Blood Safety Transcripts
DEPARTMENT OF HEALTH AND HUMAN SERVICES
ADVISORY COMMITTEE ON BLOOD SAFETY AND AVAILABILITY
Fourteenth Meeting
WHAT IF ANY ADDITIONAL ACTIONS SHOULD THE
DEPARTMENT TAKE TO PROMOTE BLOOD SAFETY AND
AVAILABILITY THROUGHOUT THE WORLD?
Volume I
8:13 a.m.
Thursday, April 19, 2001
Hyatt Regency Capitol Hill Hotel
400 New Jersey Avenue, N.W.
Washington, D.C. 20001
P A R T I C I P A N T S
Larry Allen
Michael P. Busch, M.D., Ph.D.
Rajen K. Dalal
Richard J. Davey, M.D.
Jay Epstein, M.D.
G. Michael Fitzpatrick
Ronald Gilcher, M.D.
Edward D. Gomperts, M.D.
Fernando Guerra, M.D.
Paul F. Haas, Ph.D.
William Hoots, M.D.
Harvey Klein, M.D.
John Kuhn, M.D.
Karen Shoos Lipton, J.D.
Lola Lopes, Ph.D
Gargi Pahuja
John Penner, M.D.
John Walsh
Jerry Winkelstein, M.D.
Lawrence McMurtry
Stephen D. Nightingale, M.D.
Mary E. Chamberland, M.D.
David Snyder, Rph, D.D.S.
Virginia Wannamaker
C O N T E N T S
AGENDA ITEM
Welcome, Roll Call, Conflict of Interest
Disclosures, Statement of Issue
Stephen D. Nightingale, M.D.
Executive Secretary, Advisory Committee on
Blood Safety and Availability;
Global Strategies for Improving Blood Safety
Jean Emmanuel, M.D., Director, Department
of Blood Safety and Clinical Technology,
World Health Organization
Blood Safety and Availability Initiatives
in the Americas
Jose Ramiro Cruz, Cc.D.
Pan American Health Organization
The International Consortium for
Blood Safety
Mohamed El-Nageh, M.D.
International Consortium for Blood
Safety
CDC International Activities Related
to Blood Safety
Eve Lackritz, M.D.
Centers for Disease Control
FDA International Activities Related to
Blood Safety
Jay Epstein, M.D.
Food and Drug Administration
NIH International Activities Related to
Blood Safety
Jeanne McDermott, Ph.D.
National Institutes of Health/Fogarty
International Center
ABC International Activities Related to Blood
Safety
Celso Bianco, M.D.
America's Blood Centers
AABB International Activities Related to Blood
Safety
Karen Lipton, J.D.
American Association of Blood Banks
American Red Cross International Activities
Related to Blood Safety
Jan Lane
American Red Cross
Academic Medical Center International
Activities Related to Blood Safety
Christopher Beyrer, M.D.
Johns Hopkins University
Plasma Industry International Activities
Related to Blood Safety
Barbee Whitaker, Ph.D.
American Blood Resources Association
Promotion of Appropriate Technology Transfer:
Tests for Transmissible Agents
Helen Lee, M.D.
Cambridge University
Promotion of Appropriate Technology Transfer:
Perspective from a Developing Country
Jean-Pierre Alain, M.D.
Cambridge University
Providing Access to Screening Technologies
Rajen Dalal, MBA
Chiron Corporation
Public Comment
Committee Discussion and Recommendations
P R O C E E D I N G S
DR. NIGHTINGALE: Good morning. My name
is Stephen Nightingale. This is the Fourteenth
Meeting of the Advisory Committee on Blood Safety
and Availability.
I would like to begin by calling the roll,
if I could. I know that a couple of the members
are in transit.
Mr. Allen is in transit.
Dr. Busch?
DR. BUSCH: Here.
DR. NIGHTINGALE: Dr. Caplan is, I
believe, unable to make the meeting today.
Dr. Chamberland?
DR. CHAMBERLAND: Here.
DR. NIGHTINGALE: Mr. Dalal?
MR. DALAL: Here.
DR. NIGHTINGALE: Dr. Davey?
DR. DAVEY: Here.
DR. NIGHTINGALE: Dr. Epstein?
DR. EPSTEIN: Here.
DR. NIGHTINGALE: Captain Fitzgerald
[sic], Captain Mike, is in transit.
Dr. Gilcher?
DR. GILCHER: Here.
DR. NIGHTINGALE: Dr. Gomperts?
DR. GOMPERTS: Here.
DR. NIGHTINGALE: Dr. Goosby is in Africa
and unable to make it today.
Dr. Guerra?
DR. GUERRA: Here.
DR. NIGHTINGALE: Dr. Haas?
DR. HAAS: Here.
DR. NIGHTINGALE: Dr. Hoots?
DR. HOOTS: Here.
DR. NIGHTINGALE: And a new member, Dr.
Harvey Klein. Do not be misled by his nameplate,
which he has turned around. We apologize for that.
Dr. Harvey Klein is the new representative to the
Advisory Committee because Dr. Paul McCurdy has,
once again, retired.
[Laughter.]
DR. NIGHTINGALE: Dr. McCurdy, however, is
in the audience because Dr. McCurdy is serving now
as a consultant to the Department of Health and
Human Services, and I am delighted not only to
welcome Dr. McCurdy and appreciate his willingness
to continue to serve the government, but to give me
another opportunity to thank him for his service.
It is said by many a minister that you're
always preaching to somebody else's crowd. That is
me. You are--I inherited Dr. McCurdy's church, if
you will, and it's been an honor and a privilege to
inherit that. What you've seen in the last few
meetings is what Dr. McCurdy started. Paul, thank
you very much.
[Applause.]
DR. NIGHTINGALE: And, Harvey, welcome,
and thank you very much for being here.
Dr. Kuhn?
DR. KUHN: Here.
DR. NIGHTINGALE: Ms. Lipton?
MS. LIPTON: Present.
DR. NIGHTINGALE: Dr. Lopes?
DR. LOPES: Present.
DR. NIGHTINGALE: Ms. Pahuja?
MS. PAHUJA: Here.
DR. NIGHTINGALE: Dr. Penner?
DR. PENNER: Here.
DR. NIGHTINGALE: Dr. Piliavin is teaching
this semester and is unable to attend.
Captain Snyder is in transit.
Mr. Walsh?
MR. WALSH: Here.
DR. NIGHTINGALE: Dr. Winkelstein?
DR. WINKELSTEIN: Here.
DR. NIGHTINGALE: Thank you.
I would also like to announce that joining
the staff of the committee for a 6-month detail is
Ms. Virginia Wannamaker of the Health Care
Financing Administration. Ginnie, if you are in
the room, could you identify yourself. That's Ms.
Wannamaker.
And Captain and Dr. Barbara Silverman, who
is not here this morning, but will be here this
afternoon, and will be working with the committee
half-time to help us flesh out what we accomplish
tomorrow in our discussion of how to monitor the
blood supply.
This moves me, as quickly as I'm able to
move, to the Conflict of Interest Statement, and I
noted with some relief that neither Dr. Caplan nor
Dr. Satcher are looking over my shoulder as I read
this, so not being under that pressure, you are all
seated comfortable, and I will do it as quickly as
I can.
The following announcement is made as part
of the public record to preclude even the
appearance of a conflict of interest at this
meeting:
General applicability has been approved
for all committee members. This means that unless
a particular matter is brought before this
committee that deals with a specific product or
firm, it has been determined that all interests
reported by the Advisory Committee members present
no potential conflict of interest when evaluated
against the agenda.
In particular, as specified in Title 18 of
the United States Code 208(b)(2), a special
government employee, which all committee members
are, may participate in a matter of general
applicability; for example, advising the government
about its policies relating to the Hepatitis C
epidemic, even if they are presently employed or
have the prospect of being employed by an entity,
including themselves if they are self-employed,
that might be affected by a decision of the
committee, provided--and this is the key point--that the matter will not have a special or distinct
effect on the employee or the employer other than
as a member of a class.
The example given at 5 CFR 2640.203, which
implements the U.S. Code is as follows:
A chemist employed by a major
pharmaceutical company has been appointed to serve
on an Advisory Committee established to develop
recommendations for new standards for AIDS vaccine
trials involving human subjects. Even though the
chemist's employer is in the process of developing
an experimental AIDS vaccine and therefore will be
affected by the new standards, the chemist may
participate in formulating the Advisory Committee's
recommendations. The chemist's employer will be
affected by the new standards, but only as a part
of a class of all pharmaceutical companies and
other research entities that are attempting to
develop an AIDS vaccine.
In the event the discussions involve a
specific product or a specific firm for which the
member has a financial interest, that member should
exclude him- or herself from the committee
discussion, and that exclusion will be noted in the
public record. With respect to the other meeting
participants, we ask, in the interest of fairness,
that they disclose any current or previous
financial arrangements with any specific product or
specific firm on which they plan to comment.
I will note, also, for the record that
each voting member of the Advisory Committee has,
in a packet before them, a specific waiver for the
purpose of participating in the meeting under the
terms that I just described.
When the committee was established, it had
been considered that the appointment by the
Secretary herself constituted that waiver. With
changes of administration, rules undergo review, as
do former policies and actions, and the waiver is
an additional measure I think of protection for the
committee. It confers no new rights. It does not
require your signature. We, perhaps, have
completed the piece of paperwork, which I would be
glad to discuss with any member of the committee if
they do, but the bottom line is your rights, your
responsibilities, and your protection, which is
really the bottom line here, are unchanged by that.
The title of today's meeting is what, if
any, additional action should the Department take
to promote blood safety and availability throughout
the world? I would simply say here that the title
speaks for itself. There was a lot going on in
this area, and there is obviously a lot left to do.
What I have tried to do in the confines of
a day meeting is to invite a representative section
of individuals who are involved in this effort,
both in the government, out of the government, in
nonorganizations, both in the states and abroad,
and individuals, and open the microphone for
everyone who wishes to comment.
I realize that this is not inclusive of
everyone. The Department remains interested in the
input of those who are involved in this effort and
are not capable of being here today. The process
that will follow this meeting is that the input
that we obtain through this meeting from the
committee members and from any recommendations they
may make, from the comments from the floor and from
the comments from other interested parties, will be
put into the form of a draft document that will
then be circulated throughout the public health
service for its review.
Following that, once the clearance or
assent to the document is completed, that document
will be forwarded to the secretary for whatever
necessary or appropriate action is taken. That is,
in fact, the policy that we follow for all topics
that are discussed by the Advisory Committee, and
that will be the process that we will follow for
following up on the discussions that take place
tomorrow.
The prior recommendations of the committee
at its January meeting are still under review by
the new administration, and I will report back to
the committee members and the public at-large, as
soon as that consideration by the Department has
been completed.
I wish to announce, for the record, at
this point, that we will have six vacancies
occurring on the Advisory Committee at the
completion of its term on September 30th, their
terms on September 30th of 2001. There will be a
formal announcement in the Federal Register, on or
about June the 1st, as a solicitation of
nominations.
We have received many nominations in
response to our solicitation last year. As I
announced previously, all of those nominations
remain current. It is not necessary for anyone who
has been nominated before or nominated themselves
to do so again. What I do wish to make part of the
public record is we continue to solicit
nominations, including self-nominations, from all
interested parties to this committee.
I think we are close to the end of the
announcements. There are only two more. One of
them has to do with cell phones, such as these. We
have, in the past, met in the basement. This has
not been entirely accidental because in the
basement, as many of you found out, the cell phones
don't work. Up here, they do work. For those of
you who have vibrate on yours, as do I, would you
please turn it to vibrate, and if you can't do
that, if you would keep the rings to a minimum, I
would appreciate.
Finally, I really do want to thank
specifically everyone for being here. This is an
important topic. It's also a busy time of the
year, and I realize the sacrifices that people have
made to come here. One of those who could not make
those sacrifices is Dr. Caplan. Dr. Gomperts will
chair the meeting in his absence.
Dr. Gomperts?
DR. GOMPERTS: [Presiding.] Thank you,
Dr. Nightingale, for getting us going and getting
us rolling this morning.
It's a busy session the first part of the
day. Our first presenter is Dr. Jean Emmanuel,
M.D., director, Department of Blood Safety and
Clinical Technology, World Health Organization.
Dr. Emmanuel?
DR. EMMANUEL: Thank you very much, Mr.
Chairman, Dr. Nightingale, and members of the
committee for inviting me and for, once again,
allowing me to come back to Washington.
The presentation I'm making today, which I
hope I will be able to make, is on this new
technology, and I'm not sure who's working it. I'm
certainly doing it by remote control. It looks as
if it's in front of Jay. It's always dangerous
being the first speaker anyway.
While the technology is catching up with
old-fashioned--
DR. NIGHTINGALE: Excuse me, Dr. Emmanuel,
we will have a little slack. What happened was the
computer that we had intended to use, the small
black box over there, has crashed. We try to keep
these things on time as much as possible. There
are acts beyond our control that happen, and this
is one of them. You came a long way, and we want
to hear what you have to say so we're willing to
wait.
DR. EMMANUEL: Perhaps I can just speak
about WHO a little bit prior to the slides. Many
of you have heard a lot of what I'm going to speak
about. But for those of you who don't know, WHO is
the World Health Organization responsible for
health for 191 member states. That's almost every
country in the world, with very few exceptions.
And as such, as this responsibility and all issues
of health, the Ministers of Health meet, in WHO,
once a year in May.
There is an Executive Board that meets to
prepare for that meeting in May in the January, and
proposals are put forward as resolutions, and the
resolutions are passed by the members, and they
become World Health Resolutions, which are endorsed
and are enforceable by the member states.
You'll be hearing from my colleague in
PAHO. WHO has headquarters in Geneva, Switzerland,
and six regional offices. The regional office for
the Pan American Health Organization and the
American regional office for the World Health
Organization is based here in Washington. We have
another regional office, AFRO, in Harare in
Zimbabwe. We have an office in the Eastern
Mediterranean in Cairo. We have an office for Euro
in Copenhagen. Delhi is the Southeast Asia office,
and the Western Pacific Regional Office is in
Manilla.
The six offices work together with WHO in
concert, and at each country level there is a
representative of WHO in the 191 member states.
So, together, this forms a considerable body of
people working towards the safety and improvement
of health at national level.
Now, when we look at--I hope this is all
visible for everybody--when we look at the issues
on blood safety, what I hope to address today is
addressing the problem, the themes and objectives
of the Blood Safety and Clinical Technology Unit at
WHO, defining what we consider to be safe blood or
the minimum criteria for safe blood, the strategies
that are being developed in the production of safe
blood and availability, the Blood Transfusion
Safety, our activities, and our aide memoir, which
encapsulates the essence of our four main
strategies, with an overall quality issue.
Thank you.
Now, the work of WHO is in the area of
global blood safety, as well as, as I mentioned
before, at the country level because it's at the
country level that we have the impact and the
concerns for national health authorities.
So what is the problem? When we look at
the human development index as a criteria for
defining countries, the United Nations Development
Program Human Development Index classifies
countries as having a low, medium or high HDI, and
the classification is based on the following
criteria: life expectancy, educational attainment
and adjusted income.
Using that as a basis for our global
database on gathering information for blood safety,
you can see that in the developed countries or the
high HDI that 60 percent of the blood supply is
used in the high HDI and 38 percent in the medium
HDI countries. Whereas, the poorest countries, and
most of the developing countries only have 2
percent of that blood supply.
Now, if you look at the global population
and the global blood supply, what it means here is
that you've got population on this bar and the
blood supply on this bar. And in the developing
world, you can see that the blood supply is far
less than that in the developed world, although the
population is much higher in the developing
countries.
Looking at it another way, if you've got
83 percent of the population, the high development
HDI countries are here, but 83 percent of the
population are in the low development and in the
medium development HDIs.
All of this information I can make
available to you in hard copy for those of you who
wish to have this. But when we look at the types
of donation, and we all recognize that other than
voluntary, nonremunerated blood donation, there is
a high risk in, first of all, the paid donors
clearly, and secondly the family replacement donors
which tend to be paid donors in many countries.
Now, if you look at the developing world,
you can see that they have 8 percent paid donors,
which are extremely risky, and 61 percent of their
blood donors come from so-called family replacement
which, in essence, are a large paid donor
population, a hidden paid donor population. These
figures look as if they are family replacement
simply because no one is seen to be paying them.
This is done as an internal agreement between
families with the paid donors, and only 31 percent
are the safer donors, as opposed to the developed
world, where 98 percent come from voluntary,
nonremunerated donors.
If we look at the global burden of
disease, we look at approximately $600 million
people who are infected with HIV, hepatitis B virus
and hepatitis C virus. Five percent to ten percent
of infections of HIV are caused through unsafe
blood transfusions.
So viral screening of whole blood
donations, if we look in the developed world, we
can see that there's 100-percent testing. If we
look at the developing world, the low and medium
HDI, only 57 percent are tested and 43 percent are
untested, which accounts for some 30 million
donations of blood that are transfused and are
untested.
The sero prevalence amongst blood donors
in the developed world is very low. When you look
at the least-developed countries, it is in the area
of 13 percent, on average. However, we know that
in countries in sub-Saharan Africa, that figure can
rise to 25 to 45 percent HIV positive. That's
nearly half of the population that is HIV positive
because the population that's donating blood comes
from the sexually active group. Hepatitis B, up to
32 percent, and HCV, 18 percent, again, on average,
and in some countries much higher. And when you
remember that in a previous life 43 percent of the
blood in those countries are not tested.
Now, when we're looking at our HCV panel,
we're looking at evaluating one of our biggest
drives at the moment is to bring the price of HCV
test reagents down so that they are available for
countries. On HIV, we've had a system of
evaluating test kits and bulk purchasing with the
understanding of manufacturers and brought the
price of HIV test kits down, ELISA, to less than 75
U.S. cents, and for simple rapid from between 1.2
U.S. dollars to 1.8 U.S. dollars. We are looking
at the issue of simple rapid tests for HBV and HCV.
And so what we have here on our HCV panel,
specimen panel, is positives and negatives from the
different regional serotypes, giving us a total of
257 specimen panels.
And when we look at the evaluation of HCV,
we use the Ortho test, 3.0, as our standard test,
and the sensitivity and specificity of the
different available test kits that we've evaluated
are shown on this slide. And basically the
sensitivity and specificity worked between 97.1
sensitivity up to 100 percent. Again, showing
this, on our reference assay, using the Ortho as
our standard test.
Again, we are concerned about HIV,
hepatitis B, C, Chagas, where it's appropriate, and
syphilis testing. But, again, we recognize the
immunohematology and that there is a lack of
standardization, documentation, and traceability.
There is a lack of evidence, not a lack of
evidence, but a lack of information on how many
incompatible blood transfusions are actually given
wrong blood to the wrong patient at the wrong time,
and we are aware that there are many fatalities as
a result of this problem.
So one of our other drives is to ensure
that attention is focused not only on infectivity,
but also on the importance of the correct blood
group and the compatibility of the blood.
ABO compatibility is a major cause of
mortality in developing countries, apart from the
fact that there is no blood available when it's
needed. And remember that the major requirement
for blood in developing countries is as a
consequence of pregnancy in women, children as a
result of malaria, malnutrition and trauma. Those
are the big three in that order.
Of the 250,000 women who die as a
consequence of pregnancy, nearly one-half of those
are as a result of blood loss and availability of
blood, not counting those who are infected with
blood that is not tested.
So access. When we look at this and the
figures that I've told you about previously, 17
percent of the global population has access to 60
percent of the global blood supply. This isn't a
safe blood supply. Eighty percent of the global
population has access to only 20 percent of the
blood supply that is safe and is tested. So the
vast majority of the world has got the least
availability to blood.
The organization themes of the Blood
Safety and Clinical Technology Unit then therefore
addresses not only the issue of blood safety, but
the whole area of clinical technology.
And very briefly, this is the cluster
within which my Department, which is Blood Safety
and Clinical Technology in the Center, we have the
essential drugs and medicines, and we have the
vaccines and biologicals on the right. We work
very closely within the cluster in a variety of
ways--for waste disposal, safety of injections,
diagnostic imaging, radiology, and laboratory and
clinical technology, district surgical services,
essential surgery at the district hospital or
first-referral hospital to ensure that blood is
only used when it's required and that procedures
are carried out in a proper and controlled way and
that patients are referred, when they need to be
referred, to the next level.
We also work very closely with the
Essential Drugs and Medicines on the supply of
essential drugs for minimizing blood loss, making
sure there's availability of plasma and plasma
derivatives, and crystalloids, and colloids, and
other drugs.
Within the Department, we also have the
quality and safety of plasma derivatives, the norms
and standards. Kathy Zoon is the present chairman
of the Expert Committee on Biological Standards,
and many of the people who are here today at
present have been involved in the work of the
Department in various aspects.
So our mission is to promote the safety,
quality, and adequacy of blood and blood products,
injections, diagnostic and clinical technologies,
and medical devices. The medical devices include
things like an oxygen concentrator for use in
developing countries where oxygen is not available,
the use of and production of a simple hemoglobin
screening tool, which is now available, and will
cost 2 U.S. cents per test to screen for anemia,
and so on.
Our four main objectives, then, within the
Department are to ensure policy. As I told you
earlier, WHO is responsible to 191 member states
and the health authorities. We have an enormous
responsibility to ensure that policy issues and
policy makers make the right decisions, and we
assist them in carrying out the resolutions that
they have adopted. We ensure the quality, and we
help them to ensure the quality and safety.
Access, we talked about the bulk purchasing, and we
try and promote the proper use.
To give you an example of use, for
instance, we have just published the clinical use
of blood which is going to be we had the first
workshop in India, which is a tool for self-learning for medical practitioners or prescribers
of blood with a pocket handbook that they can carry
around with them.
We also have a distance learning program
for laboratories and people working in
laboratories, and we have workshops on trying to
promote the proper usage not only of blood, but the
proper clinical application of its products.
So, when we look at blood safety as a
priority, we cut across blood transfusion safety
with policy, ensuring that we promote voluntary
nonremunerated blood donation from low-risk
population groups, ensure that they are counseled
and tested. We have all of the testing processes
that I've talked about, evaluation of HIV test
kits, bulk purchasing, the processing of blood,
which is components. We evaluate fridges and
freezers and put them into public information
sheets so that countries can identify which fridges
meet the criteria for blood usage and the clinical
use of blood.
In diagnostic technology, we are the
organization responsible for global norms and
standards--hemoglobin norms, biological standards,
and so on, and reference preparations, diagnostic
imaging and laboratory services, and under
technologies, we have district surgical services,
waste management injections, and medical devices.
Now, when you look at this, it,
unfortunately, hasn't all come out, but if you look
at our department, which is BCT, Blood Safety and
Clinical Technology, we can only work with the
assistance of our collaborating partners. The most
important of our collaborating partners are the
regional laboratory advisers, and Dr. Cruz will be
speaking after me on the activities they do at the
regional level, and through them a country level.
Now, clearly, without the regions the work
of headquarters would not be possible. And the
regional advisers represent the requirements and
issues that they have become clearly identified
with at a country level. Again, at country level
there's a World Health representative that
represents the countries and relays the information
back to the regional office and headquarters.
Our collaborating centers are very
important, as are our nongovernmental
organizations. We hope to get the American
Association of Blood Banks as an official NGO,
nongovernmental organization, in official relations
with WHO to help and share in its work and its
accreditation.
We have our resource mobilization, where
we raise money from different countries to do the
work that we have to carry out, in addition to our
regular budget. We have other UN aids and other UN
agencies such as UNICEF and so on producing
materials and evaluating test kits and so on for
them, and we have our global collaboration for
blood safety with our partners, including the
International Federation of Red Cross and Red
Crescent Societies, the International Society of
Blood Transfusion, World Federation of Hemophilia,
ABB and others. And we work within our own
clusters within WHO, such as the communicable
diseases and so on.
So what is safe blood then? So we
consider that blood is safe with transfusion when
it is donated by a healthy donor at low risk of
transmitting infection or harmful agents. The
blood is processed by the most effective testing
methods, and it is transfused only when needed to
prevent death or serious complications.
One of our major strategies now is to
educate the prescribers of blood into thinking
about when is a transfusion required and when is it
not required. In other words, this old adage of
when if you only need one unit of blood you don't
need to give blood at all I think needs to be
relooked.
If you've got a patient at 7 grams of
hemoglobin, and they will decompensate with one
unit of whole blood or packed cells will raise that
hemoglobin to 8.5, and they can go home with IM and
folic acid, then you've minimized the risks.
To look at the situation of whether you
need to be producing components or you can give
whole blood, in countries that I've shown you with
high infection prevalence, is it sensible to give
packed cells and then plasma from another unit,
doubling the risk and so on.
So we are hoping that through that we will
get doctors educated or prescribers of blood into
thinking about what they are actually doing, as
well as surgical procedures, where simple cryostats
and so on can prevent bleeding and prevent the
requirement for blood, as well as educating the
public health authorities into preventing malaria,
infections from hook worm and providing good
antenatal care can prevent the use of blood.
So government commitment and support is
one of our major strategies, and we talked about
four strategies, and this is the first strategy
here, where there is a World Health resolution of
1975, World Health resolution 28.72, where
governments agreed to the formation of national
blood transfusion services based on voluntary and
nonremunerated blood donation. We need to provide
them with the framework for national blood programs
so they can implement this legal framework
requiring that nonprofit organizations run the
blood transfusion services on a nonprofit basis,
the implementation of a policy and plan for that
blood transfusion service to ensure that the right
blood gets to the right patient at the right time,
and that they provide an adequate budget for that
process.
And to that end, we've also produced some
materials and books on costing of blood transfusion
services with an Excel file that allows them to add
up all of the costs in blood transfusion and to
provide a comprehensive budget for the government
to be able to support those services and make them
sustainable.
The second strategy is to promote and
retain voluntary blood donations from altruistic
donors that are nonremunerated and from low-risk
populations, to care for those donors, and to
provide them with counseling and follow-up and
ensure that they are regular repeat donors.
To give you an example of this, in sub-Saharan Africa, a Club 25, Pledge 25 system was
developed amongst school children from 16 until
school leaving age, which is 18 or 19, to pledge to
give 25 donations of blood within their lifetime.
They were counseled and educated. And from a
population group of 25-percent HIV positive, those
blood donors are less than .2 percent, 0.2 percent.
It's an incredible decrease in the prevalence. And
in amongst their peers who don't give blood, that
prevalence of HIV has had a major impact on
reducing the prevalence of infection in their own
peer group, and they will go out into the
population, and they have remained steadfast donors
of the Blood Transfusion Service after school.
The third strategy then is to test all
donated blood using the most appropriate and
effective methodologies for infectious agents,
blood grouping compatibility testing and quality
issues and ensure the good manufacturing practices
for blood components, as and when required.
And the fourth one is the reduction of
unnecessary transfusions through effective clinical
use of blood. You can only do that if you have the
product available to ensure that doctors get the
blood when they're required, don't order it on the
basis of maybe I'll need it, and promoting
especially the use of simple alternatives to
transfusion.
Too many countries are using plasma as a
volume expander instead of crystalloids and
colloids. This is more of a logistical issue, and
it's certainly more cost-effective and certainly
safer.
A global concern for us then is what about
all of the different agencies and assistance that's
being provided. How are we monitored and evaluated
on our own work, and how can we put all of these
agencies together? And I think this forum that Dr.
Nightingale has put together is a very good forum
for us to also discuss issues in a high-technology
area with a lot of expertise in the United States
to look at agencies through foundations and
national funding agencies that provide money for
the improvement of blood safety.
Jay Epstein was involved right at the
beginning when we had the Paris 8 Summit in 1994,
and one of the major themes of that summit was to
look at the issue of how could we improve blood
safety? It was, of course, directed towards HIV,
but they recognized that HIV wasn't the only issue,
and I've covered the other aspects of blood safety
in the previous part of the lecture.
During that meeting, blood was declared a
strategic priority, and it was carried forward
because only 40 countries and member states were
present at the Paris 8 Summit. A recommendation
was made to carry that forward to the 1995 World
Health Assembly, and the global collaboration for
blood safety was declared a priority at the World
Health Assembly, 48.27 in 1995, and all of the 191
member states supported its inception.
The Global Collaboration for Blood Safety
provides--WHO provides a secretariat within the
Blood Transfusion Safety Team. The idea is that
WHO is not trying to coerce or change people's way
of doing things, but only to get them together
around a table and provide a mutual forum for these
discussions. A lot of the people in this room have
been present at the meetings, and the premeetings
of the Global Collaboration for Blood Safety and
will be able to add to what I've said, if required.
So the Global Collaboration for Blood
Safety with my department as a secretariat looks at
a whole range of collaboration between partners who
come around the table. We have national control
authorities, other relevant parties who may be the
blood donor groups and so on. We have the plasma
industry, WHO collaborating centers who assist us
in our work. We have country experts who come in.
We have UN agencies, other international
organizations, such as--and AABB is also considered
an international organization from that point of
view, and we have patient groups.
The objectives are to build on the
existing knowledge, utilize existing expertise to
promote a dialogue between all of those members
present, where they can suggest realistic,
effective and practical mechanisms for improving
blood safety. They can look at WHO and say, why
are you not doing work in this area? We can look
to other partners and say we believe you should be
doing something in this area. We can facilitate
working groups to address specific and burning
issues, and we can move forward, through regular
meetings, to improve blood safety and the
collaboration. We can also co-op members who are
not around this table for specific issues.
The GCBS then will lead to improved global
blood safety by raising international awareness,
developing strategies and guidance that other
organizations can either adopt or assist us in our
development, identify issues of concern, and bring
together all countries through developing and
developed countries, where they can share
experiences.
Within the GCBS, of course, we can look
at, and we have, and the first report of the GCBS
is out--and I'll have copies for those who were
present at the last meeting, of the minutes of that
meeting and the recommendations--was to select
specific working groups to look at very burning
issues. And the last meeting we had three issues
that we looked at, but we started by looking at
decision-formulating policies and blood safety for
policy makers, issues on safe blood donation,
safety and testing of blood and plasma, the rights
of patients working groups, quality management, and
traceability of plasma.
Next slide, please. We came up during the
meeting that this is what we would address for the
next year and thereafter: a working group on
quality assessment and assistant for development in
countries. These two were separate groups that
were put together as one working group. As a
working group on the policy process, making
decisions--policy makers making decisions. And the
third one is the working group on plasma issues.
Basically using the norms and standards that are
developed by the expert committee on biological
standards, but to look at issue of plasma in
developing countries, plasma for fractionation,
requirements for plasma derived for medicinal
products and so on.
Next slide, please. And in summary then,
the global collaboration for blood safety will
improve safety and adequacy of blood and blood
products globally. It will bring together
developing and developed countries, which is
vitally important. And it will provide a forum for
exchange of in and identification of issues and
concerns. We don't see this as a unique body in
itself, but it is a global collaboration. There is
still a place for large countries such as the
United States to have other fora for identifying
how collaboration can be dealt with on a
coordinated and combined effort from within a large
country where not only is expertise available, but
funds are available and so on, and this can be
carried forward to a global collaboration.
Next slide, please. That, Mr. Chairman,
concludes my presentation. I'd be happy to answer
any questions in the future. Thank you very much.
[Applause.]
DR. GOMPERTS: Thank you, Dr. Emmanuel.
Are there any questions from the committee?
DR. GUERRA: First of all, thank you very
much for an excellent review of what is truly a
global concern. You didn't mention anything about
storage and distribution. Perhaps that's for
another working group that discussed that, but
would you comment about at least what--or how that
has been addressed?
DR. EMMANUEL: Are you referring to the
storage and distribution of blood and blood
products?
DR. GUERRA: Yes, sir.
DR. EMMANUEL: We have a project that is
funded by Luxembourg Government that's been going
on now for some six years. It's called the Blood
Cold Chain. We've been looking at fridges,
freezers of different sizes. We just call them
small, middle and large-type freezers. We've
evaluated fridges from all over the world, and that
will soon be in a publication called "A Public
Service Information Sheet", giving countries some
advice.
In addition to that, we've also been
working very hard on some--what we call BTTIs,
blood time temperature indicators, for blood packs,
whole blood packs and plasma, so that if they're
out of range, the color will change. We're
promoting that within our learning materials, the
distance learning materials which I have in a box
over there. All these materials I can show people
if they'd like to see them, and teaching within our
quality management project and our distance
learning project on the transport of blood and
blood products.
We, within our system, promote a
centralized system of collection and testing and
provision of blood and blood products to what we
call hospital blood banks. It's a little bit
different to the states, but we, in district
hospitals, mission hospitals and so on, we believe
that smaller centers should have a fridge and a
freezer and the staff trained to do the logistics
of what you're talking about, which is the
management of the cold chain, and insure that they
have the blood product available within the
hospital from the center, because if you look at
any developing country, whether you go from India,
China or in Africa, the largest population groups
are clearly in the main cities where the blood is
used. The smaller amount of blood is used in the
district hospital, and they haven't got the time or
the expertise or the economies of scale to insure
that they can product a quality product. So that
is a big feature of our learning materials and our
cold chain project that we have under continuous
evaluation.
DR. GOMPERTS: Thank you. Any other
questions? Yes, Dr. Busch?
DR. BUSCH: Jean, congratulations. Just
wonderful progress I think in the last five years
in coordinating both the education and the blood
consensus building.
One issue that I think you're beginning to
try to struggle with is many countries would hear
about the test advances, the best tests available,
and they would kind of use the inability to get the
best test as an excuse for not testing at all, and
understand that recently you sort of defined tiers
of safety or tiers of capacity that would be linked
to the kinds of tests, which anilide you should
test for, and perhaps the quality of testing. And
I'm wondering how that's going in terms of
acceptance.
DR. EMMANUEL: We used the HIV as the sort
of gold standard. We've been doing that for about
ten years now. We have a collaborative center in
Antwerpen. Now we have the Central Public Health
Laboratories in the UK. And with our collaborating
centers and with our regional panels, we're
evaluating test kits from manufacturers and
negotiating with manufacturers to bring that price
down. And I had a very useful and helpful
discussion with Mr. Dalal this morning and
previously on the issue of HCV.
