Blood Safety TranscriptsDEPARTMENT OF HEALTH AND HUMAN SERVICES
ADVISORY COMMITTEE ON BLOOD SAFETY AND AVAILABILITY Fourteenth Meeting WHAT IF ANY ADDITIONAL ACTIONS SHOULD THE
DEPARTMENT TAKE TO PROMOTE BLOOD SAFETY AND
AVAILABILITY THROUGHOUT THE WORLD? Volume I 8:13 a.m. Thursday, April 19, 2001 Hyatt Regency Capitol Hill Hotel 400 New Jersey Avenue, N.W. Washington, D.C. 20001 P A R T I C I P A N T S Larry Allen
Michael P. Busch, M.D., Ph.D.
Rajen K. Dalal
Richard J. Davey, M.D.
Jay Epstein, M.D.
G. Michael Fitzpatrick
Ronald Gilcher, M.D.
Edward D. Gomperts, M.D.
Fernando Guerra, M.D.
Paul F. Haas, Ph.D.
William Hoots, M.D.
Harvey Klein, M.D.
John Kuhn, M.D.
Karen Shoos Lipton, J.D.
Lola Lopes, Ph.D
Gargi Pahuja
John Penner, M.D.
John Walsh
Jerry Winkelstein, M.D.
Lawrence McMurtry
Stephen D. Nightingale, M.D.
Mary E. Chamberland, M.D.
David Snyder, Rph, D.D.S.
Virginia Wannamaker C O N T E N T S AGENDA ITEM Welcome, Roll Call, Conflict of Interest Disclosures, Statement of Issue Stephen D. Nightingale, M.D. Executive Secretary, Advisory Committee on Blood Safety and Availability; Global Strategies for Improving Blood Safety Jean Emmanuel, M.D., Director, Department of Blood Safety and Clinical Technology, World Health Organization Blood Safety and Availability Initiatives in the Americas Jose Ramiro Cruz, Cc.D. Pan American Health Organization The International Consortium for Blood Safety Mohamed El-Nageh, M.D. International Consortium for Blood Safety CDC International Activities Related to Blood Safety Eve Lackritz, M.D. Centers for Disease Control FDA International Activities Related to Blood Safety Jay Epstein, M.D. Food and Drug Administration NIH International Activities Related to Blood Safety Jeanne McDermott, Ph.D. National Institutes of Health/Fogarty International Center ABC International Activities Related to Blood Safety Celso Bianco, M.D. America's Blood Centers AABB International Activities Related to Blood Safety Karen Lipton, J.D. American Association of Blood Banks American Red Cross International Activities Related to Blood Safety Jan Lane American Red Cross Academic Medical Center International Activities Related to Blood Safety Christopher Beyrer, M.D. Johns Hopkins University Plasma Industry International Activities Related to Blood Safety Barbee Whitaker, Ph.D. American Blood Resources Association Promotion of Appropriate Technology Transfer: Tests for Transmissible Agents Helen Lee, M.D. Cambridge University Promotion of Appropriate Technology Transfer: Perspective from a Developing Country Jean-Pierre Alain, M.D. Cambridge University Providing Access to Screening Technologies Rajen Dalal, MBA Chiron Corporation Public Comment Committee Discussion and Recommendations P R O C E E D I N G S DR. NIGHTINGALE: Good morning. My name is Stephen Nightingale. This is the Fourteenth Meeting of the Advisory Committee on Blood Safety and Availability. I would like to begin by calling the roll, if I could. I know that a couple of the members are in transit. Mr. Allen is in transit. Dr. Busch? DR. BUSCH: Here. DR. NIGHTINGALE: Dr. Caplan is, I believe, unable to make the meeting today. Dr. Chamberland? DR. CHAMBERLAND: Here. DR. NIGHTINGALE: Mr. Dalal? MR. DALAL: Here. DR. NIGHTINGALE: Dr. Davey? DR. DAVEY: Here. DR. NIGHTINGALE: Dr. Epstein? DR. EPSTEIN: Here. DR. NIGHTINGALE: Captain Fitzgerald [sic], Captain Mike, is in transit. Dr. Gilcher? DR. GILCHER: Here. DR. NIGHTINGALE: Dr. Gomperts? DR. GOMPERTS: Here. DR. NIGHTINGALE: Dr. Goosby is in Africa and unable to make it today. Dr. Guerra? DR. GUERRA: Here. DR. NIGHTINGALE: Dr. Haas? DR. HAAS: Here. DR. NIGHTINGALE: Dr. Hoots? DR. HOOTS: Here. DR. NIGHTINGALE: And a new member, Dr. Harvey Klein. Do not be misled by his nameplate, which he has turned around. We apologize for that. Dr. Harvey Klein is the new representative to the Advisory Committee because Dr. Paul McCurdy has, once again, retired. [Laughter.] DR. NIGHTINGALE: Dr. McCurdy, however, is in the audience because Dr. McCurdy is serving now as a consultant to the Department of Health and Human Services, and I am delighted not only to welcome Dr. McCurdy and appreciate his willingness to continue to serve the government, but to give me another opportunity to thank him for his service. It is said by many a minister that you're always preaching to somebody else's crowd. That is me. You are--I inherited Dr. McCurdy's church, if you will, and it's been an honor and a privilege to inherit that. What you've seen in the last few meetings is what Dr. McCurdy started. Paul, thank you very much. [Applause.] DR. NIGHTINGALE: And, Harvey, welcome, and thank you very much for being here. Dr. Kuhn? DR. KUHN: Here. DR. NIGHTINGALE: Ms. Lipton? MS. LIPTON: Present. DR. NIGHTINGALE: Dr. Lopes? DR. LOPES: Present. DR. NIGHTINGALE: Ms. Pahuja? MS. PAHUJA: Here. DR. NIGHTINGALE: Dr. Penner? DR. PENNER: Here. DR. NIGHTINGALE: Dr. Piliavin is teaching this semester and is unable to attend. Captain Snyder is in transit. Mr. Walsh? MR. WALSH: Here. DR. NIGHTINGALE: Dr. Winkelstein? DR. WINKELSTEIN: Here. DR. NIGHTINGALE: Thank you. I would also like to announce that joining the staff of the committee for a 6-month detail is Ms. Virginia Wannamaker of the Health Care Financing Administration. Ginnie, if you are in the room, could you identify yourself. That's Ms. Wannamaker. And Captain and Dr. Barbara Silverman, who is not here this morning, but will be here this afternoon, and will be working with the committee half-time to help us flesh out what we accomplish tomorrow in our discussion of how to monitor the blood supply. This moves me, as quickly as I'm able to move, to the Conflict of Interest Statement, and I noted with some relief that neither Dr. Caplan nor Dr. Satcher are looking over my shoulder as I read this, so not being under that pressure, you are all seated comfortable, and I will do it as quickly as I can. The following announcement is made as part of the public record to preclude even the appearance of a conflict of interest at this meeting: General applicability has been approved for all committee members. This means that unless a particular matter is brought before this committee that deals with a specific product or firm, it has been determined that all interests reported by the Advisory Committee members present no potential conflict of interest when evaluated against the agenda. In particular, as specified in Title 18 of the United States Code 208(b)(2), a special government employee, which all committee members are, may participate in a matter of general applicability; for example, advising the government about its policies relating to the Hepatitis C epidemic, even if they are presently employed or have the prospect of being employed by an entity, including themselves if they are self-employed, that might be affected by a decision of the committee, provided--and this is the key point--that the matter will not have a special or distinct effect on the employee or the employer other than as a member of a class. The example given at 5 CFR 2640.203, which implements the U.S. Code is as follows: A chemist employed by a major pharmaceutical company has been appointed to serve on an Advisory Committee established to develop recommendations for new standards for AIDS vaccine trials involving human subjects. Even though the chemist's employer is in the process of developing an experimental AIDS vaccine and therefore will be affected by the new standards, the chemist may participate in formulating the Advisory Committee's recommendations. The chemist's employer will be affected by the new standards, but only as a part of a class of all pharmaceutical companies and other research entities that are attempting to develop an AIDS vaccine. In the event the discussions involve a specific product or a specific firm for which the member has a financial interest, that member should exclude him- or herself from the committee discussion, and that exclusion will be noted in the public record. With respect to the other meeting participants, we ask, in the interest of fairness, that they disclose any current or previous financial arrangements with any specific product or specific firm on which they plan to comment. I will note, also, for the record that each voting member of the Advisory Committee has, in a packet before them, a specific waiver for the purpose of participating in the meeting under the terms that I just described. When the committee was established, it had been considered that the appointment by the Secretary herself constituted that waiver. With changes of administration, rules undergo review, as do former policies and actions, and the waiver is an additional measure I think of protection for the committee. It confers no new rights. It does not require your signature. We, perhaps, have completed the piece of paperwork, which I would be glad to discuss with any member of the committee if they do, but the bottom line is your rights, your responsibilities, and your protection, which is really the bottom line here, are unchanged by that. The title of today's meeting is what, if any, additional action should the Department take to promote blood safety and availability throughout the world? I would simply say here that the title speaks for itself. There was a lot going on in this area, and there is obviously a lot left to do. What I have tried to do in the confines of a day meeting is to invite a representative section of individuals who are involved in this effort, both in the government, out of the government, in nonorganizations, both in the states and abroad, and individuals, and open the microphone for everyone who wishes to comment. I realize that this is not inclusive of everyone. The Department remains interested in the input of those who are involved in this effort and are not capable of being here today. The process that will follow this meeting is that the input that we obtain through this meeting from the committee members and from any recommendations they may make, from the comments from the floor and from the comments from other interested parties, will be put into the form of a draft document that will then be circulated throughout the public health service for its review. Following that, once the clearance or assent to the document is completed, that document will be forwarded to the secretary for whatever necessary or appropriate action is taken. That is, in fact, the policy that we follow for all topics that are discussed by the Advisory Committee, and that will be the process that we will follow for following up on the discussions that take place tomorrow. The prior recommendations of the committee at its January meeting are still under review by the new administration, and I will report back to the committee members and the public at-large, as soon as that consideration by the Department has been completed. I wish to announce, for the record, at this point, that we will have six vacancies occurring on the Advisory Committee at the completion of its term on September 30th, their terms on September 30th of 2001. There will be a formal announcement in the Federal Register, on or about June the 1st, as a solicitation of nominations. We have received many nominations in response to our solicitation last year. As I announced previously, all of those nominations remain current. It is not necessary for anyone who has been nominated before or nominated themselves to do so again. What I do wish to make part of the public record is we continue to solicit nominations, including self-nominations, from all interested parties to this committee. I think we are close to the end of the announcements. There are only two more. One of them has to do with cell phones, such as these. We have, in the past, met in the basement. This has not been entirely accidental because in the basement, as many of you found out, the cell phones don't work. Up here, they do work. For those of you who have vibrate on yours, as do I, would you please turn it to vibrate, and if you can't do that, if you would keep the rings to a minimum, I would appreciate. Finally, I really do want to thank specifically everyone for being here. This is an important topic. It's also a busy time of the year, and I realize the sacrifices that people have made to come here. One of those who could not make those sacrifices is Dr. Caplan. Dr. Gomperts will chair the meeting in his absence. Dr. Gomperts? DR. GOMPERTS: [Presiding.] Thank you, Dr. Nightingale, for getting us going and getting us rolling this morning. It's a busy session the first part of the day. Our first presenter is Dr. Jean Emmanuel, M.D., director, Department of Blood Safety and Clinical Technology, World Health Organization. Dr. Emmanuel? DR. EMMANUEL: Thank you very much, Mr. Chairman, Dr. Nightingale, and members of the committee for inviting me and for, once again, allowing me to come back to Washington. The presentation I'm making today, which I hope I will be able to make, is on this new technology, and I'm not sure who's working it. I'm certainly doing it by remote control. It looks as if it's in front of Jay. It's always dangerous being the first speaker anyway. While the technology is catching up with old-fashioned-- DR. NIGHTINGALE: Excuse me, Dr. Emmanuel, we will have a little slack. What happened was the computer that we had intended to use, the small black box over there, has crashed. We try to keep these things on time as much as possible. There are acts beyond our control that happen, and this is one of them. You came a long way, and we want to hear what you have to say so we're willing to wait. DR. EMMANUEL: Perhaps I can just speak about WHO a little bit prior to the slides. Many of you have heard a lot of what I'm going to speak about. But for those of you who don't know, WHO is the World Health Organization responsible for health for 191 member states. That's almost every country in the world, with very few exceptions. And as such, as this responsibility and all issues of health, the Ministers of Health meet, in WHO, once a year in May. There is an Executive Board that meets to prepare for that meeting in May in the January, and proposals are put forward as resolutions, and the resolutions are passed by the members, and they become World Health Resolutions, which are endorsed and are enforceable by the member states. You'll be hearing from my colleague in PAHO. WHO has headquarters in Geneva, Switzerland, and six regional offices. The regional office for the Pan American Health Organization and the American regional office for the World Health Organization is based here in Washington. We have another regional office, AFRO, in Harare in Zimbabwe. We have an office in the Eastern Mediterranean in Cairo. We have an office for Euro in Copenhagen. Delhi is the Southeast Asia office, and the Western Pacific Regional Office is in Manilla. The six offices work together with WHO in concert, and at each country level there is a representative of WHO in the 191 member states. So, together, this forms a considerable body of people working towards the safety and improvement of health at national level. Now, when we look at--I hope this is all visible for everybody--when we look at the issues on blood safety, what I hope to address today is addressing the problem, the themes and objectives of the Blood Safety and Clinical Technology Unit at WHO, defining what we consider to be safe blood or the minimum criteria for safe blood, the strategies that are being developed in the production of safe blood and availability, the Blood Transfusion Safety, our activities, and our aide memoir, which encapsulates the essence of our four main strategies, with an overall quality issue. Thank you. Now, the work of WHO is in the area of global blood safety, as well as, as I mentioned before, at the country level because it's at the country level that we have the impact and the concerns for national health authorities. So what is the problem? When we look at the human development index as a criteria for defining countries, the United Nations Development Program Human Development Index classifies countries as having a low, medium or high HDI, and the classification is based on the following criteria: life expectancy, educational attainment and adjusted income. Using that as a basis for our global database on gathering information for blood safety, you can see that in the developed countries or the high HDI that 60 percent of the blood supply is used in the high HDI and 38 percent in the medium HDI countries. Whereas, the poorest countries, and most of the developing countries only have 2 percent of that blood supply. Now, if you look at the global population and the global blood supply, what it means here is that you've got population on this bar and the blood supply on this bar. And in the developing world, you can see that the blood supply is far less than that in the developed world, although the population is much higher in the developing countries. Looking at it another way, if you've got 83 percent of the population, the high development HDI countries are here, but 83 percent of the population are in the low development and in the medium development HDIs. All of this information I can make available to you in hard copy for those of you who wish to have this. But when we look at the types of donation, and we all recognize that other than voluntary, nonremunerated blood donation, there is a high risk in, first of all, the paid donors clearly, and secondly the family replacement donors which tend to be paid donors in many countries. Now, if you look at the developing world, you can see that they have 8 percent paid donors, which are extremely risky, and 61 percent of their blood donors come from so-called family replacement which, in essence, are a large paid donor population, a hidden paid donor population. These figures look as if they are family replacement simply because no one is seen to be paying them. This is done as an internal agreement between families with the paid donors, and only 31 percent are the safer donors, as opposed to the developed world, where 98 percent come from voluntary, nonremunerated donors. If we look at the global burden of disease, we look at approximately $600 million people who are infected with HIV, hepatitis B virus and hepatitis C virus. Five percent to ten percent of infections of HIV are caused through unsafe blood transfusions. So viral screening of whole blood donations, if we look in the developed world, we can see that there's 100-percent testing. If we look at the developing world, the low and medium HDI, only 57 percent are tested and 43 percent are untested, which accounts for some 30 million donations of blood that are transfused and are untested. The sero prevalence amongst blood donors in the developed world is very low. When you look at the least-developed countries, it is in the area of 13 percent, on average. However, we know that in countries in sub-Saharan Africa, that figure can rise to 25 to 45 percent HIV positive. That's nearly half of the population that is HIV positive because the population that's donating blood comes from the sexually active group. Hepatitis B, up to 32 percent, and HCV, 18 percent, again, on average, and in some countries much higher. And when you remember that in a previous life 43 percent of the blood in those countries are not tested. Now, when we're looking at our HCV panel, we're looking at evaluating one of our biggest drives at the moment is to bring the price of HCV test reagents down so that they are available for countries. On HIV, we've had a system of evaluating test kits and bulk purchasing with the understanding of manufacturers and brought the price of HIV test kits down, ELISA, to less than 75 U.S. cents, and for simple rapid from between 1.2 U.S. dollars to 1.8 U.S. dollars. We are looking at the issue of simple rapid tests for HBV and HCV. And so what we have here on our HCV panel, specimen panel, is positives and negatives from the different regional serotypes, giving us a total of 257 specimen panels. And when we look at the evaluation of HCV, we use the Ortho test, 3.0, as our standard test, and the sensitivity