diastolic blood pressure must be within normal
2
limits, and 606.100(b)(2), which states that the
3
standard operating procedures for donor-qualifying
4
tests and measurements must specify maximum and
5
minimum values.
6 It is unclear why FDA has recently chosen
7
to selectively enforce this particular requirement
8
for blood pressure. There are
other
9
donor-qualifying tests and measurements that do not
10
have both upper and lower limits. For example,
11
temperature has only an upper limit, and weight,
12
hemoglobin, and age only a lower limit.
13 We have already noted the lack of uniform
14
agreement as to what constitutes a low blood
15
pressure in asymptomatic individuals.
In short,
16
while there may be a regulation that can be cited
17
as justification for this change in policy, the
18
regulation has not been enforced in the past and a
19
change in policy is unnecessary.
20 A key element of the FDA's 2004 strategic
21
action plan is efficient risk management. This
22
plan states that in all of its major policies and
55
1
regulations, FDA is seeking to use the best
2
biomedical science, the best risk management
3
science, and the best economic science to achieve
4
health policy goals as efficiently as possible. A
5
change to the requirement for donor blood pressure
6
does not meet these criteria.
7 DR. ALLEN:
Thank you.
8 Questions or comments? Yes.
9 DR. DiMICHELE:
Thank you for that. It
10
seems to me that the question at hand here is
11
whether a low blood pressure is physiologic for the
12
individual or whether it might represent
13
dehydration or for vasomotor tone and inability to
14
vasoreact in the face of acute volume reduction,
15
those kinds of issues.
16 It appears based on the epidemiologic data
17
that most of it isn't. However,
when you speak
18
about asymptomatic hypotension or asymptomatic
19
blood pressure, low blood pressure, do you--remind
20
me, I should know this because we have looked at
21
those criteria and those questions time and time
22
again--but do you ask a question in the pre-donor
56
1
screening about symptomatic hypotension or
2
symptomatic low blood pressure in the pre-donation
3
screening questionnaire?
4 MS. GREGORY:
We don't ask that
5
specifically, but we do ask things like are you
6
being treated by a doctor, things that we think
7
would elicit that information, but not that
8
specific question.
9 DR. DiMICHELE:
And the second question I
10
have is again, it is obvious that if the blood
11
pressure is physiologic for the individual, it is
12
probably not going to tend to be pathologic in any
13
way in donation, so do you have a way for multiple,
14
when you have repeat donors, to actually track
15
their blood pressures over time and to be able to
16
identify a low blood pressure that might be
17
unphysiologic for that individual?
18 MS. GREGORY:
The blood pressure is
19
recorded at each donation, and we do keep those
20
records, so I think there probably would be a way
21
to track that if we needed to.
22 DR. DiMICHELE:
So, really, basically, a
57
1
decrease in routine blood pressure that wasn't
2
previously hypotensive or certainly symptomatic
3
hypotension might be ways of picking up symptoms
4
without necessarily initiating a lower limit.
5 MS. GREGORY:
Thank you.
6 DR. ALLEN: Let
me just clarify, though, I
7
don't think when a person comes in to donate blood,
8
the information is obtained for that donation only,
9
and I don't think they go back and look at a
10
sequence of past blood pressure determinations.
11 Certainly, a change in laboratory values
12
might be noted, but I don't think that they would
13
go back and look at the pre-, you know, they don't
14
have pulled up on a computer screen or a paper
15
record that would show what the blood pressure
16
determinations were at the last two or three
17
donations.
18 DR. DiMICHELE:
That is what I was asking,
19
if that information was readily available.
20 MS. GREGORY:
That's right, we would not
21
look at it right then, but we would have the
22
ability to look at it should we think there is a
58
1
need to look at it for some reason.
2 DR. ALLEN:
Thank you. Other questions or
3
comments? Yes, Dr. Williams.
4 DR. WILLIAMS: Kay, a comment and a
5
question.
6 This was characterized as a change in
7
regulatory policy. I think that
perhaps isn't
8
correct. It might be a rift in
communication
9
particularly with respect to the industry voluntary
10
standards, but the question is what is the risk
11
side of the equation.
12 We take the point that regulation should
13
be scientifically based, but what is the impact on
14
blood collection? I would pose
the same question
15
to the PPTA speaker. What is the
donor loss, what
16
are the operational implications of recording a
17
lower blood pressure? What is
the impact?
18 MS. GREGORY: I
think the operational
19 limitations
are that we already record everything
20
under the sun, and recording one more thing might
21
not seem like it would be that difficult, but it is
22
one more chance to record it wrong and you have to
59
1
keep track of it all, and it is not that it is
2
impossible to do, it is just we would like to be as
3
efficient as we possibly could, and we don't think
4
there is a reason for recording this.
5 DR. ALLEN:
Thank you.
6 We have a written statement also from the
7
Plasma Protein Therapeutics Association. Is there
8 a
need to read that, do we have a speaker or a
9
proposed speaker? Okay. Thank
you. I will just
10
note for the record that there is a written
11
statement from PPTA also.
12 The open public hearing is now closed.
13 We will move on to the next item on the