Now, HIV, in the early days we managed to
bring the price down of test kits that met the
criteria that was set for sensitivity and
specificity, ease of use, and we produce a booklet
once a year called "Operational Characteristics",
which identifies all the characteristics that are
required for ELISAs, simple and simple rapid tests.
And we then also make recommendations with
algorithms to show what countries should be doing
if they are testing, say, 30 units a week, 10 units
a week or a day, and at what level they should be
using ELISAs.
Now, we're not disputing the value of
ELISAs. What we are disputing is the use of ELISAs
in untrained hands, and how the results are
produced.
Now, HIV, we've gone a long way on that,
and as I said previously, we have got ELISAs down
to less than 70 US cents and the simple rapids
between 1.2 and 2 US dollars per test, and their
sensitivity and specificity, as you know, is equal
to that of an ELISA, and certainly in untrained
hands is far superior to that of an ELISA.
We would like to do the same for hepatitis
B and C. Even if the sensitivity is slightly
lower, or specificity, it will certainly be well up
until the high 90s, as you saw on the HCV as an
example.
And we were talking about what is the
price. Now, remember, the one big thing is that
everybody has this emotive drive for HIV. And when
you look at our learning materials, we talk about
testing for HIV and other infectious agents. Now,
I think the funders of HIV would be disturbed to
see HIV test kits provided at, say, a US dollar,
but an HCV coming in at 5 US dollars, and say,
well, we're funding HCV and it hasn't got the same
emotional drive. But if we can get the price
around about the same and say, well, it's a dollar
a test, then we're looking at something--or $1.50
or whatever it is--we're looking at something that
we can then--as I said, one of our major drives is
through policy--to say to countries, you know, we
can shame them into using it, I think your
argument's a good one. If it's a $5 test they can
say, we can't really afford this for a disease that
might be 20 years down the line in our population
group, and looking at the burden of disease and the
cost effectiveness of a test. But if we can show
it at that kind of cost or price, we can then say,
this is something that you really have to put into
place. So that's our drive.
And we're not saying that we have--we just
have to put partnerships together or try and
coordinate, and I think you'll hear from other
speakers today how they're also going for the same
drive. But the idea is to make sure that it's not
just for HCV or HBV or HIV, but it's a
comprehensive package I've tried to show today,
that provides safe blood to the end product which
is the clinical use, and the district surgical
services for which we are responsible to show them
how a correct procedure with simple technology can
minimize the unnecessary shedding of blood.
DR. GOMPERTS: Thank you. Dr. Davey.
DR. DAVEY: Jean, as you know, there's
been interest on and off through the years about
pooling samples from a small number of donors for
basic infectious disease screening. What's the
position of WHO on pooling these days?
DR. EMMANUEL: Well, you're aware that we
did try and introduce that at the early days of
HIV, and one of the main reasons for doing this, of
course, was that it was the cost of the HIV test
kits. Now that it's come down to that low price--this was particularly driven by simple-rapid tests
that were at $5--it becomes less--more difficult to
promote pooling, and I think it's less necessary.
The dangers of pooling, of course, is in
untrained hands, as are the obvious dangers, the
lack of sensitivity and specificity. We always had
the policy that the final dilution should always
be, and the manufacturer's recommendation should be
adhered to. There's also a reluctance from
countries, who feel that pooling will
psychologically be a loss of sensitivity and
specificity.
So we haven't really pursued that to a
great extent. We'd rather pursue the
manufacturer's requirements, but reduce the price.
DR. GOMPERTS: Yeah?
DR. PENNER: Perhaps--I'm not sure if this
is appropriate, but would regional centralization
of testing be cost effective or realistic at all
since we have capabilities of moving samples very
easily from country to country and so on" Just as
you have your WHO regional areas, why not a huge or
very large testing center?
DR. EMMANUEL: Yes. I absolutely agree
with you. That model has been used, certainly,
South Africa, Zimbabwe, Zambia, Botswana and so on.
There's one criteria, obviously, and that is that
you have to have an organization that's properly
managed and you have to have a culture and system.
And the biggest problem is, is that we haven't got
countries to address the issue of dedicating a
blood transfusion service to an organization with a
proper head and a properly structured body. Once
that's done, that is exactly what we're trying to
move, and we talked about this, for example, in
India, where we discussed--clearly, people talk
about India, the blood transfusion service problem
in India, and it always amuses me because I asked
them, "Well, what about the blood transfusion
service for Africa?" And everybody says, "Well,
that's not possible." But when you look at the
population, it's one-third of the population of
India, and yet no one thinks of Africa as having a
blood transfusion with centralized testing.
Now, India can have a coordinated policy,
which is what they have got at a national level,
but state by state, organizational structures,
which means that you do have a coordination. You
have economies of scale, bulk purchasing and so on.
But even within a state such as Maharashtra, you
could have a number of smaller blood banks working
on a sort of hub and spoke sort of issue. And we
have been promoting that, and that's what they're
working towards. For instance, India had started
with 110 zonal testing centers, because it's in
these major hubs where the blood is more easily
accessible, where donor drives can take place and
providing to the periphery.
So what you're saying is it is cost
effective. It improve the quality, safety and the
price. So it is, but the problem is getting the
organization and training the staff, and this is
our quality management project at the moment, where
we're training two people from every country--not
India, of course, India would be, you know, a large
number of people, and India's dealt with as a
region on its own, and soon will China. So we have
quality managers and officers trained in the aspect
of quality, to try and promote this within their
own ranks and almost be disciples for policies and
strategies that we have developed.
DR. GOMPERTS: Dr. Emmanuel, thank you
for--we have one other question. Dr. Klein.
DR. KLEIN: This may be a little bit
unfair, but I have to take the opportunity to ask
you this. You've, obviously been involved in
global safety and availability for a much longer
time and much more intensely than most of the
people sitting around this table. So, given the
topic, what advice do you have for us for
additional activities perhaps that the department
should undertake in order to assist global safety
and availability of blood?
DR. EMMANUEL: I think if we just bring it
down to simplistics, the one most important thing
for me is that there's an adequate level of
representation at the global collaboration for
blood safety, which I think has raised a level of
awareness of what the requirements are outside the
borders of this country.
I think the next level is to say that
within the United States there are a lot of people
doing very, very good work, but there needs to be a
forum for collaboration of putting together all
these activities in a more structured way.
Now, if that can be put together in the
country and then represented at a global level to
bring it back, I think that would be a major step
forward.
DR. GOMPERTS: Any further comments?
[No response.]
DR. GOMPERTS: Dr. Emmanuel, thank you
very much.
We'll move on now to the next
presentation, Dr. Jose Ramiro Cruz, Pan American
Health Organization. Dr. Cruz.
DR. CRUZ: Thank you. It's much easier
for me to speak after Jean, because, you know, the
Pan American Health Organization is part of WHO,
although the Pan American Sanitary Bureau was
created 99 years ago, so we have our own executive
committee represented by the Ministry of Health of
34--37 countries in the Americas. That's in
America, the Caribbean, Canada, the United States.
So please don't be afraid because you know this is
in Spanish, but the actual data is going to be in
English.
[Laughter.]
DR. CRUZ: And, again, you know, what I
hope I will do in the next 15 minutes is to
convince you that it is important for us to receive
support in terms of advocacy, basically to raise
awareness of the importance of blood safety and
availability, the transfer of technology to the
countries including the training of personnel. But
again, you know, we deal with 44 countries.
Can I have the next slide? You know, this
represents the number of blood banks per country in
the region of the Americas, and you notice that,
hitting the X axis, the highest number is six, and
these are the countries in the Caribbean. These
are some other countries, and you know, we deal
with countries like Anguilla and Antigua, that have
about 3 or 4 thousand inhabitants in the whole
country, and then we have to deal with countries
like Mexico and Brazil, which are a little bit
larger than the Caribbean countries. And again,
just to give you an idea of, you know, how we--how
to approach the country level work with different
approaches, you'll see that most of the countries
in the Caribbean have just one blood bank and
that's down here.
If I can have the next slide. And this
will show you, and we have here Canada, that's the
very first country here with 18 blood banks all
together, but you'll see for instance that Bolivia
and Chile have close to 90 blood banks in the
country, and for instance, you know, Bolivia has
about 8 million people, so you can see, you know,
what the number of blood units these blood banks
collect.
If I can have the next slide. Again,
these are the larger countries, and here, we have
in Brazil with close to 2,000 blood banks.
And next, please. Just to give you an
idea of what is the number of blood units that are
collected in each of these countries, and again,
these are the Caribbean countries, and you'll
notice that the highest number here is 5,000, you
know, but most of the countries in the Caribbean
collect around 2,000, or, you know, between 1,000
and 2,000 units of blood per year in the whole
country as compared to the countries in Latin
America.
Can I have the next slide, please? You
see here that we have 60,000 and that's Costa Rica,
but okay, the first country in this graph is
Jamaica. That's the largest country in the
Caribbean. They collect about 25,000 units of
blood each year, but again, this is 60,000, and the
next slide will show you the number of unit that I
collected, you know, in the rest of the countries
with Cuba collecting 600,000 units of blood per
year.
But again, how does that compare to
population? Can I have the next slide? And again,
you know, if we use 5 percent, and that is
considered, you know, the indicator for enough
blood to be collected in a given country, you're
going to see that it's only Cuba that is about 5
percent. This is United States with a cost of 4.7.
This is Canada here, and this is Uruguay here. So,
basically most of the countries in Latin America
collect about one-fifth of what is estimated to be
sufficient for enough blood to be available in each
of the countries.
Can I have the next slide? And you know
the rate is basically the same in the Caribbean
countries, and these are the Caribbean countries
again, and again you'll see that most of these are,
you know, around 1 or even below 1. And these two
countries here are--actually, these are the Dutch
territories Aruba and Curacao.
Could I have the next slide, please? As
Dr. Emmanuel mentioned, you know, one of the
products that we have is the paid donors, and we
have five countries in the region that they
officially report to us that they have paid donors,
and those are Chile, with around 1 per 1,000; Peru,
Honduras, Bolivia and Panama. And let me tell you
that these are data from 1999. We just got the
data from the 2000 and in Panama this ratio
increased to 48 percent, and in Bolivia it went up
to 38 percent. So, again, you know, in these two
countries at least the proportion of paid donors
has increased in the last three years.
Can I have the next slide, please? But
again, you know, most of the countries rely on
replacement donors, and again here we have the
Latin American countries, and you're going to see
that basically, you know, all--the vast majority of
the blood come from the replacement donors. In
some be the minority, around 10 percent of the
blood in the region that comes from other type of
donors, and we have other countries like Nicaragua
and El Salvador that have about 40 to 50 percent
voluntary blood donors in those particular
countries.
Can I have the next slide, please? And
yesterday, give you an idea, you know, how the
promotion of voluntary blood donation associated
with the level of organization at the national
level, we have here Canada, the US and Cuba that
have 100 percent voluntary blood donation. Yeah,
you can see the number of--this is, in a simple
mean, divided the number of blood units collected
by the number of blood banks in that particular
country. In Canada, you know, the average is 15
and 9,000. In the US is about 18,000, in Cuba
about 16,000. But if you look at Colombia, Brazil,
the Dominican Republic, the numbers are much lower.
Like in the Dominican Republic the mean average of
annually collected units is about, you know, 400
per blood bank and they only have about 17 percent
voluntary blood donation. So it's quite clear to
us that, you know, the--a promotion of voluntary
blood donation is one more expression of the level
of organization of the blood banks in the
individual countries.
Can I have the next slide? What happens
with the voluntary blood donors in the countries--and let me tell you, you know, this is the Red
Cross in Keto, and this is the blood bank in Keto,
Ecuador, and they have about 92 percent voluntary
blood donors that come to that particular blood
bank. Just five blocks down the road is social
security. And I don't know if you can see it.
They only have about 5 percent voluntary donation.
So it's in a way, basically, tell everybody the
people that don't donate, it's because the
population is not educated, they are not really
knowledgeable about the benefits of voluntary blood
donation, but it's quite clear that within the same
city, you're going to see the difference, you know,
in the preparation of voluntary blood donors at a
blood bank might have been, you know, so close as
is the case in Keto. In Jamaica they have only two
blood banks. One of them is owned by the Ministry
of Health, and they have two collection centers.
One collection center is in Oxford Road, and they
have about--I think this is in the safe part of
Kingston, and they have about 90 percent voluntary
blood donors.
The other collection center is in the not-so-safe part of Kingston and people tell me they
might--they are afraid that they might give their
blood before they get to the blood bank.
[Laughter.]
DR. CRUZ: So, you know, they have only
about 4 percent voluntary blood donors in this
other collection center. So it's better that you
know the accessibility of the collection center and
also the attitude of the personnel in the blood
banks would have an impact on the proportion of
voluntary blood donors in each of the blood banks.
Can I have the next slide? It is
important, let me tell you, that, you know, we
looked at what happens in the country, and we
grouped the blood banks in Ecuador in three, those
that have less than 40 percent replacement donors,
those that have between 41 and 99 percent voluntary
blood donors, and those that--I'm sorry--replacement donors--and those who have mostly
replacement donors. And these are the markers, if
HIV, hepatitis B and hepatitis C, and these are a
proportion of donors that are positive for those
three markers in the blood banks that have the
least replacement donors.
The ones in the second group--can I have
the next--you can see that, you know. And then the
ones with the most replacement donors, you can see
that, you know, the risk of finding a positive
donor is about 1,200 higher in the blood banks
where they basically collect the blood from
replacement donors.
Can I have the next slide, please? Okay.
With this, I hope that you understand and that you
agree with our policy that, you know, one of the
expected results of the original initiative on
blood safety, is that by the year 2003, each of the
countries will have at least 50 percent voluntary
blood donors. That's one of the expected results
that we're looking for two and a half years from
now.
The other issue has to do with the
screening, and Jean mentioned this. And this again
is the percent of units that I screen, for
instance, hepatitis C, in each of the countries,
okay? And you're seeing that Bolivia, for
instance, we didn't have data for Bolivia for '99,
but now for 2000 we know that only about 28 percent
of the units that I collected in Bolivia tested for
hepatitis C. And then we have some other countries
here. We have--for instance, this is, I think,
Guatemala. That's where I come from, but only
about 50 percent of the units there are screened
for hepatitis C. But again, you know, this is our
biggest concern, really, hepatitis C, because for
HIV, basically all the countries test not, if not
100 percent, at least 99 percent of the units that
are collected. The other marker that we are
pushing for are hepatitis B, surface antigen,
syphilis, and Chagas in Latin America. In the
Caribbean, we don't recommend screening for Chagas,
because it's not prevalent there.
Can I have the next slide, please? Then
this is for T. cruzi, and this is again the agent
that causes Chagas disease. And, you know, this is
the other area we have also difficulty in terms of
screening in Latin America.
Can I have the next slide, please? Saved
blood. For hepatitis C in the Caribbean countries,
64 percent of the units that were collected were
not screened for hepatitis C, and in Latin America--this is date for 1999 again--in Latin America,
over one million units were not screened for
hepatitis C. HIV-1 and -2, we have 9 countries
that don't screen 100 percent of the units, and we
have 10 countries that don't screen 100 percent of
the units for hepatitis C. Only 16 out of the 42
countries in the region screen for the hepatitis B,
hepatitis C, HIV and syphilis.
Can I have the next slide, please? Again,
you know, 100 percent screening for hepatitis B,
hepatitis C, HIV and syphilis in 8 of the 21
Caribbean countries, and 6 if the 19 Latin American
countries plus Canada and the United States.
Can I have the next slide, please? Again,
you know, a screening is a big issue, but then what
is the specificity and sensitivity and the accuracy
of the screening? We have a regional program of
external evaluation of performance, in which at
least one major blood bank participates in this
regional program of external evaluation of
performance, and we have national programs in
basically all of the Latin American countries, and
we're setting data up in the Caribbean. But what
is very important is that when you look at the
false negative results, in the last survey that we
had in September 1999, we were able to detect that,
you know, 6 percent of the results for hepatitis C
were actually false negative. So, again, you know,
the quality of the testing is something that we
worry about. The other to inspect the results in
our initiative are that not 100 percent of the
units are tested for the five markers that I
mentioned, and the other expected result is that
100 percent of the blood banks that actually screen
blood, participate in programs of external
evaluation of performance.
Can I have the next slide, please? What
is the safety of the product that is available in
our countries? And we still use a locally-produced
cryo to treat the hemophiliacs. For instance, in
Costa Rica, 67 percent of the hemophiliacs are HIV--I'm sorry--hepatitis C positive. In Chile, 65
percent of them are positive, and in Guatemala,
again my country, only 18 percent. But, you know,
the number of hemophiliacs in Guatemala is much
lower than what is suspected. And what we figure
is that most of the hemophiliacs have left us
because, you know, they either quit treatment or
infectious. But, again, you know, when you look at
Costa Rica and Chile, that are two of the countries
that have the supposed--you know, the better health
services in Latin America, these are the rates of
positivity among hemophiliacs.
Can I have the next slide? This has to do
with age, and again, the older the patients, the
higher the prevalence of antibodies. So that means
that, you know, the more that they're exposed to
locally-produced plasma, let's say, the higher the
chance that they become infected. I think that's
the last one that I want to show, for the sake of
time.
But I'll be glad to take questions if you
have any.
[Applause.]
DR. GOMPERTS: Thank you, Dr. Cruz. Are
there any questions from the committee? Yeah, Dr.
Lipton?
DR. LIPTON: Jose, I think one of the
questions that we've been deliberating at the AABB
is all over this issue of how you encourage
volunteer donations, and we've had a lot of
discussion about is there anything that we can do
to encourage that? I'm going to talk a little bit
later about some of our standard-setting
activities, where actually the countries and
regions themselves have moved to place that into
standards. But is there something besides that
that we can assist with, because one seems to think
we know how to encourage volunteer donations fairly
well. We had a big switch here. But is there
something specific you would like to get from us
that you don't have?
DR. CRUZ: Yeah. How long can the list
be? No. You know, it's interesting, we, with the
help of a group of anthropologists, we develop a
guideline to do anthropological studies on the
factors that basically, you know, pick on or off,
you know, voluntary blood donation. And we have--you know, these studies have been applied in at
least 14 countries now, okay, including Jamaica,
and what we have found is that there are two main
factors that actually prevent voluntary blood
donation. One is the lack of information, not
education, information in the public, okay. People
don't think that there's a need, a continuous--they
don't know that there's a continuous need for
blood, so whenever there's a disaster like an
accident or an appeal on TV or on the radio, people
come and donate, because they figure that that's
the only time when there is actual need for blood.
That's one issue.
The other issue is that the accessibility
of the blood banks, and then, you know, this
business of replacement donors, when people are
asked to come, you know, to bring two or three--I
mean patients are asked to bring two or three or
four donors whenever they needed the hospital.
Then families, you know, of donors who are healthy,
might rather save their blood for, you know,
whenever a friend or a relative needs it, then go
and donate it.
So, you know, you have to deal with
informing the public, and again, you know, it's the
way that we deliver the messages. And, you know,
it's interesting, in Nicaragua somebody told us
that they only place that she saw posters of
pamphlets regarding blood donation was in the blood
bank. And she asked, you know, "Why don't you put
them in supermarkets and shopping malls, in movie
theaters? You know, you have to come to the blood
bank to actually see a poster, okay, or find a
pamphlet, you know, a flyer.
And then the other big issue is the way
the blood banks are set up, you know, because
people are forced to come and give blood and the
blood banks are usually open from 7 to 9 in the
morning. They are not--I mean, they are not donor
friendly. So basically what we have to do is both
inform the population and also--and this I think is
the biggest challenge--to change the way the blood
banks operate.
And I'm going to go back to, you know, one
of the questions there was before. We feel that
centralizing not only testing, but also the
collection of blood will improve efficiency. We
have data showing that resources--lack of resources
is not the issue in our countries. On the
contrary, we're using resources in a very
inefficient way. We have, you know, blood banks
that collect 400, 500, 1,000 blood units of blood.
And most of the loss in the countries, for
instance, required that it's a physician and--most
of the times--and hematologists that should run a
blood bank, okay? So here we have a hematologist
running a blood bank that collects 400 units of
blood a year. They have a nurse. They have
sometimes a social worker, a psychologist to
provide counseling for those who are HIV positive,
for instance. So you know, so all these resources
going to these very small centers, and they are
very, very inefficient. So what we're trying now
to do is--using, you know, the tools that WHO
develops, convince the people that they are wasting
resources.
And, again, you know, if we can implement
the standards that we have developed with the help
of AABB, then the resources could be allocated, you
know, to do what we know is needed.
DR. GOMPERTS: Others questions? Yeah,
Dr. Guerra.
DR. GUERRA: [In Spanish.] The question--
DR. CRUZ: I got that.
[Laughter.]
DR. GUERRA: The question I have for you
is that having screened out individuals that have a
variety of infectious diseases that perhaps could
be associated with transmission via transfusions,
there's a real dilemma I suspect within the blood
banking industries and programs in some of the
developing countries in terms of trying to connect
those individuals with resources beyond just
counseling, for follow-up care of some of those
conditions. How do you deal with that?
DR. CRUZ: Well, actually, you know,
that's why we have the date from Chile and Costa
Rica, for instance, because they actually provide
treatment for hepatitis C patients, okay? So it's
a--in some other countries, like in Guatemala, even
the diagnosis of hemophilia is something that I
don't think is very highly pursued, because then,
you know, the authorities will know that they will
have to do something in terms of providing
treatment and support for those patients. But,
again, you know, this is the big issue, and again,
how do we deal not only with blood banks, but also
with all the resource in terms of health services
and, you know, promoting health--efficient health
services, and that's again something that a
programming session does, and that's in general
saying, you know, I presented here, and very
quickly, what we have come up with, but again, the
work that we do, we cannot do by ourselves. I
mean, that's definite. So we work with other
divisions within PAHO, with other divisions within
WHO Geneva. We have other partners. We work, for
instance, very closely with the World Federation
for Hemophilia, again in terms of advocacy. So
it's--you know these partnerships, I think, you
know, they need to be constructed not globally,
regionally, but most important at the local level
so that people can get whatever they need in terms
of information and treatment or counseling if
necessary.
DR. GOMPERTS: Yes?
DR. NIGHTINGALE: Jose, than you very much
for being here. I would like to take the
opportunity to ask the question that Dr. Klein
asked a minute ago, which is--not to put you on the
spot, but that's why you're here--what if anything
could the Department of Health and Human Services
do that it is not doing to support you in your
work?
DR. CRUZ: No. As I said, I think
advocacy is a very important issue, just to mention
blood, you know. And when you see, for instance,
you know, the attention that HIV/AIDS and the HIV
epidemic gets, you know, for one, at least would
say that HIV, for instance, can transmit--transmit
through transfusion, that would be a big issue.
But also we are concerned about hepatitis C. And I
think everybody, since HIV has so much more
visibility, that's what we deal with, but then we
have things like hepatitis B, hepatitis C, and what
is the cost of really taking care of a patient that
is infected with hepatitis C?
I need to make a parenthesis here, we--I
mean this is something that happens--we just got a
story of--another story about another case of three
individuals getting infected units in Belize just
three weeks ago. So that's--so advocacy and
raising awareness is something that is important.
And again, when you talk about US personnel
stationed in our countries, I think that's also
very important, okay? I mean, the safety of blood--the blood that is available to your fellow
Americans, for instance.
And the other one is technology transfer,
and when I say technology transfer I just don't
mean a specific and sensitive inexpensive tests,
but things like the standards, norms, you know, and
training, you know, again, how do we deal with
running a blood bank efficiently? How do we set up
a national blood program? How do we--you know,
people were mentioning before, what is the cost
effectiveness of centralizing a testing or
promoting a voluntary blood donation, that kind of
thing?
So I think, you know, advocacy, technology
transfer and training would be things that would be
important.
DR. GOMPERTS: Any other questions? I
have a question. One thing that really struck was
the heterogeneity of the availability of quality
blood across the region. The question that I want
to ask is, to what extent are other branches of
medicine associated with the quantity of blood and
blood transfusion activities?
DR. CRUZ: I'm sorry?
DR. GOMPERTS: Other branches of medicine,
surgeons, cardiologists?
DR. CRUZ: Okay. No. Again, you know,
when I said training, and I think Jean mentioned
that the appropriate use of blood is an important
issue, but again, you know, I think what drives the
quality of blood is the way that we collect blood.
Let me give you a couple of--no, one
example, just for the sake of time. I was in the
Turks and Caicos Islands just about three weeks
ago. These people have money, okay? They invest
$8 million in sending patients to Miami just
because there's not enough blood in the country,
okay? So that tells you how the resources are
used. But how do they collect blood? The patient
is admitted into hospital, and then they go and
bring the donors forward, okay? So the donor is
brought in, for instance, in Providenciales. The
blood is collected there. And probably, you know,
the patient is in an emergency situation because he
or she has to be flown to Grand Turk, okay? So
they have these charters, okay? So they might
either bring the patient and the donors to Grand
Turk for the collection of blood, okay, or they
might collect the blood in Providenciales, test it
using rapid tests, even though the have an ELISA
reader, that they have trained people, because they
want to have the results like right away, because
otherwise--if they turn out to be reactive, then
they have to go and collect the blood from somebody
else.
So what I'm trying to tell you is that
sometimes the units are not screened, not because
there are not resources, not because there are not
trained personnel, but because there is not time
for the unit to be tested. And that's exactly what
happened in Belize, we think. The unit was
collected on Friday, the 30th of March, and the
patients were transfused during the weekend. And
then on Monday they figure out that the unit was
positive. So it's not lack of resources, is not
that, but is the way that the blood is collected
mostly that then drives the whole process.
DR. GOMPERTS: Thank you.
DR. CRUZ: And I'm sorry. Going back to
the surgeons, it's interesting. In Turks and
Caicos Islands, the minimum level of hemoglobin for
a donor to be eligible to donate is 12 grams, okay?
And we have revived the records, and there were
patients with 14.5 of hemoglobin that have been
given two units of blood. So, you know, this is
our comment. A donor with 12 grams hemoglobin can
be, you know--then they can donate a unit and then
go back to his place or to his work, and then a
patient who has 14.5 gets the units of blood.
DR. NIGHTINGALE: If I could make a quick
comment to the remaining speakers. We have time
for you. I appreciate Dr. Cruz's concern, but it
is very important for us to hear what you have to
say. I have intentionally scheduled this meeting
tight in the morning so that we hit--we were to hit
public comment at 2 o'clock. No way did I ever
think that was going to happen. I do want to hit
public comment, however, by 3 o'clock, and that
means we still have time.
So, to the remaining speakers, please tell
us what you want to tell us.
DR. GOMPERTS: Thanks, Steve. Any other
comments, other questions?
[No response.]
DR. GOMPERTS: Thank you very much.
DR. CRUZ: Thank you.
DR. GOMPERTS: We're going to be going--we
have Dr. Mohammed El-Nageh, International
Consortium for Blood Safety.
DR. EL-NAGEH: Good morning, ladies and gentlemen.
The International Consortium for Blood Safety was
established in 1998 by a group of leading blood
bankers, biologists, and public health experts. In
1999, the International Consortium for Blood Safety
received a grant from the Gates Foundation which
made it possible to start some activities in some
developing countries.
The International Consortium of Blood
Safety has a limited number of members and also
liaison members representing major international
organizations and institutions. For the time
being, there are 14 liaison members.
The ICBS has as its major goal the
achievement of universal blood safety by prevention
of transfusion-transmitted infections using
affordable and high-quality reagents.
Among the specific goals of the ICBS also
is to identify, validate, and make available
affordable, high-quality reagents and plan and
execute in some countries, in collaboration with
the central authorities, projects to achieve blood
safety in a region and then extend the experience
of that region to the neighboring regions and the
neighboring countries.
Among the specific goals also is to assist
in developing and upgrading quality assurance
programs covering the whole spectrum of transfusion
medicine.
ICBS also coordinates and arranges for
appropriate technology transfer. It aims at
coordinating with other international organizations
and societies providing educational support to
improve donor selection and clinical use of blood.
ICBS also fosters collaboration with WHO
and other major international organizations,
associations, societies, institutions, so to
maximize the resources and to complement the
efforts of each other rather than duplicating.
We know that the developing countries are
really a heterogeneous group of countries, and
problems which are faced in one country may not be
exactly the same. But there are certain problems,
some of which or all of them which could be
encountered in one country or another.
The first one is the fragmentation of the
transfusion services and the absence of independent
and well-coordinated national transfusion service
program. There is also--I think there is a problem
with the focus there.
There is also a lack of national policies
or plans aiming at self-sufficiency in blood and
blood products, and even when the plan is there,
most of the time it is not implemented.
There is unsustainable reagent supply and
significant shortage of the screening kits for some
infectious agents, and especially for hepatitis C.
And the shortage is more acute in the peripheral
areas when you go outside of the capitals and the
main cities.
There is improper evaluations and
licensing of reagents. Any kit can be sold
anywhere at any time, whatever the quality of this
kit is. And there is a lack of cooperation between
blood banks or between countries or between regions
to have a bulk purchase of reagents in order to
reduce the cost.
There is a lack of organized, community-based, regular, voluntary, non-paid donor system,
and, of course, there are limited financial
resources, the excuse which is used by all the
countries, and the lack of adequate staff training
and also the lack of continuing education. There
is poor quality assurance programs. There is lack
of adequate equipment, and certainly this is lack
of equipment maintenance, and last but not least is
the inappropriate use of blood and blood products.
The ICBS, prior to considering providing
support to any country, assesses the situation in
that country, and the assessment is mainly through
gathering information from various sources and also
by the findings of the team visits, the ICBS team
visits. And once the situation is assessed,
priorities are identified, and these priorities
have to be within the goals of the ICBS.
The ICBS tries to maximize the resources
and find out who is doing what in that country.
Sometimes there are other organizations and
agencies who are providing support, and ICBS tries
to rather coordinate and maybe even collaborate
with these providers.
There are two main prerequisites to start
supporting a developing country. First of all, the
presence of a leadership. There should be a
qualified--or more than one--and dedicated blood
transfusion specialist who is or are prepared to
take the lead in improving blood safety in their
countries, and there should be government
commitment. If these two are absent, it is very
difficult to imagine that any progress could be or
any success could be achieved.
What are the areas of support that ICBS
may consider? The ICBS assists countries to
achieve sustainable safety testing of all blood
units collected by blood banks through providing
some of the less fortunate blood banks, for a very
limited period, with screening reagents. And
usually after the assessment, we find out how much
is needed to provide--to ensure testing of all
blood units, especially at the periphery and
outside of the capitals and main cities. And the
ICBS signs an agreement or memorandum of
understanding with the government that they are
going to cover the screening for the first year,
and provided that the second year the government
commits itself to covering 50 percent and the ICBS
the other 50 percent, on the third year, hopefully,
that the government commit itself to undertake the
responsibility of covering the cost of all the
testing of the blood units using its own resources
or alternative resources.
Another point in this area is to advise on
efficient reagent purchase mechanisms, like the
bulk purchase mechanism, informing the country
about the availability of affordable and high-quality reagents in the market.
Another area of support is assisting in
the evaluation of blood safety kits available in
the market to identify the good-quality and low-cost reagents. And to achieve that, we assist in
training scientists from the developing countries
on methods, especially those countries who have
control authority laboratories, on methods of
evaluation and licensing of reagents.
The ICBS is establishing a master panel or
master panels for HIV, HBV, and HCV, and this
master panel initially is provided to those
countries who have control authority laboratories,
and they also should be trained to develop their
own panel for continuing use. And this is by
training the scientists in preparation,
characterization, and establishment of the national
panels.
We also sponsor--we are going to sponsor a
well-established center, international center,
because we are aware that most of the developing
countries they have no control authority
laboratories. And even those who have control
authority laboratories, we are very doubtful about
the performance of these laboratories. So instead
of waiting for a long time for this to happen, we
are going to support a center, an international
center for the evaluation of the blood screening
reagents to identify the affordable and high-quality screening reagents and to display the
results on a website, which will be available for
all the countries to be used whenever needed.
Also, the ICBS will provide this international
center with the master panel being prepared.
ICBS also plays an important role in
training in specific areas, especially assisting in
training of blood safety, laboratory testing
techniques, and conducting and cosponsoring the
workshops to train trainers in the principles and
practices of that quality assurance. We help some
countries, whenever or wherever appropriate, to
have central confirmatory reference laboratories.
ICBS for the time being has activities in
India, in Vietnam, in Paraguay, and the situation
has been assessed in Pakistan and Indonesia, and
the report of the assessment is being circulated to
the members for their views, after which plans will
be prepared and assistance will be provided within
the available resources.
Other countries that are being assessed
are the African countries, starting with the
French-speaking countries, and also the countries
of Central Asia.
The question how the department could help
ICBS, the department could help ICBS in many ways
to achieve their goals. First of all, capacity
building. And under capacity building, maybe to
provide training grants targeted at a range of
individuals from directors of blood transfusion
services to technologists and high specialization
level, because we believe in leaders, and without
these leaders, one would hardly imagine how
progress could be achieved; then cosponsoring
training course, the ICBS training courses and
workshops; establishing an ongoing relationship
with an institution which is most likely to
influence blood safety in a client country, and
this could be a blood transfusion center, this
could be a virology reference lab, public health
department, whatever institution is appropriate and
is foreseen that it can play a major role in the
development of blood transfusion services in that
country.
The relationship with this center should
comprise offering phased training of individuals
making a team and offering problem-solving
functions and also sending out short-term
consultants in various relevant disciplines to
check on progress and help with longer-term
planning and keep the program on track.
Maybe also to provide to the center
calibrated reference material and also advise on
how to use this.