and specificity of the different available test kits that we've evaluated are shown on this slide. And basically the sensitivity and specificity worked between 97.1 sensitivity up to 100 percent. Again, showing this, on our reference assay, using the Ortho as our standard test. Again, we are concerned about HIV, hepatitis B, C, Chagas, where it's appropriate, and syphilis testing. But, again, we recognize the immunohematology and that there is a lack of standardization, documentation, and traceability. There is a lack of evidence, not a lack of evidence, but a lack of information on how many incompatible blood transfusions are actually given wrong blood to the wrong patient at the wrong time, and we are aware that there are many fatalities as a result of this problem. So one of our other drives is to ensure that attention is focused not only on infectivity, but also on the importance of the correct blood group and the compatibility of the blood. ABO compatibility is a major cause of mortality in developing countries, apart from the fact that there is no blood available when it's needed. And remember that the major requirement for blood in developing countries is as a consequence of pregnancy in women, children as a result of malaria, malnutrition and trauma. Those are the big three in that order. Of the 250,000 women who die as a consequence of pregnancy, nearly one-half of those are as a result of blood loss and availability of blood, not counting those who are infected with blood that is not tested. So access. When we look at this and the figures that I've told you about previously, 17 percent of the global population has access to 60 percent of the global blood supply. This isn't a safe blood supply. Eighty percent of the global population has access to only 20 percent of the blood supply that is safe and is tested. So the vast majority of the world has got the least availability to blood. The organization themes of the Blood Safety and Clinical Technology Unit then therefore addresses not only the issue of blood safety, but the whole area of clinical technology. And very briefly, this is the cluster within which my Department, which is Blood Safety and Clinical Technology in the Center, we have the essential drugs and medicines, and we have the vaccines and biologicals on the right. We work very closely within the cluster in a variety of ways--for waste disposal, safety of injections, diagnostic imaging, radiology, and laboratory and clinical technology, district surgical services, essential surgery at the district hospital or first-referral hospital to ensure that blood is only used when it's required and that procedures are carried out in a proper and controlled way and that patients are referred, when they need to be referred, to the next level. We also work very closely with the Essential Drugs and Medicines on the supply of essential drugs for minimizing blood loss, making sure there's availability of plasma and plasma derivatives, and crystalloids, and colloids, and other drugs. Within the Department, we also have the quality and safety of plasma derivatives, the norms and standards. Kathy Zoon is the present chairman of the Expert Committee on Biological Standards, and many of the people who are here today at present have been involved in the work of the Department in various aspects. So our mission is to promote the safety, quality, and adequacy of blood and blood products, injections, diagnostic and clinical technologies, and medical devices. The medical devices include things like an oxygen concentrator for use in developing countries where oxygen is not available, the use of and production of a simple hemoglobin screening tool, which is now available, and will cost 2 U.S. cents per test to screen for anemia, and so on. Our four main objectives, then, within the Department are to ensure policy. As I told you earlier, WHO is responsible to 191 member states and the health authorities. We have an enormous responsibility to ensure that policy issues and policy makers make the right decisions, and we assist them in carrying out the resolutions that they have adopted. We ensure the quality, and we help them to ensure the quality and safety. Access, we talked about the bulk purchasing, and we try and promote the proper use. To give you an example of use, for instance, we have just published the clinical use of blood which is going to be we had the first workshop in India, which is a tool for self-learning for medical practitioners or prescribers of blood with a pocket handbook that they can carry around with them. We also have a distance learning program for laboratories and people working in laboratories, and we have workshops on trying to promote the proper usage not only of blood, but the proper clinical application of its products. So, when we look at blood safety as a priority, we cut across blood transfusion safety with policy, ensuring that we promote voluntary nonremunerated blood donation from low-risk population groups, ensure that they are counseled and tested. We have all of the testing processes that I've talked about, evaluation of HIV test kits, bulk purchasing, the processing of blood, which is components. We evaluate fridges and freezers and put them into public information sheets so that countries can identify which fridges meet the criteria for blood usage and the clinical use of blood. In diagnostic technology, we are the organization responsible for global norms and standards--hemoglobin norms, biological standards, and so on, and reference preparations, diagnostic imaging and laboratory services, and under technologies, we have district surgical services, waste management injections, and medical devices. Now, when you look at this, it, unfortunately, hasn't all come out, but if you look at our department, which is BCT, Blood Safety and Clinical Technology, we can only work with the assistance of our collaborating partners. The most important of our collaborating partners are the regional laboratory advisers, and Dr. Cruz will be speaking after me on the activities they do at the regional level, and through them a country level. Now, clearly, without the regions the work of headquarters would not be possible. And the regional advisers represent the requirements and issues that they have become clearly identified with at a country level. Again, at country level there's a World Health representative that represents the countries and relays the information back to the regional office and headquarters. Our collaborating centers are very important, as are our nongovernmental organizations. We hope to get the American Association of Blood Banks as an official NGO, nongovernmental organization, in official relations with WHO to help and share in its work and its accreditation. We have our resource mobilization, where we raise money from different countries to do the work that we have to carry out, in addition to our regular budget. We have other UN aids and other UN agencies such as UNICEF and so on producing materials and evaluating test kits and so on for them, and we have our global collaboration for blood safety with our partners, including the International Federation of Red Cross and Red Crescent Societies, the International Society of Blood Transfusion, World Federation of Hemophilia, ABB and others. And we work within our own clusters within WHO, such as the communicable diseases and so on. So what is safe blood then? So we consider that blood is safe with transfusion when it is donated by a healthy donor at low risk of transmitting infection or harmful agents. The blood is processed by the most effective testing methods, and it is transfused only when needed to prevent death or serious complications. One of our major strategies now is to educate the prescribers of blood into thinking about when is a transfusion required and when is it not required. In other words, this old adage of when if you only need one unit of blood you don't need to give blood at all I think needs to be relooked. If you've got a patient at 7 grams of hemoglobin, and they will decompensate with one unit of whole blood or packed cells will raise that hemoglobin to 8.5, and they can go home with IM and folic acid, then you've minimized the risks. To look at the situation of whether you need to be producing components or you can give whole blood, in countries that I've shown you with high infection prevalence, is it sensible to give packed cells and then plasma from another unit, doubling the risk and so on. So we are hoping that through that we will get doctors educated or prescribers of blood into thinking about what they are actually doing, as well as surgical procedures, where simple cryostats and so on can prevent bleeding and prevent the requirement for blood, as well as educating the public health authorities into preventing malaria, infections from hook worm and providing good antenatal care can prevent the use of blood. So government commitment and support is one of our major strategies, and we talked about four strategies, and this is the first strategy here, where there is a World Health resolution of 1975, World Health resolution 28.72, where governments agreed to the formation of national blood transfusion services based on voluntary and nonremunerated blood donation. We need to provide them with the framework for national blood programs so they can implement this legal framework requiring that nonprofit organizations run the blood transfusion services on a nonprofit basis, the implementation of a policy and plan for that blood transfusion service to ensure that the right blood gets to the right patient at the right time, and that they provide an adequate budget for that process. And to that end, we've also produced some materials and books on costing of blood transfusion services with an Excel file that allows them to add up all of the costs in blood transfusion and to provide a comprehensive budget for the government to be able to support those services and make them sustainable. The second strategy is to promote and retain voluntary blood donations from altruistic donors that are nonremunerated and from low-risk populations, to care for those donors, and to provide them with counseling and follow-up and ensure that they are regular repeat donors. To give you an example of this, in sub-Saharan Africa, a Club 25, Pledge 25 system was developed amongst school children from 16 until school leaving age, which is 18 or 19, to pledge to give 25 donations of blood within their lifetime. They were counseled and educated. And from a population group of 25-percent HIV positive, those blood donors are less than .2 percent, 0.2 percent. It's an incredible decrease in the prevalence. And in amongst their peers who don't give blood, that prevalence of HIV has had a major impact on reducing the prevalence of infection in their own peer group, and they will go out into the population, and they have remained steadfast donors of the Blood Transfusion Service after school. The third strategy then is to test all donated blood using the most appropriate and effective methodologies for infectious agents, blood grouping compatibility testing and quality issues and ensure the good manufacturing practices for blood components, as and when required. And the fourth one is the reduction of unnecessary transfusions through effective clinical use of blood. You can only do that if you have the product available to ensure that doctors get the blood when they're required, don't order it on the basis of maybe I'll need it, and promoting especially the use of simple alternatives to transfusion. Too many countries are using plasma as a volume expander instead of crystalloids and colloids. This is more of a logistical issue, and it's certainly more cost-effective and certainly safer. A global concern for us then is what about all of the different agencies and assistance that's being provided. How are we monitored and evaluated on our own work, and how can we put all of these agencies together? And I think this forum that Dr. Nightingale has put together is a very good forum for us to also discuss issues in a high-technology area with a lot of expertise in the United States to look at agencies through foundations and national funding agencies that provide money for the improvement of blood safety. Jay Epstein was involved right at the beginning when we had the Paris 8 Summit in 1994, and one of the major themes of that summit was to look at the issue of how could we improve blood safety? It was, of course, directed towards HIV, but they recognized that HIV wasn't the only issue, and I've covered the other aspects of blood safety in the previous part of the lecture. During that meeting, blood was declared a strategic priority, and it was carried forward because only 40 countries and member states were present at the Paris 8 Summit. A recommendation was made to carry that forward to the 1995 World Health Assembly, and the global collaboration for blood safety was declared a priority at the World Health Assembly, 48.27 in 1995, and all of the 191 member states supported its inception. The Global Collaboration for Blood Safety provides--WHO provides a secretariat within the Blood Transfusion Safety Team. The idea is that WHO is not trying to coerce or change people's way of doing things, but only to get them together around a table and provide a mutual forum for these discussions. A lot of the people in this room have been present at the meetings, and the premeetings of the Global Collaboration for Blood Safety and will be able to add to what I've said, if required. So the Global Collaboration for Blood Safety with my department as a secretariat looks at a whole range of collaboration between partners who come around the table. We have national control authorities, other relevant parties who may be the blood donor groups and so on. We have the plasma industry, WHO collaborating centers who assist us in our work. We have country experts who come in. We have UN agencies, other international organizations, such as--and AABB is also considered an international organization from that point of view, and we have patient groups. The objectives are to build on the existing knowledge, utilize existing expertise to promote a dialogue between all of those members present, where they can suggest realistic, effective and practical mechanisms for improving blood safety. They can look at WHO and say, why are you not doing work in this area? We can look to other partners and say we believe you should be doing something in this area. We can facilitate working groups to address specific and burning issues, and we can move forward, through regular meetings, to improve blood safety and the collaboration. We can also co-op members who are not around this table for specific issues. The GCBS then will lead to improved global blood safety by raising international awareness, developing strategies and guidance that other organizations can either adopt or assist us in our development, identify issues of concern, and bring together all countries through developing and developed countries, where they can share experiences. Within the GCBS, of course, we can look at, and we have, and the first report of the GCBS is out--and I'll have copies for those who were present at the last meeting, of the minutes of that meeting and the recommendations--was to select specific working groups to look at very burning issues. And the last meeting we had three issues that we looked at, but we started by looking at decision-formulating policies and blood safety for policy makers, issues on safe blood donation, safety and testing of blood and plasma, the rights of patients working groups, quality management, and traceability of plasma. Next slide, please. We came up during the meeting that this is what we would address for the next year and thereafter: a working group on quality assessment and assistant for development in countries. These two were separate groups that were put together as one working group. As a working group on the policy process, making decisions--policy makers making decisions. And the third one is the working group on plasma issues. Basically using the norms and standards that are developed by the expert committee on biological standards, but to look at issue of plasma in developing countries, plasma for fractionation, requirements for plasma derived for medicinal products and so on. Next slide, please. And in summary then, the global collaboration for blood safety will improve safety and adequacy of blood and blood products globally. It will bring together developing and developed countries, which is vitally important. And it will provide a forum for exchange of in and identification of issues and concerns. We don't see this as a unique body in itself, but it is a global collaboration. There is still a place for large countries such as the United States to have other fora for identifying how collaboration can be dealt with on a coordinated and combined effort from within a large country where not only is expertise available, but funds are available and so on, and this can be carried forward to a global collaboration. Next slide, please. That, Mr. Chairman, concludes my presentation. I'd be happy to answer any questions in the future. Thank you very much. [Applause.] DR. GOMPERTS: Thank you, Dr. Emmanuel. Are there any questions from the committee? DR. GUERRA: First of all, thank you very much for an excellent review of what is truly a global concern. You didn't mention anything about storage and distribution. Perhaps that's for another working group that discussed that, but would you comment about at least what--or how that has been addressed? DR. EMMANUEL: Are you referring to the storage and distribution of blood and blood products? DR. GUERRA: Yes, sir. DR. EMMANUEL: We have a project that is funded by Luxembourg Government that's been going on now for some six years. It's called the Blood Cold Chain. We've been looking at fridges, freezers of different sizes. We just call them small, middle and large-type freezers. We've evaluated fridges from all over the world, and that will soon be in a publication called "A Public Service Information Sheet", giving countries some advice. In addition to that, we've also been working very hard on some--what we call BTTIs, blood time temperature indicators, for blood packs, whole blood packs and plasma, so that if they're out of range, the color will change. We're promoting that within our learning materials, the distance learning materials which I have in a box over there. All these materials I can show people if they'd like to see them, and teaching within our quality management project and our distance learning project on the transport of blood and blood products. We, within our system, promote a centralized system of collection and testing and provision of blood and blood products to what we call hospital blood banks. It's a little bit different to the states, but we, in district hospitals, mission hospitals and so on, we believe that smaller centers should have a fridge and a freezer and the staff trained to do the logistics of what you're talking about, which is the management of the cold chain, and insure that they have the blood product available within the hospital from the center, because if you look at any developing country, whether you go from India, China or in Africa, the largest population groups are clearly in the main cities where the blood is used. The smaller amount of blood is used in the district hospital, and they haven't got the time or the expertise or the economies of scale to insure that they can product a quality product. So that is a big feature of our learning materials and our cold chain project that we have under continuous evaluation. DR. GOMPERTS: Thank you. Any other questions? Yes, Dr. Busch? DR. BUSCH: Jean, congratulations. Just wonderful progress I think in the last five years in coordinating both the education and the blood consensus building. One issue that I think you're beginning to try to struggle with is many countries would hear about the test advances, the best tests available, and they would kind of