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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

PARTICIPANTS

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

CONTENTS

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

PROCEEDINGS

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.]

 

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.]