Another area where the department could
assist ICBS is making available testing reagents
for blood safety, and this could be by contributing
to the efforts and maybe even financially
contributing to the efforts aiming at providing for
a limited period testing kits, convincing countries
to have in their Ministry of Health budget a budget
line to cover the total or initially partial
testing costs. I don't believe and I have never
believed that any country in the world have no
amount, even if it is small, of money to be
allocated for blood safety, because when we see
what money they spent in other things which are
useless, one starts to ask himself. I think they
have to have an amount which should be supplemented
by donation, and then gradually they should take
over the responsibility of covering the cost. And
I think this could be as a prerequisite before--like we do with the countries, before we start any
assistance.
Also, advising on negotiating favorable
financial terms with the companies, because many of
them, they are not experts in how to negotiate
these terms.
Also, explore and advise and train on
total or partial cost recovery. Some of the
developing countries, they have started to use the
system of cost recovery of testing, and to have it
as a revolving fund to ensure sustainability of
testing.
The other advice that I would like to give
is avoid providing or donating inappropriate
equipment, which is most likely to remain unused or
break down after a short period of use due to the
lack of expertise and lack of maintenance. Those
of you who have visited developing countries, you
will see masterpieces, very expensive pieces, lying
in a corner somewhere. You can identify the
chronological order, the age, by the layers of dust
in it, and it has never been used. So I don't
think that it was appropriate to give it in the
first time. We should give what they need, what
they can use. And prior to specific technology
transfer--I am very happy that the program is
including a lot of talks about the appropriate
technology transfer--we should look into the
critical factors contributing to the successful
transfer of such technology, and it should be
identified.
Thank you very much.
[Applause.]
DR. GOMPERTS: Questions? Dr. Hoots?
DR. HOOTS: You had mentioned in terms of
collaboration between, say, people or expertise in
the United States or perhaps over the developed
world, and the previous two speakers had talked
about collaborations that they have with the World
Federation of Hemophilia. There's one program
that's been very efficient, I think, in terms of
just sharing knowledge, perhaps resources as well,
but particularly knowledge, which is a twinning
program that exists between established hemophilia
treatment centers in developed countries, primarily
U.S., Europe, Australia, and Japan, with developing
centers of expertise in the developing world.
And I wondered if that sort of model had
been looked at particularly for early involvement
in helping perhaps just first as a dialogue between
people with expertise who have an interest in
helping out somewhere, and then establishing a
relationship, perhaps even establishing an
educational track of an ongoing continuity of
continuing medical education for transfusion.
DR. EL-NAGEH: Well, I do agree with you,
and in my previous life--because my previous life
was with WHO, and I believe very much in twinning.
And I have looked to centers of excellence around
the world where you can twin them with the
activities in developing countries. And the story
is always a success.
I think this is a very valid approach, and
I am pretty sure that the global collaboration at
the WHO is looking also into that.
DR. GOMPERTS: Thank you.
Dr. Epstein?
DR. EPSTEIN: Yes, thank you, Dr. El-Nageh. I think that was a very complete picture
that you painted.
However, I notice that it's in many ways
very similar to what the WHO described as its
strategy, and I wonder if you could comment on the
current degree of coordination between what WHO is
doing in some of the same regions, for example,
India, and ICBS.
DR. EL-NAGEH: WHO--and Jean Emmanuel is
here--is one of the pioneers of establishing the
ICBS. One of the objectives and the goals of the
ICBS is to closely collaborate with WHO.
For example, when we are talking about the
evaluation of the kits, we know that WHO is doing a
good job on HIV, so we are not going to touch on
that, but, rather, we are going to fill the gap.
We try to avoid duplication and overlapping and,
you know, unuseful spending of money. So the
center will only evaluate, if you are mentioning to
that, the hepatitis kits, the hepatitis reagents.
In other areas, wherever we go, first of
all we inform the WHO representative in a country,
the regional office in that region. We find out
what is going on, who is doing what, what
governments are providing support. So we try to
get in touch with these people, how we can fill the
gaps, where are the areas that could be
supplemented and complement their activities rather
than duplicate. And we try to do our best at this
way.
But we believe and we will always believe
that close collaboration with WHO is a must for
ICBS.
DR. GOMPERTS: Thank you.
Dr. Chamberland? Then Dr. Davey.
DR. CHAMBERLAND: Thank you very much for
a nice presentation. I wonder if you could give
the committee sort of an update on--I think India
is probably one of your first projects that has
been ongoing more than others. Just give us an
idea of the actual progress that you've been able
to make in the areas that you outlined, because I
think what you're trying to do is very concrete,
you know, supplying panels, reagents, getting
countries to be self-sufficient. So it would be
good to hear how that actually has worked out in a
country where you've been in place for a while.
DR. EL-NAGEH: Okay. In India, it is an
example where we tried to really collaborate with
WHO. We had meetings with the--we have assessed
the situation. The situation, Jean Emmanuel knows
it even better. There are certain blood banks that
collect ten blood units a month, and there are
certain blood banks that they collect a lot.
The situation is different from one state
to another, so with the federal state we sat down,
and with the people from the WHO also because they
have the regional office there, and we discussed
with them where we can complement. And we had very
long discussions with them to convince them
starting testing for hepatitis C, because hepatitis
C will be a big problem, and we will cry ten years
from now when it is too late, because we are not
testing for hepatitis C and it will be a bigger
problem than hepatitis B. We all know that HIV is
important, but HBV and HCV, they are not less
important.
So there was a good response from the
Government of India, and they were planning to
start testing, and we are very glad to see in The
Lancet, I think last month, that starting July they
will test all blood units collected in India for
hepatitis C. And this is a good move.
So the areas which were identified with
them, first of all, they have a panel to evaluate
the kits, and their panel was not really very
satisfactory, even by what they have mentioned and
what we have found. So a temporary panel for HCV
has been provided to the national control authority
laboratories. Someone from India came to CDC
Atlanta to be trained on the characterization and
establishment of a panel and also in the proper
evaluation of the kits.
We thought that there was also--we didn't
give reagents because we thought that they have
enough resources to cover for the reagents. And
any positive result, maybe false positive or false
negative, but at least the false positives, they
are not confirmed at all. They have no
confirmatory laboratory there. And we have agreed
with the Government of India to help them establish
a national reference confirmatory lab in New Delhi,
in Delhi, and it is being established. We have
provided some equipment, and there is an excellent
lady expert who is responsible there. She is now
at New York being trained on the confirmatory
testing using NAT technique.
DR. GOMPERTS: Thank you.
Dr. Davey?
DR. DAVEY: Thank you, Dr. El-Nageh. One
of your very useful suggestions was that the
department may want to consider establishing
training grants for people in developing countries.
One of the vexing problems that I'm sure you're
aware of with such training in a developed country
is that the trainees often don't go home. There's
a brain drain, if you will, for people who come to,
say, this country or other developed countries, get
extensive training, and decide to stay.
Do you have any suggestions or comments on
how we could get around that problem?
DR. EL-NAGEH: First of all, I'm aware
that the immigration rules are very strict now, so
I don't think that they can get away with that if
they come to the States. But I didn't say that you
have to train them in the United States. You could
train them in other developing countries with a
successful story. They can go to a developing
country with similar conditions or nearly similar
conditions, and they have succeeded and they see
that it is possible to succeed.
For example, we are going to train certain
people from Africa in Ivory Coast because they have
succeeded to establish a voluntary blood donor
system, an excellent centralization of testing. So
it is feasible. The trainer could be in the United
States, in a developed country, or developing
countries.
DR. GOMPERTS: Any other questions?
MR. DALAL: Dr. El-Nageh, just a
clarification on the use of the term "technology
transfer" as it's used by ICBS. Is the emphasis on
the transfer of assays and instruments under terms
of sale and technical support, or is it on the
transfer of know-how and licenses for the local
development and manufacture of the product?
DR. EL-NAGEH: By definition, technology
is not only instruments or reagents. By
definition, technology is also procedures, methods,
and approaches. The technology is a whole
spectrum. Whatever is useful to improve the
situation of blood safety in that country could be
studied and then tailored to their needs, and the
transfer should be appropriate in a way to survive
and to be used and utilized. But it is not only
for the equipment. Yes, the equipment or the
manufacturing of reagents, yes, why not, if they
are capable to do that. They are doing it anyhow.
They are doing it badly. They are producing kits
in these countries and they are using it with
doubtful specificity and sensitivity and quality.
So why not help them do it right?
DR. GOMPERTS: Thank you. Yes?
DR. PENNER: Just a quick question. The
tourist industries are often very powerful in Third
World countries, and they really have a stake in
having safe blood available for the populations
that they're transporting over. Do they get
involved at all or participate in some of your
programs?
DR. EL-NAGEH: I didn't get your question.
DR. PENNER: The tourist industries in
many of our Third World countries are pretty
powerful. Are they participating at all in any of
your programs? Because it's really very important
when our patients are going over to Kenya and
elsewhere, we just tell them we'll fly them back if
they get into trouble because we don't want you to
have any blood over there.
DR. EL-NAGEH: Unfortunately, not as yet.
But surely they are welcome. Anyone is welcome
really to contribute. We have a small grant from
Gates Foundation. It is not enough. It was $5
million over five years for the whole world. You
can see that it is not enough. We have a lot of
ideas to be considered, but we are looking for the
resources, and when we say the resources, it is the
expertise and funds.
DR. PENNER: I'm just suggesting you might
to try to galvanize them into action because they
really have a need here.
DR. EL-NAGEH: Surely I will take that and
consider it.
DR. GOMPERTS: Thank you very much, Dr.
El-Nageh.
We need to take a brief break, and we'll
reconvene at 10:15.
[Recess.]
DR. NIGHTINGALE: Could I ask the
committee members and the audience to please take
their seats? At least begin to do so. Folks,
could I ask you once again to please take your
seats? We are now almost 50 minutes behind
schedule. That means we're 10 minutes ahead of
schedule. That means we don't have a lot of slack.
DR. GOMPERTS: Our first presenter in this
part of the session is Dr. Lackritz, Centers for
Disease Control.
DR. LACKRITZ: Is everybody back? Okay.
I'm from CDC. I'm going to start by
talking about the new LIFE initiative, which is
CDC's program through the Global AIDS Program, and
then specifically get more into the blood safety
agenda.
The LIFE Initiative was started last year,
which was an emergency appropriation to USAID, HHS,
Department of Defense, to address the global AIDS
crisis, to curb not only the threat of the epidemic
to the nations but also to the health security and
economic stability of the world.
So a comprehensive plan was drawn up for
action, and that included the following bullets on
the screen: primary prevention of HIV, that's
through sexual, mother-child, and also bloodborne,
which is probably most relevant to the group here;
AIDS treatment and care, including improving access
to antiretroviral therapy, prevention and treatment
of OIs in the periphery and community-based care;
and, finally, to expand surveillance system and
capacity building among national AIDS programs.
Next slide.
There are a number of U.S. agencies
working on this. USAID is the coordinating agency;
HHS, including CDC and HRS; Department of Defense;
and this year, in 2001, Department of Labor and
Department of Commerce were added to the
initiative.
Next slide.
Our allocation last year, these emergency
funds for CDC, totaled $35 million. This year that
appropriation increased to $104 million; $3 million
of that goes to HRSA. So in terms of a
comprehensive AIDS program for the world, it's
limited. But I think we can develop very practical
initiatives that we can start to fill the gaps that
are needed in developing countries.
Next slide.
The year 2000 countries are in sort of
grayish-yellow color. 2001, we've added more
countries in Africa, Brazil, Guyana, Haiti, and
three countries in Southeast Asia. The priority
countries were identified where the epidemic was
hitting hardest. All these countries are extremely
resource-limited.
Next slide.
Our general approach to how we're going to
address our scope of work is working strongly with
country nationals in developing country leadership
and ownership of the initiative. We're focusing on
priority needs identified by the country and
promotion of in-country expertise and institutions.
This initiative is going to require a lot
of coordination and collaboration with multiple
governmental and nongovernmental organizations, and
I hope that this forum is a good opportunity to
start forging some of those partnerships with
agencies that can assist in making a difference.
Next slide.
Okay. So let's start thinking about the
blood safety component of this, then. I just
wanted to show this slide first to get at the
burden of disease that's facing many developing
countries. My presentation is generally going to
be very Africa-focused and very HIV-focused, but I
think that this is relevant to blood safety in
other countries and to other components of blood
safety.
This data is actually from Kenya, a study
that we did some years ago, where we surveyed all
children who came onto the pediatric ward. Twenty-nine percent of all pediatric admissions had
hemoglobins below 5. Twenty-one percent of all
children who entered that hospital received a blood
transfusion. Mortality rates among those severely
anemic children were staggering. We had 18 percent
mortality rate and that compared with 8 percent
among those with hemoglobins of 5 or greater.
Among all children who died in hospital, 48
percent, nearly half of those, had a hemoglobin
below 5.
When we followed kids out for two month
after their discharge from hospital, in a subset of
these we had a 29 percent mortality rate.
Next slide.
Children and women are particularly hard
hit in Africa, in particular. Children both in
Cote d'Ivoire and Kenya are shown on this slide;
similar data is available out of Tanzania, Malawi,
former Zaire. Children generally receive about
two-thirds of all blood transfusions, primarily for
the treatment of malaria-associated anemia, and
often complicated by nutritional deficiencies.
Women receive basically about the next
one-third of all transfusions, primarily because of
obstetrical complications, complications of
pregnancy, narrow child spacing, and severe anemia
during pregnancy.
Next slide.
The other challenge then is not only you
have the frequent use of blood, but how then do we
get safe transfusions to these folks who need it?
When we look at HIV prevalence--this is in a multi-center evaluation of six hospitals in Kenya. HIV
prevalence in the donor population is very high.
This is 1994 data. It's actually increased since
this time. We had 20 percent HIV prevalence in two
of the hospitals. And as Jean Emmanuel indicates,
throughout the continent it can be even higher.
Next slide.
And that's because the epidemic is so
staggering in many countries, and this slide shows
the HIV prevalence in the general adult population,
which means that identifying safe donor populations
in this kind of context is very difficult.
Next slide.
When we actually looked at the risk of HIV
transmission in these six hospitals in Kenya, this
was in a very high prevalence area with
decentralized blood transfusion systems where
testing is done in peripheral hospitals. We found
that one-third of all HIV-positive donations were
not removed from the blood supply. This was in a
study where we were providing test kits to the
hospitals if they didn't have them. So there are a
number of problems going on that contribute to this
risk. There were recording and labeling errors.
One hospital was not screening transfusions that
were collected from the mother and given to the
child under the erroneous assumption that mothers
and children all had the same HIV status.
We breaks in the cold chain. We saw
equipment problems. And in some cases, there was
some suggestion that there was testing after the
transfusion had occurred, similar to what we heard
from the Latin American experiences.
Now, what you can see and probably the
most important bullet of the whole talk, I think,
is that we found that 1 in 50 transfusions in this
multi-center study transmitted HIV. This risk is
unacceptable. We have inexpensive and practical
technologies that can virtually eliminate this
risk.
So I think in answer to Dr. Klein's
question on what can the HHS do to address this
performance, I would expand that to sort of what
can the HHS in partnership with all these other
agencies, many represented here in this room today,
what can we all do?
I think that we have an opportunity now to
step up to the plate and share the amazing
technical capacity that we have in the United
States and decrease the global inequity in this
most preventable mode of HIV transmission.
Next slide.
Now, building capacity, one of the things
that we need to do in terms of the practical
application of this--could you back up one slide?
I think we skipped--are we going forward or
backward now? Okay, now forward. There you go.
Great.
Now, addressing the problems in blood
safety in developing countries is challenging
because safe transfusion involves this series of
complex and interrelated activities. There needs
to be an adequate supply of blood collected from
low-risk donors. Blood needs to be tested for
infectious diseases. There needs to be good ABO
typing, perhaps cross-matching. It needs to be
stored and available for immediate use.
There's a large amount of severe anemia
developing in the community. Those folks have to
access health care facilities, and then in the
facilities, severe anemia needs to be recognized or
other indications for transfusion. Transfusion
indications need to be appropriate, and blood needs
to be available, transported to the wards, and
given to the patient and monitored effectively.
Next slide.
So, in that setting, it's challenging
because each one of those steps, it's sort of links
in a chain, and any weakness in one link is
difficult to address the whole system. But we do
need to develop comprehensive programs to address
the problems that we're facing. And I'm going to
go through about four slides now about these
different components and what in the CDC Global
AIDS Program we plan to approach.
One is sort of in strengthening
organizational capacity of the countries. We hope
to work closely with WHO and other international
partners to promote development of national blood
transfusion services. We need to strengthen the
managerial capacity and regulatory oversight of
transfusion services, quality laboratory testing,
and quality management. We need to develop
national policies on transfusion services,
laboratory standards, and the appropriate use of
blood.
Next slide.
Our approach is to develop strategies that
are appropriate for the local condition. Now, this
is going to vary a lot by country. We recently
received a request, for example, from the
Democratic Republic of Congo, formerly Zaire, which
reported to us that they have two functioning ELISA
machines in the entire nation. So one of our
strategies, then, among these appropriate
technologies is to provide laboratory equipment for
blood storage and infectious disease testing. We
need to evaluate and implement inexpensive testing
technologies that are appropriate for each of these
local settings.
Training is a big component of this. This
has been emphasized in the other talks this morning
in terms of testing, recordkeeping, stock
management, not only of reagents but also of the
blood products themselves.
Training of supervisors and managers is
key to ensure that there's an uninterrupted supply
of reagents, that there's functioning equipment,
and there's quality testing.
Next slide.
Okay. So what about availability of blood
and trying to increase donations from volunteer
blood donors? We do need to identify strategies
that will work to improve recruitment and retention
of low-risk donors. In many countries there's no
functioning system to do this at all, and we need
to learn how to promote voluntary donorship.
We'll be providing assistance and rapid
assessments to try to identify low-risk donor
populations, be those young donors, old donors,
different ways to bring those folks in and keep
them HIV-negative through rigorous education
programs.
We need to support development of
volunteer blood donor education and mobilization
programs, assist in the development of donor
deferral strategies that are relevant to the local
setting, and strengthen capacity for HIV
prevention, education, and post-test counseling of
blood donors to keep those folks negative, and to
make blood donorship an inroad for HIV prevention
programs.
Next slide.
Then I think it was emphasized in the
other talks as well, but there needs to be a very
important focus on increasing the appropriate use
of blood. If we do have an increase in the amount
of blood stored and available, we have to make sure
that it's not abused. We need to assist in
development of national and local guidelines on
appropriate use of blood, support training of
health care providers on the use of blood, promote
access to and use of volume expanders for acute
blood loss, such as crystalloids. Very often, very
simple interventions of this are just not
available.
Again, improve laboratory capacity for
hemoglobin screening in the outpatient and
inpatient settings. A lot of places don't even
have these simple technologies available to them or
their laboratories are organized in such a way that
you just can't get a hemoglobin any time of day, on
the weekends, during nights, that type of thing.
And, finally, I think a very important
component that's often overlooked because we think
of transfusion as a hospital-based activity, but we
need to strengthen primary health care programs to
prevent severe anemia from ever happening in
children and pregnant women. Even when people come
in for transfusion, their chance of survival is
very poor. It's very much a last-ditch effort.
And we need to figure out how to access those folks
earlier and prevent them from ever coming in to
need blood.
Next slide.
Now, improving the capacity of countries
and the safety of blood overseas benefits the U.S.
public health directly. For the obvious reasons
that were just brought up earlier, we reduce the
risk to U.S. travelers abroad. In addition to
that, we need to assess performance of commercially
available HIV assays among non-B subtypes that are
found in other countries. We need to develop
seroconverter panels for non-B subtypes. We need
this for two reasons. One is we're assuming that
the assays we're using are the best ones to use
overseas, and we really don't have any data to know
that. Secondly, we do live in a global village.
We do have many travelers coming to the U.S.
donating blood, and we need to make sure that the
assays that we use on our U.S. blood donations used
for transfusion to U.S. patients is picking up
those HIV variants that are found internationally.
Similarly, we need to monitor for
emergence of HIV variants not detected by
commercially available assays. Group O is a good
example of this. A lot of variants do come from
Africa. It's always been a source of importation
to the U.S. and a risk to the U.S. blood supply.
And, finally, as we monitor for new and
emerging pathogens internationally, these
pathogens, that gives us information on how we can
prevent transmission of these pathogens in the U.S.
Most recently, HHV-8 I think is a good example
where that's being debated here, and we currently
have a study ongoing in Uganda where the HIV
prevalence--sorry, the HHV-8 prevalence is
extremely high, about 40 percent whole blood used
for transfusion. And so we can probably get sort
of a more rapid assessment on the risk of HHV-8
transmission more quickly.
Next slide.
I think in addition to our programmatic
agenda, we need to develop and closely link with an
evaluation and strong operational research agenda.
I think there are numerous research issues that
need to be pursued by CDC, by NIH, by our other
nongovernmental partners. I've listed a few of the
more key and basic operational research questions
here. It's a short list and doesn't really
adequately list sort of what are the opportunities
in research internationally. But I think we need
to figure out how to identify low-prevalence donors
in these very high-prevalence populations.
Many blood banks have gone to younger and
younger age donors in an effort to get safer blood
because the prevalence of HIV is less. Often blood
campaigns are conducted in secondary schools in
many African countries. However, those are very
high incidence populations, and we need to assess
the incidence among donor populations to decrease
the possible risk of window-period donations. We
have no information on this currently.
We need to improve our understanding of
volunteer blood donation in the context of local
cultures, norms, and taboos. And we need to
evaluate the impact of HIV testing and counseling
on donor recruitment and testing. A lot of people
are afraid of donation because of an HIV test.
There's a lot of stigma, even more so in Africa
than even here, and we need to figure out how to
address that barrier.
Next slide.
And, finally, there are a lot of risks to
transfusions in this setting, both HIV-uninfected
people but also in the prevalence of HIV is so high
in the population, there is a whole area of
research that we haven't quite yet figured out
about whether transfusion and when transfusion is
beneficial to folks who are--to patients who are
HIV-infected. We don't know how transfusion is
affecting their hematologic recovery, which can--they can get probably a lot of bone marrow
suppression. We don't know how transfusion is
improving their chance of survival.
There are also a number of pathogens that
are not screened, typically, in resource-restricted
countries such as HCV. This may disproportionately
put HIV-infected persons at risk. Other pathogens,
such as CMV, malaria, and we could go on.
But, in general, there are a number of
research and programmatic activities that need to
be addressed. It's a very ambitious program. But
I think it's a good challenge for us at this time
and an opportunity for all of us to work in
partnership here and to start to tap the expertise.
Much of it is available even here in this room to
move forward and make a difference.
Thank you.
[Applause.]
DR. GOMPERTS: Thank you, Dr. Lackritz.
Questions from the committee? Dr. Hoots?
DR. HOOTS: Since women and children are
the primary recipients of the high-risk blood and
since obviously one of your goals is to reduce need
for blood--and you mentioned screening--what is the
status in particularly Equatorial Africa? I mean,
in terms of--I know adjustments have been made
based on perinatal HIV, in terms of breast feeding,
but in other contexts it was encouraged and then
discouraged, and then somewhere in between.
But I presume the same issues that relate
to screening of blood relate to other laboratory
assessments of the population, even something as
simple as iron deficiency assessments.
Is there a broad approach--because I would
surmise, at least particularly since dietary-wise
they're not likely to get high amounts of diet, and
perhaps after multiple pregnancies, the women are
going to deplete all their iron supplies because
the baby's going to take it away. Is there any
sort of across-the-board programmatic look at the
impact that iron deficiency has in these two groups
and whether perhaps even just dietary intervention
across the board might be the most cost-effective
way to reduce the demand for blood in women and
children?
DR. LACKRITZ: Yes, I think there are two.
In fact, I would say dietary and second I would say
malaria prevention.
DR. HOOTS: Right.
DR. LACKRITZ: In terms of community-based
dietary efforts--and, you know, perhaps WHO would
want to comment on this--the strategies could be
fortification of foods, which we do in the U.S.
generally, I mean, that's not universally accepted
intervention.
What I also didn't--but also you could do
iron supplementation or else mass education on
using available foods and preparing them in such a
way that it improves bioavailable iron in the diet.
There are a lot of iron-rich foods that
are inexpensive in the community. They need to be
used and they need to be prepared properly.
Okay. So even without fortification or
iron supplementation, there are some more basic
activities that could take place in the community.
What I also didn't show is all those
children are generally under two years of age.
They're very young. And what tends to happen in
these types of environments is when you have these
infants born in malarious areas and once their
maternal antibody to malaria wanes, then they
become at very severe risk.
Now, this is also the time where you get a
weaning diet on top of that, so I think the fact
that you bring up both of these is important.
In terms of nutrition, again, what happens
is you sort of have a distribution--I didn't bring
my distribution curves with me, but you have a
distribution of hemoglobin in the community, and
it's very alarming. In this setting, you have
about 20 percent of the kids walking around in the
community under two have hemoglobins below 7. So
one other malaria insult is going to completely put
them in a very high-risk population. Okay. So
that's the community side.
Interestingly, too, this is not recognized
clinically, of course. Anemia doesn't really have
a symptom. It doesn't have a fever or jaundice or,
you know, you don't get diarrhea. So it's a
completely silent epidemic. And unless we take a
public health initiative to address it, people are
not going to come in for care to treat it.
In terms of malaria, it has been shown--there are a number of things that have been shown
to be effective: impregnated bed nets at the
community level reduces transmission and increases
the hemoglobin distribution of the community.
The second thing is use of effective
antimalarials. There is chloroquine resistance
across the continent right now and in many other
areas as well. And yet chloroquine continues to be
used under the false pretense that it's--well, it's
inexpensive, I guess, but it doesn't do anything.
In Kenya, we have 90 percent sort of moderate or
severe resistance to chloroquine.
Now, there's a very large research agenda
now to look at other effective treatments. Even
using something like fancidar (ph), which is about,
you know, a 20-cent single-dose treatment, will
radically change the children's capacity to
increase their hemoglobin.
When we looked at--and sorry I'm going on
so much about it. I'm very passionate about this
topic. So when we actually compared people who
were transfused, non-transfused, people who got
chloroquine versus fancidar, basically if you got
malaria after your transfusion, it negated the
benefit of the transfusion. So if you were
transfused and you received an effective
antimalarial, basically it cleared the parasites so
that your body could re-tick up again.
So I would say effective malaria
treatment, community-based prevention of malaria,
and community-based efforts for nutrition.
DR. GOMPERTS: Dr. Davey?
DR. DAVEY: Following along on that, if I
recall your study from Zaire, one of the other key
issues was the timing of transfusion, that these
children, if they needed transfusion, got it early,
it was beneficial. But many got transfusion a day
or two later, and in that case it just entailed the
risk of transfusion because they were going to
probably survive with malaria treatment at that
point. Is that correct?
DR. LACKRITZ: Yes, that's correct. And I
think that--what Rick's talking about is that what
was happening is when children come in with severe
anemia, they tend to die very quickly. Now, in
this setting, there's no system for collection of
blood from volunteer donors, testing it, storing
it, so it's not available. What tends to happen is
a patient comes in, the family member has to go
out, usually buy a bag of blood, if one's not
available, and then find the donor to donate the
blood. So that takes--and then it's tested. So it
takes generally days before that transfusion
becomes available.
So what happens is the people who needed
it didn't get it. The people who were at risk of
death have already died. And then what that leaves
you is a lot of misuse of blood because these
people who--there's a clear survival phenomenon,
and the people who are able to survive two days of
hospitalization are at very low risk of death.
So, I mean, the band-aid on the blood
safety problem, of course, is putting rapid tests
in every district hospital all over the place as
much as you can. But that still doesn't get at the
system problem that we're also going to need to
address on the longer term, which requires a lot
more long-term and expensive capacity building.
DR. GOMPERTS: Dr. Dalal, you had a
question?
MR. DALAL: In your comments and in the
comments of some of the speakers preceding you,
there were suggestions made with regards to the
availability of low-risk donors and approaches
towards accessing them.
My observation is that in some of the
developing countries low-risk and high-risk donor
pools often break down on societal lines, income
lines, ethnic lines, geographic, lifestyle, and so
on. And while it's clear that you can make a
separation between volunteer and paid donors, to
what extent is it practical to actively identify
and solicit only low-risk donor groups versus the
population at large?
DR. LACKRITZ: Some countries with very
severe epidemics, such as Uganda, Zimbabwe, have
been able to do this. They require donors. They
give them a lot of education, HIV prevention
strategies, and they try to retain them for repeat
donation. And that's been the strategy.
So in Uganda, for example, where now
probably 15 percent of the adult population, they
have less than 5 percent of HIV in their donor
pool. In Zimbabwe, it's even lower than that.
There's another interesting--I mean,
studies have been done, for example, in Cote
d'Ivoire where they were able to identify deferral
strategies such as contact with commercial sex
workers and history of STDs.
The other interesting thing I'd like to
add is that after the bombing of the U.S. embassy,
there was extreme shortage of blood in Kenya. And
many volunteers poured out from all over the
capital city of Nairobi, and the marker rate at
that point was about 2 percent, which is a lot
lower than their general 7 percent. So whatever--I
mean, of course, we have no information on those
people because it was during sort of a catastrophe.
But it points to the fact that people somehow self-select, and somehow people in the community are
low-risk and maybe know they're low-risk, and we
have to just figure that out. It's up to us, I
think, to learn that.
DR. GOMPERTS: Dr. Gilcher?
DR. GILCHER: My question is similar, and
it relates to rates of seroconversion. In general,
if you want a large number quickly of people who
are negative, you go to your younger population.
On the other hand, if you want people who will
sustain negativity, you go to the older population.
And that in a way would be of help in selecting a
low-risk donor base. That was similar to your
question.
Could you comment on that?
DR. LACKRITZ: Yes, I think that's a very
good question. There was--Willie McFarland did a
study in Zimbabwe and found that the risk of
prevalent donations were sort of opposite--and this
makes sense--were opposite that of the risk of
incident donations, that those young unmarried
donors had very high incidence; older donors had
very high prevalence, you know, probably close to
30 percent, if I recall, but very low incidence.
So potentially--so we don't--you know, I
mean, I think that's the research agenda. We have
to figure out what the best strategy is. It may be
to go to older donor populations, screen out your
30 percent, and retain the 60 percent for continued
donation.
I think there are a lot of practical
opportunities, and we just have to explore them and
pursue them.
DR. GOMPERTS: Mr. Allen?
MR. ALLEN: Kind of a two-part question
here. What are some of the barriers that you may
be experiencing with the government agencies in
some of these countries? Are there any issues,
first of all? And, secondly, I work with people
that have lived--you know, were born in either
Nigeria, Liberia, Malawi, and Ethiopia, and there
seems to be a common thread when I talk to them
about blood safety and the issue of HIV. And part
of that issue is that in a lot of these villages
the people tend to feel more comfortable with the
local, say, medicine man or medicine person versus
going to one of the local clinics. They say
there's a lot of fraud and things that have gone on
in the past and that kind of prevents them from
even considering going to one of the local clinics
versus the medicine person. But they said if the
medicine person in a lot of these cases were either
willing to listen to some of the local health
people and maybe at least tell his people that are
seeing him to not necessarily, you know, don't use
the local facilities as well, that that might open
up the door, at least to get some of these people
educated on some of the other opportunities there.
Do you see any of that?
DR. LACKRITZ: No. I think we've
underutilized traditional health workers in the
provision of health care and in community health
education. And so I think we really need to
strengthen those ties, because I think if we think
we can go in with some kind of vertical program
through Western medical systems, I don't think
they'll be nearly as effective as if we try to work
with the traditional healers in the community.
I mean, they're not only sort of--they're
not only medical people in, I think, the sense that
we think of like going to a doctor--maybe it is. I
don't know. But they're really leaders in the
community, and there's almost--not quite a
religious component to it, but there's sort of a--yeah, that's right, and a belief system.
You know, and we--it's like anything. You
really can't impose your structure on somebody
else. You have to figure out how to work within
their structure. So I think that's a good point.
Did you have a point before that?
MR. ALLEN: I was just wondering if you
have any--
DR. LACKRITZ: Oh, barriers with
governments. Yes, I think it's interesting, too,
even working with--I think governments across the
board have requested our assistance in blood
safety. I think the U.S. has been very
underrepresented in their capacity to provide
technical assistance internationally.
The transfusion services that we've seen
have primarily been supported by the EU. The U.S.
has a very small role--has had traditionally a very
small role to play. And we have a lot of
resources. We have a huge amount of technical
capacity. So I think this gets to Dr. Klein's
question, is we have an opportunity here to harness
some small proportion of our resources and
intelligence that's in this room and try to make a
difference.
There are a lot of barriers not
necessarily to working with--there are
organizational structure barriers that Dr. Emmanuel
mentioned that are very real. Transfusion services
are often under medical services organizationally.
They don't have a protected budget. I mean, there
are sort of--so transfusion needs to be heightened
in terms of its presence in government because,
otherwise, the budget falls to some district
hospital. They've got a lot of competing health
priorities and often transfusion can't be supported
adequately.
I think the other barrier is that we do
all these fancy things in the industrialized world.
You know, they see us doing P24 testing, NAT
testing. Now we're going to try to tell them to
use rapid tests that aren't even licensed in our
country? I mean, you know, nobody buys that.
So, you know, they think we're trying to
sell them some kind of second-best thing that we
wouldn't use in our own country, and what's often
difficult to translate is what we do in our country
is often not really based on--well, excuse me, I--
[Laughter.]
DR. LACKRITZ: I'll just stop there. You
know, attention to cost-effectiveness, or even in
treatment algorithms, we just make our best guess.
And then that becomes our policy, and, you know,
it's very difficult to then try to develop a
practical strategy.
DR. GOMPERTS: Dr. Lackritz, thank you for
the information as well as the input and
perspective. We do need to move on.
DR. LACKRITZ: Thank you.
DR. GOMPERTS: Dr. Epstein, FDA
perspective.
DR. EPSTEIN: Thank you and good morning.