use the inability to get the best test as an excuse for not testing at all, and understand that recently you sort of defined tiers of safety or tiers of capacity that would be linked to the kinds of tests, which anilide you should test for, and perhaps the quality of testing. And I'm wondering how that's going in terms of acceptance. DR. EMMANUEL: We used the HIV as the sort of gold standard. We've been doing that for about ten years now. We have a collaborative center in Antwerpen. Now we have the Central Public Health Laboratories in the UK. And with our collaborating centers and with our regional panels, we're evaluating test kits from manufacturers and negotiating with manufacturers to bring that price down. And I had a very useful and helpful discussion with Mr. Dalal this morning and previously on the issue of HCV. Now, HIV, in the early days we managed to bring the price down of test kits that met the criteria that was set for sensitivity and specificity, ease of use, and we produce a booklet once a year called "Operational Characteristics", which identifies all the characteristics that are required for ELISAs, simple and simple rapid tests. And we then also make recommendations with algorithms to show what countries should be doing if they are testing, say, 30 units a week, 10 units a week or a day, and at what level they should be using ELISAs. Now, we're not disputing the value of ELISAs. What we are disputing is the use of ELISAs in untrained hands, and how the results are produced. Now, HIV, we've gone a long way on that, and as I said previously, we have got ELISAs down to less than 70 US cents and the simple rapids between 1.2 and 2 US dollars per test, and their sensitivity and specificity, as you know, is equal to that of an ELISA, and certainly in untrained hands is far superior to that of an ELISA. We would like to do the same for hepatitis B and C. Even if the sensitivity is slightly lower, or specificity, it will certainly be well up until the high 90s, as you saw on the HCV as an example. And we were talking about what is the price. Now, remember, the one big thing is that everybody has this emotive drive for HIV. And when you look at our learning materials, we talk about testing for HIV and other infectious agents. Now, I think the funders of HIV would be disturbed to see HIV test kits provided at, say, a US dollar, but an HCV coming in at 5 US dollars, and say, well, we're funding HCV and it hasn't got the same emotional drive. But if we can get the price around about the same and say, well, it's a dollar a test, then we're looking at something--or $1.50 or whatever it is--we're looking at something that we can then--as I said, one of our major drives is through policy--to say to countries, you know, we can shame them into using it, I think your argument's a good one. If it's a $5 test they can say, we can't really afford this for a disease that might be 20 years down the line in our population group, and looking at the burden of disease and the cost effectiveness of a test. But if we can show it at that kind of cost or price, we can then say, this is something that you really have to put into place. So that's our drive. And we're not saying that we have--we just have to put partnerships together or try and coordinate, and I think you'll hear from other speakers today how they're also going for the same drive. But the idea is to make sure that it's not just for HCV or HBV or HIV, but it's a comprehensive package I've tried to show today, that provides safe blood to the end product which is the clinical use, and the district surgical services for which we are responsible to show them how a correct procedure with simple technology can minimize the unnecessary shedding of blood. DR. GOMPERTS: Thank you. Dr. Davey. DR. DAVEY: Jean, as you know, there's been interest on and off through the years about pooling samples from a small number of donors for basic infectious disease screening. What's the position of WHO on pooling these days? DR. EMMANUEL: Well, you're aware that we did try and introduce that at the early days of HIV, and one of the main reasons for doing this, of course, was that it was the cost of the HIV test kits. Now that it's come down to that low price--this was particularly driven by simple-rapid tests that were at $5--it becomes less--more difficult to promote pooling, and I think it's less necessary. The dangers of pooling, of course, is in untrained hands, as are the obvious dangers, the lack of sensitivity and specificity. We always had the policy that the final dilution should always be, and the manufacturer's recommendation should be adhered to. There's also a reluctance from countries, who feel that pooling will psychologically be a loss of sensitivity and specificity. So we haven't really pursued that to a great extent. We'd rather pursue the manufacturer's requirements, but reduce the price. DR. GOMPERTS: Yeah? DR. PENNER: Perhaps--I'm not sure if this is appropriate, but would regional centralization of testing be cost effective or realistic at all since we have capabilities of moving samples very easily from country to country and so on" Just as you have your WHO regional areas, why not a huge or very large testing center? DR. EMMANUEL: Yes. I absolutely agree with you. That model has been used, certainly, South Africa, Zimbabwe, Zambia, Botswana and so on. There's one criteria, obviously, and that is that you have to have an organization that's properly managed and you have to have a culture and system. And the biggest problem is, is that we haven't got countries to address the issue of dedicating a blood transfusion service to an organization with a proper head and a properly structured body. Once that's done, that is exactly what we're trying to move, and we talked about this, for example, in India, where we discussed--clearly, people talk about India, the blood transfusion service problem in India, and it always amuses me because I asked them, "Well, what about the blood transfusion service for Africa?" And everybody says, "Well, that's not possible." But when you look at the population, it's one-third of the population of India, and yet no one thinks of Africa as having a blood transfusion with centralized testing. Now, India can have a coordinated policy, which is what they have got at a national level, but state by state, organizational structures, which means that you do have a coordination. You have economies of scale, bulk purchasing and so on. But even within a state such as Maharashtra, you could have a number of smaller blood banks working on a sort of hub and spoke sort of issue. And we have been promoting that, and that's what they're working towards. For instance, India had started with 110 zonal testing centers, because it's in these major hubs where the blood is more easily accessible, where donor drives can take place and providing to the periphery. So what you're saying is it is cost effective. It improve the quality, safety and the price. So it is, but the problem is getting the organization and training the staff, and this is our quality management project at the moment, where we're training two people from every country--not India, of course, India would be, you know, a large number of people, and India's dealt with as a region on its own, and soon will China. So we have quality managers and officers trained in the aspect of quality, to try and promote this within their own ranks and almost be disciples for policies and strategies that we have developed. DR. GOMPERTS: Dr. Emmanuel, thank you for--we have one other question. Dr. Klein. DR. KLEIN: This may be a little bit unfair, but I have to take the opportunity to ask you this. You've, obviously been involved in global safety and availability for a much longer time and much more intensely than most of the people sitting around this table. So, given the topic, what advice do you have for us for additional activities perhaps that the department should undertake in order to assist global safety and availability of blood? DR. EMMANUEL: I think if we just bring it down to simplistics, the one most important thing for me is that there's an adequate level of representation at the global collaboration for blood safety, which I think has raised a level of awareness of what the requirements are outside the borders of this country. I think the next level is to say that within the United States there are a lot of people doing very, very good work, but there needs to be a forum for collaboration of putting together all these activities in a more structured way. Now, if that can be put together in the country and then represented at a global level to bring it back, I think that would be a major step forward. DR. GOMPERTS: Any further comments? [No response.] DR. GOMPERTS: Dr. Emmanuel, thank you very much. We'll move on now to the next presentation, Dr. Jose Ramiro Cruz, Pan American Health Organization. Dr. Cruz. DR. CRUZ: Thank you. It's much easier for me to speak after Jean, because, you know, the Pan American Health Organization is part of WHO, although the Pan American Sanitary Bureau was created 99 years ago, so we have our own executive committee represented by the Ministry of Health of 34--37 countries in the Americas. That's in America, the Caribbean, Canada, the United States. So please don't be afraid because you know this is in Spanish, but the actual data is going to be in English. [Laughter.] DR. CRUZ: And, again, you know, what I hope I will do in the next 15 minutes is to convince you that it is important for us to receive support in terms of advocacy, basically to raise awareness of the importance of blood safety and availability, the transfer of technology to the countries including the training of personnel. But again, you know, we deal with 44 countries. Can I have the next slide? You know, this represents the number of blood banks per country in the region of the Americas, and you notice that, hitting the X axis, the highest number is six, and these are the countries in the Caribbean. These are some other countries, and you know, we deal with countries like Anguilla and Antigua, that have about 3 or 4 thousand inhabitants in the whole country, and then we have to deal with countries like Mexico and Brazil, which are a little bit larger than the Caribbean countries. And again, just to give you an idea of, you know, how we--how to approach the country level work with different approaches, you'll see that most of the countries in the Caribbean have just one blood bank and that's down here. If I can have the next slide. And this will show you, and we have here Canada, that's the very first country here with 18 blood banks all together, but you'll see for instance that Bolivia and Chile have close to 90 blood banks in the country, and for instance, you know, Bolivia has about 8 million people, so you can see, you know, what the number of blood units these blood banks collect. If I can have the next slide. Again, these are the larger countries, and here, we have in Brazil with close to 2,000 blood banks. And next, please. Just to give you an idea of what is the number of blood units that are collected in each of these countries, and again, these are the Caribbean countries, and you'll notice that the highest number here is 5,000, you know, but most of the countries in the Caribbean collect around 2,000, or, you know, between 1,000 and 2,000 units of blood per year in the whole country as compared to the countries in Latin America. Can I have the next slide, please? You see here that we have 60,000 and that's Costa Rica, but okay, the first country in this graph is Jamaica. That's the largest country in the Caribbean. They collect about 25,000 units of blood each year, but again, this is 60,000, and the next slide will show you the number of unit that I collected, you know, in the rest of the countries with Cuba collecting 600,000 units of blood per year. But again, how does that compare to population? Can I have the next slide? And again, you know, if we use 5 percent, and that is considered, you know, the indicator for enough blood to be collected in a given country, you're going to see that it's only Cuba that is about 5 percent. This is United States with a cost of 4.7. This is Canada here, and this is Uruguay here. So, basically most of the countries in Latin America collect about one-fifth of what is estimated to be sufficient for enough blood to be available in each of the countries. Can I have the next slide? And you know the rate is basically the same in the Caribbean countries, and these are the Caribbean countries again, and again you'll see that most of these are, you know, around 1 or even below 1. And these two countries here are--actually, these are the Dutch territories Aruba and Curacao. Could I have the next slide, please? As Dr. Emmanuel mentioned, you know, one of the products that we have is the paid donors, and we have five countries in the region that they officially report to us that they have paid donors, and those are Chile, with around 1 per 1,000; Peru, Honduras, Bolivia and Panama. And let me tell you that these are data from 1999. We just got the data from the 2000 and in Panama this ratio increased to 48 percent, and in Bolivia it went up to 38 percent. So, again, you know, in these two countries at least the proportion of paid donors has increased in the last three years. Can I have the next slide, please? But again, you know, most of the countries rely on replacement donors, and again here we have the Latin American countries, and you're going to see that basically, you know, all--the vast majority of the blood come from the replacement donors. In some be the minority, around 10 percent of the blood in the region that comes from other type of donors, and we have other countries like Nicaragua and El Salvador that have about 40 to 50 percent voluntary blood donors in those particular countries. Can I have the next slide, please? And yesterday, give you an idea, you know, how the promotion of voluntary blood donation associated with the level of organization at the national level, we have here Canada, the US and Cuba that have 100 percent voluntary blood donation. Yeah, you can see the number of--this is, in a simple mean, divided the number of blood units collected by the number of blood banks in that particular country. In Canada, you know, the average is 15 and 9,000. In the US is about 18,000, in Cuba about 16,000. But if you look at Colombia, Brazil, the Dominican Republic, the numbers are much lower. Like in the Dominican Republic the mean average of annually collected units is about, you know, 400 per blood bank and they only have about 17 percent voluntary blood donation. So it's quite clear to us that, you know, the--a promotion of voluntary blood donation is one more expression of the level of organization of the blood banks in the individual countries. Can I have the next slide? What happens with the voluntary blood donors in the countries--and let me tell you, you know, this is the Red Cross in Keto, and this is the blood bank in Keto, Ecuador, and they have about 92 percent voluntary blood donors that come to that particular blood bank. Just five blocks down the road is social security. And I don't know if you can see it. They only have about 5 percent voluntary donation. So it's in a way, basically, tell everybody the people that don't donate, it's because the population is not educated, they are not really knowledgeable about the benefits of voluntary blood donation, but it's quite clear that within the same city, you're going to see the difference, you know, in the preparation of voluntary blood donors at a blood bank might have been, you know, so close as is the case in Keto. In Jamaica they have only two blood banks. One of them is owned by the Ministry of Health, and they have two collection centers. One collection center is in Oxford Road, and they have about--I think this is in the safe part of Kingston, and they have about 90 percent voluntary blood donors. The other collection center is in the not-so-safe part of Kingston and people tell me they might--they are afraid that they might give their blood before they get to the blood bank. [Laughter.] DR. CRUZ: So, you know, they have only about 4 percent voluntary blood donors in this other collection center. So it's better that you know the accessibility of the collection center and also the attitude of the personnel in the blood banks would have an impact on the proportion of voluntary blood donors in each of the blood banks. Can I have the next slide? It is important, let me tell you, that, you know, we looked at what happens in the country, and we grouped the blood banks in Ecuador in three, those that have less than 40 percent replacement donors, those that have between 41 and 99 percent voluntary blood donors, and those that--I'm sorry--replacement donors--and those who have mostly replacement donors. And these are the markers, if HIV, hepatitis B and hepatitis C, and these are a proportion of donors that are positive for those three markers in the blood banks that have the least replacement donors. The ones in the second group--can I have the next--you can see that, you know. And then the ones with the most replacement donors, you can see that, you know, the risk of finding a positive donor is about 1,200 higher in the blood banks where they basically collect the blood from replacement donors. Can I have the next slide, please? Okay. With this, I hope that you understand and that you agree with our policy that, you know, one of the expected results of the original initiative on blood safety, is that by the year 2003, each of the countries will have at least 50 percent voluntary blood donors. That's one of the expected results that we're looking for two and a half years from now. The other issue has to do with the screening, and Jean mentioned this. And this again is the percent of units that I screen, for instance, hepatitis C, in each of the countries, okay? And you're seeing that Bolivia, for instance, we didn't have data for Bolivia for '99, but now for 2000 we know that only about 28 percent of the units that I collected in Bolivia tested for hepatitis C. And then we have some other countries here. We have--for instance, this is, I think, Guatemala. That's where I come from, but only about 50 percent of the units there are screened for hepatitis C. But again, you know, this is our biggest concern, really, hepatitis C, because for HIV, basically all the countries test not, if not 100 percent, at least 99 percent of the units that are collected. The other marker that we are pushing for are hepatitis B, surface antigen, syphilis, and Chagas in Latin America. In the Caribbean, we don't recommend screening for Chagas, because it's not prevalent there. Can I have the next slide, please? Then this is for T. cruzi, and this is again the agent that causes Chagas disease. And, you know, this is the other area we have also difficulty in terms of screening in Latin America. Can I have the next slide, please? Saved blood. For hepatitis C in the Caribbean countries, 64 percent of the units that were collected were not screened for hepatitis C, and in Latin America--this is date for 1999 again--in Latin America, over one million units were not screened for hepatitis C. HIV-1 and -2, we have 9 countries that don't screen 100 percent of the units, and we have 10 countries that don't screen 100 percent of the units for hepatitis C. Only 16 out of the 42 countries in the region screen for the hepatitis B, hepatitis C, HIV and syphilis. Can I have the next slide, please? Again, you know, 100 percent screening for hepatitis B, hepatitis C, HIV and syphilis in 8 of the 21 Caribbean countries, and 6 if the 19 Latin American countries plus Canada and the United States. Can I have the next slide, please? Again, you know, a screening is a big issue, but then what is the specificity and sensitivity and the accuracy of the screening? We have a regional program of external evaluation of performance, in which at least one major blood bank participates in this regional program of external evaluation of performance, and we have national