I'm going to just describe briefly the areas of
FDA's engagement in international collaboration for
blood safety and availability, and I'm going to
highlight the following areas: the role of U.S.
regulatory standards, our involvement in developing
WHO reference reagents and standards, cooperation
that we have with a variety of international policy
groups, some particular bilateral agreements with
developing countries, the general area of
scientific exchange, and a few additional ad hoc
activities. These are summarized on the first
overhead, and we'll just move quickly to the second
one, please.
So, in the area of U.S. regulatory
standards, it's been pointed out by many of the
previous speakers that a national program,
including government engagement, support, and
oversight, is fundamental to the existence let
alone the health of a blood transfusion system.
And, in particular, FDA's statutes, regulations,
and guidance documents are widely used as models by
national control authorities, both in the developed
and the developing world. The U.S. has been on
this model for about 100 years now, starting with
the Virus Serum Toxin Act.
Now, additionally, it needs to be
recognized that the FDA is a net exporter of blood
products, particularly plasma derivatives, and that
blood products conforming to FDA standards meet
many international needs.
The United States treats the export of
U.S.-marketed products as interstate commerce, and
we make no distinction. So if a product is legal
in U.S. commerce, it's legal to export. And,
indeed, the FDA does not and cannot under existing
law control whether the product stays domestic or
is exported.
Let me note, however, that there are also
provisions in the law for exemption for U.S.
licensed manufacturers to manufacture non-U.S.
products; in other words, they can be made solely
for export. So we're involved then with providing
both products and standards and do provide a large
part of the world need for certain blood products.
Next, please.
Now, in the area of reference reagents and
international standards, Dr. Emmanuel mentioned
that FDA is a WHO collaborating center in the area
of biologics, that CBER's director--that's the
Center for Biologics Evaluation and Research, one
of the FDA centers, where I work. Our director
currently chairs the WHO expert committee on
biologic standards and through that mechanism
contributes to global standards. Additionally,
many FDA staff members participate in a variety of
WHO work groups across a broad spectrum of issue
areas, including blood diagnostics, blood
standards, but as well as vaccines and others.
Furthermore, FDA scientists routinely help
the WHO to develop international reference
materials and standards, and some of the examples
in the blood area include the antibody standards
for HIV-1, HIV-2, as well as hepatitis viruses.
More recently, we've been involved with the
developing the international standards for RNA for
HIV and hepatitis C. There are also efforts now
going on for hepatitis B Parvovirus. We have
developed reference materials for standardization
of the potency of clotting factors, also blood
grouping reagents, and an ongoing current
initiative is to develop reference materials for
transmissible spongiform encephalopathies.
Next, please.
The FDA also has historically been highly
involved with a number of international groups
involved in policy, and it's been gratifying to
hear earlier this morning how well people seem to
understand the fundamental role that policymaking
plays in the utilization of resources and
establishment of appropriate controls. So some of
our activities in this area include the following:
We have been very active as participants
with the Council of Europe, which develops annually
a document called the "Guide to the Preparation,
Use, and Quality Assurance of Blood Components."
Similar to FDA's standards and guidance, this is
the recognized EU standard. And although the
standards of the EU and the standards of the U.S.
are not identical, there is a process whereby
harmonization is driven by the fact of scientific
exchange. You know, if you bring together the
experts who are responsible for the policymaking,
they talk together and they tend to reach
consensus, and that is then reflected in the
policies being harmonized.
And just as the U.S. standards are a model
for developing countries, likewise the guidance
document of the EU becomes a model for difficult.
Essentially, this guide is a series of monographs
on how to make and quality control all the various
blood components.
Additionally, as has been said, we have
participated from the inception in the Global
Collaboration for Blood Safety. The United States
was one of the 40 or so nations which endorsed the
1994 declaration on global safety as well as
signing the subsequent resolution of the World
Health Assembly. And we have remained an active
participant in the preparatory meetings and last
November's first actual meeting of the GCBS.
Additionally, we have been a founding
member and participant in a body which is called
the International Conference on Harmonisation.
This is an international group which includes
governmental bodies as well as industry, and it has
met for the better part of the last decade to talk
about harmonization of international standards for
the evaluation of pharmaceutical products.
Now, the focus of the ICH has not been on
labile blood components, the things that are
directly transfused. However, within its scope,
there is the inclusion of plasma derivatives, which
are in most places in the world regarded as
pharmaceuticals.
And let me also mention that we have had
international contact with consumer-driven
organizations. Of course, we are very active
domestically with consumer advocacy groups, many of
which are themselves parts of international groups.
And one example is the World Federation of
Hemophilia where we have participated regularly in
the international meetings. And, of course, the
bilateral exchange contributes to our thinking and
hopefully assists us to be most appropriate as we
develop product standards and transfusion-related
policies.
Next, please.
With respect to bilateral agreements, I
think the important point here is that our existing
regulations, which I've cited here--21 CFR 20.89--do permit to share regulatory information with
established national regulatory control authorities
of other countries. Now, we, however, maintain
close relationships with a fairly small set of
countries. In particular, in the Western
Hemisphere, we have annual and biennial meetings
with Canada and Mexico. We also have what we call
trilateral meetings that used to involve the U.K.
but now involve an EU representative. We also have
had historic close cooperation with the regulatory
authorities in the U.K. and in Japan.
Now, we have also some bilateral
agreements at the level of assistance, development
assistance. However, I need to explain that these
are indirect. Usually they come about when we have
a funding source outside of the agency, such as the
USAID, which approaches the agency and says, Would
you cooperate in this initiative? And under that
umbrella, we have engaged in specific assistance
projects in India, in Egypt, and most recently in
Russia.
Next, please.
Other speakers have drawn attention to the
need to provide expert training in the area of
transfusion medicine and blood banking. FDA is
highly involved in such training through scientific
exchange programs. We sponsor fellowship training,
and we hire visiting scientists, primarily through
the Fogarty International Center. For example, at
this point in time, just within the blood program,
we have six funded Fogarty positions, and these
research fellowships provide opportunity for
scientists to come and train at the FDA where they
learn about regulation and control as well as doing
laboratory work. For example, we have a person
from Cameroon who visited us and worked on virus
variants, including HIV-1 Group O. But also these
kinds of contacts foster future cooperations and
dovetail very neatly with a second area of
scientific exchange, which is simply scientist-to-scientist collaboration.
The FDA scientists freely collaborate with
their international colleagues, and, for example,
right now in the blood office we have projects
ongoing on HIV variants, HCV epidemiology, and
diagnostics for leishmaniasis.
Next, please.
There were some activities that I found
hard to throw into one of the previous bins, so I
just called them ad hoc. We provide technical
advice. Many countries simply contact the FDA on
an ad hoc basis for advice on blood products and on
blood regulation, for example, product safety
standards, manufacturing methods, and techniques of
regulatory control and authority. And we do our
best to respond to these requests.
Assistance of that form generally is
handled through the Deputy for Medical and
International Affairs, who previously was Dr.
Elaine Esber, who has now just retired from CBER.
However, the office is still maintained and I
presume that at some point there will be a
successor.
And, additionally, when they have
occurred, we have provided support to blood
initiatives at the international level, a recent
example of which is the World Health Day, where we
were contributory both to the WHO initiative and to
the initiative of PAHO.
So, in summary, on the last transparency,
the FDA will continue to support the WHO and the
Global Collaboration for Blood Safety, for which
WHO is the Secretariat, as well as other
international efforts. We do maintain contact with
other groups such as the Red Cross, the AABB,
various academics, et cetera, who have these
international engagements. It's my personal
opinion that FDA's best role is to provide
leadership for policy and for product standards
because we are not funded to any significant degree
to provide material support. However, we can
provide limited scientific training and technical
assistance through the kinds of exchange that I
described. And lastly, because we are research-based, we also provide collaboration through
support of international research.
Thank you very much.
[Applause.]
DR. GOMPERTS: Thank you, Dr. Epstein.
Any questions? Yes?
DR. LOPES: I was reading about a purified
hemoglobin product that's being derived from cattle
blood and tested in South Africa. Is it your
assessment that these kinds of substitute products
are going to make a big difference in the near
term?
DR. EPSTEIN: Well, I think that the
relative risk and benefit of these products is, in
fact, very different in different countries. In
the South African situation, where you have a very,
very high rate of HIV and, you know, a resource-stressed environment, there may be willingness to
consider products whose safety profile may not be
optimal in the United States, where despite, you
know, the tremendous anxiety that surrounds use of
blood products and transmissible disease, blood
products are, in fact, astoundingly safe. And so
we have a tremendous challenge to figure out the
role that so-called blood substitutes might
logically play.
Blood substitutes are also somewhat a
misnomer. They are actually resuscitation
solutions. In some cases, they may be bridging
therapies until there is availability of a
transfusion. They have short half-lives in the
body and, therefore, in many instances cannot avert
an allogeneic transfusion. And so figuring out
their best therapeutic niche is itself a challenge.
So I remain optimistic about these
technologies. I think that, you know, the fact
that you can sustain life in people with
astoundingly low red cell hemoglobins by providing
oxygen-carrying compounds, including hemoglobin-based pharmaceuticals, is amazing. But we have yet
to figure out what the best medical use or
validated medical claim for these products will be
in the U.S. environment where the therapeutic ratio
of blood products is itself, you know, tremendous.
So I think worldwide they certainly offer
a new venue for technological advancement and that
they will play a role. Exactly what the role will
be in the U.S. I think it not so straightforward.
DR. GOMPERTS: Thank you, Dr. Lopes.
Other comments? Dr. Davey?
DR. DAVEY: Jay, as you remember from the
last meeting of the GCBS, one of the issues--I
think Jean mentioned this also--was perhaps the
development of a series of graded sets of
standards, if you will, maybe three different sets
of standards, all of which meet minimal
requirements but can be applied to countries in
different levels of development.
Do you see the FDA playing an active role
in the development of these standards, or what are
your comments about that?
DR. EPSTEIN: Well, yes, through the GCBS
I see us playing a very active role. I myself
chaired the working group of the GCBS on this
policy group. We have had--I think it was three
preparatory meetings prior to the first meeting of
the GCBS where we talked about this issue.
I'm very much of the mindset that the
technology and its use have to be appropriate for
the global health system. There are those who have
called this the public health wellness model; in
other words, try to look at the whole and then do
what is appropriate by whatever measure, whether
that's a cost-effectiveness measure, an outcome
measure, et cetera. And the notion has come about
that one needs to try to replace, you know, the
quest for high technology with the quest for
appropriate interventions at any particular stage
of development. And there is this concept that if
we can conceptualize a continuum of development
where there can be benchmarks and, with that,
appropriate recognition that stages of blood safety
and appropriate use have been reached, that this
might go a long way toward alleviating this natural
pressure to, you know, just bring in the PCR
machine, whether or not you have an infrastructure
to support it and whether or not you're delivering,
you know, even generation one antibody screening to
the majority of blood recipients.
So, yes, I think that we do have a role to
play, and I think that we are willing to step up to
the plate. And I think that one of the insights
here has been that this process is also of value in
the developed world for just the reason that Dr.
Lackritz flirted with, which is that there are
elements of irrationality in the developed world,
and that if we can bring about some kind of
conceptual framework where we talk about, you know,
good policymaking, then, you know, hopefully to
clarify the technology challenge, you know, the
available tools, their cost, their effectiveness,
and benchmark monitoring, that that would also
advance the situation of the developed world. So
it's sort of a two-way street.
DR. GOMPERTS: One last question. Dr.
Guerra?
DR. GUERRA: Jay, thank you for a very
informative presentation. You made reference to
some of the countries having regulators that I
guess perhaps would be somewhat comparable to the
FDA. But some of the countries that need to have
regulators were not on your list.
Is there some hope for the future that
they will have them? And in those instances where
there are regulators, how comparable are they to
the FDA? Do they have the clout to really move
quickly and do recalls or get things done that have
to be done?
DR. EPSTEIN: Well, of course, the
spectrum is very, very wide. You know, you have
some countries where there's no effective national
body dealing with transfusion safety, and then you
have countries that have bodies quite analogous to
the U.S. where there are central laboratories,
where there is a foundation in law, where there are
inspectional programs, where there are effective
controls of reagents, where there are recalls, et
cetera.
You know, in broad brush, you have very
effective systems in places like Australia, Japan,
Canada, Western Europe. And you have sort of areas
where there is significant development and they're
not quite to that level, such as in India, and you
have, you know, many areas where these kinds of
controls are lacking.
I'm really not the best person to speak to
that. I mean, Jean Emmanuel is here and has, you
know, vast direct experience interacting with
governments around the world and assessing the
status of the national authorities. I think the
most important point to recognize here is that it
is a fundamental principle that you cannot have a
safe transfusion system in a country that lacks a
national perspective on the importance of
transfusion, that there has to be a government role
and that there has to be some centralized system,
at least of oversights and standards.
DR. GOMPERTS: Dr. Busch?
DR. BUSCH: Jay, we've discussed the
issues of test technology and blood substitutes in
terms of the high standard of safety that's imposed
by developed countries like the U.S., and at some
point that sort of precludes the availability of
less expensive, perhaps more practical
technologies.
The third area is pathogen inactivation
where, again, we're seeing technologies developed
with the orientation toward, you know, resource-rich countries and, therefore, the requirement that
these compounds be removed with expensive
technologies, et cetera.
From your knowledge of the technical
capacity of these methods, do you see a role for a
broadly capable pathogen inactivation method that
could even perhaps preclude the need to do testing
in developed countries? And then if so--in terms
of do they have the capacity to actually remove the
pathogen at a level that would be required? And
then, if so, is there a way to create a sort of
two-tiered strategy that these companies could be
motivated to develop a technology that could be
inexpensive and broadly applicable in resource-poor
countries?
DR. EPSTEIN: Yes, well, I again am
optimistic. I think that we're seeing some
marvelous technology development in pathogen
inactivation that will be suitable for the labile
blood components, the transfusable components.
As I said before, I think that the
risk/benefit profiles need to be examined in the
country-specific context and that some of them, as
you know, are already in use. I mean, gentian
violet is used in many parts of South America to
kill Chagas. You know, methylene blue is used also
in many parts of Europe to treat fresh frozen
plasma.
We have made tremendous strides in the
U.S. with viral inactivation technologies for all
the plasma derivatives, and we have one pooled
plasma product, as you know, which is solvent
detergent treated.
The question that you're asking is: Can
it ever be cost-effective in the developing world
and would it ever supplant screening? Well, I'm in
no position to comment on what could be done with
cost. You know, certainly there are material costs
and labor costs in processing a unit of blood to
treat it to inactivate pathogens. Those will never
be zero, and whether they'll ever be affordable, I
can't comment.
With respect to the need to additionally
screen, I think there are sort of two edges to that
sword. On the one side, you could say, well, if
it's highly effective, you don't need to screen.
On the other hand, there's always the notion that
you want to keep the input burdens low so that you
can assure the effectiveness of the inactivation
technology. You know, you'd like to be treating
low-level contaminations rather than high-level
contaminations. And then there's always the notion
of just, you know, belt and suspenders.
Whether we would ever move off that
paradigm and simply accept inactivation I'm not
prepared to say, but I think that that will be a
very lively debate.
DR. GOMPERTS: We do need to move on.
Thank you, Dr. Epstein.
Our next presentation is Dr. McDermott,
NIH international activities.
DR. McDERMOTT: Well, I've gone really low
tech with overheads. I don't know if that's
because I've worked too long in developing
countries or because I'm just a control freak.
But, anyway.
I want to thank the organizers for
providing me with this opportunity to address the
committee and to talk a little bit about some of
the blood safety activities that NIH has been
undertaking. And I'm going to focus basically on
the activities within the Fogarty International
Center because that appears to represent most of
the NIH efforts.
First of all, I'll give you some
background about the Fogarty programs to help you
understand how the blood safety activities fit
within those. So the next overhead, please.
The Fogarty International Center is a
center within NIH with the mission of promoting and
supporting scientific discovery, support scientific
research and training internationally to reduce
disparities in global health.
And in the next overhead, FIC fulfills
this mission by basically advancing both biomedical
and behavioral research and research training to
prepare current and future health scientists.
Next?
And I'm going to focus on the training
programs and the extramural training programs, and
these are programs in addition to the programs that
Dr. Epstein just talked about, which are considered
more the intramural ones.
Basically, the training grants are awarded
in a competitive process, generally to--institutional training grants generally to U.S.
universities but not exclusively. And the awardees
are generally grantees who have current NIH
research and also demonstrate research
collaboration with the foreign research institutes.
So each one of these training grants, the PIs need
to identify major foreign collaborators and
institutions within the countries that they're
going to support the training.
Basically, the purpose of the training
grants are to support training for research
capacity building for scientists from the
developing countries. So the bulk of the money is
used to train foreign scientists.
Having the program set up in this way
actually does help prevent some of this brain drain
because it works two ways. If there's ongoing
research in the country, once people are trained
there is something for them to go back to. And I
also think the quality of the research coming from
these collaborations improves when you have people
in-country who are understanding the research and
understanding what you're trying to do.
Okay, next overhead.
Okay. Basically, the support that's
available through the training grants are long-term
training, including master's, doctoral degrees, and
post-doctoral fellowships, and also short courses,
either within the U.S. or in-country short courses.
In addition, in order to also support
trainees when they return home, there's grants to
support the in-country research, to support either
their thesis or doctoral degrees, and also some re-entry grants for trainees when they've completed
their training.
There's very limited salary and
administrative support for the collaborating
institutions, and the overhead is limited to 8
percent in these training grants. So, again, the
bulk of the money does go toward training.
Okay, next overhead.
The goal of these training grants is to
support locally appropriate research, and that's to
support--to provide training and infrastructure
support to strengthen the local capacity to
undertake appropriate biomedical and behavioral
research. And I think we've heard over and over
again this morning that it needs to be appropriate
for the country. And one way to do that is to have
the local people be trained because they are the
best ones to identify what's going to work in their
country.
It also provides an opportunity for the
Western collaborators to understand the local
conditions, the health care systems, and the
culture in which they need to work with the
collaborators in developing the research.
Next?
Basically, we found that this is
definitely training for capacity building, and both
types, both the short- and long-term training, are
needed to ensure future local leadership, to build
the capacity for the laboratory support, to
strengthen the capacity for testing and counseling,
and that's become increasingly evidence with the
AIDS epidemic, that the voluntary counseling and
testing is a real bottleneck.
To also strengthen the capacity for
program management and administration, and also to
build capacity for program evaluation. And, again,
we also use this "train the trainer" model where
you get people in-country who can then train the
next generation of people within country.
And I think it's really important to
recognize that you really need people on the ground
who understand issues, and particularly the blood
safety issues. In order to really make progress
and also to maximize any kind of investments you're
making in equipment or reagents or something, you
really need on-the-ground people to understand.
Okay, next overhead.
There are various different training
grants that Fogarty has, and I sort of listed them
on the side. When I looked at where our blood
safety activities were concentrated, it was in the
HIV/AIDS research and training program that we
have. However, there certainly are opportunities
for integrating blood safety activities in the
training programs that are related to infectious
diseases, environmental and occupational health,
certainly occupational exposure, and blood safety
is an important part. Maternal and child health,
if most of the transfusions are going to women and
children, then there's an avenue there. And also
malaria.
We're also initiating a new clinical
operational health services research and training
program, and I think there's a big opportunity for
blood safety activities within that program.
However, I'll focus--okay, next overhead.
Thanks. I'll focus on the AITRP, or the AIDS
training program, because that's where most of our
activities are ongoing.
Now, this is the oldest program that
Fogarty has. It's in its third five-year cycle.
It's in its 13th year, and we've gradually
increased the number of grants within the program,
and currently, with last year's competition, we
have 23 universities funded.
The next overhead will show you all the
different programs, and I tried to bold the ones
that have some blood safety activities going on.
But you can see that it's a wide spectrum, and they
work basically all over the world: Asia, Latin
America, former Soviet Union, and Africa.
Okay. Next overhead.
Last year, we moved into blood safety
through some competing supplements to the current
AITRP applicants, but also through some recompeting
awards. This effort was supported by the National
Heart, Blood, and Lung Institute in terms of half a
million dollars a year to support these efforts.
So two of the renewing programs at Brown and at
State University of New York at Brooklyn were
provided with some funds to support activities.
Brown is working in India, the
Philippines, and Cambodia, and they're in the
process of identifying trainees for training and
looking at blood utilization practices and
transfusion methods.
State University of New York at Brooklyn
downstate is working in Russia, and they are
funding a blood safety fellowship at the New York
Blood Center.
Cornell University was provided a
supplement to look at blood safety in Haiti.
That's where they've been working the longest,
looking at blood banking and blood utilization and
trying to look at not only urban but also rural
areas.
And then Johns Hopkins was awarded three
supplements to work in China, India, and
Laos/Thailand, and I'm going to let Chris Beyrer
talk about these programs later on in the program.
Also, Chris will talk about a very, very good
example of what we're calling, for lack of a better
word, South-to-South training in the fact that some
countries do have the ability to train people
within their region, they're at a higher level.
And, in fact, that may be a more appropriate
training place for people than coming to the United
States or to Europe to learn the very, very high
tech, which makes it really difficult for them to
transfer that to their country. While they see a
country in their region who's progressed to a
higher level, it's a more realistic goal for them
to strive for.
Okay, next slide.
There are also some activities that are
being supported through the base awards, the AITRP
program. UCLA is beginning a study looking at
blood safety in China. UC-Berkeley is training a
fellow to look at this issue in Brazil. They're
beginning discussions in India. And, in fact, in
Zimbabwe, more than five years ago they were
looking at donor deferral--that should be referral
strategies.
Case Western also in the past, working in
Uganda, has trained three people in the Uganda
National Blood Supply in the Ministry of Health.
And Maryland, working in Nigeria, is
beginning to look at trying to develop a rapid test
to use in a study to look at the prevention of
transfusions associated with HIV, and the study
will be done within a World AIDS Foundation grant.
So there's some great examples of collaboration, of
using funding from very different sources to
achieve your goal.
And the University of Illinois at Chicago
is beginning to develop some activities. They're
working in Malawi, Chile, and Indonesia. This is a
program that's very interesting because their
collaborators are the School of Public Health in
Illinois and the School of Nursing, with the School
of Nursing in these three countries. And I think
when we talk about some of these blood safety
activities, we need to not just think of
physicians, but we also need to think at the people
who are providing a lot of the care, and the nurses
and midwives in these countries are the mainstays
of your public health systems.
Okay, next slide.
So, anyway, these are the NIH websites if
you--and I have copies of the handout for the
committee. So you can look at the Fogarty website,
the NIH website, and also there's a section on the
NIH website where you can look at research and
training opportunities at NIH.
Next overhead.
Certainly, if you have any questions, feel
free to give me a call or send me an e-mail.
I think all of us at Fogarty and NIH look
forward to collaborating with everybody to expand
this work. I just want to point out that I think
we do have an excellent network through which work
can be done to provide the opportunities for
building the capacity in countries, and I think
because the networks are well-established networks,
these efforts can be moved through the system quite
quickly through our existing grants.
Thank you.
[Applause.]
DR. GOMPERTS: Thank you, Dr. McDermott.
Any questions?
[No response.]
DR. GOMPERTS: I have a question before we
let you go. From the point of view of strategy, is
there any attempt or thoughts around the issue of
strategy from the point of view of allocating
resources for blood banking, blood safety?
DR. McDERMOTT: Basically, I mean, we're--and I don't know if any of you know Ken Bridboard
(ph), who's the division director, but Ken is very
good at mobilizing resources toward Fogarty.
Fogarty is probably one of the least funded centers
at NIH. So we try to partner with, as the example
here, Heart, Lung, and Blood to mobilize resources
toward these efforts.
The way the extramural grant programs are
set up, basically we solicit applications for
activities related to blood safety, and then we
actually let the applicants determine what would be
most appropriate for the work that they're doing.
So there's not a definite amount of money or, you
know, just focus on certain areas. We sort of
leave it flexible and general so that people can
meet the needs within their countries. But
certainly resources are always welcome.
DR. GOMPERTS: Thank you very much.
DR. McDERMOTT: Thank you.
DR. GOMPERTS: We're having a minor change
in the agenda. Dr. Lipton needs some set-up time,
so we will have Dr. Bianco and also Dr. Lane, who
will present just before the lunch break. Thank
you.
Dr. Bianco?
DR. BIANCO: I'm going to be low-tech and
short. I'm Celso Bianco. I'm the executive vice
president of America's Blood Centers.
America's Blood Centers, or ABC, is an
association of 75 not-for-profit, community-based
blood centers that collect half of the U.S. blood
supply from volunteer donors. ABC thanks Dr.
Nightingale and the committee for bringing such an
important issue to public discussion.
Globalization of the world economy,
travel, and commission created a new set of
parameters for the diffusion of wealth,
information, and disease. We're all together in
the same world, and the safety of the U.S. blood
supply is linked to the safety of the blood supply
around the world.
ABC has been involved in international
collaboration since its inception. Our members
have trained a large number of individuals from
many countries, developing and developed, and have
traveled to those countries to share experience,
expertise, and technology. Our members have also
supported every other blood banking organization in
their international efforts. Dr. Paul Holland, CEO
of Sacramento, is the current president of the
International Society for Blood Transfusion, a
leading organization in efforts to improve
transfusion safety in less fortunate areas of the
globe.
You heard earlier today a presentation
from the ICBS. It was created at the New York
Blood Center with the mission of providing
affordable screening tests to the developing world.
ABC directly supports, with money and expertise,
safety efforts in former Soviet Republics.
On a personal note, I was born in Brazil,
I saw the problems that the country confronted, the
immense amount of energy the Brazilians have
applied to the development of today's sophisticated
blood system that is based on government-supported
regional centers that co-exist with the private
sector. I saw this system evolve and reach an
inviolable level of safety. Brazil reached that
goal because of the foresight and dedication of a
number of individuals that were trained in the U.S.
and Europe and their influence in the Brazilian
public health system. Brazil is a success story in
blood safety, and I'm very proud of having been a
minor participant in that process.
In addition, I have personally dedicated
many days of my life to blood safety and
availability in countries of Latin America and
Asia. For these reasons, I consider myself
sensitive to blood transfusion issues of the
developing world and would like to share with you
some thoughts derived from the experience of ABC
members and from my own experience.
Obviously, my words are tainted by my own
personal biases, and I hope you would excuse me for
that.
First, I would like to address the
question: What do developing countries say they
want? The answer is almost unanimous. They want
blood systems that are identical to those in the
U.S. and in the rest of the developed world. They
have learned everything about the American model of
blood transfusion safety through the individuals
that were trained here, publications, and by
advertisements by manufacturers of technology.
They want the same technologies, the same approach.
They do not want to be considered second-rate.
The example is a recent decision made by
the health authorities in India where rapid tests
are not acceptable for HCV or HIV screening, only
ELISA-type assays. Essentially, most developing
countries want to be state of the art. They want
the same standards and the same tests. They do not
want to feel insufficient or primitive. They
reject less sophisticated tests. What they ask for
is money to do the same thing we do. In many ways,
they are right. They are struggling because of
economic factors, not because of intellectual
factors.
Another important element is national
pride and the sanctity of blood. Brazil wrote into
its constitution that blood cannot be
commercialized or exported, a reaction to abuses
that took place 30 years ago. China has forbidden
payment of blood donors as recently as two years
ago on a national basis.
Unfortunately, our current approaches to
assist developing countries contribute to the
feelings that I have just expressed. Whenever we
talk about assistance to developing countries, we
talk about technology. And I'm partially wrong
because today I heard a lot of things from some of
the people. Since it is easier to have a single
contact point, we focus our efforts on government.
We provide short-term financial assistance, we
provide training in American institutions, and we
provide equipment and supplies.
Trainees come to the AABB meeting, look at
the technology exhibit, and are mesmerized. They
want it all. They return to their countries of
origin and dream about setting up blood banks
identical to those that they saw abroad.
Some actually succeed in doing so. Then
they realized that the system depends on the
availability of qualified blood donors. This was
not part of their training and was not mentioned by
the local salesmen pitching technology wares.
Trainees did not learn how to recruit volunteer
blood donors. They did not learn how to create a
sense of duty among the members of their community.
They did not have resources to develop methods to
deal with the frequent cultural barriers and myths
about blood donation.
In despair, they maintained their
traditional replacement donors. Those are
patients' friends, family members, or, not
infrequently, individuals paid under the table to
complete the blood donation quota required by the
hospital where they are going to have surgery.
The result is unfortunately clear. Every
donor is a first-time donor, and a substantial
portion of the collections is discarded because of
test results.
The situation is aggravated by the
uncritical adoption of U.S. testing standards. For
instance, Brazilian regulations require screening
of all donors for hepatitis B core antibodies.
Between 20 and 40 percent of the donors in the
Amazon area are positive in the test. Between 10
and 20 percent in other areas of the country, the
units are collected and discarded.
Furthermore, overzealous regulators in
Brazil require the performance of two different
tests for HIV, Chagas, and syphilis. I would love
to see these wasted resources diverted to donor
recruitment efforts, leading to a stable base of
loyal repeat donors.
I must note that there are bright stars
and that several Brazilian centers are focusing on
volunteer donor recruitment and report great
success.
I believe that to some degree we bear
responsibility for the confusion about blood safety
standards around the world. Despite the
communications and interaction between regulatory
agencies and blood banking organizations among
developed countries, we cannot agree among
ourselves on procedures for the management of the
safety of the blood supply. We are driven by fear,
politics, and sometimes demagoguery.
The examples that we give to the
developing world are utterly embarrassing. There
is no better example than the plethora of
irrational measures adopted to prevent a
theoretical risk of variant CJD by transfusion.
England burns the plasma for every unit of blood it
collects and buys plasma from the U.S. source
plasma to fill its plasma fractionation plants.
Portugal imports plasma for transfusion from
Germany. Germany is considering discarding their
plasma and obtaining it from other countries. And
the two blood systems in Canada play a game of
Chicken Little to see who will defer more donors to
protect the blood supply.
And in the U.S., a major blood banking
organization decides that the recommendation of
world actors on transmissible spongiform
encephalopathies assembled by the Food and Drug
Administration did not go far enough and wants to
defer 6 to 9 percent of blood donors because of
travel to Europe. This lack of coherence confuses
everybody, including our own blood donors.
ABC members want to contribute to the
safety of the world blood supply and are ready to
participate in every effort undertaken by HHS and
by other blood banking organizations.
ABC members believe that the department
can support worldwide safety, and in answer to your
questions, it can support by supporting
harmonization of rational international standards
in blood safety. We believe that an international
committee on blood safety should attempt to reach
consensus about rational safety measures. This
could be done under the auspices of WHO, PAHO,
ISPT, and must involve FDA and European regulatory
agencies.
HHS can support the activities, too, by
supporting the role of FDA as the ultimate guardian
of the safety of the U.S. supply and promoting
consistent policies in our country; by supporting
dissemination of expertise, for instance, by our
military forces stationed abroad, DOD has the
people and the knowledge to help communities
develop effective blood programs; by publicly
admitting that safety measures applied in the U.S.
may not be appropriate for other countries, as, for
instance, core antibodies to hepatitis B; by
funding training programs in donor recruitment and
retention at U.S. blood centers, particularly those
that have a strong community base and are effective
at recruiting donors; by promoting community-based
recruitment efforts beyond government agencies
through funding by organizations like World Bank
and sister organizations; by direct support of PAHO
and WHO efforts; by supporting the international
activities of the Centers for Disease Control; and
by increasing support for the NIH Fogarty program.
I want to emphasize that ABC members are
committed to blood safety at home and abroad. ABC
members are also committed to the preservation of
the supply of safe volunteer blood donors for all
patients in need because no blood is a real risk,
it is not a theoretical risk. I re-emphasize that
we are ready to participate in your efforts.
Thank you again for the opportunity to
present our point of view.
[Applause.]
DR. GOMPERTS: Thank you, Dr. Bianco.
Any questions? Yes, Dr. Epstein?
DR. EPSTEIN: Well, Celso, you echoed Dr.
Davey's earlier concern about the drive to high
tech, and I just wonder what's your thought about
the solution.
DR. BIANCO: The solution is complex
because whatever we try to do to address that, we
are competing with a lot of messages that are
reaching the same public and that confuse them.
And they can show it. For instance, you go to many
blood banks in any Latin American country, be it
Mexico, Brazil, Argentina, every one of them has
several pieces of apheresis equipment sitting
there. Obviously no donors in the chair. They
don't have the money for the software, the donors
recruited, but every one of them has that piece of
equipment. And this was sold to them not by us.
They saw it. They have read the articles. They
saw it at AABB, and they can show it to the people
that walk through their service. But it doesn't
contribute to the local thing.
I think that the best thing is still
education, and a lot of the education has to be not
them coming to us only and seeing what we do, but
us going to them and learning what our issues are,
what the problems are, and being able to
participate with them in the resolution of those
issues.
DR. GOMPERTS: Thank you.
Other questions?
[No response.]
DR. GOMPERTS: Okay. Thank you. We'll
move on to Dr. Lane, American Red Cross.
MS. LANE: With all due respect, it's not
"doctor," simply a master's. What can I say? But
I am joined by our physician colleague, Dr. Roger
Dodd, and our chief medical officer, Dr. Rebecca
Haley. And I work daily for a doctor, Dr.
Bernadine Healy. So thank you.
First of all, one of the things we've
talked about during break is we want to thank you
for this forum. It has been energizing to hear
from the various components who are involved in the
international activities, and we'd like to share
with you some of the efforts that we've been able
to undertake through our unique position as a
member of the International Red Cross movement.
Our congressional charter of 1905 calls
upon the Red Cross to play a leading role in
providing humanitarian assistance through an
international system. Much of this effort is
coordinated with our Red Cross and Red Cross sister
societies around the world; 113 of those societies
are involved in some aspect of blood banking in
their home countries.
At the multilateral, bilateral, and
individual level, we have collaborated in a number
of ways to responding to requests for knowledge
sharing and technology transfer. At the 27th
International Conference of the Red Cross and Red
Cross Societies in Geneva in late 1999, the Red
Cross pledged to take a proactive role in sharing
our technological expertise in blood quality
assurance with other Red Cross societies, and this
assistance will continue as resources allow and
will be coordinated to complement our other
international and regional priorities. Presently,
we're engaged in a number of activities in the
Americas and in Eastern Europe, and we are
expanding efforts into Africa and Asia.
With regard to our collaborative efforts--or multilateral efforts, I should say, we have been
involved in a number of public health and AIDS
education and awareness initiatives around the
world, which will, through a collateral effect,
improve the safety of the blood supply in those
countries that are hit hardest by the AIDS
epidemic. We have joined forces with the Centers
for Disease Control in 14 African countries and in
India through the Leadership and Investment in
Fighting the Epidemic, or the LIFE Initiative that
you may have heard about.
At the clinical level, the LIFE program
aims to change blood collection and screening
processes in targeted countries to help ensure a
safe blood supply and reduce the HIV incidence
rates. We've also collaborated with PAHO in its
development of regional blood safety initiatives
that are aimed at improving the efficiencies of the
laboratories that act as the screening centers,
help develop the national quality assurance
programs, and establish external performance
evaluation programs, and, most importantly, as
we've heard repeatedly, promote voluntary, non-remunerated blood donation.
But Dr. Lackritz focused this morning on
one of those key areas, which is preventing the
need for transfusion in the first place. And how
do you strengthen primary health care in the
vulnerable groups of women and children? In late
1999, we joined with PAHO in a Healthy Children
Goal 2002 program aimed at some of these primary
health care initiatives. As you probably know,
200,000 children under the age of five die every
year in the region covered by PAHO. We are working
with a minimal--it's a $6 million investment in ten
countries in that region to go for the community-based programs, to identify and work with local
health care providers to help them address, as my
international services colleagues keep trying to
get me to remember it, the DAMMM diseases:
diarrhea, acute respiratory, malnutrition, malaria,
and measles. And that program is going quite well,
and I think it's one of those, as Dr. Lackritz
identified it, practical opportunities that we have
with improving blood safety and availability.
We've also been involved in a number of
bilateral relationships to improve blood safety and
availability. Through the World Hemophilia
Federation, about a year ago we donated $1 million
of anti-hemophiliac factor to be used through the
American Red Cross Cares 2000 program, and that
will be used worldwide.
We've also recently donated a year's
supply of albumin to a not-for-profit organization
in Nicaragua, and that is geared to help burn
victims in a large hospital there which receives
over 1,000 pediatric burn cases a year.
One of the major strengths of the Red
Cross movement is the ability to take a developed
society and work side by side with a less developed
society and help them build capacity, through staff
interchanges and, again, technology transfer and
knowledge sharing. And in those areas, we've been
in a number of places: Jamaican Red Cross, working
with a Together We Can program, targeting teens and
young adults through HIV prevention, ultimately
helping us to build a group of safe donors.
We've also partnered with the Tropical
Disease Institute at Ohio University to improve
blood safety in Ecuador. And we're working
alongside our sister societies in Honduras, Egypt,
China, and the Ukraine.
And, lastly, of course, as you've heard,
and I think as Dr. Bianco was saying, it's those
individual relationships that we have with blood
banking colleagues throughout the world, and
certainly Dr. Dodd and others at Holland Laboratory
have been for years working on a one-to-one basis.
So, again, I thank you for the opportunity
to share with you some of the efforts we've been
involved in. We're certainly energized and looking
forward to see what comes out of the forum as far
as future initiatives.
[Applause.]
DR. GOMPERTS: Thank you.
Any questions for Ms. Lane?
[No response.]
DR. GOMPERTS: Well, thank you very much.
MS. LANE: Thank you.
DR. NIGHTINGALE: Just a procedural note.
It is now about three minutes to 12:00. If we
begin promptly at 1 o'clock, we will be beginning
one hour after the stated time on the agenda, but
exactly when I hoped we would be able to begin. If
we begin at 1:00, we will do everything we can to
get out of here at 4:30, which is at the time when
the discourses of this sort start to degrade.
[Laughter.]
DR. NIGHTINGALE: If you could please be
back here at 1 o'clock, we will continue and have a
productive day, and I thank everybody for their
contributions so far.
[Whereupon, at 11:56 p.m., the meeting
recessed, to reconvene at 1:00 p.m., this same
day.]
Â
A F T E R N O O N S E S S I O N
(1:10 p.m.)
DR. GOMPERTS: Our first presentation this
afternoon is by Karen Lipton, a doctor of laws.
[Laughter.]
MS. LIPTON: Thank you very much. As you
know, the AABB has been really involved for quite a
long time in a lot of international activities. We
are part of the Global Collaboration for Blood
Safety. We are a member of the PAHO task force
that is preparing the plan for strengthening blood
in the region of the Americas. And we're also now
in the process of pursuing our former liaison
relationship with WHO.
But I'm not going to talk about those
activities today. Rather I'd like to speak about
something else, and that is how AABB focuses its
international activities.
We are the professional association for
about 8,000 individual members and 2,000
institutions. All of these individuals and
entities are engaged in the collection, processing,
testing, distribution and transfusion of blood and
blood components. Interestingly enough today, over
15 percent of our AABB--excuse me--that should be
individual members--are from outside the United
States, and we really didn't even recognize that
until a couple of years ago, and I think as Celso
mentioned this morning, even in our annual meeting,
anywhere from 15 to 20 percent of the people who
attend come from outside the US. And all these
members reside in over 75 countries around the
world.
The AABB mission is to establish and
promote the highest standards of care for patients
and donors and all aspects of blood banking,
transfusion medicine, hematopoietic, cellular and
gene therapies and tissue transplantation. And if
you think about all the activities we're engaged
in, we really fulfill our mission primarily through
our standard-setting activities for blood banks and
transfusion services, and through the accreditation
of these institutions against our standards. We
started our standard-setting activities in 1947.
That was the first edition of standards for blood
banks and transfusion services. We're, by the way,
in the process, I think, of the 21st edition now.
And not only do we have standards for
blood banks and transfusion services, just to let
you know, we also set standards for the collection
and processing of hematopoietic progenitor cells,
we set standards for reference laboratories,
another separate set of standards for core blood
collection and processing. We also set standards
for paternity testing, and just recently, we
released a draft for publication and for comment in
the perioperative arena, where we are now going to
be setting standards and accrediting those
individuals and organizations that provide those
services.
Outside of the United States we have 15
facilities who have requested AABB accreditation
against our existing standards. We have about 40
who are in the process of seeking accreditation,
and all of our standards, and even our other
publications, most notably, our technical manual,
have been translated now into Spanish, Polish,
Russian, Japanese, Chinese and Armenian.
One of the difficulties that we found is
that the global implementation of AABB standards
has been somewhat problematic. I think Celso
actually referenced some of the issues this morning
when he talked about setting public health
priorities through our standards for other
countries. The biggest request that we get for a
variance from our standards relate to testing
requirements, when people say, "We don't see a need
in our country to do HIV antigen." Core antibody
has been a particularly sticky issue. And then
there are a number of other issues, particularly
NAT testing. And so since 1985 we've seen
increasing requests for variances from these
standards at the committee level.
Now, in 1994, we were actually approached
by PAHO, specifically Jose Ramiro Cruz, to develop--help them develop uniform regional standards for
the region of the Americas, and said sure, we would
like to help. And took a look at our AABB
standards. And the first thing that we found was
that our existing model simply was not workable
outside of the United States, because it did
mandate the application of technologies that were
not widely available outside of the US, either for
resource or other reasons, and it really did force
our public health priorities on other countries and
regions of the world.
Now, at the same time, interestingly
enough, within the United States, we were getting
increasing pressure from the FDA to improve and
control blood bank operations, we were also getting
increasing public pressure to improve safety and
quality. And it was at this time that we began to
explore with the American Association of Blood
Banks, a real switch in our standards away from
just delineating technical and operational
requirements, to incorporating what we call quality
system essentials into our standards, and
essentially that is a quality management program.
I'm going to talk a little bit about how
we took that model of the quality system
essentials, and how we developed that into
something that we call the AABB model standards for
blood banks and transfusion services.
We took the quality management principles,
and we essentially established those as the
standards, and the principles that we agreed to
adopt were really based on universally-accepted
quality management principles. They're totally
consistent with ISO. They're also consistent with
just about any other quality management system that
you could come up with. And underneath those
particular requirements, then we incorporated
operational and the every technical requirements
that simply reinforce the quality management
principles in the blood bank and transfusion
service setting.
Now, under these model standards the whole
purpose is that they are specifically designed to
be adapted to the public health requirements and
the resource limitations of different countries and
regions, and I'm going to show a little bit about
how we do this with an example. I'm not going to
spend a lot of time. The standards themselves are
quite long and detailed, but I'm just going to show
you how we set this system up.
We built these model standards in three
separate layers of requirements. The first were
called the core requirements. Second were the
regional requirements, and then under regional
requirements, we actually allowed building up
reference requirements which are highly technical.
At the top level, those core requirements are
requirements that were developed by blood banking
and transfusion medicine specialists from around
the world. When we went to look at the quality
principles, we invited a number of different
experts from all across the country and throughout
the world to come in and tell us, please identify
for us the very critical requirements that you
think should apply in any blood bank or transfusion
service around the world. These core requirements
broadly define what must be done. At that very
highest level they never tell you how to do
something, but they establish that you must fulfill
some requirement. They specifically contain the
quality management principles I talked about, and
again, they are universally applicable.
The whole point of this is we don't think
that these core requirements should be changed in a
particular region or country, that there ought to
be some sort of universal acceptance of what is
applicable in any blood bank.
Now, at the regional level, it's a little
different, because under our model standards the
regional requirements are then developed by blood
banking and transfusion medicine specialists who
are present in the country and in the region, and
this includes experts that we've identified from
WHO, with the help of Dr. Emmanuel, and PAHO. So
that when we try to work in a specific region, we
get those experts who talk about their own public
health issues. We try to make sure there's some
consensus, and we have some external experts from
WHO and PAHO to give some validation to some of the
things that they come up with.
Again, at the regional level they are
defining what must be done, but they're only
defining what must be done in that region, specific
to that region.
The reference requirements are what blood
bankers love to call the heart and soul of their
operations. They're the things that we're most
familiar with. I'll give you an example later.
But they are developed by the blood banking and
transfusion medicine specialists in the country and
region again, including WHO and PAHO experts. They
include very, very specific technical requirements.
For example, testing requirements, what types of
tests need to be done on donations, storage
temperatures, donor screening questions, things
like that.
So I'm going to just walk you through a
little model, and this is a truncated model, but
just to show you how this operates. There happen
to be 21 different elements of the model standards.
I picked 15, which is storage, distribution and
transportation, because it's the shortest and it
was the easiest to get up here. But you notice
that the very top level, what it says is, "The
blood bank shall establish and maintain policies,
processes and procedures for storage, distribution
and transportation of materials in process and
final products." It doesn't tell you how to do it,
but it does tell you that you have to have
something in place that addresses these issues.
Now, at the regional level--and I picked a
specific region that we're working in, just so you
can see--they developed their own standard
underneath that, what they thought in their region
was most important in terms of making sure that
that happened. And what they wrote was: "The
blood bank shall establish and maintain processes
and procedures for storing blood and blood
components, including blood from perioperative
collections from the time of collection to the
point of administration", and then it says
specifically, "The storage duration and temperature
shall be for periods of time and at temperatures
that conform to CRS reference requirements." That
is the very specific requirements that they've
established. And what they said was that these
requirements have to be designed to be optimal for
function and safety of blood and blood components.
I thought it was very interesting that
they actually specifically put this last line in,
which is probably an indicator of one of the major
challenges they had in their country, "There shall
be provisions for power failures and other
disruptions."
They had very specific refrigeration
requirements, that we, frankly, would not have
thought of writing into our refrigeration units
because ours are fairly standardized. They said
they have to be equipped with a fan for circulating
air because some of them are not, and they have to
be of capacity and design to insure the proper
temperature is maintained throughout the
refrigerator. They specifically wrote in some
requirements about temperature monitoring and how
often that had to be done, and specifically noted
that it had to be recorded every 12 hours.
They had some different issues with alarms
too. They said alarms had to activate at
appropriate temperatures, and they had to make sure
that when they were activated, there was enough
time--they were first--the alarm was heard in an
area that someone could actually hear it and it was
staffed--that was an important issue--and secondly,
that it had to be allowed within a temperature
range that allowed them enough time to get there
and take some action before any of the blood or
blood products were no longer acceptable.
Now, here, underneath that--we talked
about some of the reference requirements, and
here's where you get into the detail, and rather
than writing these things out, most of this is done
in chart format now. So they went through and
listed all of the types of products they provide.
I've only listed the first five, but they actually
have a lot more. And they wrote down the storage
temperatures that would be acceptable, transport,
expiration, and they actually went through--these
look very familiar to us, but there were also some
products and components that we don't really use in
the United States that they had, but they were
writing specific requirements for.
Now, after we developed this with PAHO, we
actually found that we were able to work and try to
implement these standards in a number of places.
One of the first set of standards in the model
standards was standards for the region of the
Americas, which were translated into Spanish, and
they were developed in collaboration with PAHO and
experts from that region. These are currently
being piloted in Uruguay, and I think one of the
interesting things was that some of the physicians
from Uruguay actually participated in the
development of these standards, and so to them,
they are their standards. They're not AABB
standards. These standards belong to that region
and that country, and they take real ownership and
pride in them.
Another group that's been really
fascinating to work with are the 22 countries in
the Caribbean. The Caribbean Area Regional
Standards and Accreditation Program is something
that we have developed in cooperation with PAHO and
with the Caribbean Area Regional Epidemiology
Center, which is an extremely good center.
It's actually part of--is it part of WHO,
Jean? It's part of PAHO, but it's a center.
They have pulled together a group of
representatives from 22 of the nations, and we sat
down and went through a process of taking these
model standards and developing standards that were
appropriate for that region.
And, finally, in Armenia, it was very
interesting too, we were asked by the Armenians to
come and work with them. We are right now
developing standards there based on the model
standards in collaboration with the Armenian
Ministry of Health, who helped us set up the newly
formed Armenian Blood Bank Association, and the
Ministry of Health has specifically delegated to
the Armenian Blood Bank Association the
responsibility for writing standards and
regulations in blood banking.
This project is particularly difficult,
because whereas you can generally find people who
speak Spanish, it's very hard to find people who
speak Armenian, and the translation issues in that
country are very difficult. Luckily, or I guess
unluckily and sadly, there are more Armenians
living outside of Armenia than inside Armenia, but
that means also that they have a lot of help in the
United States, and we've pulled heavily from a
number of those organizations.
So that's really where AABB focuses most
of its activities. When we talk about our future
developments in the international field, what we'd
really like to begin to do is once these regional
standards are developed, is to develop regional
accreditation programs that are based on those
regional or country-specific standards, that would
be consistent with the model blood bank standards,
but that essentially those accreditation programs
are run by the individuals in that country, and our
role is simply one of helping them set up the
system, helping to train them, helping to set up
maintenance procedures and processes and
periodically come in to review where they are.
We really envision the development of
regional standards by voluntary or government
organizations that incorporate the core standards,
the quality management requirements, and include
locally relevant and applicable, operational and
technical requirements.
In conclusion, what I just want to talk to
you a little bit about, is that if you think about
this activity--and it's really been, I think,
marvelous for everyone in the AABB--but it is right
now primarily supported by AABB member dues, and I
will tell you that this was all developed, our
budget for international activities within the
American Association of Blood Banks is $5,000. And
we've developed these standards, and I think made
the decision that because it is so critically
important to us to see these standards developed,
really implemented and maintained in the countries,
that we have made the decision that when people
come to us and ask us to translate the standards,
although we copyright the standards, we allow them
to just simply translate the standards and work
with them. And our role has been to try to talk to
them about developing their own model standards.
It's difficult because within the
organization there is an infrastructure issue.
These standards need to be maintained. We have to
consistently work on maintaining the core
standards, and it does get to be expensive to pull
a number of people together. But I think the thing
that's so important for us is that in our mind
we're creating an infrastructure or something that
supports a lot of these other activities we've
talked about. If you've introduced testing
technology into a country but you don't have the
standards or you don't have the controls, it's not
going to be sustaining. And we see our role with
the standards as setting up, as I said, an
infrastructure, a template against which people in
different countries can work, and which becomes
theirs. It is not owned by us, it's owned by them.
And that's really, I think--you know, I've
listened to some of the budgets today, and, gee, I
wish we had $5 million. We could do a lot with it.
But as I said, I think the organization has really
made a commitment. We have something that was
developed by this entire community that's really a
wonderful tool, and we're very excited to be able
to try to introduce it into other countries and
give it to them for their use.
[Applause.]
DR. GOMPERTS: Thank you, Karen. Any
questions?
DR. BUSCH: Karen, the process of
discriminating--of the standards that are generated
by the Standards Committee, which I guess are
really the US AABB regional standards, which of
those become sort of the core international
standards as you disseminate this? That would seem
to be similar to what Jay was alluding to about the
harmonization process of WHO. How does--
MS. LIPTON: Well, all of the quality--if
you look at--if you know about the AABB standards,
that they're now written under ten quality system
essentials, those would be the same standards in
terms of harmonization that are incorporated into
the model standards. What those standards then
suggest under that are issue that need to be
addressed in each country, and as we've gone in and
facilitated this discussion with the experts, our
role isn't facilitating. We actually have created
those model standards with some of the things that
we do in the US, not testing and issues like that,
but we go through and we say, "You need to worry
about addressing your--how you control your storage
temperatures." And it becomes a dialog. We show
them sometimes what we do, and we tell them what
we're trying to get to in the US is the goal of the
standard, not this is how you must accomplish that
goal, because many times if you look at our
standards, we have both a goal and then we tell
you, "and this is precisely how you have to do it
step by step." You don't always need to do it that
way. And what's more important is that you've
maintained a consistent storage temperature, not
that you've used a particular device that's
approved by the FDA or not. What you need to do is
show that you used something that you validated and
showed that it worked again and again and again,
and that you really are using it.
DR. GOMPERTS: Other questions?
[No response.]
DR. GOMPERTS: Thank you, Karen. My guess
is we'll come back to a number of principles that
you've delineated here in the discussion.
Okay. Moving on to Dr. Beyrer, Academic
Medical Center International Activities.
DR. BEYRER: Thank you very much. And I'd
also, I'd like to thank the committee on behalf of
the Hopkins faculty, who were involved in these
blood safety initiatives, who are not here. I'm
happy to say they're not here because we have a
whole flotilla of Hopkins faculty in Chindu in
China this week, doing a week-long intensive and
blood safety for all the provincial blood banking
service directors in China. But those faculty
include Dr. Paul Ness, who I'm sure is known to
some people here as the director of our blood bank
at Johns Hopkins; Professor Ken Nelson, who's an
infectious disease epidemiologist, and Dr. Wa Chan
[ph], who's a Chinese-American, who is the
associate director of our blood bank, and actually
is the lead person on our China supplemental grant.
You heard earlier this morning from Dr.
Jeanne McDermott, who is our project officer at
Fogarty for the AITRP awards. These are the AIDS
International Training and Research Program Awards.
On her slide you saw that the first of these awards
were made now 13 years ago. Hopkins, happily, was
one of the first institutions in that initial
round, and we have maintained Fogarty training
fellowship awards through the three grant cycles.
So we now are in year 13 of offering advanced
training and research support for developing
country scientists in HIV/AIDS.
In the last three years, we've had an
additional Fogarty training award, which I also
direct, in tuberculosis prevention and control.
And then two years ago, for the first time, Heart
Lung and Blood partnered with Fogarty and made the
announcement that there were going to be made
available training grants in blood and blood
product safety. And is the usual mechanism, these
were competitive. They were open to grantees who
had existing AIDS training awards or some of the
other initiatives. And the idea is modeled to some
extent on the AIDS training awards, which is really
to look at existing collaborations. We're, unlike
some of the organizations here, not global, we're a
university of course, with a somewhat limited
collaborative capacity, and we focus on a couple of
countries and institutions within those countries
and researchers with the idea of long-term
development of research capacity.
So we put in several of these competitive
awards, and I'm happy to say that three of them
were funded in that first initial cycle. These are
three-year awards. They're relatively small.
They're somewhat more than the AABB folks have
internationally and somewhat less than the Gates'
initiatives. These are about $100,000 each for
each of three years, so all together it's about
900,000 in training monies.
And the three countries that we've
proposed and are working in are China, India and a
collaboration between Laos--the Laos People's
Democratic Republic--and Thailand.
So before I get into each of those
programs, and I'd like to just very briefly
describe the training focus because each one of
these awards for India, China and Laos is somewhat
different and rather distinct. I think, perhaps, a
little bit of sort of justification for why we
chose those countries and what our overarching
interest it.
Of course, we all are aware, I think, of
the gravity of the HIV/AIDS epidemic in sub-Saharan
Africa and the extent to which some of the
institutes that are now kicking in international
monies like Heart Lung and Blood, which are, to an
extent, a response to this situation. But Asia,
unfortunately, is also experiencing very serious,
although very heterogeneous epidemics of HIV/AIDS
and that certainly is the driving force behind
these blood safety initiatives. That is not to
say, obviously, that they don't have a lot of other
issues, and that there haven't been extensive
activities in dealing with the hepatitis viruses,
malaria transmission and a whole range of other
health aspects of blood and blood product safety.
But it certainly is the case that the HIV epidemic
in Asia has somewhat jump-started these activities
and been a real driving force behind
collaborations.
So that said, on the Hopkins side, who are
the collaborators? Well, basically, in the School
of Public Health, it's really three departments,
our department, which is Epidemiology, Infectious
Disease, where we offer training in Epi and
training in biostatistics; the Molecular
Microbiology and Immunology Department, where we
can offer training in laboratory detection of
pathogens; the School of Medicine, and specifically
the blood bank under Dr. Ness, but also Brooke
Jackson's lab in HIV diagnostics, which is our
principal training site for assays. And then we
have a partnership as well with the school-wide
Bioethics Institute, and we have some separate
funding in bioethics. I think one of the things
that's really very important in dealing with this
international work is that there very often are
ethical issues and bioethical issues around some of
the efforts that we're all engaged with, and very
often this is an area where there really is a need
for capacity building in developing countries. A
number of the countries we work in really don't
have card-carrying bioethicists, and these issues
really are not to be neglected.
In terms of the partnerships in the
countries, they really are quite distinct, and
perhaps I'll begin with China, a very hard country
to ignore. Obviously, with $100,000 per year and
five or six faculty who are interested, we really
have to think about what kind of impacts we can
really have, and on a country of the scale of
China, clearly, the only model, it seemed to us,
that's going to work is training trainers. We can
really offer training to people who we hope are
going to be leaders in this field, and who can then
more widely offer that training in-country.
So our approach in China, actually to some
extent, is national, and what we've been doing is
trying to bring together the leadership in each of
the provinces for this kind of intensive week-long
something of a state-of-the-art of blood safety and
procedures. But clearly, also focusing for them on
one very important unmet need, which is the
recruitment and maintenance of low-risk voluntary
donors. China is one of those countries that has a
strong resistance to voluntary donation. They have
relied heavily on paid donors. You may have heard
that two years ago they passed regulations
prohibiting the use of paid donors, but the
implementation of that law has been very
problematic. And China has a very unique situation
where they're sort of mounting evidence that blood
donation itself has often been associated with risk
for HIV, and in fact, repeat donors tend to have
rising rates of HIV prevalence, which is a somewhat
unique situation and one that we're certainly very
engaged with trying to deal with.
We will have our first group of Chinese
fellows on this program--actually, I should say
our second group--coming this summer to Hopkins for
an intensive course, and that training is going to
involve the American Red Cross Blood Bank and also
some labs in Maryland, in addition to time at the
Hopkins blood bank, and then also, for a couple of
people, specific training in infectious disease
epidemiology.
The India program is really the newest
one. It's just getting going. The focus is
Maharashtra State. And that program is led by Dr.
Bob Bollinger [ph], who's been working in
Maharashtra and Punea [ph], the National AIDS
Research Institute for, I guess, 9 or 10 years now.
And also with Mumbi [ph], with BK Hospital there,
and they're about to launch what I think will be
India's first perinatal HIV prevention trial. And
in the context of the work that they've already
been doing, focusing on blood safety and training
specifically for Maharashtra, and the idea here is
to have something of a model program. Maharashtra,
of course, in and of itself, is considerably larger
than a number of the African states, population-wise, that were presented today. So even though
our program is relatively small and it's focused
only in that one place, the burden is enormous.
The Lao project is perhaps the most unique
of these. Laos, of course, is one of the world's
least developed countries. It's the ninth poorest
country on earth. It's been a very isolated
communist country. It still is. And the health
standards are really at sub-Saharan African or
lower levels, which is tragic in some ways, because
of course, Laos borders a couple of other countries
that are doing much better, and specifically
Thailand. We've been running HIV/AIDS training
programs now in Thailand for 13 years, and we have
a number of Thai colleagues and fellows, many of
whom are in leadership positions in the country
now, including in blood banking services, and
rather fortuitously, Thai and Lao are cognate
languages, mutually intelligible. Laos have
essentially not access to outside media, except
that everybody has TV antennas and they can all
watch Thai television and listen to Thai radio. So
even though they don't learn Thai language in
school, they pretty much all understand it.
So the focus of our training there, we
basically trained all the Lao colleagues we could
find who had sufficient English to come to the
states in about the first year and a half of the
program. Since then the focus has really been
training Laos in Thailand, and we have partnered
with Chang Mai [ph] University's blood bank, which
is the largest tertiary care hospital in northern
Thailand, but actually has a very--for developing
country standards, really excellent blood banking
services. We've partnered with the Thai Red Cross
and with the Thai Ministry of Public Health, and
also with the Thai NIH in Bangkok which has
reference capacity.
So what we're doing is bringing Lao
scientists, laboratory technicians, nurses, public
health folks to Chang Mai University for training,
supporting Thai faculty to go to Laos, and bringing
people also for degree training at Thai
universities, but using Fogarty monies to do this.
And this has been described as a kind of south-south collaboration. It is a tremendous money
saver for us. It costs about one-eighth the amount
for a degree for an MPH at a Thai university, but
also allows us to train people who just simply
would never be able to cover the English for the
US.
I think perhaps more importantly, it also
allows people to get training in blood safety,
blood banking, laboratory assays with technology
that they might actually be able to replicate.
Laos, it's going to be a long time before Laos can
reach the US standard, but they may reasonably make
some of, say, the Thai provincial standards without
undue burdens, and within what actually could be
their financial capacity as a country. So we're
hopeful that this program is really going to have
an impact.
There was a question or a comment earlier
today about, you know, the value of these training
grants and how do you do in terms of bringing
people, getting them to actually go home to their
country, use their training there and make a
contribution. We've, of course, grappled with
this. Everybody who does international training
work I think has to, and I think we've really been
quite successful. There is somewhat of a country-specific issue. We've actually had two countries
where we had training grants where we have not been
successful in having folks go home, and that's
Rwanda and Haiti, and I think in both cases those
are really political events, pretty much out of the
control of the people we trained.
But certainly with Thailand, China and
India, we've been doing very well, and I think that
there are sort of two or perhaps three crucial
reasons for that. One is you have to have ongoing
relationships with these folks. They can't go home
to a vacuum and feel that they got their training,
and they don't have the equipment to use it, and
then they never hear from you again. So the fact
that we've had, you know, ten years or more
involvement in investment, and Hopkins faculty are
regularly going, coming back and forth, keeps
people feeling that they're still part of
international medicine.
The second is the small reentry awards,
and talk about small, these are 10 to $15,000
reentry grants when somebody has been trained.
It's not a lot of money, but 100 percent of those
funds are used by the fellow in their home country,
and it allows people to get some preliminary data,
to really be able to buys some reagents, to do some
work on their own. Very importantly, it allows
them often to access other NIH monies and RO1s, and
a number of our fellows with Hopkins collaborators,
have been able to turn these $12,000 awards into
major RO1s and really sort of join the research
stream. And that is a crucial piece of having
people go home, they have to be able to access the
research that they're trained to do, and the simple
fact is that in many of these countries, there just
really are not research dollars available,
particularly in these kind of health care fields.
The third thing I think that really has
helped is that we continue to support people after
they've done research if they present at
international meetings or to come to international
association gatherings, and we set aside monies
very year, particularly, for example, for the
International AIDS Meetings. If somebody has an
abstract accepted for an oral, and they're a fellow
of ours, then we try and support them and bring
them to those meetings. And that really keeps
people involved and engaged in part of the global
research effort, which I think, you know,
particularly with talented junior people, if one
doesn't do that, they quickly join some of these
other agencies which are out there in the world,
like WHO, I'm sorry to say, and get pulled out of
the country and end up really being health
bureaucrats, which is a very important role, but
it's not the same thing as staying in a university
hospital and making sure the blood bank is running
well.
So those are a couple of strategies that
we've used. I think they've been relatively
successful. I'm happy to say, coming on our 14th
year in Thailand, we still are working on 100
percent rate of return, so I think we're doing
something right. Thanks.
[Applause.]
DR. GOMPERTS: Thank you. Any questions?
Comments? Yeah, Larry.
MR. ALLEN: You mentioned the donors in
China that--repeat donors that are coming up HIV
positive. Are they doing any studies, or how long
has this been noticed?
DR. BEYRER: There isn't anything out that
I know of in the published literature. There have
been a couple of studies. We actually just saw
some data, the very first of this data from the
national system, looking at rates of HIV prevalence
in repeat donors over time. I think the question
about whether or not that's going to be published
and whether or not the authorities are going to
allow it to be published is really a very important
question. It's sort of a public health question.
It's, to some extent, a human rights question. I
don't really know the answer. I don't think it's
clear. But it certainly is clear that this is an
extremely sensitive issue if you talk to Chinese
authorities. There's a high level of awareness,
not so much of what's happened within, say,
government services or the mainstream services, but
rather in this large, gray area of illicit and
private blood banking services.
I mentioned earlier that a major problem
for China has been a longstanding cultural
resistance to voluntary donation. At the same
time, because they have been developing rapidly and
moving more and more toward western medicine,
there's also been clearly an increase in the demand
for blood and the need for blood, and in many more
procedures like bypass surgery, which 20 years ago
just weren't happening, caesarean section, which
increasingly are happening in modern China. So you
have on the one hand problems with supply, rising
demand, and there has been a real illicit industry
that has grown up to support this, and at least
some relatively reasonable evidence that for
example collection equipment is reused repeatedly
in an effort to save money, and the hepatitis
viruses are implicated here as well.
India, you know, is not dissimilar and has
a large private and illicit blood banking industry,
and it's been devilishly difficult for the central
authorities to regulate these problems, and it
seems to us and our Chinese partners, one of the
long-term solutions to this is the improvement of
voluntary donation and the recruitment of low-risk
donors, and so we're opting on that strategy for
China.
MR. ALLEN: Do you have any numbers on how
many people are infected?
DR. BEYRER: I think the numbers are
pretty much all speculation, but with India and
with China, you don't need something to be terribly
common, you don't need the rates to be very high
for the numbers of people to be enormous.
MR. ALLEN: Exactly, okay.
DR. GOMPERTS: Dr. Epstein?
DR. EPSTEIN: Enjoyed your presentation
very much. I have a question that I'm asking you,
but it's really something that puzzles me a great
deal. How do you decide where to engage? You
know, it's a big world. There are a lot of
countries in need, and it strikes me that a lot of
what is being done is driven by the interest of the
donor party rather than the need of the recipient
party. You know, from a public health point of
view it's comfortable to be dealing at sort of a
global level because you look at all regions. But,
you know, once you get outside of that framework
and you're looking for sort of bilateral help, what
is it that drives the decision where to engage and
how did that come about in the Hopkins experience?
DR. BEYRER: Well, that obviously is a
hugely important question. And if you saw the genes
map of sort of how many of these fellowships were
actually awarded, how many training grants there
are, it's five all together. There's only five of
these, and we have three of them. So it's somewhat
an embarrassment of riches.
But, I think, the answer to that question
is partially that these kinds of decisions get made
based on where you think you're competitive and
competitiveness is defined by where you have
collaborators, where you've had other grant
support, where you've been able to get
publications, where you have some kind of track
record. And behind that is perhaps a much more
fundamental question, which is, you know, who is
open to US joint collaborative activities in
research? Where is there an HIV problem? Because--we didn't get into this--but the epidemiology in
Asia is interesting and very heterogeneous. There
are a number of countries where you really couldn't
do, for example, the kind of HIV prevention
research that is more my own work. You know, if
you need a relatively high level of incidents,
you're not going to be able to do this kind of
research in Singapore. You can't do it in Taiwan.
It's not going to happen in South Korea, Japan.
There are plenty of countries that really don't
have sufficient HIV spread. On the other hand, you
have countries like Burma, that have catastrophic
problems, and where there really is not the
political will for collaboration, and you're really
sort of closed out. So I think Thailand,
certainly, and India, are both examples of,
unfortunately, countries with sufficient HIV
problems, with the political will or openness to
engage in research with the US, and where Hopkins'
investigators have collaborations. But you
correctly pointed out the interest factor, and you
know, that to me is rather unfortunate. I don't
think this should be driven by sort of where people
on a given faculty know people and have interests,
but I think that in fact is the case.
And we certainly have attempted to go into
other countries because there was a problem there.
China is a good example. When the HIV epidemic--when it became clear that China was really having
epidemic spread, and at that point was largely in
injection drug-users, a number of universities got
going. We added China to our Fogarty core in the
last funding cycle, as did, I think, four other
universities. So there's give universities working
in China, mostly working on issues relating to HIV
and injection drug users. And then two of the
universities have blood safety programs.
But, you know, is it comprehensive? Is it
reasonable? Is there any overarching strategy? I
think we would need significant infusions of DHHS
funds for training grants to have something that
looked comprehensive. That was a pitch, by the
way.
[Laughter.]
DR. GOMPERTS: DR. Guerra.