programs in basically all of the Latin American countries, and we're setting data up in the Caribbean. But what is very important is that when you look at the false negative results, in the last survey that we had in September 1999, we were able to detect that, you know, 6 percent of the results for hepatitis C were actually false negative. So, again, you know, the quality of the testing is something that we worry about. The other to inspect the results in our initiative are that not 100 percent of the units are tested for the five markers that I mentioned, and the other expected result is that 100 percent of the blood banks that actually screen blood, participate in programs of external evaluation of performance. Can I have the next slide, please? What is the safety of the product that is available in our countries? And we still use a locally-produced cryo to treat the hemophiliacs. For instance, in Costa Rica, 67 percent of the hemophiliacs are HIV--I'm sorry--hepatitis C positive. In Chile, 65 percent of them are positive, and in Guatemala, again my country, only 18 percent. But, you know, the number of hemophiliacs in Guatemala is much lower than what is suspected. And what we figure is that most of the hemophiliacs have left us because, you know, they either quit treatment or infectious. But, again, you know, when you look at Costa Rica and Chile, that are two of the countries that have the supposed--you know, the better health services in Latin America, these are the rates of positivity among hemophiliacs. Can I have the next slide? This has to do with age, and again, the older the patients, the higher the prevalence of antibodies. So that means that, you know, the more that they're exposed to locally-produced plasma, let's say, the higher the chance that they become infected. I think that's the last one that I want to show, for the sake of time. But I'll be glad to take questions if you have any. [Applause.] DR. GOMPERTS: Thank you, Dr. Cruz. Are there any questions from the committee? Yeah, Dr. Lipton? DR. LIPTON: Jose, I think one of the questions that we've been deliberating at the AABB is all over this issue of how you encourage volunteer donations, and we've had a lot of discussion about is there anything that we can do to encourage that? I'm going to talk a little bit later about some of our standard-setting activities, where actually the countries and regions themselves have moved to place that into standards. But is there something besides that that we can assist with, because one seems to think we know how to encourage volunteer donations fairly well. We had a big switch here. But is there something specific you would like to get from us that you don't have? DR. CRUZ: Yeah. How long can the list be? No. You know, it's interesting, we, with the help of a group of anthropologists, we develop a guideline to do anthropological studies on the factors that basically, you know, pick on or off, you know, voluntary blood donation. And we have--you know, these studies have been applied in at least 14 countries now, okay, including Jamaica, and what we have found is that there are two main factors that actually prevent voluntary blood donation. One is the lack of information, not education, information in the public, okay. People don't think that there's a need, a continuous--they don't know that there's a continuous need for blood, so whenever there's a disaster like an accident or an appeal on TV or on the radio, people come and donate, because they figure that that's the only time when there is actual need for blood. That's one issue. The other issue is that the accessibility of the blood banks, and then, you know, this business of replacement donors, when people are asked to come, you know, to bring two or three--I mean patients are asked to bring two or three or four donors whenever they needed the hospital. Then families, you know, of donors who are healthy, might rather save their blood for, you know, whenever a friend or a relative needs it, then go and donate it. So, you know, you have to deal with informing the public, and again, you know, it's the way that we deliver the messages. And, you know, it's interesting, in Nicaragua somebody told us that they only place that she saw posters of pamphlets regarding blood donation was in the blood bank. And she asked, you know, "Why don't you put them in supermarkets and shopping malls, in movie theaters? You know, you have to come to the blood bank to actually see a poster, okay, or find a pamphlet, you know, a flyer. And then the other big issue is the way the blood banks are set up, you know, because people are forced to come and give blood and the blood banks are usually open from 7 to 9 in the morning. They are not--I mean, they are not donor friendly. So basically what we have to do is both inform the population and also--and this I think is the biggest challenge--to change the way the blood banks operate. And I'm going to go back to, you know, one of the questions there was before. We feel that centralizing not only testing, but also the collection of blood will improve efficiency. We have data showing that resources--lack of resources is not the issue in our countries. On the contrary, we're using resources in a very inefficient way. We have, you know, blood banks that collect 400, 500, 1,000 blood units of blood. And most of the loss in the countries, for instance, required that it's a physician and--most of the times--and hematologists that should run a blood bank, okay? So here we have a hematologist running a blood bank that collects 400 units of blood a year. They have a nurse. They have sometimes a social worker, a psychologist to provide counseling for those who are HIV positive, for instance. So you know, so all these resources going to these very small centers, and they are very, very inefficient. So what we're trying now to do is--using, you know, the tools that WHO develops, convince the people that they are wasting resources. And, again, you know, if we can implement the standards that we have developed with the help of AABB, then the resources could be allocated, you know, to do what we know is needed. DR. GOMPERTS: Others questions? Yeah, Dr. Guerra. DR. GUERRA: [In Spanish.] The question-- DR. CRUZ: I got that. [Laughter.] DR. GUERRA: The question I have for you is that having screened out individuals that have a variety of infectious diseases that perhaps could be associated with transmission via transfusions, there's a real dilemma I suspect within the blood banking industries and programs in some of the developing countries in terms of trying to connect those individuals with resources beyond just counseling, for follow-up care of some of those conditions. How do you deal with that? DR. CRUZ: Well, actually, you know, that's why we have the date from Chile and Costa Rica, for instance, because they actually provide treatment for hepatitis C patients, okay? So it's a--in some other countries, like in Guatemala, even the diagnosis of hemophilia is something that I don't think is very highly pursued, because then, you know, the authorities will know that they will have to do something in terms of providing treatment and support for those patients. But, again, you know, this is the big issue, and again, how do we deal not only with blood banks, but also with all the resource in terms of health services and, you know, promoting health--efficient health services, and that's again something that a programming session does, and that's in general saying, you know, I presented here, and very quickly, what we have come up with, but again, the work that we do, we cannot do by ourselves. I mean, that's definite. So we work with other divisions within PAHO, with other divisions within WHO Geneva. We have other partners. We work, for instance, very closely with the World Federation for Hemophilia, again in terms of advocacy. So it's--you know these partnerships, I think, you know, they need to be constructed not globally, regionally, but most important at the local level so that people can get whatever they need in terms of information and treatment or counseling if necessary. DR. GOMPERTS: Yes? DR. NIGHTINGALE: Jose, than you very much for being here. I would like to take the opportunity to ask the question that Dr. Klein asked a minute ago, which is--not to put you on the spot, but that's why you're here--what if anything could the Department of Health and Human Services do that it is not doing to support you in your work? DR. CRUZ: No. As I said, I think advocacy is a very important issue, just to mention blood, you know. And when you see, for instance, you know, the attention that HIV/AIDS and the HIV epidemic gets, you know, for one, at least would say that HIV, for instance, can transmit--transmit through transfusion, that would be a big issue. But also we are concerned about hepatitis C. And I think everybody, since HIV has so much more visibility, that's what we deal with, but then we have things like hepatitis B, hepatitis C, and what is the cost of really taking care of a patient that is infected with hepatitis C? I need to make a parenthesis here, we--I mean this is something that happens--we just got a story of--another story about another case of three individuals getting infected units in Belize just three weeks ago. So that's--so advocacy and raising awareness is something that is important. And again, when you talk about US personnel stationed in our countries, I think that's also very important, okay? I mean, the safety of blood--the blood that is available to your fellow Americans, for instance. And the other one is technology transfer, and when I say technology transfer I just don't mean a specific and sensitive inexpensive tests, but things like the standards, norms, you know, and training, you know, again, how do we deal with running a blood bank efficiently? How do we set up a national blood program? How do we--you know, people were mentioning before, what is the cost effectiveness of centralizing a testing or promoting a voluntary blood donation, that kind of thing? So I think, you know, advocacy, technology transfer and training would be things that would be important. DR. GOMPERTS: Any other questions? I have a question. One thing that really struck was the heterogeneity of the availability of quality blood across the region. The question that I want to ask is, to what extent are other branches of medicine associated with the quantity of blood and blood transfusion activities? DR. CRUZ: I'm sorry? DR. GOMPERTS: Other branches of medicine, surgeons, cardiologists? DR. CRUZ: Okay. No. Again, you know, when I said training, and I think Jean mentioned that the appropriate use of blood is an important issue, but again, you know, I think what drives the quality of blood is the way that we collect blood. Let me give you a couple of--no, one example, just for the sake of time. I was in the Turks and Caicos Islands just about three weeks ago. These people have money, okay? They invest $8 million in sending patients to Miami just because there's not enough blood in the country, okay? So that tells you how the resources are used. But how do they collect blood? The patient is admitted into hospital, and then they go and bring the donors forward, okay? So the donor is brought in, for instance, in Providenciales. The blood is collected there. And probably, you know, the patient is in an emergency situation because he or she has to be flown to Grand Turk, okay? So they have these charters, okay? So they might either bring the patient and the donors to Grand Turk for the collection of blood, okay, or they might collect the blood in Providenciales, test it using rapid tests, even though the have an ELISA reader, that they have trained people, because they want to have the results like right away, because otherwise--if they turn out to be reactive, then they have to go and collect the blood from somebody else. So what I'm trying to tell you is that sometimes the units are not screened, not because there are not resources, not because there are not trained personnel, but because there is not time for the unit to be tested. And that's exactly what happened in Belize, we think. The unit was collected on Friday, the 30th of March, and the patients were transfused during the weekend. And then on Monday they figure out that the unit was positive. So it's not lack of resources, is not that, but is the way that the blood is collected mostly that then drives the whole process. DR. GOMPERTS: Thank you. DR. CRUZ: And I'm sorry. Going back to the surgeons, it's interesting. In Turks and Caicos Islands, the minimum level of hemoglobin for a donor to be eligible to donate is 12 grams, okay? And we have revived the records, and there were patients with 14.5 of hemoglobin that have been given two units of blood. So, you know, this is our comment. A donor with 12 grams hemoglobin can be, you know--then they can donate a unit and then go back to his place or to his work, and then a patient who has 14.5 gets the units of blood. DR. NIGHTINGALE: If I could make a quick comment to the remaining speakers. We have time for you. I appreciate Dr. Cruz's concern, but it is very important for us to hear what you have to say. I have intentionally scheduled this meeting tight in the morning so that we hit--we were to hit public comment at 2 o'clock. No way did I ever think that was going to happen. I do want to hit public comment, however, by 3 o'clock, and that means we still have time. So, to the remaining speakers, please tell us what you want to tell us. DR. GOMPERTS: Thanks, Steve. Any other comments, other questions? [No response.] DR. GOMPERTS: Thank you very much. DR. CRUZ: Thank you. DR. GOMPERTS: We're going to be going--we have Dr. Mohammed El-Nageh, International Consortium for Blood Safety. DR. EL-NAGEH: Good morning, ladies and gentlemen. The International Consortium for Blood Safety was established in 1998 by a group of leading blood bankers, biologists, and public health experts. In 1999, the International Consortium for Blood Safety received a grant from the Gates Foundation which made it possible to start some activities in some developing countries. The International Consortium of Blood Safety has a limited number of members and also liaison members representing major international organizations and institutions. For the time being, there are 14 liaison members. The ICBS has as its major goal the achievement of universal blood safety by prevention of transfusion-transmitted infections using affordable and high-quality reagents. Among the specific goals of the ICBS also is to identify, validate, and make available affordable, high-quality reagents and plan and execute in some countries, in collaboration with the central authorities, projects to achieve blood safety in a region and then extend the experience of that region to the neighboring regions and the neighboring countries. Among the specific goals also is to assist in developing and upgrading quality assurance programs covering the whole spectrum of transfusion medicine. ICBS also coordinates and arranges for appropriate technology transfer. It aims at coordinating with other international organizations and societies providing educational support to improve donor selection and clinical use of blood. ICBS also fosters collaboration with WHO and other major international organizations, associations, societies, institutions, so to maximize the resources and to complement the efforts of each other rather than duplicating. We know that the developing countries are really a heterogeneous group of countries, and problems which are faced in one country may not be exactly the same. But there are certain problems, some of which or all of them which could be encountered in one country or another. The first one is the fragmentation of the transfusion services and the absence of independent and well-coordinated national transfusion service program. There is also--I think there is a problem with the focus there. There is also a lack of national policies or plans aiming at self-sufficiency in blood and blood products, and even when the plan is there, most of the time it is not implemented. There is unsustainable reagent supply and significant shortage of the screening kits for some infectious agents, and especially for hepatitis C. And the shortage is more acute in the peripheral areas when you go outside of the capitals and the main cities. There is improper evaluations and licensing of reagents. Any kit can be sold anywhere at any time, whatever the quality of this kit is. And there is a lack of cooperation between blood banks or between countries or between regions to have a bulk purchase of reagents in order to reduce the cost. There is a lack of organized, community-based, regular, voluntary, non-paid donor system, and, of course, there are limited financial resources, the excuse which is used by all the countries, and the lack of adequate staff training and also the lack of continuing education. There is poor quality assurance programs. There is lack of adequate equipment, and certainly this is lack of equipment maintenance, and last but not least is the inappropriate use of blood and blood products. The ICBS, prior to considering providing support to any country, assesses the situation in that country, and the assessment is mainly through gathering information from various sources and also by the findings of the team visits, the ICBS team visits. And once the situation is assessed, priorities are identified, and these priorities have to be within the goals of the ICBS. The ICBS tries to maximize the resources and find out who is doing what in that country. Sometimes there are other organizations and agencies who are providing support, and ICBS tries to rather coordinate and maybe even collaborate with these providers. There are two main prerequisites to start supporting a developing country. First of all, the presence of a leadership. There should be a qualified--or more than one--and dedicated blood transfusion specialist who is or are prepared to take the lead in improving blood safety in their countries, and there should be government commitment. If these two are absent, it is very difficult to imagine that any progress could be or any success could be achieved. What are the areas of support that ICBS may consider? The ICBS assists countries to achieve sustainable safety testing of all blood units collected by blood banks through providing some of the less fortunate blood banks, for a very limited period, with screening reagents. And usually after the assessment, we find out how much is needed to provide--to ensure testing of all blood units, especially at the periphery and outside of the capitals and main cities. And the ICBS signs an agreement or memorandum of understanding with the government that they are going to cover the screening for the first year, and provided that the second year the government commits itself to covering 50 percent and the ICBS the other 50 percent, on the third year, hopefully, that the government commit itself to undertake the responsibility of covering the cost of all the testing of the blood units using its own resources or alternative resources. Another point in this area is to advise on efficient reagent purchase mechanisms, like the bulk purchase mechanism, informing the country about the availability of affordable and high-quality reagents in the market. Another area of support is assisting in the evaluation of blood safety kits available in the market to identify the good-quality and low-cost reagents. And to achieve that, we assist in training scientists from the developing countries on methods, especially those countries who have control authority laboratories, on methods of evaluation and licensing of reagents. The ICBS is establishing a master panel or master panels for HIV, HBV, and HCV, and this master panel initially is provided to those countries who have control authority laboratories, and they also should be trained to develop their own panel for continuing use. And this is by training the scientists in preparation, characterization, and establishment of the national