DR. GUERRA: I'd be interested in knowing
an institution that has really led the way in so
many important areas of public health and certainly
with infectious disease that affect large segments
of the population, deals with the--perhaps even
more complex set of circumstances, where there are
subsets of populations around the world that are
victims of catastrophic type of events or war or
hostile activities, where there is an incredible
need constantly for blood and blood products. How
do you train those individuals that come from those
parts of the world as part of this learning
experience to deal with those, whether it's a
matter of prioritizing, whether it's really trying
to orient them to the use of other interventions,
et cetera?
DR. BEYRER: Well, that's an excellent
question. I guess I would have to give you a two-part answer. The first part is, there is something
that I tend to think of as stability bias, which is
that it's very hard to compete for NIH or other
grant monies, which is what we at Hopkins feed
ourselves and our families on. And it's hard to
compete for those kind of awards if you don't have
some level of political stability. You have to be
able to have consistency over time. So, you end up
with a lot more grants, activities, and research
going on in Thailand, because it's stable and is
relatively open to collaboration, than, for
example, in the current Indonesian situation, or
certainly in Burma, where there's very little
activity or even Cambodia.
The second answer to that is that I think
where we're beginning to expand in those areas,
there's a tremendous interest on the part of our
students and fellows to get into relief,
humanitarian kinds of work. We get more and more
people who actually are coming from organizations
like Doctors Without Borders, Medecins Sans
Frontieres, Medecins Du Monde, who have that as
their professional base and want some theoretical
depth. And that really, sad to say, is not so much
happening in my department, in epidemiology, as it
is in international health. Gil Burnam created a
new center of refugee health and disaster medicine,
which is really a rapidly-growing program. And
trying to build, if you will, the sort of
methodologic base for assessing those kinds of
situations. Just two examples I'll give you.
One is an assessment of--an indirect
assessment method for trying to assess the North
Korean famine by doing sampling of interviewees who
have escaped into China and trying to develop,
basically, demographic tools for assessing what's
going on in North Korea. And we're now taking that
and attempting a validation study on the Thai-Burma
border, doing the same thing, trying to assess
what's really going on some of the ethnic areas in
Burma by interviewing refugees in Thailand. So I
think, you know, the theoretical base for that kind
of work is something that needs to be built, and
it's happening.
When you get into the blood safety aspects
of those kind of problems, you know, it's obviously
a hugely challenging situation, and there are
certain particular issues in our region in
Southeast Asia, like land mines that are, you know,
relatively highly correlated with needing
transfusions acutely, and certainly Cambodia,
Burma, Laos, these are countries that are just
stuttered with land mines. There's, you know, more
land mines than people in Cambodia, and that
certainly is true in some parts of Burma as well.
Laos has unbelievable tonnage of unexploded US
ordnance, and land mine injuries and bomb injuries
are actually a big part of their trauma need for
blood.
And the way it happens now is basically
the only screening they can do in most of rural
Laos is malaria thick films. They're just looking
for malaria. And if the person--if the donor
doesn't have malaria, they transfuse, and they try
and do family members. So we have a long way to
go.
DR. GOMPERTS: Unfortunately, we do need
to move on. Thank you very much.
DR. BEYRER: Thanks.
DR. GOMPERTS: Moving on, Dr. Barbee
Whitaker from ABRA PPTA.
DR. WHITAKER: Thank you for the
opportunity to speak with you today. While he's
hooking up the AV, I'd like to mention that today
I'm representing both ABRA, the collection side of
the plasma industry; and PPTA, which is the
fractionation side of the industry. And I am
senior director for standards and certification.
Our standards activities are primarily
devoted towards the developed world, and I'll talk
about what we've done, and I'll point out some
opportunities where we can--we have developed a
framework for expansion of this to the developing
world.
Next slide, and thank you, Jay.
What I'd like to point out is that our
industry has put into place standards over the past
ten years or so that have identified the--have
worked with the plasma supply, working from the
population, and gradually varying levels of safety,
including donor screening and deferral, donor
testing, NAT testing, inventory management in the
form of our 60-day inventory hold, and viral
removal and activation, so that by the time that
the product gets to the patients, it is really as
safe as it can possibly be.
Next slide, please. First I'm going to
talk about some initiatives that ABRA has put
together over the past ten years in its
international quality plasma program, and then
second, I will discuss the initiatives that the
PPTA, Plasma Protein Therapeutics Associations, has
developed within the last year or so.
We have three different levels or three
different areas of standards with iQPP, primarily
collection-center oriented standards, and those are
the iQPP standards proper. We have a viral markers
standard and a quality assurance standard that I'll
talk about.
Next slide, please. The history of this
program is that it was established in 1991, and it
was built primarily for the American Source Plasma
Collection Centers. The standards that we
developed assumed a baseline of FDA compliance, and
that these standards were in place in the centers.
Building upon this baseline, we've introduced
standards that essentially raise the bar and that
insure a high-qualify of source plasma. When we
put them into place initially, they were a way of
rewarding companies for doing a good job, for going
beyond what was initially necessary, and what's
happened in the past ten years is that they've
really become a gold standard, and that these iQPP
standards that we have and the certification
associated with that, is really very, very
essential to doing business and providing high-quality plasma in the United States and also in
Western Europe primarily, as well as certain other
places.
And one of the things that we see as a
possibility for moving forward is that the
standards that we've developed building on a
baseline of the FDA standards, are something that
we could put forth to develop high-quality plasma
pheresis opportunities in countries where that
infrastructure isn't necessarily there. And one
big piece of that is the quality assurance standard
that we put forth in 1999. And this is--I'll talk
about that a little bit more in detail in a few
minutes, but that provides more of a framework that
goes throughout the center itself, not specifically
focusing on things that are--what before were above
and beyond the current FDA requirements.
Last year in 2000 we expanded our program,
iQPP, to be international, and it's now available
in Western Europe. There are approximately 25
source plasma collection centers in Germany,
Austria and Sweden. There are also some centers
outside of Western Europe in the Eastern European
countries, and we are in discussions now, talking
with people over there to see if there's some
interest in expanding and using iQPP as a way to
raise the quality of the source plasma and
collected there.
Next slide, please. iQPP standards
generally cover donor screening, facility, quality
and appearance, personnel competency and training,
and continuous improvement.
Next slide. We have about ten different
categories of standards that we cover with iQPP.
The qualified donor standard I'm going to talk
about quite a bit. Some of the other standards
I'll just mention briefly right now. We have
personnel training standards and requirements,
education as well as training, and competency.
Participation in our National Donor Deferral
Registry is required to be QPP certified. We
screen donors for drugs of abuse, primarily
opiates. We have expanded donor education and
additional donor referral criteria, and it also
includes a donor qualification of sorts, where we
ask the donors--we provide the donors with an
opportunity to prove that they understand what the
high-risk issues are. We draw from a community-based donor population and we have a bunch of
different facility standards, which address the
workings of the facility and the size and
effectiveness and adequacy of it.
Next slide, please. I'm going to talk a
bit about the qualified donor standard, which we
see as one of the most important standards, and a
standard that has really added tremendously to the
quality of our products. We only provide products
for the manufacturer into therapeutics from
qualified donors. And in order for a donor to be
qualified, he must--he or she must successfully go
through two health history interviews and have two
panels requiring screening tests, and I've got a
slide that will describe that a little bit better.
This standard applies to both new donors
and also to donors that have been out of the
program for up to six months. So that would be a
returning donor as well. And as I said before,
units of applicant-only donors cannot be used.
Next slide. So the way that the
qualification process starts, a donor would come
into a center here, have a consultation with a
medical professional prior to donation. This would
include donor screening, donor health history
questionnaire and so on. Assuming that the donor
was acceptable, the donor would be--would give a
unit of plasma by plasma pheresis, and in some
cases--and this is done in some of our European
centers--they give only a sample, but they do go
through the medical consultation prior to giving
that sample. The unit or sample is screened for a
variety of tests, for a variety of viruses, HIV,
HCV, HBV, and also some other additional required
tests for blood and plasma donation.
If on any of these tests, the donor is
positive for any of the viruses or other
conditions, the donor is rejected, the unit is
destroyed, the donor is put on our National Donor
Deferral Registry, so that that donor can't come
back and donate again and endanger either patients
or health professionals in a donor center.
Now, if the donation is negative or the
screening test is negative, the first unit is
quarantined until that donor comes back, goes
through the process once again, and is screened
negative on the second donation or the second
screening test sample. And at that time the donor
becomes qualified.
Next slide, please. And this is the same
thing, but I just want to show that with a
qualified donor, once that negative donation comes
through, it's put into temporary inventory hold for
60 days prior to being released to fractionation.
So we have found that this is one of our
primary opportunities for standardization, which
has improved the qualify of plasma. And in fact,
in Sweden, the transfusion services have demanded
that all blood be from qualified donors for
transfusion. So it's something that we believe can
provide an opportunity for a very safe source of
labile products, as well as for products for
further fractionation.
Next slide, please. Another one of our
standards is our National Donor Deferral Registry.
This is a computer system, basically, where we have
a database of all donors who have been deferred
based on test results through the source plasma
collection system in the United States. So any new
donor that comes into a center would be checked in
the registry, and if the donor was in the system,
that donor would be rejected from donating plasma.
We're expanding that.
This summer we are bringing on a new
system called NDDR Online, and this would be a
Windows-based, Internet-based opportunity for us to
check donors in the system, and it also--it's
really nice, because not only do we have the
opportunity to check soc. numbers or a variety of
algorithms that we use to check a donor, but we can
check by very--you know, a selection of different
search categories, so you can really have a good
opportunity to look and to see if a donor's been
deferred before. We're also exploring additional
deferral categories based on high-risk behavior at
this time.
Next slide. Our viral markers standard--and this standard is shared with PPTA as well--requires that plasma centers participate in our
data center activities by sending in their viral
marker rates and donor histories on a monthly
basis, so that we have an idea of what's going on
in the centers on a very timely--in a timely
manner. And centers are required to maintain viral
marker rates of confirmed positive qualified donors
for HIV, HCV, HBsAg that meet or exceed our
standards. And we evaluate centers on each of
these individual viruses, but also on a composite
of the three viruses. So that we're looking at
slightly different things there. For each virus we
want to look and see if there's a problem, but also
if they're drawing from a population that's really
unsafe, you might see a balance of the three, none
of which was extremely high, but if you combine
them together, it would be out of line, out of
range. And then we require that each center have a
process for corrective action should they fail to
meet our standard.
And the next slide, please. And this just
shows a little bit the timeline that we have. We
do a six-month review period, followed by a month
of analysis reporting, and then a months of
analysis. And at two months following the review
period, we determine whether centers have met our
standard, and if they have not, they have 30 days
during which to respond with corrective action.
Following that 30 days, they have a six-month corrective action period, during which they
are scrutinized carefully for their viral marker
results, and if at the end of that six-month time
period, they still do not meet our standard, their
QPP certification is withdrawn.
Next slide. Our quality assurance
standard, introduced in 1999, requires the
independence of quality assurance unit. We have
identified ten critical areas of quality, based on
the FDA guideline, but also working with our
international colleagues. These seem to be really
the critical quality assurance areas. And we've
developed a checklist specific to the collection of
course plasma. So what we've done is tried to
establish GMPs for our industry.
Next slide. And these are the areas for
which we've specifically focused our checklist and
our standards, ranging from SOPs, training and
competency, through validation, which is a big
issue for us, and then into adverse reactions,
deviations, tracking and trending and audits.
Next slide. So what we find is that our
iQPP, the International Quality Plasma Program, is
a framework where source plasma collection centers
can set and achieve high standards for safety and
quality. And this is an opportunity where we might
be able to set up a framework to help centers in
countries where they don't have a strong regulatory
framework, but that there is some kind of
infrastructure to develop the critical areas for
collection of plasma for fractionation.
Next slide. What we're doing, this isn't
a static program. We are constantly working to
develop new standards. Right now we're working
with the collectors of recovered plasma to develop
standards that enhance the quality of recovered
plasma which embody the principles of QPP for
safety and quality. We're also working with ICBA
[ph] to develop EDI standards, electronic data
interchange standards, for transmitting information
about plasma and plasma products and laboratory
standards.
Next slide. Now I'm going to talk a bit
about the Q Seal program, which was announced last
June at our plasma forum, and this is a
fractionator base program. Q Seal represents
quality standards of excellence assurance and
leadership, and it is the auditing of the voluntary
standards that you've heard about before from PPTA.
Next slide. The four standards are the
qualified donor, which addresses issues of donor
management, the inventory hold, the 60-day
inventory hold, which is unit management, NAT
testing, sub-pool and pool management, and center
management via the viral marker standard.
I've gone into some detail about the
qualified donor standard and the viral marker
standard. Our unit management standard, which is
the inventory hold, is that units are held for 60
days following collection, and any information that
comes into the knowledge of the organization that
either collects or fractionates the product, is
applied to that unit, and the unit is rejected,
destroyed if there's any information that comes in
that would challenge the safety or quality of that
unit. As far as NAT testing goes, we have a
standard right now for NAT testing for HIV, HCV and
hepatitis B virus, which is in place.
And right now we are in the process of
auditing about ten different fractionation
facilities in our first round of certifications
with this program.
Next slide. Also, with the Q Seal program
we are working very aggressively to develop new
standards. We have a standard for parvovirus B19.
We're working on standards for recovered plasma,
intermediates and NAT technical standards.
Next slide. The parvovirus B19 standard,
the idea is to prevent the high-titer units from
getting into manufacturing pools so that we can
improve the safety of the product for immuno-compromised patients and pregnant women. The
status of this particular standard is that we have
a proposed standard on our website right now.
We've been circulating that with our stakeholders,
and we're looking to publish a final standard in
the coming months.
Next slide. I'm losing my voice. The
recovered plasma standard, we were working with
ABRA and with the collectors of recovered plasma,
to define a single quality standard for starting
materials. Right now we're meeting monthly and
even more than monthly with the people who are
involved I collecting recovered plasma, and our
interest is the use of the highest quality starting
material in plasma-based therapeutics regardless of
the source.
Next slide. We're also working to develop
standards for intermediates, so that all of our
starting materials are meeting these high
standards. We've had some meetings to begin with.
We have a draft standard that's due out at the end
of this month, but there's probably some internal
comment that we're working on for the next couple
of months, but we anticipate having a standard out
by the end of the year. A lot of the interest on
this is to standardize the documentation and
control requirements for intermediate products.
And as I said, we're focusing on documentation
issues, and also just chain of control and chain of
documentation quality assurance release and so on
with this standard.
Next slide. And the last standard that I
spoke about is our NAT technical standards, and
this has been a really interesting effort because
we've really gone outside of PPTA, and we've been
working with representatives of a variety of
different NAT testing groups, laboratorians across
the world really, both the regulators from here in
the states, FDA and also the Paula Ehrlich [ph]
Institute, and NIBSC in London. And we've got a
group of people who are very knowledgeable about
NAT testing, NAT laboratories, and we are defining--we're working to define a common global
understanding of what NAT testing should be and
should entail. There are a variety of different
ways of performing the test, and what we're trying
to do is define what the critical elements of a NAT
test should be, so that we have some comparability
throughout the world when people start talking
about testing results.
Next slide. I'd like to close with this
quote from last year's World Health Day from Frau
Andrea Fischer of the German Health Authority.
"Today the risk of HIV transmission from a blood
transfusion is about 1 in a million in the western
world, that is, which means that in a million
transfusions, one HIV transmission can occur. With
plasma products such as Factor VIII for
hemophiliacs, there does not remain a measurable
remaining risk."
Next slide, please. And I'd like to
commit that PPTA and ABRA are continually committed
to raising the bar and to working toward higher
standards for quality and safety and to expanding
those worldwide. Thank you.
[Applause.]
DR. GOMPERTS: Thank you, Dr. Whitaker.
Time is moving on, and if we could move to
the next presentation. Dr. Lee, Promotion of
Appropriate Technology Transfer.
[Pause.]
DR. LEE: I realize the power base is over
here, but I have a problem with my back to the rest
of the people, so with the permission of the
chairman, I'm going to turn around this way. I
can't wander off. I'm on a tight leash.
[Laughter.]
DR. LEE: I have been specifically asked
by the chairman to address the tests and the
technologies that is appropriate for developing
countries, so I'm going to divide my talk in three
parts. The first part is really quite general.
What are the general requirements of a test for
developing countries, which, obviously, like some
of the inner cities in the developed countries, are
extremely resource limited. The second part I will
talk about what we're doing in Cambridge, and the
third part is what I visualize to be, I think, the
ideal test for the blood bank in developing
countries.
Next. Well, to start off with, I want to
make a statement that the diagnostics for
developing countries is to this day an unmet need.
The reason is really quite simple. The private
sector will not do it because of the low or no-return of investment. Anybody who has any stocks
on the Wall Street will see that everybody's
worried about the next quarterly return, including
us. And also, the rapid test, which I--you will
see later on, I will develop, that I think is a
format that will meet at least 80 percent of the
testing needs in the developing countries.
Actually, unlike the other alternate EIA or the
beads test, has a very low profit margin. That is
because it is made in ones, rather than in a chain,
as you have--for instance, if you have a microtiter
well, you coat 96 at a time, so you can do
millions. If you coat beads, you put it in a
column, you can do millions. But the rapid test,
particularly if it has to do with casing, is done
one by one, and thereby more expensive.
Obviously, the marketing and distribution
channel in developing countries are problematic and
expensive. But at the moment the rapid test is a
bimodal distribution. Either you have a few large
companies that's making rapid tests most of the
time in very lucrative markets such as pregnancy,
ovulation predictions for the home testing, they're
of good quality, because in many ways large
companies do have internal quality standards, or
you end up having a lot of the small company. And
many of them I've seen recently are coming from
China, which you probably know for some time
recently a lot of the army actually had a lot of
money, so they invest into locally to start these
new enterprises. So anything goes.
And so you end up having a lot of small
companies from anywhere making particularly
infectious disease testing. So that in fact today
none of the--I think it's true--rapid tests in HIV
or hepatitis B is licensed by FDA.
So going to the large companies, if they
have good quality but they have an existing
production line that has been validated,
documented, they are not going to change that
procedure to make some test that is suitable for
developing countries.
The last thing, which is totally ironic,
is that the test that's made in developed countries
are not good enough for developing countries. All
of our quality control for stability and storage
are done assuming you have rapid transport, 4
degrees, minus 20s, and that anyone who has ever
shipped anything to Africa, knows that is just not
the case. So that as all things, one of the first
things that goes for a test is the stability. So
in high heat, high humidity, anybody who's in test
development knows the sensitivity goes.
Next. The unmet need is also not met by
academia because of the lack of product development
expertise in this environment, which requires
validation, scale-up, documentation, and for that
matter, patent protection. Also, the applied
research, unfortunately, is not really valued by
the environment. And finally, it's really not
their raison d'etre.
Next. So what is the assay format that
will be suitable of developing countries? It
should be inexpensive, rapid and easy to use. And
later on I will define these qualities more
specifically. I've already made the point of the
fact that it needs to be stable for high humidity
and poor storage and transport conditions. But to
make things more difficult, there is no point
having a cheap test, but a good test, if the front
end of the sample collection costs you that much
money, so you really need to be hooked up to a non-invasive sample such as saliva, urine or finger
prick, which imposes itself a certain level of
challenge. And for all those things that you're
asking for, there is no way to do it using current
technology. You have to think outside the boxes to
incorporate some of the cutting-edge technology.
As an example, we use these enzymes that
are thermal stable in PCR that gets cooked up and
down. Why not use some of these for color? It's
gone--oh good--for color for the coloring part of
the test. So I think that it is not difficult to
make rapid test. It's extremely difficult to make
good rapid test, and you really have to improve on
the current technology.
Next. So I'm going to talk about
dipstick, and--oh, wow, this is pretty fancy.
Okay. So the dipstick assay is made of three
parts. This top part is what I call the garbage
can, which is really where all the use of reagent
goes, okay. The second part is the business end of
the dipstick, which is usually made of a natural
cellulose membrane, onto which you align a reagent
which could be a antibody or something that is a
capture reagent. The next part is what is called a
conjugate pad, which is an antibody also against a
anilide you're directing, but this antibody is
coated onto some color particle, such as gold or
color latex particle to give you a visual signal.
Next. So imagine you have a pot of urine,
and the red is the anilide you are looking for.
And so when you dip this dipstick into this sample,
what happens is that all your chemical reagents are
dried up already in this particular dipstick, and
your sample itself is the liquid that dissolves
everything as it goes up.
Next. And what you see next happens, the--because this is a wicking pad also, your urine or
your plasma starts moving up, and as it moves up,
it dissolves this dried reagent, and as it meets
here, if the anilide is present in your sample, it
will be recognized by the antibody and forming a
complex. And next, as it moves even further, you
will see that it moves by this capture line, and so
it gets captured by the other antibody that
recognize this anilide. In a way you can visualize
it as a river going upstream with all kinds of
fish. Let's say I'm looking for salmon here. And
so what happens is that in this river, you put a
lot of lanterns here which only recognize the scale
of the salmon. As the salmon moves by, this
lantern will catch on the salmon. And here is the
dike. All the fish go toward the dike. On the
dike you have these hooks that can also only
recognize the salmon. So by the time they get
through here, the salmon are lit up, not the
minnows--is that what you say--or the crayfish, and
the salmon gets caught over here, and you see a
color.
Next. However, it isn't so simple. Go
ahead.
[Laughter.]
DR. LEE: Because I already showed you
that you have the wicking pad, the natural
cellulose in the ridge and pad. They are made of
different material, of different density, different
softness, and so also the natural cellulose, as you
know, is very brittle. It needs to be backed onto
some kind of plastic. So in a way dipstick is
extremely complex because there's a simplicity,
because not only do you have to put the chemicals
already dried up, unlike the normal EIA, no
incubation, no washing away, no reputting another
reagent. Everything has to happen on the run.
And not only that, it needs to pass
through different kinds of material, so it's
chemistry in a liquid flow, and that liquid flow is
made further complicated by the fact that if you
imagine on plasma, this is not just some simple
water. It could be like the Mississippi River or
it could be like the Charles River. You have some
plasma that's lipemic, others that are hemolytic.
You are not moving through the same liquid, and you
have to do all of that in 15 minutes.
Next. Next. So I mentioned how a
dipstick work for antigen antibody. You can also
imagine a dipstick can work for a nucleic acid. If
this is a target sequence, you can imagine putting
on the capture line, a sequence that complements
the target. You can also imagine having a
detection probe to which you have labeled, and the
colored antibody recognize. So you can still have
a color reaction at the capture zone for nucleic
acid.
Next.
But the nucleic acid is even more
complicated because you first have to have sample
preparation to release the DNA or the RNA. You
have to figure out what is the best condition to
hybridize. Then, only then, can you detect by
visual signal on a dipstick platform. But what is
not so much recognized is the fact that most often
your visual signal is achieved by antibody or
protein. And here you're talking about
hybridization between nucleic acid. The conditions
that's right for one often kills the reaction for
the other, so you are always looking for the right
compromise and optimization.
Next?
So, in a word, the challenge of a nucleic
acid dipstick is that it is reducing extreme
complexity to extreme simplicity, and that to make
it right you need a visual signal without pre-amplification. And often if you then want to put
the front end in the non-invasive samples, then the
organism load obviously is lower, and in some cases
one doesn't even know exactly what is the organism
load.
Next?
So I'm moving to the second part of what
we are trying to do in Cambridge. A few of us who
worked at Harvard for different reasons decided
that we would like to do something about developing
country testing in Cambridge. So, first of all, we
tried to obtain institutional support from the
university and from the East Anglia Blood Bank to
get the space, and we obtained public funding from
NIH, WHO, and the Wellcome Trust. We attracted
scientists from industry. We're doing technology
development that goes beyond prototype, that goes
validation, scale-up, field trial, and clinicals,
and most of all, we want to at the end of it do
technology transfer for developing countries.
I've always said if all we ended up doing
is a good test, a good publication, and didn't make
it really available to developing countries, then
we have failed.
Next?
So our goal then is to make available--and
I really mean make available to developing
countries--simple, rapid, and inexpensive
diagnostic tests, but with good performance
characteristics. Our first phase in sexually
transmitted disease were funding for chlamydia, and
we want to move on to transfusion-related diseases
and finally to other diseases.
Next?
We all talked about simple, rapid, and
what do we really mean--and inexpensive. We set
ourselves the specific goal. It needs to be less
than 30 minutes from beginning to end. It should
be so simple that it should be trainable in ten
minutes, inexpensive in the sense it should cost no
more than 40 cents for the production cost. It
must be stable with one-year shelf life, and that
means accelerated tests or, in our case, one month
at 40 degrees. It should use non-invasive samples,
but most importantly, to reduce the cost and to
increase efficiency, it should be multiplex. By
that I mean several analytes that should be in the
same sample.
Next?
And it is also important to think about
production requirements as you're developing your
assay. It is not possible or it's very difficult
to squeeze out cost when you've already gone
through the end of your production line. And so
it's very difficult and I personally think it's not
totally achievable to adapt existing tests for the
developing countries. You have to really design it
almost de novo by saying where I am doing this
test, who is doing this test, what educational
level are they, and what do they really need. So
that it means that we need to design it for
simplicity and large volume. It needs to be a
flexible format to meet regional needs. For
instances, some places we need to test for Chagas.
Others may need to test for other diseases, and for
sure, scale-up, validation, and documentation for
technology transfer.
Next?
So we have looked at DNA, RNA, and
antigen. We obviously focused very much on
chlamydia, but we use that as a means to develop
technologies that should be applicable to others.
For instance, what we learned on the DNA we've
applied to HLA typing. What we learned on RNA for
the chlamydia, we have done some work on HIV. And
on the antigen, we also have tried on the hepatitis
B, which I will show you quickly.
Next?
So we now have a prototype for chlamydia,
both on the DNA and ribosomal RNA test.
Next?
But we also--I want to show you here that
one of the problem for rapid test is a decreased
sensitivity, and so we are doing a lot of things on
labeling. Here you see if you have only one label,
by the time you dilute it to 10-3, you almost lost
the signal. But if you do multiple labeling, look
at how much further 100- or 1,000-fold it will go.
Next?
We also learned a great deal--I think
we'll skip this. Something is wrong with this.
I mentioned that one of the biggest
problems for rapid test is reduced sensitivity
because it's happening too fast and in a very dried
format. So we realized from the beginning that we
have to increase the sensitivity by increasing the
signal. So we worked out a signal amplification
method, which is one of the nine patterns we have
already applied, and you can see that this is the
lipopolysaccharide concentration, this is negative,
this is 420, and further to the right, lower the
concentration. You can see in the non-amplified
you have a faint signal here, but if you have
amplified signal, you see how much further it goes.
Next?
We applied this to hepatitis B surface
antigen. By the way, this result is the result of
moonlighting. We just wanted to know whether that
signal amplification also worked in another system,
so we chose hepatitis B. And these are the antigen
concentration of 6, 3, 1.5, 0.75 nanogram, and this
is the signal that we have, and this is the Abbott
test, which I think is one of the best. And you
can see that it is positive as 6, really very, very
faint by here, and our sensitivity with the signal
amplification is much higher.
Next?
And just to show you that I think the
Abbott test is better in the sense that we looked
at three--there are many rapid hepatitis B tests,
and I've bracketed where the signal is, from 25,
12, 6, 3 nanogram per ml, and the Abbott is around
here somewhere. And the other tests could be 25,
and it's a lot less sensitive.
Next?
What I'm trying to say is that with a
signal amplification we are able to make the rapid
test I think at the sensitivity range of automated
EIA test.
So, finally, just two slides to looking to
the future. I don't need to re-emphasize what has
been said this morning. If you look in the blood
bank, hepatitis B, C, and HIV, whether it's a
volunteer or replacement donor, if you add all
three markers together, it's really 9 to 20-some
percent of your blood donors coming in.
Next?
Therefore, the sensible thing to do is to
have what I call a triplex test, that is, HIV, HBV,
HCV, all at the same time.
Next?
And I just want to say this for the cost.
It not only makes it simpler, but it also can
reduce the cost because you're multiplexing things
together. And, in fact, I just want to show this
in general that the automated EIA test actually is
cheaper than the rapid test. This morning Jean
Emmanuel also said, even for WHO, they are paying
twice as much for rapid test than for automated EIA
test, and never mind about nucleic acid testing.
Next?
And we set up the goal. At the moment our
cost, depending how we package, is 13 P or 16P,
well below the goal of 40 cents that we have set.
Next?
So, finally, this slide shows whether the
number is absolutely accurate, the disparity
between the developed countries and developing
countries. If you look at HIV and HCV, the
prevalence obviously is lower, and Ghana is already
not one of the worst countries that you can
imagine. The residual risk for U.S. for HIV is in
the millions, and in HCV it's 250,000. But look at
what happens in Ghana: for HIV 1:1,500, and for
HCV 1:700.
Next?
And this is my last slide, which is to say
that at the moment, if you look at the Kumasi Blood
Bank in Ghana, with Jean-Pierre Alain will talk
about more, if you--given the hepatitis B
prevalence rate, if you have no intervention, the
risk is 1:675. If you use an agglutination, which
is what they use and it's not very sensitive and
actually very difficult to read the endpoint and a
lot of false positives, you at least can make it
better to 1:4,000. If you do EIA, not the best
EIA, post-donation, you can make it 1:40,000. And
if we can have a rapid test that is good quality,
pre-donation, so that if someone is infected you
don't even take the blood, then you can imagine to
improve the risk to this number, which at lunchtime
I asked Harvey whether--what the number should be,
he thought if the test is really very sensitive,
the number should be much higher than this. But
for the conservative number, we'll put it this way.
And I think that this group is the one group that
should be able to do something about making the
test available and making a difference in the
developing country.
Thank you very much.
[Applause.]
DR. GOMPERTS: Thank you very much. You
made a difficult situation very intelligible.
Thank you, and quite understandable.
Any questions?
DR. EPSTEIN: Helen, I share the
perception that this is quite an eye opener and
very encouraging and much to your credit.
When you spoke of technology transfer,
implicitly you're implying that the product should
be made locally. Is that indeed the concept that
you're working on?
DR. LEE: Absolutely. In fact, we're
already identifying possible institutions and
individuals which is really the main thing, one in
Africa, one in Asia, and we haven't identified
someone in South Africa yet. We are in the process
of writing other manufacturing documentation,
quality control. We're scaling up to 120,000 tests
per batch. We want to have people from these
countries come and work with us, do the scale-up,
and look at the documentation and bring it back to
their country. I want to have it made over there
because it's the only way to carry on. And
hopefully later on these sites serve as secondary
technology transfer for the continent.
DR. GUERRA: Ed, could I ask her just to
clarify something?
The estimates that you give here are from
the general population without pre-selecting those
individuals that would have had, at least in their
history, some risk factors and/or, for example, the
recently discovered, fairly significant prevalence
of hepatitis C in individuals that have had tattoo
applications or, you know, in this country, about
22, 23 percent that have had tattoos are found to
be hepatitis C positive.
If you selected--or excluded those
individuals, then the risk would be even less,
wouldn't it?
DR. LEE: I'm sure, as all places--I don't
know what the number is. Perhaps Jean-Pierre can
mention it, discuss it. I'm not even sure that
it's necessarily available. I'm sure wherever you
do a better job for donor screening you are going
to reduce the risk. But I have to say I come from
China, and I know the Chinese will not give blood.
And I'm sure one of the reasons the HIV rate is
going up in the so-called repeat donor is because
they're the paid repeat donors. And so there are
times that they try to entice people to go, and
just the need for blood in that traumatic situation
is such that I don't know how much choice one has,
except right by the bedside to make sure that that
particular unit doesn't really have what you don't
want.
DR. GOMPERTS: Keith?
DR. HOOTS: You said you can do DNA. Have
you thought about looking at the other side, which
is to use--to screen to reduce demand? One that
comes to mind would be like sickle cell. If you
screened in Equatorial Africa for sickle cell where
maybe the survival rate's not high, but certainly
most people do survive to adulthood even there with
sickle cell, and you could use this rapid test, and
you could do prospective sort of interventional
things that may reduce their transfusion
requirements, for instance, if you knew ahead of
time that they were candidates to need transfusions
multiply?
DR. LEE: I have to admit I hadn't thought
about that. But I will now when I go back and talk
to a friend of mine who happens to be a sickle cell
expert.
Part of the problem, I think, for all of
us is that, as you grow old, you have so limited
energy and time, so you try to go for what really
counts. I don't know a damn thing about sickle
cell anemia.
[Laughter.]
DR. GOMPERTS: I have a question. The
initiative that your organization has shown in
developing technology for this application and
certainly recognizing the issues around
reimbursement, et cetera, but technology does move.
And the potential for technologic applications with
chip technology, RNA, DNA, just superficially from
where I sit looks particularly attractive.
What are your thoughts on that one?
DR. LEE: I think I'm jaded. As a
scientist, I'm totally seduced by chip technology.
As a practical person, when there isn't even
electricity or I couldn't do EIA in China because
the water turns everything yellow, and I think
about chip technology, I just say to myself forget
it, because I don't even trust the PCR data from
many of the American labs. So I think it's a long
way in time with the way technology does move so
quickly. I hope one day it will happen in other
countries.
But one of the problems with chip
technology, I have to say--and I haven't figured it
out, and I don't know that much about it--is that
if you're looking for infectious diseases, if you
use very small volume, by definition you've made
your life much more difficult just because the
infectious agent is not going to be in that one or
two microliter.
The second thing is I haven't figured out
how you're going to do the quality control for each
of the dots.
DR. GOMPERTS: Thank you.
Yes?
DR. PENNER: Just a quick comment on the
donor population in China. There's that huge
captive population they call the Army.
DR. LEE: Yes.
DR. PENNER: Isn't that available for
blood donors? Because that can be pretty much
enforced, I would think.
DR. LEE: One of the nice things about
being a minority and a woman is you can say things
you white men cannot get away with.
[Laughter.]
DR. LEE: I'll tell you, the Chinese Army
right now is so busy trying to find the people to
kill to sell the organs--
[Laughter.]
DR. LEE: No. I'm sure you're right.
[Laughter.]
DR. GOMPERTS: That's moving into a
different target.
[Laughter.]
DR. GOMPERTS: No pun intended.
DR. LEE: That was not a racist comment.
DR. GOMPERTS: We have to move on. Thank
you.
[Applause.]
DR. GOMPERTS: Professor Jean-Pierre
Alain, focusing on the promotion of appropriate
technology transfer from the point of view of a
developing country.
DR. ALAIN: Good afternoon. First I want
to thank Steve Nightingale for inviting me to
present here something that's going to be very much
bottom to top as opposed to what we have seen so
far.
Another question you might ask is why
somebody from the University of Cambridge can talk
about Sub-Saharan Africa. The reason is that two
years ago I decided to spend a sabbatical year
there, so I went there, and I had to shed all I
knew about blood transfusion when I saw how
inadequate it was for the local situation. And I
tried to do what Dr. Lipton mentioned, which was to
keep the goal--to focus my attention, but to adapt
the ways of reaching the goal which made sense in
the local situation. So I'm going to try to walk
you through some of the issues I have been faced
with during that time, and I'm still continuing
very close collaboration with the blood bank there.
The first problem--and I'm going to focus
on blood screening--is that--the first inadequacy
if the prevalence, which has been mentioned by
other speakers, and actually from Jean Emmanuel to
some others, we can see here the range of
prevalences of anti-HIV, HBsAg, and anti-HCV on the
one hand, which is about 100 times or more than it
is in Northern countries, and also, as already has
been mentioned, the poor percentage of screening
except for HIV, the reason being that testing is
provided by external aids as opposed to internal
screening.
So what are the factors driving blood
screening in Africa, at least some of them? As I
mentioned, the prevalence is high. Also, most
blood banks are small, hospital-based, like the one
I was to, which was in the middle of Ghana, in a
university hospital, collecting about 7,000 units,
which I think is fairly representative of a lot of
what's happening in Sub-Saharan Africa and other
countries.
One main issue also is that people pay.
There is absolutely no health coverage, and
obviously this is a major problem because, as soon
as you discuss anything to do with health care, the
first question is how much does it cost; otherwise,
people don't do it.
Also, this is also one of the consequences
that the government is not doing anything. They
eventually give directives and say, for instance,
by 2002, 100 percent of blood donors in Ghana have
to be voluntary donors, except they don't give
anything to do it, except providing anti-HIV
screening.
One very important question is
communication, and this affects--that's one of the
first things I noticed. It affects dramatically
what you can do. In particular, in Ghana, and most
of West Africa, probably a number of other
countries, people don't have an address. They
don't have a telephone. You cannot communicate
with them. So, so much for having donor panel and
repeat donors because you cannot call them.
On the other hand, they are listening to
radio all the time, and so radio--FM radio is a
very good way of communicating, and I'm going to
show you that we have been using that to call
donors. Also, obviously, transport is very
difficult, particularly in the rainy season. So if
you have a centralized system, you cannot give
blood to a district hospital as they need it, so
you have to have at least for a number of countries
these relatively small places collecting and
testing blood if you want to be able to treat the
patients.
Finally, the screening assays, as I
mentioned, as we know them are inappropriate
because--I'm going to discuss that--it takes lots
of time, so you can only do that post-donations,
and since you cannot contact the donors, they are
gone, you cannot get back to them, the cost is very
high. And the throughput is much too high. For
instance, in the blood bank I was, the average is
20 donations per day. So what can you do with a
96-plate except use your controls and increase your
cost?
So now what is the background of the
Kumasi Blood Bank I was involved with? It was in a
teaching hospital. We collected seven units in
2000. There were 17 staff members, 87 square
meters for the whole thing, which represented 0.5
percent of the total hospital flow surface. And we
had in 2000 about 50-50 volunteer replacement
donors, and the year before it was 35 percent
volunteer donors, and this year in the first three
months we have been up to 65 percent volunteer
donors. And that's probably the best we can do to
improve the safety of the blood supply, is to
collect as much volunteer donors as possible, as
I'm going to demonstrate to you.
The routine blood screening which is
currently done, as Helen mentioned, is essentially
HBsAg by agglutination pre-donation, anti-HIV by
EIA post-donation, and there is no anti-HCV,
although I had a grant when I was there, which
allowed to test for anti-HCV. So we have some
epidemiological data. And the total budget--I'm
going to come back to that--was $70,000, which I'm
sure is a number you certainly don't recognize
around here.
So the donors are essentially two sorts.
One is volunteer donors, and they come essentially
from secondary schools, as you can see here, some
of them coming to give blood. So they are
basically ranging between 16 and 20 years of age.
And they represent approximately 70 percent of the
volunteer blood donors.
But we have also these blood drives with
the help of local FM station, like this one we had
ten days ago, where we collected 350 units in one--between 7 o'clock in the morning and 2:00 in the
afternoon. And we can do that with this particular
FM station four or five times a year when we need
it, essentially when the schools are closed.
So this represents about 20 percent or 25
percent of our volunteer blood donors. And the
rest of them are replacement donors collected in
the hospital. You can see that the walls are
peeling, so the particular circumstances are not
very good. So we are trying to reduce as much as
we can replacement donors. The reason is that, as
you can see here, the distribution in blue of
volunteer donors, you can see that they are mostly
less than 20 years of age, decreasing this way,
when the replacement donors have a median age of
32, which obviously has a major impact on HIV
prevalence, which is about 10 times more than it is
in volunteer donors; hence, the reason we wanted to
increase volunteer donation. And for nosocomial
reasons, it is the same for HCV, so the prevalence
is significantly lower in volunteer blood donors
than replacement. It's 0.6 versus 2.5 percent in
these two populations.
So let's now talk about the field
experience we had of pre-donation screening in this
blood bank. We essentially concentrated--I'm going
to show you why--on HBsAg pre-donation, essentially
by agglutination initially, since November '99, and
then anti-HIV. First we did some evaluation of the
test and then using it in a small scale and very
specific condition pre-donation, and then we
evaluated a number of tests to try to meet our
needs.
So the conditions for effective pre-donation screening as far as our thinking over
there was, was that it was worth doing for several
reasons. One was that if you test pre-donation, as
I said, you can intervene to the donors and do some
information counseling, et cetera; otherwise, they
disappear, except in the schools, for a few years.
Second was that if you do pre-donation
screening, you save a lot of money on your
consumables, in particular, blood bags and blood
grouping, for instance. But it is worth doing.
Only the cumulative prevalence of HBV, HIV, and HCV
is about 10 percent.
Also, importantly, arrangements for
confidential testing should be met, particularly if
you get into the HIV area, which is, as has been
mentioned previously by Eve and others, kind of
problematic. So it is important to do the testing
in a room separated from the donors so that
confidentiality can be maintained, or you can do it
in an open setting if you cannot distinguish in the
test, as Helen mentioned, because HIV, HBV, and HCV
testing, and then you reflect it with an
information pre-counseling available inside, and
reflect donors who have been eliminated from
donating to the blood center for diagnosis and
proper counseling. So these are the conditions we
have been trying to put together for developing
pre-donation screening.
And we have tested a number of tests for
anti-HIV, for instance. We tested this dipstick
from Roche, which was developmental, and I'm not
sure you can see--except if you are very close, you
can see the bands at the bottom which indicate
positivity as opposed to the procedural control up
there. You can see that we had some false
positives, but interestingly, the procedural
control band was stronger than this one as opposed
to here when it was the reverse, and then some
negative. And this test takes ten minutes.
We also tried a filtration-based rapid
test produced in this country by Akers, which was
very attractive initially because what you have is
these tubes with reagents in glass ampules for HIV
here, for instance, and then you can take a bit of
serum, there is a mark here, put it in this tube,
break the ampule, shake it, and after one minute of
racking, you can have an answer by putting five
drops for HIV on this compartment. And if it is
negative, the particles go through the filter and
you can see the color in negative samples. If it's
positive, it doesn't go through.
However, we had major problems with this
technology, although it was very attractive,
because in about 50 percent of the time we have
false positive because the quality of the serum we
used was not adequate. So we very rapidly realized
that we couldn't use that kind of technology.
So now let's concentrate on HBsAg, and the
reason why we concentrated on that is shown here,
that when we tested with latex agglutination,
whether it was replacement or volunteer donors, we
had 13 percent positive. And when we tested the
negative by EIA, we had an extra 2 percent
positive. So basically the prevalence, whether in
replacement or volunteer donors, is over 15
percent. So if you could by pre-donation save the
13 percent or even better, 15 percent, of your
blood bank's consumables, that would be very
considerable.
And we did it, as an example, in this
radio station, by agglutination. So what it takes
is essentially two pieces of instrument: the
centrifugation--the centrifuge here to prepare the
serum, and then this agglutination packs and stir
to do the agglutination. And all of this can be
done in about 15 minutes.
However, it takes two--draw a pre-donation
sample from each donor to prepare the serum and do
the testing, but apparently this has never been a
deterrent for any of our donors, and they do that
happily, in part because it's providing to them
some free health care, which they really appreciate
considering the circumstances.
And then, once we have identified
positives, they are immediately informed here is a
houseman from the hospital who has been
specifically trained in HBV infection who is
telling these donors that they should come to the
hospital, and in the hospital we would confirm the
test and tell them whether they are really infected
or not, and then do ALT to find out what is the
state of their liver disease, and possibly enter
them into a treatment program.
So just as a summary of what we have done
in over a year, we basically screened 8,677 donors.
We by agglutination found about 10 percent are
HBsAg positive, and 62 percent of these individuals
did come to the blood center, were properly
counseled, tested for ALT, and given information
about HBV infection properly, which we would have
not been able to do unless we were doing pre-donation screening. And then 11 percent of these
individuals had elevated ALT, but only 1 percent of
them had substantially elevated ALTs, and those
were entered into a treatment program.
As controls, we tested by EIA these
positives. In some cases, we found, unfortunately,
that about 10 percent of those were false positive.
But they provided a control group with only one
with elevated ALT, which certainly differs from
that particular group.
Now, if we summarize, I'm sorry you cannot
read what's here in terms of testing HBV. If you
don't do anything, you have 0 percent detection of
infectious blood. But if you do agglutination, the
sensitivity is about 82 percent. And the
sensitivity of this technique is over--or equals 13
nanogram/ml. If you use a dipstick, as Helen
described, you can have about a sensitivity of 5
nanogram and detect 92 percent of your infectious
unit. If you use EIA post-donation, you go--sorry,
there was a shift in the numbers, 98 percent
detection, and possibly if you use NAT in addition
to that, you might be able to detect 100 percent.
I put a question mark because it was really--it's
ongoing. I don't really have the answer.
Now, so that's the difference in
sensitivity with a different kind of strategy you
can use. The one we have chosen was to use
agglutination pre-donation, EIA post-donation.
However, the hospital couldn't buy the test, so
what we are going to do is actually take this
route, which is test only with the dipstick EIA,
which has not optimal sensitivity, but is doing a
fairly good job, because this has to be related, as
Jay Epstein mentioned, to the situation in--sorry,
that's why you couldn't read--in the recipients.
And that's what we did. We tested the recipients
for HBV markers, and this is less than 10 years of
age, 10 to 15, et cetera, so by intervals of ten
years. And you can see that already in the 10 to
19, about 85 percent of the potential recipients
have markers, anti-HBC in this case, and HBsAg is
shown here. So basically the at-risk population is
the pediatric population, which has been mentioned
already by several speakers. And you can see that
about 70 to 80 percent of your pediatric population
is susceptible to HBV infection. But it represents
about 40 to 45 percent of the blood use.
Now, we tested for field usage two anti-HIV dipsticks. We tested Roche post-donation, as I
mentioned, and we found a specificity over 99
percent, whether in volunteer or replacement
donors, and a concordance with EIA of 100 percent.
And now we tested in this new program we have
ongoing now the Abbott determine in replacement
donors only, and we have 98 percent specificity,
100 percent concordance with EIA.
So this new program is doing simultaneous
pre-donation screening of HBsAg and anti-HIV in
replacement donors. And the reason why we chose
replacement donors is because, since we have to use
two separate tests, which were very easy to
recognize, we couldn't do it in open setting, and
we did it only in replacement donors because the
lab is in a different room compared to the donation
area.
So these are the results, and you can see
that we had a number of reactive and deferred
donors, 12 percent for HBsAg, 4.4 for anti-HIV, but
only 10.4 percent were confirmed positive for
HBsAG, and 3.5 percent for H--with this number of
false positives. But if you extrapolate that in
terms of adjusted number of deferred donors and
potential saving, you can see that you are
deferring 166 donors, 139 of whom have, however,
HB--are infectious either for HBV or HIV, and
actually waste only 27 donors.
So you have to look at that now in the
economic context, and I put here the data recently
collected about the budget I told you of $70,000,
just to put things in perspective. You can see
that only 19 percent of the budget is staff cost,
but the supplies is 78 percent of the cost, and
blood bags on their own represent 43 percent of the
cost. So, obviously, if you save 20 percent of
your blood bags, that has a massive impact on the
budget for the blood bank. And the HBV kits, the
agglutination test is 17 percent. And as you can
see, equipment amortization, transport overhead is
really minimum. So all together, the real cost is
$10 per unit, and the government has decided on a
certain price for reimbursement per blood unit,
which actually corresponds to 6.3 percent, so
basically a third is paid by the hospital.
So if we look at the impact of pre-donation screening on the blood bank budget, it has
an impact on blood bags because it represents 43
percent of the budget, on blood grouping, possibly
on staff cost, although this is not a major issue.
So in terms of saving, if you prevent 10 percent of
the blood waste, you save 6.4 percent of your total
budget. If it is 20 percent, it's 13 percent of
your total budget. So, obviously, with this kind
of saving, you can do other things which can be
very useful for blood safety.
So the impact of pre-donation is reducing
the consumables, potentially the staff cost. It
very importantly, as I mentioned, allows immediate
public health intervention. It may create, as I
mentioned, in this particular context an incentive
for donation if donor care is in place. And the
saving you are doing can be used for donor care,
ALT testing, diagnosis and confirmation, counseling
and referral, but it could also be used to use
other tests, because the $1 test which was
mentioned by Jean Emmanuel this morning represents--if you use a $1 test, add to your budget, it's 10
percent of your budget for $1 test added to the
whole thing. So the impact is absolutely enormous,
and this is certainly to be kept in mind.
So if we define what would be necessary in
this kind of situation as far as pre-donation
screening, it would be rapid test, taking less than
15 minutes; otherwise, if you wait too long, your
volunteer donors are going to tend to disappear.
It should be high performance, over 99 percent
sensitivity, over 98 percent specificity. It
should be robust. As I mentioned to you, the
quality of serum made a difference, but it could be
used plasma, hemolyzed sample, potentially whole
blood. Easy to use, in a single-step assay
requiring no instrument, at low cost, certainly
much lower than $1 per test, as I mentioned,
considering the impact on the budget. And it
should be multiplex, one test for all three
markers, and it should be compatible with
confidential screening.
So, unfortunately, at the moment, what we
have is separate tests that could eventually be
used for HBsAg, for anti-HCV, although the choice
and the performance is not very good, or anti-HIV.
So this is doable in some ways, but not
satisfactory.
So the strategy for blood screening in
poor resource countries in high prevalence area
should be rapid test, a multiplex by which you can
perform pre-donation, by which using--if you use
that, you can have a go/no go. You can take the
donor or you can't. If you can't, you tell--you
inform the donors there is something in their blood
that prevents from using their blood, and then you
reflect them to information and offering
confidential differential diagnosis and donor care.
And I think this is totally strange to what all of
us are accustomed to, but I think it is a kind of
strategy which is well adapted to the situation I
had at least in this particular part of West
Africa.
Thank you very much.
[Applause.]
DR. GOMPERTS: Thank you very much.
Any questions or comments? Yes?
MR. ALLEN: You mentioned at one point
there were 350 donations in the first day there.
Of those 350--I don't know if I missed it or not,
but how many of those donations were you actually
able to use?
DR. ALAIN: Okay. You have to realize
that this, as has been mentioned, is a random
population. It's people from the street, it has
been advertised by the FM radio, and people just
show up.
But the percentage, as you would expect,
of pre-donation screening that have been taken
away, out of these 334 donors pre-screened, 32 were
HBsAg positive, so this has been taken away, but
only one post-donation was HIV positive. So I
think the phenomenon of self-exclusion actually is
considerable because the general population HIV
prevalence in Ghana is about 4 percent. So it's
certainly not representative of the general
population.
MR. ALLEN: And the people that are
identified with some kind of agent in their blood,
you say they're counseled to go to the hospital for
further care.
DR. ALAIN: Yes.
MR. ALLEN: You mentioned earlier, of
course, that there's really no payment process, or
insurance, rather, so how are these people taken
care of?
DR. ALAIN: Well, as I said, what we do is
we offer them--when we do the information
immediately after screening, we tell them to come
to the hospital and we are going to examine
clinically their liver and spleen, and we are going
to do free ALTs to find out whether their livers
suffer or not, and then if they have ALTs above 80
international units per liter, then we refer them
to the internist in the hospital who takes them on
to a treatment program.
MR. ALLEN: So at that point the hospital
absorbs the cost of treatment or--
DR. ALAIN: From then on, when they go to
the internist, then it is for the patient to
support the cost. But all the upstream is taken
care by the hospital and the blood bank.
DR. GOMPERTS: I--sorry?
DR. GILCHER: I'm concerned about the
false positives receiving counseling as though they
are true positives.
DR. ALAIN: Okay. We are not counseling
them. We are informing them, and we tell them we
have a test that was positive--actually, by the
way, in this particular session, 100 percent of the
agglutination positives turned out--were confirmed
by EIA. But overall we have 10 percent.
So what we tell them is that there is
something that makes the blood unsuitable, to come
to the hospital for confirmation, and once it is
confirmed by EIA in the meantime, because they come
typically two to three days afterwards, then we
have confirmation, then we counsel them properly.
And those false positives, we tell them it was a
laboratory problem, they are okay.
DR. GOMPERTS: I have a question. The
environment that the blood bank was functioning in
was a community hospital in this particular city?
DR. ALAIN: It was a university hospital.
DR. GOMPERTS: University hospital. Was
this the only facility within that area?
DR. ALAIN: Actually, this is the only
facility that collects blood in this big city of
1.2 million inhabitants.
In the region, there are some district
hospitals who collect blood, and if they don't have
enough, then they eventually come to us for blood.
DR. GOMPERTS: Okay. So some of the blood
would be used outside the university hospital?
DR. ALAIN: Yes.
DR. GOMPERTS: Okay. Thank you.
DR. ALAIN: Including private clinics that
are in the city.
DR. GOMPERTS: Okay. Thank you.
Any other comments?
[No response.]
DR. GOMPERTS: Thank you very much.
The final presentation before the break is
Raj Dalal, talking on providing access to screening
technologies. Thanks, Raj.
MR. DALAL: We've had several stimulating
and important presentations today, and as a
committee member, I'd like to make sure that we all
have time to discuss what's been presented. So
I'll try to make my comments succinct, and I'll
speak as quickly as possible.
I approach the subject of the worldwide
blood safety from three perspectives:
First, as a member of this committee, I
participate with you in guiding policy toward a
uniform standard in the United States for both
safety and availability, a standard that I believe
for the most part can serve as a model for other
countries.
Secondly, I speak as an executive of a
biotechnology company that has been credited with
developing many of the techniques, the molecular
biology techniques that led to the discovery of the
hepatitis C virus, and also that contributed to
numerous innovations in HIV testing. In that
capacity, I want to share that I personally believe
that market-based-economy approaches towards
technology commercialization can lead to
sustainable business solutions to the problems that
we're addressing today.
And, third, similar to Celso Bianco, on a
personal basis, I speak as an individual who was
born in a developing country where the prevalence
of HIV is on the rapid rise and where HCV lurks
just below the surface of national consciousness,
and as such, I am keenly aware that governments,
such as the Government of India and others around
the world, are under pressure to strike the
appropriate balance between investing and life-saving medical technologies and juggling the
necessary resources to meet the basic necessities
of their people.
In order to address these somewhat
different but necessary perspectives, I support
three approaches. The first of these three is that
high-performance assays and instrumentation should
be made available to all nations. Second, as we've
heard from many speakers, education, training, and
standardization of operating procedures in blood
banks must be supported. And, third, the political
consensus must be developed to pay for the cost of
blood safety throughout the world, and this I
believe must be achieved as well.
In terms of making high-performance assays
and instrumentation available, Chiron and its
immunoassay development and markets partner, Ortho
Clinical Diagnostics, are committed to providing
the countries of the world with high-quality
hepatitis C and HIV microtiter plate format ELISA
tests. In doing so, however, we do and must
continue to recognize the varying needs and
infrastructures of these countries, and we've had
some very good presentations that point this out
only too clearly. And just to add to that point,
we should remind ourselves that while the world's
most populous and poorest nations where the need
for such tests are greatest are often lumped under
one general economic term of "developing
countries." But as has been pointed out repeatedly
today, they do not necessarily have uniform
characteristics. For example, in some of the
larger developing countries, they have both a
private market or a private segment as well as a
very large and needy public health care system.
I estimate that the size of the private
segment is approximately 10 percent of the total
blood donations. This is only an informed guess.
I have not seen the hard data to support it, and
there are other views that would suggest it's more
or less. But it is mostly urban, that is, the
private market is mostly urban. It's managed by
knowledgeable and dedicated medical professionals,
many of whom you have known personally. The
relatively small but self-paying patient base is
conscious of the risks of transfusion-transmitted
HIV and HCV. And both physicians and the patients
in this segment demand high testing standards,
including in some cases nucleic acid testing, where
available, and they may also demand either
autologous or directed donation. And this has been
pointed out several times today as well.
The HIV and the HCV tests in this segment
are sold generally under commercial terms, and the
performance of these tests satisfies exacting
international standards of performance and good
manufacturing practices.
The installation of these complex systems
is typically handled by the international branch of
health care companies that train--they train the
technicians, they train the supervisors, and
provide ongoing technical troubleshooting.
Distribution and routine field testing of the
equipment is often provided by trained local
representatives who the international health care
companies train sometimes in their U.S. locations.
These local representatives have access for the
most part to cold storage facilities,
transportation networks, and skilled manpower to
handle labile biological products, including
vaccines, diagnostic reagents, in some of the
larger countries, reagents for biomedical research.
They also have experience in managing cross-border
joint ventures and other commercial relationships
for other products that they might distribute.
In some instances, these local
representatives expand their businesses by
substituting imports with locally manufactured
disposables and other components, and over time
they could produce products with lower costs with
domestic components, with an eye towards expanding
into the public market where the unmet medical
need, as we have talked about, is the greatest.
This process, through the private segment
that I talked about, of technology transfer not
only provides access to valuable technology in the
near term, but it often contributes to building a
sustainable, market-economy-based, domestic
biomedical business infrastructure in developing
countries.
In contrast, the public market, which we
have spent quite a bit of time talking about,
accounts for approximately 90 percent of the blood
donations in the developing world, and, as has been
pointed out, is fragmented across numerous smaller
urban and rural centers. Price sensitivity is
high, costs must be low, and government
participation appears to be essential.
Chiron and Ortho Clinical Diagnostics are
committed to providing these public markets with
immunoassay products at a lower price than we would
provide to the private markets. We would do so in
cooperation with governments at the national level
in bilateral contracts but also with international
agencies such as the World Health Organization, and
we have had some productive discussions with Jean
Emmanuel on this matter, and also with others such
as PAHO.
I also believe that a rational approach
towards intellectual property matters is necessary.
We need to pursue an approach that allows
technology to be made available to fulfill these
unmet needs in the public segment, an approach that
can involved public and private financial support,
and an approach that would preserve the long-term
characteristics of market economies, including
continuing incentives for innovation, preservation
of the private component of the large developing
countries, and also preservation of the economics
of providing such products in our own country.
While providing access to affordable,
high-quality immuno products can substantially
reduce the risk of transfusion-transmitted HIV and
hepatitis C, I agree very strongly with what others
have said, that technology alone is an incomplete
remedy. If we think of the technology component,
the assay and the instrument, as the hardware, then
management skills, training, education, and
operating procedures are the software of a
successful screening process.
While it may be difficult to quantify the
total costs of these software components, it's my
belief that the added software costs for testing
alone per unit of safe blood delivered to the
patient in developing countries as a result of
donor recruitment costs, infrastructure, waste,
labor, transportation, et cetera, is very high, and
probably a lot higher than the cost of the tests
themselves. Regardless, better studies and
analyses, I would recommend, are needed to fully
account for the total cost of all these software
components.
I also believe that additional studies are
needed to assess the economic impact of new testing
algorithms in the public markets. For example,
we've heard about donor qualification testing and
rapid, that is, point of donation rapid tests for
HIV and HCV, and also HBV. What is the likely
impact of these tests on the total cost?
While technology does exist now in the
U.S. to perform rapid and accurate tests at the
point of donation, its impact on the public market
on currently employed donor recruitment practices,
acceptance of donors, counseling, et cetera, is not
well understood.
We had a question with regards to Jean-Pierre's presentation with regards to what do you
tell the donor. We know what the answer is for our
country and for Europe and probably Japan.
As a result, studies must be undertaken to
determine whether the overall costs in the public
segment can be reduced by the adoption of new
testing algorithms.
We also support multiplexing for the
obvious operational benefits that might result from
a single test which gives a yes-no kind of answer.
And, finally, in agreement with other
presentations, we would say that the potential
quality improvements and cost/benefits from further
consolidation of the fragmented blood banks should
be more deeply explored. And I know a lot of
thinking has gone into this.
As important as access to technology,
which was the first of my comments, and access to
education and standardization, which was the second
of my comments, we believe equally important is the
need for building the political consensus in these
countries that we intend to support. Dr. Alain and
Jay talked about it at some length.
Most citizens in developing countries do
not have the legal means by which they can hold
public health officials accountable for blood
safety. That puts the onus of the leadership of
these countries to take the initiative to establish
reasonable local standards, to mandate change in
their countries, and establish clear local
accountability for blood safety.
There are many examples when, in fact,
such action has been taken. One example, albeit
outside of the blood testing area and the area of
vaccines, is the manner in which a new generation
of HIV vaccines--these are nucleic acid-based
vaccines--are being developed--their development is
being championed by the government of one large
developing country. In this particular instance,
they're forging risk-sharing alliances with
domestic biomedical companies, internationally
agencies, and biotechnology manufacturers. The
biotechnology company would transfer the
technology, train personnel, manufacture clinical
supplies, and enable local representatives to
conduct clinical studies, eventually manufacture in
a scaled-up manner, and commercialize the products
at an affordable price, because in this case the
country would have borne some of the technical risk
up front. There's no assurance that one of these
vaccines will provide the prophylactic profile
that's desirable, despite how promising the product
looks right now.
We say that such commercially driven
efforts should be applauded and expanded to other
areas, including development of new products in
blood testing where they make sense.
And, finally, we certainly would continue
to support, apart from the product development, we
would continue to support all the safety efforts of
international agencies like the WHO and PAHO and
what we've heard about the NIH and other
organizations, the AABB, the Red Cross, CDC, et
cetera. And we're particularly gratified when WHO
and PAHO made world blood safety the focus of last
year's World Health Day program.
So, in conclusion, I believe that a global
effort to implement blood safety programs with U.S.
participation would be supported by American
businesses and would be supported by the taxpaying
American public. And such investment and its
implications would be fully understood by
interested parties around the world. And I'd say
that for HHS to take this kind of approach, that
this is not only for hepatitis C and HIV and HBV,
but also for the control and rapid response to
other potential transfusion-transmitted agents.
Let me end my comments with that. Thank
you.
[Applause.]
DR. GOMPERTS: Raj, thank you.
Any comments? Questions? Yes, Jay?
DR. EPSTEIN: Well, as we've asked other
speakers, what in your opinion is the role that the
department should play, particularly with the
interface with the business community, from which
perspective you've been speaking?
MR. DALAL: Sure. Let me make two or
three comments that I think might lead into the
discussion that we want to have later on, and not
all of them will address the connection with the
business community.
But, first of all, a company like mine
looks at HIV broadly. The prevention of the
growing incidence of HIV will result from all the
software things we talked about, not only in blood
screening but also the development of prophylactic
approaches, such as vaccines and blood screening
tests and eventually therapeutics.
From HHS' perspective, this is one
contributing effort to reduce the incidence, and
what makes it particularly unique is that, unlike
vaccines and therapeutics, here's an area where we
know that technology works. If you apply the
technology as per the package insert, it works.
And it can stop the transmission of transfusion-transmitted HIV, HCV, and HBV. So here's one
variable that, from a technological perspective, we
have real control over, and I'm focusing on the
hardware of what I talked about, the assay and the
instrument. So that's one perspective.
To develop this technology, industry has
contributed and government labs have contributed.
And the blood banking sector in the United States
has contributed significantly to it, and here's an
example of a partnership. We've got this
technology. Let's use it.
We would continue to support all aspects
of education and standardization and would incent
international health care companies that already do
this, albeit in a narrow commercial focus, to
expand it. Most blood banking-related test
developers tend to have a more narrow focus with
regard to the testing component as opposed to the
donor recruitment and the training of physicians
and so on. But there's a possibility of enlisting
this large worldwide, well-trained, highly
disciplined organization in support of all the
software that we talked about.
Let me leave you with those two, and we
can talk about more.
DR. GOMPERTS: Any other comments?
DR. NIGHTINGALE: One last question. Raj,
do you have any idea what the multiplier is of the
dollars spent in a developing country on health
care in general or blood safety in particular? Do
you think it's 1.0? Do you think it's greater?
MR. DALAL: Sorry, the multiplier of the
test--
DR. NIGHTINGALE: I'm talking to a
graduate of the University of Chicago School of
Business. What's the multiplier, if any? What do
you think the multiplier of a dollar spent on
health care in a developing country would be on
health care in general or on blood safety in
particular? In other words, are there specific
benefits? For example, the generation of economic
activity in the developing country rather than the
drain of those dollars to, say, Miami.
MR. DALAL: Right. Well, you know, I
think that's a very good question, and, clearly,
the World Bank and other institutions are thinking
very hard about this when they, for example, make
available hundreds of millions of dollars to a
country like India in order to bring HIV incidence
lower. But, Steve, I don't know the exact number
of what that multiplier is.
DR. GOMPERTS: With that, we'll take a 15-minute break. We'll reconvene at 5 to 4:00. Thank
you.
DR. NIGHTINGALE: If anyone in the
audience wishes to make a public comment, would
they please contact me? I'm not aware of anyone
who wishes to make a public comment.
[Recess.]
DR. GOMPERTS: Okay. We need to
reconvene.
Is there any person that wishes to make a
public comment on this topic?
[No response.]
DR. GOMPERTS: At this point I see none.
Going, going--
[Laughter.]
DR. GOMPERTS: Okay. Gone.
That brings us to the committee discussion
and recommendations. Any comments? Yes, Karen?
MS. LIPTON: I don't necessarily have a
resolution to this issue, but there are two things
that came up that really struck me today. One is
that somehow, with all of these things that are
going on worldwide, we need to really coordinate
these efforts in some way. I don't know that
that's necessarily a role of the Federal
Government, but it just seems to me that there are
so many ways in which, if we happen to work
together and to join forces on things that we could
literally, you know, make the contribution so much
more significant.
That being said, that I don't know that
there's necessarily a governmental role in that, I
also think that it's critically important that
whatever we do today, you know, what additional
actions do we need to promote blood safety, we
really need to ensure that we allow our FDA and NIH
and CDC to remain players in this international
field. And so if it's necessary to take some
action to ensure that that continues to happen, I
guess I would see that as being very important.
DR. GOMPERTS: John?
MR. WALSH: Dr. Lee has made a believer
out of me, and at the very least, I would strongly
recommend that the committee discuss how we might
ask the department to evaluate and, I would say,
support--evaluate a way to support the triplex or
multiplex rapid testing device, and also not
forgetting the technology transfer piece to that.
It makes perfect sense the way it was described by
two of the presenters that we ought to be looking
at that in the developing countries.
Also, there's a lot of tests out there
from what I've understood with sidebars that are
not accurate, and I think there's some need for an
appropriate monitoring of devices or testing
packages to see if they really work or they're
being--you know, people are being sold up the river
with bad testing, you know, whether it be a
validation process--I'm not asking the FDA to
regulate all that, as they certainly could not, but
some way that the international community could
validate a testing device before it was embraced.
DR. GOMPERTS: Thank you.
Yes, Rich?
DR. DAVEY: Well, I would agree with the
comments that have just been made. We've certainly
heard a lot of information today, critical
information. Consciousness has been raised on what
the challenges are, the opportunities are, and what
different people in agencies are doing in this
area. And there's a lot that we could include in a
resolution.
But I tend to support, again, the line
that Karen was suggesting, and actually, I would
suggest perhaps two resolutions. I've drafted a
couple for your consideration.
The first one is along the lines of
recognizing what the government's already doing,
and I would suggest something like: The committee
recognizes the importance of international issues
in blood safety and availability. As such, the
committee endorses the present activities of
government agencies to enhance international blood
safety and availability. So we're endorsing what's
already going on and saying it's good work, let's
keep it up.
The second, again, is addressing the issue
of perhaps coordinating our activities in some
better way, and a possibility would be: The
committee asks DHHS to establish and support an
international coordinating committee or similar
body to ensure the exchange of information,
technology transfer, coordination of activities,
and determination of priorities among governmental
and appropriate nongovernmental agencies.
So we're looking at, number one,
supporting existing activities and, number two,
establishing some coordinating body. So I would
suggest those two possibilities, Mr. Chairman, as
something for the committee to consider.
DR. GOMPERTS: Okay. Jay?