panels. We also sponsor--we are going to sponsor a well-established center, international center, because we are aware that most of the developing countries they have no control authority laboratories. And even those who have control authority laboratories, we are very doubtful about the performance of these laboratories. So instead of waiting for a long time for this to happen, we are going to support a center, an international center for the evaluation of the blood screening reagents to identify the affordable and high-quality screening reagents and to display the results on a website, which will be available for all the countries to be used whenever needed. Also, the ICBS will provide this international center with the master panel being prepared. ICBS also plays an important role in training in specific areas, especially assisting in training of blood safety, laboratory testing techniques, and conducting and cosponsoring the workshops to train trainers in the principles and practices of that quality assurance. We help some countries, whenever or wherever appropriate, to have central confirmatory reference laboratories. ICBS for the time being has activities in India, in Vietnam, in Paraguay, and the situation has been assessed in Pakistan and Indonesia, and the report of the assessment is being circulated to the members for their views, after which plans will be prepared and assistance will be provided within the available resources. Other countries that are being assessed are the African countries, starting with the French-speaking countries, and also the countries of Central Asia. The question how the department could help ICBS, the department could help ICBS in many ways to achieve their goals. First of all, capacity building. And under capacity building, maybe to provide training grants targeted at a range of individuals from directors of blood transfusion services to technologists and high specialization level, because we believe in leaders, and without these leaders, one would hardly imagine how progress could be achieved; then cosponsoring training course, the ICBS training courses and workshops; establishing an ongoing relationship with an institution which is most likely to influence blood safety in a client country, and this could be a blood transfusion center, this could be a virology reference lab, public health department, whatever institution is appropriate and is foreseen that it can play a major role in the development of blood transfusion services in that country. The relationship with this center should comprise offering phased training of individuals making a team and offering problem-solving functions and also sending out short-term consultants in various relevant disciplines to check on progress and help with longer-term planning and keep the program on track. Maybe also to provide to the center calibrated reference material and also advise on how to use this. Another area where the department could assist ICBS is making available testing reagents for blood safety, and this could be by contributing to the efforts and maybe even financially contributing to the efforts aiming at providing for a limited period testing kits, convincing countries to have in their Ministry of Health budget a budget line to cover the total or initially partial testing costs. I don't believe and I have never believed that any country in the world have no amount, even if it is small, of money to be allocated for blood safety, because when we see what money they spent in other things which are useless, one starts to ask himself. I think they have to have an amount which should be supplemented by donation, and then gradually they should take over the responsibility of covering the cost. And I think this could be as a prerequisite before--like we do with the countries, before we start any assistance. Also, advising on negotiating favorable financial terms with the companies, because many of them, they are not experts in how to negotiate these terms. Also, explore and advise and train on total or partial cost recovery. Some of the developing countries, they have started to use the system of cost recovery of testing, and to have it as a revolving fund to ensure sustainability of testing. The other advice that I would like to give is avoid providing or donating inappropriate equipment, which is most likely to remain unused or break down after a short period of use due to the lack of expertise and lack of maintenance. Those of you who have visited developing countries, you will see masterpieces, very expensive pieces, lying in a corner somewhere. You can identify the chronological order, the age, by the layers of dust in it, and it has never been used. So I don't think that it was appropriate to give it in the first time. We should give what they need, what they can use. And prior to specific technology transfer--I am very happy that the program is including a lot of talks about the appropriate technology transfer--we should look into the critical factors contributing to the successful transfer of such technology, and it should be identified. Thank you very much. [Applause.] DR. GOMPERTS: Questions? Dr. Hoots? DR. HOOTS: You had mentioned in terms of collaboration between, say, people or expertise in the United States or perhaps over the developed world, and the previous two speakers had talked about collaborations that they have with the World Federation of Hemophilia. There's one program that's been very efficient, I think, in terms of just sharing knowledge, perhaps resources as well, but particularly knowledge, which is a twinning program that exists between established hemophilia treatment centers in developed countries, primarily U.S., Europe, Australia, and Japan, with developing centers of expertise in the developing world. And I wondered if that sort of model had been looked at particularly for early involvement in helping perhaps just first as a dialogue between people with expertise who have an interest in helping out somewhere, and then establishing a relationship, perhaps even establishing an educational track of an ongoing continuity of continuing medical education for transfusion. DR. EL-NAGEH: Well, I do agree with you, and in my previous life--because my previous life was with WHO, and I believe very much in twinning. And I have looked to centers of excellence around the world where you can twin them with the activities in developing countries. And the story is always a success. I think this is a very valid approach, and I am pretty sure that the global collaboration at the WHO is looking also into that. DR. GOMPERTS: Thank you. Dr. Epstein? DR. EPSTEIN: Yes, thank you, Dr. El-Nageh. I think that was a very complete picture that you painted. However, I notice that it's in many ways very similar to what the WHO described as its strategy, and I wonder if you could comment on the current degree of coordination between what WHO is doing in some of the same regions, for example, India, and ICBS. DR. EL-NAGEH: WHO--and Jean Emmanuel is here--is one of the pioneers of establishing the ICBS. One of the objectives and the goals of the ICBS is to closely collaborate with WHO. For example, when we are talking about the evaluation of the kits, we know that WHO is doing a good job on HIV, so we are not going to touch on that, but, rather, we are going to fill the gap. We try to avoid duplication and overlapping and, you know, unuseful spending of money. So the center will only evaluate, if you are mentioning to that, the hepatitis kits, the hepatitis reagents. In other areas, wherever we go, first of all we inform the WHO representative in a country, the regional office in that region. We find out what is going on, who is doing what, what governments are providing support. So we try to get in touch with these people, how we can fill the gaps, where are the areas that could be supplemented and complement their activities rather than duplicate. And we try to do our best at this way. But we believe and we will always believe that close collaboration with WHO is a must for ICBS. DR. GOMPERTS: Thank you. Dr. Chamberland? Then Dr. Davey. DR. CHAMBERLAND: Thank you very much for a nice presentation. I wonder if you could give the committee sort of an update on--I think India is probably one of your first projects that has been ongoing more than others. Just give us an idea of the actual progress that you've been able to make in the areas that you outlined, because I think what you're trying to do is very concrete, you know, supplying panels, reagents, getting countries to be self-sufficient. So it would be good to hear how that actually has worked out in a country where you've been in place for a while. DR. EL-NAGEH: Okay. In India, it is an example where we tried to really collaborate with WHO. We had meetings with the--we have assessed the situation. The situation, Jean Emmanuel knows it even better. There are certain blood banks that collect ten blood units a month, and there are certain blood banks that they collect a lot. The situation is different from one state to another, so with the federal state we sat down, and with the people from the WHO also because they have the regional office there, and we discussed with them where we can complement. And we had very long discussions with them to convince them starting testing for hepatitis C, because hepatitis C will be a big problem, and we will cry ten years from now when it is too late, because we are not testing for hepatitis C and it will be a bigger problem than hepatitis B. We all know that HIV is important, but HBV and HCV, they are not less important. So there was a good response from the Government of India, and they were planning to start testing, and we are very glad to see in The Lancet, I think last month, that starting July they will test all blood units collected in India for hepatitis C. And this is a good move. So the areas which were identified with them, first of all, they have a panel to evaluate the kits, and their panel was not really very satisfactory, even by what they have mentioned and what we have found. So a temporary panel for HCV has been provided to the national control authority laboratories. Someone from India came to CDC Atlanta to be trained on the characterization and establishment of a panel and also in the proper evaluation of the kits. We thought that there was also--we didn't give reagents because we thought that they have enough resources to cover for the reagents. And any positive result, maybe false positive or false negative, but at least the false positives, they are not confirmed at all. They have no confirmatory laboratory there. And we have agreed with the Government of India to help them establish a national reference confirmatory lab in New Delhi, in Delhi, and it is being established. We have provided some equipment, and there is an excellent lady expert who is responsible there. She is now at New York being trained on the confirmatory testing using NAT technique. DR. GOMPERTS: Thank you. Dr. Davey? DR. DAVEY: Thank you, Dr. El-Nageh. One of your very useful suggestions was that the department may want to consider establishing training grants for people in developing countries. One of the vexing problems that I'm sure you're aware of with such training in a developed country is that the trainees often don't go home. There's a brain drain, if you will, for people who come to, say, this country or other developed countries, get extensive training, and decide to stay. Do you have any suggestions or comments on how we could get around that problem? DR. EL-NAGEH: First of all, I'm aware that the immigration rules are very strict now, so I don't think that they can get away with that if they come to the States. But I didn't say that you have to train them in the United States. You could train them in other developing countries with a successful story. They can go to a developing country with similar conditions or nearly similar conditions, and they have succeeded and they see that it is possible to succeed. For example, we are going to train certain people from Africa in Ivory Coast because they have succeeded to establish a voluntary blood donor system, an excellent centralization of testing. So it is feasible. The trainer could be in the United States, in a developed country, or developing countries. DR. GOMPERTS: Any other questions? MR. DALAL: Dr. El-Nageh, just a clarification on the use of the term "technology transfer" as it's used by ICBS. Is the emphasis on the transfer of assays and instruments under terms of sale and technical support, or is it on the transfer of know-how and licenses for the local development and manufacture of the product? DR. EL-NAGEH: By definition, technology is not only instruments or reagents. By definition, technology is also procedures, methods, and approaches. The technology is a whole spectrum. Whatever is useful to improve the situation of blood safety in that country could be studied and then tailored to their needs, and the transfer should be appropriate in a way to survive and to be used and utilized. But it is not only for the equipment. Yes, the equipment or the manufacturing of reagents, yes, why not, if they are capable to do that. They are doing it anyhow. They are doing it badly. They are producing kits in these countries and they are using it with doubtful specificity and sensitivity and quality. So why not help them do it right? DR. GOMPERTS: Thank you. Yes? DR. PENNER: Just a quick question. The tourist industries are often very powerful in Third World countries, and they really have a stake in having safe blood available for the populations that they're transporting over. Do they get involved at all or participate in some of your programs? DR. EL-NAGEH: I didn't get your question. DR. PENNER: The tourist industries in many of our Third World countries are pretty powerful. Are they participating at all in any of your programs? Because it's really very important when our patients are going over to Kenya and elsewhere, we just tell them we'll fly them back if they get into trouble because we don't want you to have any blood over there. DR. EL-NAGEH: Unfortunately, not as yet. But surely they are welcome. Anyone is welcome really to contribute. We have a small grant from Gates Foundation. It is not enough. It was $5 million over five years for the whole world. You can see that it is not enough. We have a lot of ideas to be considered, but we are looking for the resources, and when we say the resources, it is the expertise and funds. DR. PENNER: I'm just suggesting you might to try to galvanize them into action because they really have a need here. DR. EL-NAGEH: Surely I will take that and consider it. DR. GOMPERTS: Thank you very much, Dr. El-Nageh. We need to take a brief break, and we'll reconvene at 10:15. [Recess.] DR. NIGHTINGALE: Could I ask the committee members and the audience to please take their seats? At least begin to do so. Folks, could I ask you once again to please take your seats? We are now almost 50 minutes behind schedule. That means we're 10 minutes ahead of schedule. That means we don't have a lot of slack. DR. GOMPERTS: Our first presenter in this part of the session is Dr. Lackritz, Centers for Disease Control. DR. LACKRITZ: Is everybody back? Okay. I'm from CDC. I'm going to start by talking about the new LIFE initiative, which is CDC's program through the Global AIDS Program, and then specifically get more into the blood safety agenda. The LIFE Initiative was started last year, which was an emergency appropriation to USAID, HHS, Department of Defense, to address the global AIDS crisis, to curb not only the threat of the epidemic to the nations but also to the health security and economic stability of the world. So a comprehensive plan was drawn up for action, and that included the following bullets on the screen: primary prevention of HIV, that's through sexual, mother-child, and also bloodborne, which is probably most relevant to the group here; AIDS treatment and care, including improving access to antiretroviral therapy, prevention and treatment of OIs in the periphery and community-based care; and, finally, to expand surveillance system and capacity building among national AIDS programs. Next slide. There are a number of U.S. agencies working on this. USAID is the coordinating agency; HHS, including CDC and HRS; Department of Defense; and this year, in 2001, Department of Labor and Department of Commerce were added to the initiative. Next slide. Our allocation last year, these emergency funds for CDC, totaled $35 million. This year that appropriation increased to $104 million; $3 million of that goes to HRSA. So in terms of a comprehensive AIDS program for the world, it's limited. But I think we can develop very practical initiatives that we can start to fill the gaps that are needed in developing countries. Next slide. The year 2000 countries are in sort of grayish-yellow color. 2001, we've added more countries in Africa, Brazil, Guyana, Haiti, and three countries in Southeast Asia. The priority countries were identified where the epidemic was hitting hardest. All these countries are extremely resource-limited. Next slide. Our general approach to how we're going to address our scope of work is working strongly with country nationals in developing country leadership and ownership of the initiative. We're focusing on priority needs identified by the country and promotion of in-country expertise and institutions. This initiative is going to require a lot of coordination and collaboration with multiple governmental and nongovernmental organizations, and I hope that this forum is a good opportunity to start forging some of those partnerships with agencies that can assist in making a difference. Next slide. Okay. So let's start thinking about the blood safety component of this, then. I just wanted to show this slide first to get at the burden of disease that's facing many developing countries. My presentation is generally going to be very Africa-focused and very HIV-focused, but I think that this is relevant to blood safety in other countries and to other components of blood safety. This data is actually from Kenya, a study that we did some years ago, where we surveyed all children who came onto the pediatric ward. Twenty-nine percent of all pediatric admissions had hemoglobins below 5. Twenty-one percent of all children who entered that hospital received a blood transfusion. Mortality rates among those severely anemic children were staggering. We had 18 percent mortality rate and that compared with 8 percent among those with hemoglobins of 5 or greater. Among all children who died in hospital, 48 percent, nearly half of those, had a hemoglobin below 5. When we followed kids out for two month after their discharge from hospital, in a subset of these we had a 29 percent mortality rate. Next slide. Children and women are particularly hard hit in Africa, in particular. Children both in Cote d'Ivoire and Kenya are shown on this slide; similar data is available out of Tanzania, Malawi, former Zaire. Children generally receive about two-thirds of all blood transfusions, primarily for the treatment of malaria-associated anemia, and often complicated by nutritional deficiencies. Women receive basically about the next one-third of all transfusions, primarily because of obstetrical complications, complications of pregnancy, narrow child spacing, and severe anemia during pregnancy. Next slide. The other challenge then is not only you have the frequent use of blood, but how then do we get safe transfusions to these folks who need it? When we look at HIV prevalence--this is in a multi-center evaluation of six hospitals in Kenya. HIV prevalence in the donor population is very high. This is 1994 data. It's actually increased since this time. We had 20 percent HIV prevalence in two of the hospitals. And as Jean Emmanuel indicates, throughout the continent it can be even higher. Next slide. And that's because the epidemic is so staggering in many countries, and this slide shows the HIV prevalence in the general adult population, which means that identifying safe donor populations in this kind of context is very difficult. Next slide. When we actually looked at the risk of HIV transmission in these six hospitals in Kenya, this was in a very high prevalence area with decentralized blood transfusion systems where testing is done in peripheral hospitals. We found that one-third of all HIV-positive donations were not removed from the blood supply. This was in a study where we were providing test kits to the hospitals if they didn't have them. So there are a number of problems going on that contribute to this risk. There were recording and labeling errors. One hospital was not screening transfusions that were collected from the mother and given to the child under the erroneous assumption that mothers and children all had the same HIV status. We breaks in the cold chain. We saw equipment problems. And in some cases, there was some suggestion that there was testing after the transfusion had occurred, similar to what we heard from the Latin American experiences. Now, what you can see and probably the most important bullet of the whole talk, I think, is that we found that 1 in 50 transfusions in this multi-center study transmitted HIV. This risk is unacceptable. We have inexpensive and practical technologies that can virtually eliminate this risk. So I think in answer to Dr. Klein's question on what can the HHS do to address this performance, I would expand that to sort of what can the HHS in partnership with all these other agencies, many represented here in this room today, what can we all do? I think that we have an opportunity now to step up to the plate and share the amazing technical capacity that we have in the United States and decrease the global inequity in this most preventable mode of HIV transmission. Next slide. Now, building capacity, one of the things that we need to do in terms of the practical application of this--could you back up one slide? I think we skipped--are we going forward or backward now? Okay, now forward. There you go. Great. Now, addressing the problems in blood safety in developing countries is challenging because safe transfusion involves this series of complex and interrelated activities. There needs to be an adequate supply of blood collected from low-risk donors. Blood needs to be tested for infectious diseases. There needs to be good ABO typing, perhaps cross-matching. It needs to be stored and available for immediate use. There's a large amount of severe anemia developing in the community. Those folks have to access health care facilities, and then in the facilities, severe anemia needs to be recognized or other indications for transfusion. Transfusion indications need to be appropriate, and blood needs to be available, transported to the wards, and given to the patient and monitored effectively. Next slide. So, in that setting, it's challenging because each one of those steps, it's sort of links in a chain, and any weakness in one link is difficult to address the whole system. But we do need to develop comprehensive programs to address the problems that we're facing. And I'm going to go through about four slides now about these different components and what in the CDC Global AIDS Program we plan to approach. One is sort of in strengthening organizational capacity of the countries. We hope to work closely with WHO and other international partners to promote development of national blood transfusion services. We need to strengthen the managerial capacity and regulatory oversight of transfusion services, quality laboratory testing, and quality management. We need to develop national policies on transfusion services, laboratory standards, and the appropriate use of blood. Next slide. Our approach is to develop strategies that are appropriate for the local condition. Now, this is going to vary a lot by country. We recently received a request, for example, from the Democratic Republic of Congo, formerly Zaire, which reported to us that they have two functioning ELISA machines in the entire nation. So one of our strategies, then, among these appropriate technologies is to provide laboratory equipment for blood storage and infectious disease testing. We need to evaluate and implement inexpensive testing technologies that are appropriate for each of these local settings. Training is a big component of this. This has been emphasized in the other talks this morning in terms of testing, recordkeeping, stock management, not only of reagents but also of the blood products themselves. Training of supervisors and managers is key to ensure that there's an uninterrupted supply of reagents, that there's functioning equipment, and there's quality testing. Next slide. Okay. So what about availability of blood and trying to increase donations from volunteer blood donors? We do need to identify strategies that will work to improve recruitment and retention of low-risk donors. In many countries there's no functioning system to do this at all, and we need to learn how to promote voluntary donorship. We'll be providing assistance and rapid assessments to try to identify low-risk donor populations, be those young donors, old donors, different ways to bring those folks in and keep them HIV-negative through rigorous education programs. We need to support development of volunteer blood donor education and mobilization programs, assist in the development of donor deferral strategies that are relevant to the local setting, and strengthen capacity for HIV prevention, education, and post-test counseling of blood donors to keep those folks negative, and to make blood donorship an inroad for HIV prevention programs. Next slide. Then I think it was emphasized in the other talks as well, but there needs to be a very important focus on increasing the appropriate use of blood. If we do have an increase in the amount of blood stored and available, we have to make sure that it's not abused. We need to assist in development of national and local guidelines on appropriate use of blood, support training of health care providers on the use of blood, promote access to and use of volume expanders for acute blood loss, such as crystalloids. Very often, very simple interventions of this are just not available. Again, improve laboratory capacity for hemoglobin screening in the outpatient and inpatient settings. A lot of places don't even have these simple technologies available to them or their laboratories are organized in such a way that you just can't get a hemoglobin any time of day, on the weekends, during nights, that type of thing. And, finally, I think a very important component that's often overlooked because we think of transfusion as a hospital-based activity, but we need to strengthen primary health care programs to prevent severe anemia from ever happening in children and pregnant women. Even when people come in for transfusion, their chance of survival is very poor. It's very much a last-ditch effort. And we need to figure out how to access those folks earlier and prevent them from ever coming in to need blood. Next slide. Now, improving the capacity of countries and the safety of blood overseas benefits the U.S. public health directly. For the obvious reasons that were just brought up earlier, we reduce the risk to U.S. travelers abroad. In addition to that, we need to assess performance of commercially available HIV assays among non-B subtypes that are found in other countries. We need to develop seroconverter panels for non-B subtypes. We need this for two reasons. One is we're assuming that the assays we're using are the best ones to use overseas, and we really don't have any data to know that. Secondly, we do live in a global village. We do have many travelers coming to the U.S. donating blood, and we need to make sure that the assays that we use on our U.S. blood donations used for transfusion to U.S. patients is picking up those HIV variants that are found internationally. Similarly, we need to monitor for emergence of HIV variants not detected by commercially available assays. Group O is a good example of this. A lot of variants do come from Africa. It's always been a source of importation to the U.S. and a risk to the U.S. blood supply. And, finally, as we monitor for new and emerging pathogens internationally, these pathogens, that gives us information on how we can prevent transmission of these pathogens in the U.S. Most recently, HHV-8 I think is a good example where that's being debated here, and we currently have a study ongoing in Uganda where the HIV prevalence--sorry, the HHV-8 prevalence is extremely high, about 40 percent whole blood used for transfusion. And so we can probably get sort of a more rapid assessment on the risk of HHV-8 transmission more quickly. Next slide. I think in addition to our programmatic agenda, we need to develop and closely link with an evaluation and strong operational research agenda. I think there are numerous research issues that need to be pursued by CDC, by NIH, by our other nongovernmental partners. I've listed a few of the more key and basic operational research questions here. It's a short list and doesn't really adequately list sort of what are the opportunities in research internationally. But I think we need to figure out how to identify low-prevalence donors in these very high-prevalence populations. Many blood banks have gone to younger and younger age donors in an effort to get safer blood because the prevalence of HIV is less. Often blood campaigns are conducted in secondary schools in many African countries. However, those are very high incidence populations, and we need to assess the incidence among donor populations to decrease the possible risk of window-period donations. We have no information on this currently. We need to improve our understanding of volunteer blood donation in the context of local cultures, norms, and taboos. And we need to evaluate the impact of HIV testing and counseling on donor recruitment and testing. A lot of people are afraid of donation because of an HIV test. There's a lot of stigma, even more so in Africa than even here, and we need to figure out how to address that barrier. Next slide. And, finally, there are a lot of risks to transfusions in this setting, both HIV-uninfected people but also in the prevalence of HIV is so high in the population, there is a whole area of research that we haven't quite yet figured out about whether transfusion and when transfusion is beneficial to folks who are--to patients who are HIV-infected. We don't know how transfusion is affecting their hematologic recovery, which can--they can get probably a lot of bone marrow suppression. We don't know how transfusion is improving their chance of survival. There are also a number of pathogens that are not screened, typically, in resource-restricted countries such as HCV. This may disproportionately put HIV-infected persons at risk. Other pathogens, such as CMV, malaria, and we could go on. But, in general, there are a number of research and programmatic activities that need to be addressed. It's a very ambitious program. But I think it's a good challenge for us at this time and an opportunity for all of us to work in partnership here and to start to tap the expertise. Much of it is available even here in this room to move forward and make a difference. Thank you. [Applause.] DR. GOMPERTS: Thank you, Dr. Lackritz. Questions from the committee? Dr. Hoots? DR. HOOTS: Since women and children are the primary recipients of the high-risk blood and since obviously one of your goals is to reduce need for blood--and you mentioned screening--what is the status in particularly Equatorial Africa? I mean, in terms of--I know adjustments have been made based on perinatal HIV, in terms of breast feeding, but in other contexts it was encouraged and then discouraged, and then somewhere in between. But I presume the same issues that relate to screening of blood relate to other laboratory assessments of the population, even something as simple as iron deficiency assessments. Is there a broad approach--because I would surmise, at least particularly since dietary-wise they're not likely to get high amounts of diet, and perhaps after multiple pregnancies, the women are going to deplete all their iron supplies because the baby's going to take it away. Is there any sort of across-the-board programmatic look at the impact that iron deficiency has in these two groups and whether perhaps even just dietary intervention across the board might be the most cost-effective way to reduce the demand for blood in women and children? DR. LACKRITZ: Yes, I think there are two. In fact, I would say dietary and second I would say malaria prevention. DR. HOOTS: Right. DR. LACKRITZ: In terms of community-based dietary efforts--and, you know, perhaps WHO would want to comment on this--the strategies could be fortification of foods, which we do in the U.S. generally, I mean, that's not universally accepted intervention. What I also didn't--but also you could do iron supplementation or else mass education on using available foods and preparing them in such a way that it improves bioavailable iron in the diet. There are a lot of iron-rich foods that are inexpensive in the community. They need to be used and they need to be prepared properly. Okay. So even without fortification or iron supplementation, there are some more basic activities that could take place in the community. What I also didn't show is all those children are generally under two years of age. They're very young. And what tends to happen in these types of environments is when you have these infants born in malarious areas and once their maternal antibody to malaria wanes, then they become at very severe risk. Now, this is also the time where you get a weaning diet on top of that, so I think the fact that you bring up both of these is important. In terms of nutrition, again, what happens is you sort of have a distribution--I didn't bring my distribution curves with me, but you have a distribution of hemoglobin in the community, and it's very alarming. In this setting, you have about 20 percent of the kids walking around in the community under two have hemoglobins below 7. So one other malaria insult is going to completely put them in a very high-risk population. Okay. So that's the community side. Interestingly, too, this is not recognized clinically, of course. Anemia doesn't really have a symptom. It doesn't have a fever or jaundice or, you know, you don't get diarrhea. So it's a completely silent epidemic. And unless we take a public health initiative to address it, people are not going to come in for care to treat it. In terms of malaria, it has been shown--there are a number of things that have been shown to be effective: impregnated bed nets at the community level reduces transmission and increases the hemoglobin distribution of the community. The second thing is use of effective antimalarials. There is chloroquine resistance across the continent right now and in many other areas as well. And yet chloroquine continues to be used under the false pretense that it's--well, it's inexpensive, I guess, but it doesn't do anything. In Kenya, we have 90 percent sort of moderate or severe resistance to chloroquine. Now, there's a very large research agenda now to look at other effective treatments. Even using something like fancidar (ph), which is about, you know, a 20-cent single-dose treatment, will radically change the children's capacity to increase their hemoglobin. When we looked at--and sorry I'm going on so much about it. I'm very passionate about this topic. So when we actually compared people who were transfused, non-transfused, people who got chloroquine versus fancidar, basically if you got malaria after your transfusion, it negated the benefit of the transfusion. So if you were transfused and you received an effective antimalarial, basically it cleared the parasites so that your body could re-tick up again. So I would say effective malaria treatment, community-based prevention of malaria, and community-based efforts for nutrition. DR. GOMPERTS: Dr. Davey? DR. DAVEY: Following along on that, if I recall your study from Zaire, one of the other key issues was the timing of transfusion, that these children, if they needed transfusion, got it early, it was beneficial. But many got transfusion a day or two later, and in that case it just entailed the risk of transfusion because they were going to probably survive with malaria treatment at that point. Is that correct? DR. LACKRITZ: Yes, that's correct. And I think that--what Rick's talking about is that what was happening is when children come in with severe anemia, they tend to die very quickly. Now, in this setting, there's no system for collection of blood from volunteer donors, testing it, storing it, so it's not available. What tends to happen is a patient comes in, the family member has to go out, usually buy a bag of blood, if one's not available, and then find the donor to donate the blood. So that takes--and then it's tested. So it takes generally days before that transfusion becomes available. So what happens is the people who needed it didn't get it. The people who were at risk of death have already died. And then what that leaves you is a lot of misuse of blood because these people who--there's a clear survival phenomenon, and the people who are able to survive two days of hospitalization are at very low risk of death. So, I mean, the band-aid on the blood safety problem, of course, is putting rapid tests in every district hospital all over the place as much as you can. But that still doesn't get at the system problem that we're also going to need to address on the longer term, which requires a lot more long-term and expensive capacity building. DR. GOMPERTS: Dr. Dalal, you had a question? MR. DALAL: In your comments and in the comments of some of the speakers preceding you, there were suggestions made with regards to the availability of low-risk donors and approaches towards accessing them. My observation is that in some of the developing countries low-risk and high-risk donor pools often break down on societal lines, income lines, ethnic lines, geographic, lifestyle, and so on. And while it's clear that you can make a separation between volunteer and paid donors, to what extent is it practical to actively identify and solicit only low-risk donor groups versus the population at large? DR. LACKRITZ: Some countries with very severe epidemics, such as Uganda, Zimbabwe, have been able to do this. They require donors. They give them a lot of education, HIV prevention strategies, and they try to retain them for repeat donation. And that's been the strategy. So in Uganda, for example, where now probably 15 percent of the adult population, they have less than 5 percent of HIV in their donor pool. In Zimbabwe, it's even lower than that. There's another interesting--I mean, studies have been done, for example, in Cote d'Ivoire where they were able to identify deferral strategies such as contact with commercial sex workers and history of STDs. The other interesting thing I'd like to add is that after the bombing of the U.S. embassy, there was extreme shortage of blood in Kenya. And many volunteers poured out from all over the capital city of Nairobi, and the marker rate at that point was about 2 percent, which is a lot lower than their general 7 percent. So whatever--I mean, of course, we have no information on those people because it was during sort of a catastrophe. But it points to the fact that people somehow self-select, and somehow people in the community are low-risk and maybe know they're low-risk, and we have to just figure that out. It's up to us, I think, to learn that. DR. GOMPERTS: Dr. Gilcher? DR. GILCHER: My question is similar, and it relates to rates of seroconversion. In general, if you want a large number quickly of people who are negative, you go to your younger population. On the other hand, if you want people who will sustain negativity, you go to the older population. And that in a way would be of help in selecting a low-risk donor base. That was similar to your question. Could you comment on that? DR. LACKRITZ: Yes, I think that's a very good question. There was--Willie