DR. EPSTEIN: I like the proposals, Rick,
but on the second proposal, I think we should be a
little bit cautious, because WHO already exists and
provides this kind of function, and I think that if
we are making a recommendation to the department,
it ought to focus a little bit more specifically on
the U.S. So I'm inclined to favor the notion that
the department could play a constructive role and
perhaps should be then encouraged to play a role in
facilitating coordination of U.S. effort rather
than charging it with establishing some
international body since one exists.
DR. DAVEY: Jay, I guess in my draft, when
I said international coordinating committee, I did
mean a committee to coordinate U.S. international
activities. So that was--the wording was a little
off. I didn't mean to preempt the activities of
WHO. This would be a U.S. activity.
DR. GOMPERTS: Fernando?
DR. GUERRA: Yes. You know, lest we put
all of our eggs into one basket that, you know,
obviously offers tremendous hope for preventing the
spread of a number of these infectious agents,
somehow we need to link it to some of the other
efforts that are going on in terms of vaccine
development and what those opportunities might hold
for the future and also some of the pharmacotherapeutic agents that maybe will allow us to try
to address in a significant way the cumulative
backlog of cases of those individuals that have
already been infected, because I think that, you
know, there is so much desperation and hopelessness
that I think presently exists.
The other is that, you know, there are
some missing pieces of information that maybe some
of the presenters perhaps have a little bit of
knowledge about this, and one is certainly the
comorbidity of some of these conditions that were
described today affecting the blood supply, but
that, you know, when they co-exist with whether
it's tuberculosis or cancers or whatever, I mean,
are there opportunities for screening from the
prospective donor pool for some of these others, to
truly keep it within the public health context of
trying to identify those populations and those
individuals that carry a tremendous burden of
disease and where I think the cumulative impact of
that really lessens the prospective donor pool
beyond just the infectious agents.
DR. GOMPERTS: Other comments? Yes, John?
DR. PENNER: It seems since we've been
hearing this, everything so far today has
emphasized the fact that this is a local problem
that is being handled locally, that there's no way
that one can leap into the 21st century with Third
World countries. There are just too many levels to
have to go through. And the local aspects, I like
the idea that someone had brought up as the sister
institution situation, which is ongoing in a lot of
our institutions. But could this be encouraged,
that institution to institution on a local level
may be able to be most effective in bringing, say,
a little greater activity, because you can
understand at that level as opposed to working at a
governmental level or a centralized level.
I'm just reflecting anecdotally, if I can
take a minute. One of my hematology fellows went
over to one of the African countries, and I sent
with her colorimeter and also a centrifuge so she
could be able at least to check the hemoglobins on
her patients. I got back a frantic phone call
after about a month or so, and she said, you know,
we don't have much electricity here, and I'm
sitting here with a colorimeter and a centrifuge,
and they're just sitting and I'm not doing
anything, and do you have anything that would work?
And there are a few of us who remember
back in medical school--I see a head nodding over
there--a little thing we called a hemoglobinometer.
And I said, Well, I've got this Sally hemoglobinometer that if you add the blood and add a
drop of hydrochloric acid and boot it up, you can
read it directly from a finger stick. And she
said, That's perfect.
So I sent that over. So in the next three
months she checked everybody in that village, had
all of their hemoglobins and knew exactly what was
going on.
I think it was about $6.95 for that little
hemoglobinometer, and I must have spent about $500
for the colorimeter and another $500 for the
centrifuge.
So it seems to me those are the things
that we're getting at, and there's already--Dr. Lee
had mentioned this--something simple, quick, and
not too expensive. And it doesn't have to be
super-accurate, but it can play such a major role
in a small village or small area that this is the
way we ought to be thinking instead of looking in
terms of the PowerPoints and the rest of it that we
have available to us.
DR. GOMPERTS: Thanks, John.
Yes, Harvey?
DR. KLEIN: I have a question actually
that I'd like to direct toward Jay, because I was
impressed with the fact that they clearly are
leaders in the FDA in standards and reference
materials and panels. And he made the comment that
obviously they couldn't provide these because of
funding, and I appreciate that, and I wonder
whether this might be something that we should be
recommending that there be sufficient funding so
that an agency like the FDA, which is a world
leader in reference standards, might be able to
provide those.
DR. EPSTEIN: Well, we do work with the
WHO to develop standards that are provided
internationally, and in some subset of these
instances, the FDA actually does create the reagent
that is then distributed, though not directly by
us.
What I was suggesting is that our budget
does really not allow us to be primarily a provider
of material support toward development. In other
words, we're not going to be purchasing and
providing, you know, test kits.
But through our work with WHO, we often
are, in fact, a provider of reference reagents.
But I certainly support the idea that such a role
could be expanded.
DR. KLEIN: That was really the question,
whether it should be.
DR. EPSTEIN: I think it brings up another
more general point, which is that one statement we
could potentially make through the department is
that within the available resources, effective
programs in the agencies be enhanced, because we
heard about a number of, I thought, quite effective
programs.
DR. GOMPERTS: Yes, Mike?
DR. BUSCH: Just continuing on that theme,
I think we did hear how a very modest amount of
money can make a big impact in the right context.
The Fogarty programs I think have done--the Hopkins
programs have been wonderful. What we heard from
Eve Lackritz about their studies in Africa have had
a huge impact in terms of what really can be done
and how effective these things are, and the program
that Eve described, the expanded program, in
talking to her afterwards, and they're talking
about something like $5 million over the next
several years, directed toward that expanded blood
safety activity.
Over the last six to 12 months, this
committee has been involved in discussions that
have recommended expanded NAT testing, which is
about close to half a billion a year in this
country alone, leukoreduction, half a billion
dollars a year. You know, a modest increase in the
tens of millions of dollars directed toward
enhanced research and policy development in
international blood safety channeled through CDC,
NIH, FDA could have a huge impact. I think this
committee should come out strongly encouraging
additional resources be directed to that.
DR. GOMPERTS: Yes, thank you.
Karen?
MS. LIPTON: My comment was only on--I've
been thinking about this coordinating function, and
I guess I would rather see a coordinating function
be carried out outside of the Federal Government,
for a number of reasons. I think I've articulated
this to you, Steve, before, and even though I'm a
government employee today, I'm allowed to say
something that--
DR. NIGHTINGALE: You all can say anything
you want. You have a letter to prove it.
MS. LIPTON: I really think that in some
cases, for example, speaking from the AABB
perspective--and we do have a mission, and there
may be times when something that we would want to
do politically would, frankly, not be politically
acceptable to the Federal Government. And I would
rather not see that come into play here, that if we
do do it, there's a coordinating function outside
the Federal Government that the Federal Government
is clearly a party in, but that it doesn't have
that overlay. It just makes more comfortable.
I think we have a long history in this
country of, you know, philanthropic organizations
being able to coordinate, and I would hate to see
that suddenly become a government function.
DR. GOMPERTS: Yes, Ron?
DR. GILCHER: What I heard today was that
there were really four issues. I'm in a sense
getting a little more basic than what has just been
said.
The first issue is an adequate number of
low-risk donors, and I'm going to call that
recruitment as the issue.
The second was testing of all blood donors
worldwide for HIV, HBV, and HCV, and we'll call
that testing.
The third was reducing unnecessary
transfusions, truly make available the limited
resource to those who need. I'll call that
utilization.
And then the fourth one was really
developing standards and guidelines that were
effective at local levels, and I call that
standards.
In a sense, I'm trying to say if we could
look at it that way and then really direct our
recommendations that would focus along those lines.
DR. GOMPERTS: Yes. That's useful. Thank
you.
Other comments?
DR. LOPES: On the recruitment issue, I
was particularly taken by how frequently we heard
it expressed that the way we do it here with lots
of volunteer donors is necessarily what has to be
gotten in these other countries. I think that's
going to be a pretty tough goal to achieve given
some of the cultural differences. And I just
wonder whether or not we would be well served to
think in terms of other models. I mean, even like
our plasma industry here is based on quite a
different model for gaining donors, and yet they
are able to achieve a high level of safety. I
wonder whether or not there are ways to use market
models to get around some of the issues, and here
obviously we've heard it several times that it's a
violation of sensibilities to sell one's tissues.
And yet it might not be a violation to reimburse
people for regularly coming in and being tested
and, in essence, creating a group of people who are
regular safe donors because they're well known. I
just think that trying to quickly get to the point
where these other nations are like us is something
we're not going to see happen.
DR. GOMPERTS: Good point.
Yes, Raj?
MR. DALAL: Two comments. First, one
about recruitment, and the other about testing.
The recruiting of low-risk donors was
discussed quite a lot today, and at one level it's
a promising approach, but it's also potentially
disturbing. It's promising if what was meant was
donor questionnaires, surveillance of repeat
donors, those kinds of things. It would be
disturbing, on the other hand, if the end, which is
the end in showing a safe, non-HIV, HCV, HBV
supply, meant that, for example, in India donor
recruitment was focused on a particular
socioeconomic cut, or if in Uganda it meant you go
to one tribe and not to the other, or in South
Africa, where the problem is self-evident.
So I think everybody has thought about
this, but I'm wondering whether there is something
more that needs to be said about this, particularly
in situations where federal resources are made
available in order to streamline blood testing in
various countries.
The second comment, also, which is fairly
self-evident, is that we've talked about the
developing countries not really as a homogeneous
group. We've said private markets, public markets.
We've talked about Zaire and Kenya and so on. And
then we've talked about the public markets in
China, where the problems are different, and India
and so on.
What became apparent to me was that this
environment that we're trying to make a difference
in can be segmented in several different ways and
that there may be unique solutions to different
segments. For example, the solution in Malawi may
be--and I'm not suggesting this, but just an
example--to have a very top-down, orchestrated,
well-financed, and supported institution where you
parachute in a couple of labs and you've solved the
problem. I'm not suggesting this is appropriate
for Malawi. I'm just using it as an example.
On the other hand, the private--or the
solution to the public market in Chindu or Tianjin
may be an approach that involves close
collaboration with the government and other blood
banks and so on. So all I'm saying is that the
market may be fairly complex, consisting of three,
four, five distinct segments, each of which might
have a generic solution, and I think some work
needs to go into trying to define that.
DR. GOMPERTS: Thank you.
Other comments?
[No response.]
DR. GOMPERTS: You know, what I heard
during the day was a number of things. First of
all, there are a number of activities going on
within the United States that is focused on this
issue, and there are some dollars going into this.
And yet there does not seem to be much coordination
or strategy around that. I think that came across
fairly clear. And that's certainly one thing that
we can focus on from a point of view of
recommendation, and Rich is developing such a
recommendation.
But there were a couple of other issues
that I think we could perhaps address or at least
talk about addressing, and one is the brain drain
issue, and that is the extensive training within
the United States of people who would become
technically competent with the objective of these
individuals returning to their home country, but
they're not returning, or returning and then coming
back to the U.S. at a later stage. So if there are
resources that are going to be provided through our
strategic interactions, it needs to be focused on
local problems as best we can.
Another issue is if they are going to be
problem solving, they need to be locally focused,
and we heard that very clearly from Dr. Lee and Dr.
Professor Alain, as well as others.
There are some pretty innovative ideas
that we heard today. So how we're going to pull
all this together within our own deliberations and
recommendations is up to the ingenuity of this
group.
Jay?
DR. EPSTEIN: I just wanted to add another
thought, which is that I was struck by the
frequency with which research efforts were having
very useful spin-off on national development. And
I wonder if we couldn't capture the idea that we
should encourage the government to foster research
activities that are likely or can be designed to
concurrently aid in development, because it just
seems to be one of the things that works. Just as
I think we also heard the assessment that this
concept of twinning, having, you know, a
partnership arrangement, whether it's institution
to institution or government to government, when
you have these kind of bilateral engagements, it
seems to work. It works at a human level, and then
it seems to work in terms of development outcome.
So, you know, the idea is to capitalize on
these observations by trying to select for them, or
where you see that that might be possible, why,
then, encourage it.
DR. GOMPERTS: Yes. Mike?
DR. BUSCH: I think the point about the
brain drain reminded me, when Ms. McDermott or Dr.
McDermott was speaking earlier, about the Fogarty
program, and I've had some experience with fellows
through the Berkeley program that have all gone
back and, as we heard from Hopkins, Rich, all these
people go back because the program has a
continuity, the people have support for continued
research activities, getting a program going there,
coming back on a regular basis, ongoing
interchange. The whole mission we heard from
Fogarty is exactly what we're looking for here, the
ability to sort of break down, help break down the
barriers in equity between what's here and what's
available in these countries.
You know, as I heard her speaking, I was
wondering, is there a potential that we could
actually create a whole program within Fogarty
focused on transfusion safety, and, you know, that
significant additional funding could be channeled?
That would give you the trainees, the partnership
development that Jay was alluding to very
naturally, expanding that program.
DR. GOMPERTS: Or to focus on the training
of nurse practitioners and laboratory technologists
and blood bank technologists.
Yes?
MR. ALLEN: One of the things that I kind
of--it brought home to me was the fact that even in
my community, there's been an issue regarding
recruitment, and a lot of that revolves around
trust in the medical community and whatever. But
it just strikes me that with any culture or any
different community, what I think we need to be
doing is looking at ways of understanding their
belief system, if you will, and working on a way of
assisting them that is something that they feel is
usable.
I liked the models that Dr. Lipton used
earlier in terms of changing some of the
regulations and whatever the AABB uses in this
country to work with other people, because I think
that's just how it's going to have to be. I know
that's the same issue for us here. What may work
for a blood drive in Chicago for the sickle cell
community may not work in New York or L.A. or
whatever. So, you know, these are issues that hit
us pretty close to home.
So I think anything that we can do to kind
of get a better understanding of what works for
them and what they don't want to do, I think other
than that we're just kind of spinning our wheels
and wasting money.
DR. GOMPERTS: Yes, absolutely. Thank
you.
Yes, Fernando?
DR. GUERRA: A couple of points. I guess
that, you know, having such a safe and effective
vaccine to protect against hepatitis B, I wonder,
you know, whether that would fit into a discussion
in terms of some cost/benefit that maybe could
preclude having to at least in certain select
populations screen for that. That's one question.
And the other thought that occurs to me
is, you know, what are some of the other emerging
threats out there that we have to be prepared for
and that we need to begin to develop the prototype
technologies to be sure that we have in place at
least something that can quickly screen for some of
these other infectious agents that are out there.
Then the other, which I think we heard
quite a bit about today, is certainly the very
limited capacity that exists in some of the more
remote areas of the developing world that has to do
with just such simple things as fridges and
freezers, and how, you know, closely that parallels
the same dilemma that we face with protecting the
cold chain for vaccines and whether or not there
might be some emerging new technology that could
perhaps make it easier to store and to maintain
inventories of some of these products.
I know that with some of the vaccines,
going back to the drawing board and we're able to
come up with products that were perhaps not so
fragile in terms of the cold chain. I don't know
if that's going to be doable with blood and blood
products.
DR. GOMPERTS: Rich, it may be an idea to
get your recommendations in writing, and then we
could start wordsmithing it. I think we do have a
scribe assistant.
DR. NIGHTINGALE: I believe that's the
Director of the Office of Blood Research and Review
from the Food and Drug Administration. Talk about
overqualified.
[Laughter.]
DR. NIGHTINGALE: While our overqualified
scribe is setting up, may I invite once again any
member of the audience who has a thought on the
conversations of the committee to just state--to
make any comment they wish. Dr. Haley?
DR. HALEY: I would like to speak briefly,
if I may.
DR. NIGHTINGALE: Take the microphone
that's just to your right arm.
DR. HALEY: I would like to speak to the
subject of paying blood donors. I have a
colleague, Dr. Dean Elfath (ph), who is from Egypt,
and they had essentially a paid donor program in
Egypt. The dregs of society showed up at the blood
bank. The infection rates were comparable. And it
was something that no self-respecting person would
do, to give blood.
What they did, they asked him over because
he's a very well-respected blood banker in this
country, and he worked with some of the socially
active, responsible people--I think it was the
wives' club of the physicians in the hospital,
which is certainly a typical avenue for these
things to be organized--and organized a volunteer
blood donor program, and the blood donor program
that they organized was all volunteer, was very
celebrated, and they had then a very different
group of society showing up, and they actually
quadrupled the blood supply.
So the thought that, well, sprinkle a
little money and that takes care of it, money
sometimes attracts the folks that you don't want to
attract. So I would offer that as something to
keep in mind.
DR. GOMPERTS: Thank you.
DR. NIGHTINGALE: While the typing
continues, I believe Dr. El-Nageh wished to make a
comment.
DR. EL-NAGEH: I think it would have been
better served by Jean Emmanuel than myself, but
maybe he will help me later on. There was a
suggestion or recommendation why not to have paid
donors who come regularly and we pay them and we
know that they are safe. This is a very dangerous
approach. It is not only from the ethical point of
view. The failure of having a regular, voluntary,
non-paid, community-based donor system is because
we have not invested enough in donor recruitment
and motivation. We spend a lot of money for buying
kits or reagents, and we don't spend enough money
and resources and train people to establish their
community-based donor system.
So one of the recommendations you may
consider is to try to spend on these issues, try to
establish--the people are aware. It is not true
that cultural difference is a barrier. This is not
true. Because when there is a disaster, you see
streams of people in front of the blood bank. They
are coming voluntarily, without being asked, to
give their blood. Why they came? Because the
threshold was so high and they were aware that
their blood is needed.
What is needed is to establish a program
where they feel that their blood is always needed,
not only in disasters or catastrophes. Paid donors
is a very dangerous concept, and having worked in
WHO, I would never endorse it.
DR. GOMPERTS: Thank you.
Paul--yes, Jean-Pierre?
DR. ALAIN: I just wanted to raise an
issue about training which has not been discussed,
really. What has been discussed is people from
developing countries coming to developed countries
for training and the problem of not returning.
That's one thing that has been talked about. The
other thing, which I think can be very productive,
is South-to-South type of training. But what has
not been discussed is a very productive way, which
is people from developed countries going there to
train because it has two advantages: one, when
they go there, they are confronted with the real
situation and see that their standard is totally
inadequate. So they change their mind. And then
they can use their knowledge and background to
adapt what they know to the local situations, when
they know it. But if they don't go there, they
cannot know the local situation.
So I think in the training program sending
people for a significant period of time in
developing countries can be probably the most
productive way of doing it.
DR. GOMPERTS: Thank you.
Paul?
DR. HAAS: It's always helpful for me to
sit through a day like this and have my
ethnocentric roots shaken up a little bit. I'd
like to say intellectually I should not have been
surprised by anything I heard today, but I just
don't dabble in that world.
What it says to me is that in a country
like the United States, we fail to define what we
mean by health, safety, and we've struggled with
those things with this committee. And as much as--how do I say so I don't put my foot in my mouth?
In the sense that we've identified or it has been
identified for us these dramatic needs that are out
there around the rest of the world, and we're
sitting on a nice soft cushion, so to speak, in the
United States.
As we think about what it is that this
committee should recommend and the Federal
Government or all the agencies might get involved
in, I'm a little afraid that if we don't force
ourselves to do a better job than we usually do to
think in terms of priorities that we'll put tons of
things on the table and all those items will be in
a big basket, and each individual one becomes so
diluted that, in effect, nothing gets done.
So I think that we really have to start
trying to figure out how do we go after this
massive problem but go after it in a way with a
little bit of systemization as opposed to saying
we're going to solve the problem today, because we
obviously aren't.
DR. GOMPERTS: Jean?
DR. EMMANUEL: Permission to stop biting
my tongue. Stephen asked me to be well behaved
today, so I've been trying my best.
[Laughter.]
DR. NIGHTINGALE: I hereby retract the
request.
DR. GOMPERTS: But you have been well
behaved.
DR. EMMANUEL: Or at least not as
disruptive as usual.
I want to just say very rapidly,
obviously, absolutely out paying blood donations, I
think we have enough evidence to prove that it can
be done and there's no question about that, and I
won't belabor this issue. Any form of payment in a
developing country where economies are short just
encourages exactly the sort of people you don't
want. So it's not a long-term solution to the
problem.
I think I would support what Jean-Pierre
Alain said about people going to countries. I
think my only difficulty with that is in some cases
the people should do it in a way that's understood
to be approaching it in strategies that are
approved internationally. Otherwise, each person
can go in an idiosyncratic way, meaning well and
doing things in different ways, so that you could
get three or four people in one country saying
exactly different things. I'm not saying that's in
the case of Jean-Pierre Alain, but I'm just saying
that this is an issue that we really need to look
at.
Which all brings us back to this
coordination, and what I've been struck with today
is the enormous amount, as Jay has said, that is
being done in this country. But, again, each time
I heard a story, I could tell another thousand
stories of the same country, whether it's Laos or
Cambodia, about I know four other agencies doing
the same thing, whether it's Japan, the EU, and so
on, but each one hand doesn't know what the other
one's doing, and we do, and it's this sense of
frustration that cries out from inside me to say
can't we get together and just do this in one
concerted effort, even if it's one town in
Cambodia, for instance, where it appears nothing's
been done. There's a very good WHR there, world
health representative, called Bill Pickett (ph),
and he just sees this new revolution of things
happening. And, you know, there's a facility to do
things, and there's this twinning that can go and
take place.
So I really want to say that this
opportunity of the coordination within the United
States of what the United States is doing would be
invaluable to its effort globally, which means it
also provides--that should then provide the link to
access information and coordination with other
agencies that are doing work and have a vast body
of knowledge not only just in blood transfusion but
we've talked about inappropriate use of blood,
surgical procedures, and we have a lot of
collaborators who are doing that in the States and
other areas, World Orthopedic Concern, World
Surgeons, and Surgical Colleges, et cetera.
And so I think putting all that together
into diagnostic imaging, which is also
ultrasonography and X-rays, which prevent
unnecessary operations and transfusion, the whole
thing is a composite picture, and we shouldn't lose
sight of that.
So this coordination that comes from
within the United States can then access the
availability of a large volume of information
that's available outside, to put together a really
comprehensive package. And whether we do it in
piecemeal or organized, it's very important that we
address countries as to what they actually need and
what we can do and make a difference, with the
minimum of resources we have.
Thank you.
DR. GOMPERTS: Karen?
MS. LIPTON: Actually, I was just going to
make a comment about going to the countries, too.
I think it's critically important. You have a
certain view here, but until you've been there and
seen what the situation is, I don't think it's
particularly helpful to do your training here. We
do all our training in the country where we're
working.
I guess the other thing--I'll just save it
for later. Just I agree with what Jean Emmanuel
just said, and just in looking at this resolution,
I wonder, you know, should we not be tying this
somehow to WHO and PAHO priorities that, frankly,
have already been established in this area.
DR. NIGHTINGALE: If I could make a
comment? This is Steve Nightingale for the record.
I sense the very obvious sentiment around the table
in the room and I think in the blood community to
establish some sort of coordinating process for the
activities that are going on in the United States.
And I also sense a little bit of concern, it being
ten minutes of 5:00, that we have only ten minutes
to discover the ideal mechanism for doing so.
I would like to disabuse myself and my
colleagues of that urgency. When I opened the
meeting, I said that this would be the initiation
of a process whereby we would continue a dialogue
among the interested parties, and I see the initial
role of my office as facilitating that dialogue
over the next two months until we have a document
on which there is sufficient consensus that it can
be brought to the top of the department.
This does not negate my previous and
future policy that any formal resolution of the
Advisory Committee must be made here and not
subject to any subsequent wordsmithing. But I
think this isn't a case where we don't have an
exception when we have initiated a process, and
that, in fact, was exactly what I wanted to do when
I went to Dr. Satcher and asked for permission to
hold this meeting.
DR. GOMPERTS: One last comment, and then
we'll need to debate the propositions.
MR. DODD: Thank you very much. Roger
Dodd. This time I'll make my commercial plea,
largely in support of what Jean just said. And I
would ask that any resolution dealing with
coordination bring into it some thought about two-way coordination; in other words, we need input
from outside. And I would remind you that there
was a lot of discussion about the Global
Collaboration on Blood Safety, and I think this is
a potential mechanism for channeling at least some
of this two-way traffic, perhaps a connection point
for whatever coordination mechanism is undertaken.
And I say this advisedly because I'm currently the
Chair of that body and would like to hear from you.
DR. GOMPERTS: Thank you.
Okay. For the committee, we have two
recommendations up there for discussion,
wordsmithing, and ultimately voting on. How much
more do you have there?
DR. NIGHTINGALE: Not much.
DR. GOMPERTS: Yes?
DR. EPSTEIN: Well, I would suggest that
in point one, where we say specifically the
committee encourages DHHS to foster research and
training activities, it would be good to add also
standard-setting activities. So research training
and standard setting.
DR. NIGHTINGALE: Before we go much
further, could I ask the scribe to make sure that
the save button has been pushed?
[Laughter.]
DR. GOMPERTS: Okay. I would make a
suggestion as well. Right at the top, that very
first sentence, the committee recognizes the
importance of international issues in blood safety
and availability and its importance to the public
health in the United States, I think we need to
link it.
Mike, do you have a comment?
DR. BUSCH: Yes, I was going to suggest an
addition in the last sentence in number one, adding
something about development of appropriate
technologies. I think we heard that NIH has funded
some of Helen Lee's work and that kind of funding
from NHLBI perhaps to develop assay kits and other
technologies, including inactivation methods, et
cetera, that are really intended and designed for
the international application.
DR. EPSTEIN: Yes, I would say development
and transfer of appropriate technologies for the
developing world.
DR. GOMPERTS: Let's just finish this one.
Ron?
DR. GILCHER: In sentence two: As such,
the committee endorses the present activities of
government agencies in this area and supports the
enhancement of these activities through recruitment
and testing. I want to get recruitment and testing
in there specifically.
DR. GOMPERTS: Just one second. Rich is
busy scribing.
[Pause.]
DR. GOMPERTS: Minor wordsmithing will
deal with it. Rich, Ron has a change.
DR. GILCHER: In fact, I now want to add
another word.
[Laughter.]
DR. GOMPERTS: That's technically
challenging.
DR. GILCHER: Going back to what I said
originally, I said there were four issue, and, in
fact, a fifth issue was raised, which was training.
I wanted to get at the end of the second sentence,
where it said enhancement of these activities, and
the three issues that I wanted in there were
recruitment, testing, and utilization, because they
really support the blood safety and availability,
but it spells it out, I think.
DR. NIGHTINGALE: Recruitment, testing
and--
DR. GILCHER: Utilization.
DR. GOMPERTS: How about: and supports
the enhancement of recruitment, testing, and--
DR. GILCHER: Utilization.
DR. GOMPERTS: And utilization activities.
Okay? Recruitment, testing. And recruitment--sorry, utilization activities.
Any other comments?
DR. KUHN: Too many appropriate's.
DR. GOMPERTS: There are a lot of
appropriate's, I think.
DR. NIGHTINGALE: I've already deleted
one.
DR. GOMPERTS: Okay. Are we ready to vote
on these?
DR. EPSTEIN: I think we've muddied the
second sentence.
DR. GOMPERTS: Okay.
DR. EPSTEIN: I think we had a cleaner
sentence when we said that the committee endorses
the present activities and supports their
enhancement. It should just be period, and then
reference to activities related to recruitment,
testing, and utilization should be one of the
specific points. Perhaps we can make bullets out
of the specific points.
DR. NIGHTINGALE: Actually, we may--I am
seconding Dr. Epstein's proposal here because what
I'm going to do with this in the letter that Dr.
Gomperts will send to the Secretary, this is going
to be bolded. And I've been advised by the
Secretary's staff to keep it simple. So I think
that Jay, once again, hit the nail on the head that
we're right where we need to be right now, but I
can assure Dr. Gilcher that the points that he's
raised are going to be incorporated.
DR. GILCHER: In fact, I concur with that,
but what I want to add here is that it's really
five bullet points then that we want to be sure
that we address.
DR. NIGHTINGALE: Those will definitely be
incorporated into the final work product of this
meeting.
DR. GOMPERTS: Mike?
DR. BUSCH: Is there any value to getting
a little more specific with respect to enhancement
of these activities, not in any detailed context,
but in the sense of additional financial resources,
a general statement like enhancement, adequate,
earmarking funds towards international blood
safety.
DR. NIGHTINGALE: What I'm looking--I can
put that into the white space, the unbolded part of
the letter or part of the supporting documents.
This is optimal length right now for my purposes,
if it is acceptable to the committee.
DR. GOMPERTS: Any further discussion?
Yes, Larry?
DR. NIGHTINGALE: Larry, were you moving
this?
MR. ALLEN: Yes.
DR. GOMPERTS: Okay.
DR. NIGHTINGALE: Is there a second?
DR. KUHN: Second.
DR. GOMPERTS: All those in favor of the
first recommendation?
[A show of hands.]
DR. GOMPERTS: Good. Any abstentions--
DR. NIGHTINGALE: Excuse me. For the
record, none were opposed and none abstained,
except for the chairman, who only votes to break a
tie.
DR. GOMPERTS: Good. The proposal for the
second recommendation.
DR. KUHN: In that recommendation, for the
committee to support the establishment of a
coordinating committee, my concern is that we're
establishing another committee. Is it not a fact
that we already have an entity or entities already
in existence, such as WHO, PAHO, and the ICBS, that
we could somehow endorse the programs and what they
are doing already to kind of address this issue
right here or this recommendation?
DR. NIGHTINGALE: May I make a suggestion
to the wording? That suggestion would be that the
committee supports the establishment or appointment
of a coordinating agency--
DR. PENNER: How about identification?
DR. KLEIN: Wouldn't it be better to
develop a mechanism rather than say an agency,
office, committee, whatever?
DR. GOMPERTS: That's a good point. A
mechanism.
DR. NIGHTINGALE: Of a coordinating
mechanism.
DR. DAVEY: Or similar body.
DR. NIGHTINGALE: Coordinating mechanism
seems to have a lot of support.
DR. PENNER: And it should be a mechanism
to coordinate. You can't get coordinating
mechanisms.
[Pause.]
MS. LIPTON: How about just supports the
establishment of a mechanism to coordinate the
exchange of information. That makes it--get rid of
the rest--
DR. NIGHTINGALE: Karen's got it.
MS. LIPTON: The committee supports the
establishment of a mechanism to coordinate the
exchange of information, activities, and creation
or establishment of priorities--I can't read,
unfortunately, even in 14 type up there.
DR. EPSTEIN: Well, perhaps it should be a
mechanism to establish priorities and coordinate--I'm suggesting perhaps the sentence were expressed
if it's the establishment of a mechanism to
establish priorities and coordinate the exchange of
information and activities.
MS. LIPTON: That's good.
DR. PENNER: How about identify
priorities? You can remove most of that. Then
activities and determination of priorities. Just
exchange of information among government, yeah, and
appropriate government agencies.
DR. GOMPERTS: Yes, but there does need to
be coordination of activities.
DR. PENNER: Well, you're going to say
coordinate the exchange of information and
activities, just the way--
DR. GOMPERTS: Okay.
DR. BUSCH: Is there any role in this
statement for some effort to monitor the impact of
the program over time? It's difficult, obviously,
but part of this process would be, you know,
evaluating whether there's been an impact of all
this effort in this committee.
DR. GOMPERTS: How about the final
sentence: This coordination should include
appropriate linkages with international
organizations and ongoing monitoring of overall
activities should be ongoing.
DR. GILCHER: How about this coordinated
effort should include appropriate...
DR. BUSCH: Maybe of these activities and
global blood safety and availability, because in a
sense, that brings it back to the U.S. I mean, in
a sense, our mandate is to make sure that the--
DR. GOMPERTS: Okay.
DR. KLEIN: Perhaps at the end of the
first sentence you might to just put in the United
States.
DR. GOMPERTS: Yes.
DR. NIGHTINGALE: Again, since the
sentence is getting a little long and the meaning
is, I think, pretty clear, the last six words after
issues could be cut, I think, that the meaning of
the resolution is pretty clear. Just put the
period after these issues.
DR. GUERRA: I would suggest maybe a third
paragraph there that would pick up the public
health surveillance of those conditions of
interest. That's why we're doing it, to try to
reduce--it's beyond monitoring the activities and
issues, and I think there has to be a way to
maintain better surveillance of those conditions.
DR. GOMPERTS: Do you want to recommend
some verbiage?
DR. GUERRA: Well, I don't know if it
would fit in two or just as a separate paragraph,
but I don't know--
DR. NIGHTINGALE: Fernando, if it's
already in there, I'm still groping with the
appropriate style to deal with the new
administration. But I have been repeatedly advised
in my not terribly fashionable bureaucratic efforts
to keep it brief, and I find that very difficult to
do.
I think we've got the ideas in here. I'm
trying--what I'm advising the committee is
something of this length and not more will have a
maximum impact on the Secretary. And if we don't
need to get any longer than this, I suggest we
don't at this point.
DR. GOMPERTS: Are you okay with that?
DR. GUERRA: I just think somewhere we
need to include the notion of surveillance.
DR. NIGHTINGALE: Absolutely. The reason
why we have a transcript and we have a summary of
our transcript is to include--is to ensure that
ideas that don't fit conveniently into four
sentences in two paragraphs get included in the
broader description of the issue, and the
surveillance is very obviously a key factor not
only in what we're doing, but what you've described
this morning that CDC is doing with its broader
programs.
DR. GOMPERTS: Okay. Ron?
DR. GILCHER: Again, second sentence, take
out the word coordination. It doesn't modify
correctly with what's in the prior sentence, and
say: This effort should include appropriate
linkages.
DR. GOMPERTS: Okay. Are we ready to
vote? A proposal?
DR. PENNER: So moved.
Dr. GUERRA: Second.
DR. GOMPERTS: Fernando. Okay. Those in
favor of the recommendation?
[A show of hands.]
DR. GOMPERTS: Any against? Abstentions?
Great.
DR. NIGHTINGALE: May the record show that
the vote--it was a unanimous vote for, there were
not votes against, there were no abstentions,
except for the Chair, but that's only to break a
tie.
DR. GOMPERTS: Good. We're now done for
the day, and we'll reconvene tomorrow morning at
8:00 a.m. Thank you.
[Whereupon, at 5:10 p.m., the meeting was
adjourned, to reconvene at 8:00 a.m., Friday, April
20, 2001.]