McFarland did a study in Zimbabwe and found that the risk of prevalent donations were sort of opposite--and this makes sense--were opposite that of the risk of incident donations, that those young unmarried donors had very high incidence; older donors had very high prevalence, you know, probably close to 30 percent, if I recall, but very low incidence. So potentially--so we don't--you know, I mean, I think that's the research agenda. We have to figure out what the best strategy is. It may be to go to older donor populations, screen out your 30 percent, and retain the 60 percent for continued donation. I think there are a lot of practical opportunities, and we just have to explore them and pursue them. DR. GOMPERTS: Mr. Allen? MR. ALLEN: Kind of a two-part question here. What are some of the barriers that you may be experiencing with the government agencies in some of these countries? Are there any issues, first of all? And, secondly, I work with people that have lived--you know, were born in either Nigeria, Liberia, Malawi, and Ethiopia, and there seems to be a common thread when I talk to them about blood safety and the issue of HIV. And part of that issue is that in a lot of these villages the people tend to feel more comfortable with the local, say, medicine man or medicine person versus going to one of the local clinics. They say there's a lot of fraud and things that have gone on in the past and that kind of prevents them from even considering going to one of the local clinics versus the medicine person. But they said if the medicine person in a lot of these cases were either willing to listen to some of the local health people and maybe at least tell his people that are seeing him to not necessarily, you know, don't use the local facilities as well, that that might open up the door, at least to get some of these people educated on some of the other opportunities there. Do you see any of that? DR. LACKRITZ: No. I think we've underutilized traditional health workers in the provision of health care and in community health education. And so I think we really need to strengthen those ties, because I think if we think we can go in with some kind of vertical program through Western medical systems, I don't think they'll be nearly as effective as if we try to work with the traditional healers in the community. I mean, they're not only sort of--they're not only medical people in, I think, the sense that we think of like going to a doctor--maybe it is. I don't know. But they're really leaders in the community, and there's almost--not quite a religious component to it, but there's sort of a--yeah, that's right, and a belief system. You know, and we--it's like anything. You really can't impose your structure on somebody else. You have to figure out how to work within their structure. So I think that's a good point. Did you have a point before that? MR. ALLEN: I was just wondering if you have any-- DR. LACKRITZ: Oh, barriers with governments. Yes, I think it's interesting, too, even working with--I think governments across the board have requested our assistance in blood safety. I think the U.S. has been very underrepresented in their capacity to provide technical assistance internationally. The transfusion services that we've seen have primarily been supported by the EU. The U.S. has a very small role--has had traditionally a very small role to play. And we have a lot of resources. We have a huge amount of technical capacity. So I think this gets to Dr. Klein's question, is we have an opportunity here to harness some small proportion of our resources and intelligence that's in this room and try to make a difference. There are a lot of barriers not necessarily to working with--there are organizational structure barriers that Dr. Emmanuel mentioned that are very real. Transfusion services are often under medical services organizationally. They don't have a protected budget. I mean, there are sort of--so transfusion needs to be heightened in terms of its presence in government because, otherwise, the budget falls to some district hospital. They've got a lot of competing health priorities and often transfusion can't be supported adequately. I think the other barrier is that we do all these fancy things in the industrialized world. You know, they see us doing P24 testing, NAT testing. Now we're going to try to tell them to use rapid tests that aren't even licensed in our country? I mean, you know, nobody buys that. So, you know, they think we're trying to sell them some kind of second-best thing that we wouldn't use in our own country, and what's often difficult to translate is what we do in our country is often not really based on--well, excuse me, I-- [Laughter.] DR. LACKRITZ: I'll just stop there. You know, attention to cost-effectiveness, or even in treatment algorithms, we just make our best guess. And then that becomes our policy, and, you know, it's very difficult to then try to develop a practical strategy. DR. GOMPERTS: Dr. Lackritz, thank you for the information as well as the input and perspective. We do need to move on. DR. LACKRITZ: Thank you. DR. GOMPERTS: Dr. Epstein, FDA perspective. DR. EPSTEIN: Thank you and good morning. I'm going to just describe briefly the areas of FDA's engagement in international collaboration for blood safety and availability, and I'm going to highlight the following areas: the role of U.S. regulatory standards, our involvement in developing WHO reference reagents and standards, cooperation that we have with a variety of international policy groups, some particular bilateral agreements with developing countries, the general area of scientific exchange, and a few additional ad hoc activities. These are summarized on the first overhead, and we'll just move quickly to the second one, please. So, in the area of U.S. regulatory standards, it's been pointed out by many of the previous speakers that a national program, including government engagement, support, and oversight, is fundamental to the existence let alone the health of a blood transfusion system. And, in particular, FDA's statutes, regulations, and guidance documents are widely used as models by national control authorities, both in the developed and the developing world. The U.S. has been on this model for about 100 years now, starting with the Virus Serum Toxin Act. Now, additionally, it needs to be recognized that the FDA is a net exporter of blood products, particularly plasma derivatives, and that blood products conforming to FDA standards meet many international needs. The United States treats the export of U.S.-marketed products as interstate commerce, and we make no distinction. So if a product is legal in U.S. commerce, it's legal to export. And, indeed, the FDA does not and cannot under existing law control whether the product stays domestic or is exported. Let me note, however, that there are also provisions in the law for exemption for U.S. licensed manufacturers to manufacture non-U.S. products; in other words, they can be made solely for export. So we're involved then with providing both products and standards and do provide a large part of the world need for certain blood products. Next, please. Now, in the area of reference reagents and international standards, Dr. Emmanuel mentioned that FDA is a WHO collaborating center in the area of biologics, that CBER's director--that's the Center for Biologics Evaluation and Research, one of the FDA centers, where I work. Our director currently chairs the WHO expert committee on biologic standards and through that mechanism contributes to global standards. Additionally, many FDA staff members participate in a variety of WHO work groups across a broad spectrum of issue areas, including blood diagnostics, blood standards, but as well as vaccines and others. Furthermore, FDA scientists routinely help the WHO to develop international reference materials and standards, and some of the examples in the blood area include the antibody standards for HIV-1, HIV-2, as well as hepatitis viruses. More recently, we've been involved with the developing the international standards for RNA for HIV and hepatitis C. There are also efforts now going on for hepatitis B Parvovirus. We have developed reference materials for standardization of the potency of clotting factors, also blood grouping reagents, and an ongoing current initiative is to develop reference materials for transmissible spongiform encephalopathies. Next, please. The FDA also has historically been highly involved with a number of international groups involved in policy, and it's been gratifying to hear earlier this morning how well people seem to understand the fundamental role that policymaking plays in the utilization of resources and establishment of appropriate controls. So some of our activities in this area include the following: We have been very active as participants with the Council of Europe, which develops annually a document called the "Guide to the Preparation, Use, and Quality Assurance of Blood Components." Similar to FDA's standards and guidance, this is the recognized EU standard. And although the standards of the EU and the standards of the U.S. are not identical, there is a process whereby harmonization is driven by the fact of scientific exchange. You know, if you bring together the experts who are responsible for the policymaking, they talk together and they tend to reach consensus, and that is then reflected in the policies being harmonized. And just as the U.S. standards are a model for developing countries, likewise the guidance document of the EU becomes a model for difficult. Essentially, this guide is a series of monographs on how to make and quality control all the various blood components. Additionally, as has been said, we have participated from the inception in the Global Collaboration for Blood Safety. The United States was one of the 40 or so nations which endorsed the 1994 declaration on global safety as well as signing the subsequent resolution of the World Health Assembly. And we have remained an active participant in the preparatory meetings and last November's first actual meeting of the GCBS. Additionally, we have been a founding member and participant in a body which is called the International Conference on Harmonisation. This is an international group which includes governmental bodies as well as industry, and it has met for the better part of the last decade to talk about harmonization of international standards for the evaluation of pharmaceutical products. Now, the focus of the ICH has not been on labile blood components, the things that are directly transfused. However, within its scope, there is the inclusion of plasma derivatives, which are in most places in the world regarded as pharmaceuticals. And let me also mention that we have had international contact with consumer-driven organizations. Of course, we are very active domestically with consumer advocacy groups, many of which are themselves parts of international groups. And one example is the World Federation of Hemophilia where we have participated regularly in the international meetings. And, of course, the bilateral exchange contributes to our thinking and hopefully assists us to be most appropriate as we develop product standards and transfusion-related policies. Next, please. With respect to bilateral agreements, I think the important point here is that our existing regulations, which I've cited here--21 CFR 20.89--do permit to share regulatory information with established national regulatory control authorities of other countries. Now, we, however, maintain close relationships with a fairly small set of countries. In particular, in the Western Hemisphere, we have annual and biennial meetings with Canada and Mexico. We also have what we call trilateral meetings that used to involve the U.K. but now involve an EU representative. We also have had historic close cooperation with the regulatory authorities in the U.K. and in Japan. Now, we have also some bilateral agreements at the level of assistance, development assistance. However, I need to explain that these are indirect. Usually they come about when we have a funding source outside of the agency, such as the USAID, which approaches the agency and says, Would you cooperate in this initiative? And under that umbrella, we have engaged in specific assistance projects in India, in Egypt, and most recently in Russia. Next, please. Other speakers have drawn attention to the need to provide expert training in the area of transfusion medicine and blood banking. FDA is highly involved in such training through scientific exchange programs. We sponsor fellowship training, and we hire visiting scientists, primarily through the Fogarty International Center. For example, at this point in time, just within the blood program, we have six funded Fogarty positions, and these research fellowships provide opportunity for scientists to come and train at the FDA where they learn about regulation and control as well as doing laboratory work. For example, we have a person from Cameroon who visited us and worked on virus variants, including HIV-1 Group O. But also these kinds of contacts foster future cooperations and dovetail very neatly with a second area of scientific exchange, which is simply scientist-to-scientist collaboration. The FDA scientists freely collaborate with their international colleagues, and, for example, right now in the blood office we have projects ongoing on HIV variants, HCV epidemiology, and diagnostics for leishmaniasis. Next, please. There were some activities that I found hard to throw into one of the previous bins, so I just called them ad hoc. We provide technical advice. Many countries simply contact the FDA on an ad hoc basis for advice on blood products and on blood regulation, for example, product safety standards, manufacturing methods, and techniques of regulatory control and authority. And we do our best to respond to these requests. Assistance of that form generally is handled through the Deputy for Medical and International Affairs, who previously was Dr. Elaine Esber, who has now just retired from CBER. However, the office is still maintained and I presume that at some point there will be a successor. And, additionally, when they have occurred, we have provided support to blood initiatives at the international level, a recent example of which is the World Health Day, where we were contributory both to the WHO initiative and to the initiative of PAHO. So, in summary, on the last transparency, the FDA will continue to support the WHO and the Global Collaboration for Blood Safety, for which WHO is the Secretariat, as well as other international efforts. We do maintain contact with other groups such as the Red Cross, the AABB, various academics, et cetera, who have these international engagements. It's my personal opinion that FDA's best role is to provide leadership for policy and for product standards because we are not funded to any significant degree to provide material support. However, we can provide limited scientific training and technical assistance through the kinds of exchange that I described. And lastly, because we are research-based, we also provide collaboration through support of international research. Thank you very much. [Applause.] DR. GOMPERTS: Thank you, Dr. Epstein. Any questions? Yes? DR. LOPES: I was reading about a purified hemoglobin product that's being derived from cattle blood and tested in South Africa. Is it your assessment that these kinds of substitute products are going to make a big difference in the near term? DR. EPSTEIN: Well, I think that the relative risk and benefit of these products is, in fact, very different in different countries. In the South African situation, where you have a very, very high rate of HIV and, you know, a resource-stressed environment, there may be willingness to consider products whose safety profile may not be optimal in the United States, where despite, you know, the tremendous anxiety that surrounds use of blood products and transmissible disease, blood products are, in fact, astoundingly safe. And so we have a tremendous challenge to figure out the role that so-called blood substitutes might logically play. Blood substitutes are also somewhat a misnomer. They are actually resuscitation solutions. In some cases, they may be bridging therapies until there is availability of a transfusion. They have short half-lives in the body and, therefore, in many instances cannot avert an allogeneic transfusion. And so figuring out their best therapeutic niche is itself a challenge. So I remain optimistic about these technologies. I think that, you know, the fact that you can sustain life in people with astoundingly low red cell hemoglobins by providing oxygen-carrying compounds, including hemoglobin-based pharmaceuticals, is amazing. But we have yet to figure out what the best medical use or validated medical claim for these products will be in the U.S. environment where the therapeutic ratio of blood products is itself, you know, tremendous. So I think worldwide they certainly offer a new venue for technological advancement and that they will play a role. Exactly what the role will be in the U.S. I think it not so straightforward. DR. GOMPERTS: Thank you, Dr. Lopes. Other comments? Dr. Davey? DR. DAVEY: Jay, as you remember from the last meeting of the GCBS, one of the issues--I think Jean mentioned this also--was perhaps the development of a series of graded sets of standards, if you will, maybe three different sets of standards, all of which meet minimal requirements but can be applied to countries in different levels of development. Do you see the FDA playing an active role in the development of these standards, or what are your comments about that? DR. EPSTEIN: Well, yes, through the GCBS I see us playing a very active role. I myself chaired the working group of the GCBS on this policy group. We have had--I think it was three preparatory meetings prior to the first meeting of the GCBS where we talked about this issue. I'm very much of the mindset that the technology and its use have to be appropriate for the global health system. There are those who have called this the public health wellness model; in other words, try to look at the whole and then do what is appropriate by whatever measure, whether that's a cost-effectiveness measure, an outcome measure, et cetera. And the notion has come about that one needs to try to replace, you know, the quest for high technology with the quest for appropriate interventions at any particular stage of development. And there is this concept that if we can conceptualize a continuum of development where there can be benchmarks and, with that, appropriate recognition that stages of blood safety and appropriate use have been reached, that this might go a long way toward alleviating this natural pressure to, you know, just bring in the PCR machine, whether or not you have an infrastructure to support it and whether or not you're delivering, you know, even generation one antibody screening to the majority of blood recipients. So, yes, I think that we do have a role to play, and I think that we are willing to step up to the plate. And I think that one of the insights here has been that this process is also of value in the developed world for just the reason that Dr. Lackritz flirted with, which is that there are elements of irrationality in the developed world, and that if we can bring about some kind of conceptual framework where we talk about, you know, good policymaking, then, you know, hopefully to clarify the technology challenge, you know, the available tools, their cost, their effectiveness, and benchmark monitoring, that that would also advance the situation of the developed world. So it's sort of a two-way street. DR. GOMPERTS: One last question. Dr. Guerra? DR. GUERRA: Jay, thank you for a very informative presentation. You made reference to some of the countries having regulators that I guess perhaps would be somewhat comparable to the FDA. But some of the countries that need to have regulators were not on your list. Is there some hope for the future that they will have them? And in those instances where there are regulators, how comparable are they to the FDA? Do they have the clout to really move quickly and do recalls or get things done that have to be done? DR. EPSTEIN: Well, of course, the spectrum is very, very wide. You know, you have some countries where there's no effective national body dealing with transfusion safety, and then you have countries that have bodies quite analogous to the U.S. where there are central laboratories, where there is a foundation in law, where there are inspectional programs, where there are effective controls of reagents, where there are recalls, et cetera. You know, in broad brush, you have very effective systems in places like Australia, Japan, Canada, Western Europe. And you have sort of areas where there is significant development and they're not quite to that level, such as in India, and you have, you know, many areas where these kinds of controls are lacking. I'm really not the best person to speak to that. I mean, Jean Emmanuel is here and has, you know, vast direct experience interacting with governments around the world and assessing the status of the national authorities. I think the most important point to recognize here is that it is a fundamental principle that you cannot have a safe transfusion system in a country that lacks a national perspective on the importance of transfusion, that there has to be a government role and that there has to be some centralized system, at least of oversights and standards. DR. GOMPERTS: Dr. Busch? DR. BUSCH: Jay, we've discussed the issues of test technology and blood substitutes in terms of the high standard of safety that's imposed by developed countries like the U.S., and at some point that sort of precludes the availability of less expensive, perhaps more practical technologies. The third area is pathogen inactivation where, again, we're seeing technologies developed with the orientation toward, you know, resource-rich countries and, therefore, the requirement that these compounds be removed with expensive technologies, et cetera. From your knowledge of the technical capacity of these methods, do you see a role for a broadly capable pathogen inactivation method that could even perhaps preclude the need to do testing in developed countries? And then if so--in terms of do they have the capacity to actually remove the pathogen at a level that would be required? And then, if so, is there a way to create a sort of two-tiered strategy that these companies could be motivated to develop a technology that could be inexpensive and broadly applicable in resource-poor countries? DR. EPSTEIN: Yes, well, I again am optimistic. I think that we're seeing some marvelous technology development in pathogen inactivation that will be suitable for the labile blood components, the transfusable components. As I said before, I think that the risk/benefit profiles need to be examined in the country-specific context and that some of them, as you know, are already in use. I mean, gentian violet is used in many parts of South America to kill Chagas. You know, methylene blue is used also in many parts of Europe to treat fresh frozen plasma. We have made tremendous strides in the U.S. with viral inactivation technologies for all the plasma derivatives, and we have one pooled plasma product, as you know, which is solvent detergent treated. The question that you're asking is: Can it ever be cost-effective in the developing world and would it ever supplant screening? Well, I'm in no position to comment on what could be done with cost. You know, certainly there are material costs and labor costs in processing a unit of blood to treat it to inactivate pathogens. Those will never be zero, and whether they'll ever be affordable, I can't comment. With respect to the need to additionally screen, I think there are sort of two edges to that sword. On the one side, you could say, well, if it's highly effective, you don't need to screen. On the other hand, there's always the notion that you want to keep the input burdens low so that you can assure the effectiveness of the inactivation technology. You know, you'd like to be treating low-level contaminations rather than high-level contaminations. And then there's always the notion of just, you know, belt and suspenders. Whether we would ever move off that paradigm and simply accept inactivation I'm not prepared to say, but I think that that will be a very lively debate. DR. GOMPERTS: We do need to move on. Thank you, Dr. Epstein. Our next presentation is Dr. McDermott, NIH international activities. DR. McDERMOTT: Well, I've gone really low tech with overheads. I don't know if that's because I've worked too long in developing countries or because I'm just a control freak. But, anyway. I want to thank the organizers for providing me with this opportunity to address the committee and to talk a little bit about some of the blood safety activities that NIH has been undertaking. And I'm going to focus basically on the activities within the Fogarty International Center because that appears to represent most of the NIH efforts. First of all, I'll give you some background about the Fogarty programs to help you understand how the blood safety activities fit within those. So the next overhead, please. The Fogarty International Center is a center within NIH with the mission of promoting and supporting scientific discovery, support scientific research and training internationally to reduce disparities in global health. And in the next overhead, FIC fulfills this mission by basically advancing both biomedical and behavioral research and research training to prepare current and future health scientists. Next? And I'm going to focus on the training programs and the extramural training programs, and these are programs in addition to the programs that Dr. Epstein just talked about, which are considered more the intramural ones. Basically, the training grants are awarded in a competitive process, generally to--institutional training grants generally to U.S. universities but not exclusively. And the awardees are generally grantees who have current NIH research and also demonstrate research collaboration with the foreign research institutes. So each one of these training grants, the PIs need to identify major foreign collaborators and institutions within the countries that they're going to support the training. Basically, the purpose of the training grants are to support training for research capacity building for scientists from the developing countries. So the bulk of the money is used to train foreign scientists. Having the program set up in this way actually does help prevent some of this brain drain because it works two ways. If there's ongoing research in the country, once people are trained there is something for them to go back to. And I also think the quality of the research coming from these collaborations improves when you have people in-country who are understanding the research and understanding what you're trying to do. Okay, next overhead. Okay. Basically, the support that's available through the training grants are long-term training, including master's, doctoral degrees, and post-doctoral fellowships, and also short courses, either within the U.S. or in-country short courses. In addition, in order to also support trainees when they return home, there's grants to support the in-country research, to support either their thesis or doctoral degrees, and also some re-entry grants for trainees when they've completed their training. There's very limited salary and administrative support for the collaborating institutions, and the overhead is limited to 8 percent in these training grants. So, again, the bulk of the money does go toward training. Okay, next overhead. The goal of these training grants is to support locally appropriate research, and that's to support--to provide training and infrastructure support to strengthen the local capacity to undertake appropriate biomedical and behavioral research. And I think we've heard over and over again this morning that it needs to be appropriate for the country. And one way to do that is to have the local people be trained because they are the best ones to identify what's going to work in their country. It also provides an opportunity for the Western collaborators to understand the local conditions, the health care systems, and the culture in which they need to work with the collaborators in developing the research. Next? Basically, we found that this is definitely training for capacity building, and both types, both the short- and long-term training, are needed to ensure future local leadership, to build the capacity for the laboratory support, to strengthen the capacity for testing and counseling, and that's become increasingly evidence with the AIDS epidemic, that the voluntary counseling and testing is a real bottleneck. To also strengthen the capacity for program management and administration, and also to build capacity for program evaluation. And, again, we also use this "train the trainer" model where you get people in-country who can then train the next generation of people within country. And I think it's really important to recognize that you really need people on the ground who understand issues, and particularly the blood safety issues. In order to really make progress and also to maximize any kind of investments you're making in equipment or reagents or something, you really need on-the-ground people to understand. Okay, next overhead. There are various different training grants that Fogarty has, and I sort of listed them on the side. When I looked at where our blood safety activities were concentrated, it was in the HIV/AIDS research and training program that we have. However, there certainly are opportunities for integrating blood safety activities in the training programs that are related to infectious diseases, environmental and occupational health, certainly occupational exposure, and blood safety is an important part. Maternal and child health, if most of the transfusions are going to women and children, then there's an avenue there. And also malaria. We're also initiating a new clinical operational health services research and training program, and I think there's a big opportunity for blood safety activities within that program. However, I'll focus--okay, next overhead. Thanks. I'll focus on the AITRP, or the AIDS training program, because that's where most of our activities are ongoing. Now, this is the oldest program that Fogarty has. It's in its third five-year cycle. It's in its 13th year, and we've gradually increased the number of grants within the program, and currently, with last year's competition, we have 23 universities funded. The next overhead will show you all the different programs, and I tried to bold the ones that have some blood safety activities going on. But you can see that it's a wide spectrum, and they work basically all over the world: Asia, Latin America, former Soviet Union, and Africa. Okay. Next overhead. Last year, we moved into blood safety through some competing supplements to the current AITRP applicants, but also through some recompeting awards. This effort was supported by the National Heart, Blood, and Lung Institute in terms of half a million dollars a year to support these efforts. So two of the renewing programs at Brown and at State University of New York at Brooklyn were provided with some funds to support activities. Brown is working in India, the Philippines, and Cambodia, and they're in the process of identifying trainees for training and looking at blood utilization practices and transfusion methods. State University of New York at Brooklyn downstate is working in Russia, and they are funding a blood safety fellowship at the New York Blood Center. Cornell University was provided a supplement to look at blood safety in Haiti. That's where they've been working the longest, looking at blood banking and blood utilization and trying to look at not only urban but also rural areas. And then Johns Hopkins was awarded three supplements to work in China, India, and Laos/Thailand, and I'm going to let Chris Beyrer talk about these programs later on in the program. Also, Chris will talk about a very, very good example of what we're calling, for lack of a better word, South-to-South training in the fact that some countries do have the ability to train people within their region, they're at a higher level. And, in fact, that may be a more appropriate training place for people than coming to the United States or to Europe to learn the very, very high tech, which makes it really difficult for them to transfer that to their country. While they see a country in their region who's progressed to a higher level, it's a more realistic goal for them to strive for. Okay, next slide. There are also some activities that are being supported through the base awards, the AITRP program. UCLA is beginning a study looking at blood safety in China. UC-Berkeley is training a fellow to look at this issue in Brazil. They're beginning discussions in India. And, in fact, in Zimbabwe, more than five years ago they were looking at donor deferral--that should be referral strategies. Case Western also in the past, working in Uganda, has trained three people in the Uganda National Blood Supply in the Ministry of Health. And Maryland, working in Nigeria, is beginning to look at trying to develop a rapid test to use in a study to look at the prevention of transfusions associated with HIV, and the study will be done within a World AIDS Foundation grant. So there's some great examples of collaboration, of using funding from very different sources to achieve your goal. And the University of Illinois at Chicago is beginning to develop some activities. They're working in Malawi, Chile, and Indonesia. This is a program that's very interesting because their collaborators are the School of Public Health in Illinois and the School of Nursing, with the School of Nursing in these three countries. And I think when we talk about some of these blood safety activities, we need to not just think of physicians, but we also need to think at the people who are providing a lot of the care, and the nurses and midwives in these countries are the mainstays of your public health systems. Okay, next slide. So, anyway, these are the NIH websites if you--and I have copies of the handout for the committee. So you can look at the Fogarty website, the NIH website, and also there's a section on the NIH website where you can look at research and training opportunities at NIH. Next overhead. Certainly, if you have any questions, feel free to give me a call or send me an e-mail. I think all of us at Fogarty and NIH look forward to collaborating with everybody to expand this work. I just want to point out that I think we do have an excellent network through which work can be done to provide the opportunities for building the capacity in countries, and I think because the networks are well-established networks, these efforts can be moved through the system quite quickly through our existing grants. Thank you. [Applause.] DR. GOMPERTS: Thank you, Dr. McDermott. Any questions? [No response.] DR. GOMPERTS: I have a question before we let you go. From the point of view of strategy, is there any attempt or thoughts around the issue of strategy from the point of view of allocating resources for blood banking, blood safety? DR. McDERMOTT: Basically, I mean, we're--and I don't know if any of you know Ken Bridboard (ph), who's the division director, but Ken is very good at mobilizing resources toward Fogarty. Fogarty is probably one of the least funded centers at NIH. So we try to partner with, as the example here, Heart, Lung, and Blood to mobilize resources toward these efforts. The way the extramural grant programs are set up, basically we solicit applications for activities related to blood safety, and then we actually let the applicants determine what would be most appropriate for the work that they're doing. So there's not a definite amount of money or, you know, just focus on certain areas. We sort of leave it flexible and general so that people can meet the needs within their countries. But certainly resources are always welcome. DR. GOMPERTS: Thank you very much. DR. McDERMOTT: Thank you. DR. GOMPERTS: We're having a minor change in the agenda. Dr. Lipton needs some set-up time, so we will have Dr. Bianco and also Dr. Lane, who will present just before the lunch break. Thank you. Dr. Bianco? DR. BIANCO: I'm going to be low-tech and short. I'm Celso Bianco. I'm the executive vice president of America's Blood Centers. America's Blood Centers, or ABC, is an association of 75 not-for-profit, community-based blood centers that collect half of the U.S. blood supply from volunteer donors. ABC thanks Dr. Nightingale and the committee for bringing such an important issue to public discussion. Globalization of the world economy, travel, and commission created a new set of parameters for the diffusion of wealth, information, and disease. We're all together in the same world, and the safety of the U.S. blood supply is linked to the safety of the blood supply around the world. ABC has been involved in international collaboration since its inception. Our members have trained a large number of individuals from many countries, developing and developed, and have traveled to those countries to share experience, expertise, and technology. Our members have also supported every other blood banking organization in their international efforts. Dr. Paul Holland, CEO of Sacramento, is the current president of the International Society for Blood Transfusion, a leading organization in efforts to improve transfusion safety in less fortunate areas of the globe. You heard earlier today a presentation from the ICBS. It was created at the New York Blood Center with the mission of providing affordable screening tests to the developing world. ABC directly supports, with money and expertise, safety efforts in former Soviet Republics. On a personal note, I was born in Brazil, I saw the problems that the country confronted, the immense amount of energy the Brazilians have applied to the development of today's sophisticated blood system that is based on government-supported regional centers that co-exist with the private sector. I saw this system evolve and reach an inviolable level of safety. Brazil reached that goal because of the foresight and dedication of a number of individuals that were trained in the U.S. and Europe and their influence in the Brazilian public health system. Brazil is a success story in blood safety, and I'm very proud of having been a minor participant in that process. In addition, I have personally dedicated many days of my life to blood safety and availability in countries of Latin America and Asia. For these reasons, I consider myself sensitive to blood transfusion issues of the developing world and would like to share with you some thoughts derived from the experience of ABC members and from my own experience. Obviously, my words are tainted by my own personal biases, and I hope you would excuse me for that. First, I would like to address the question: What do developing countries say they want? The answer is almost unanimous. They want blood systems that are identical to those in the U.S. and in the rest of the developed world. They have learned everything about the American model of blood transfusion safety through the individuals that were trained here, publications, and by advertisements by manufacturers of technology. They want the same technologies, the same approach. They do not want to be considered second-rate. The example is a recent decision made by the health authorities in India where rapid tests are not acceptable for HCV or HIV screening, only ELISA-type assays. Essentially, most developing countries want to be state of the art. They want the same standards and the same tests. They do not want to feel insufficient or primitive. They reject less sophisticated tests. What they ask for is money to do the same thing we do. In many ways, they are right. They are struggling because of economic factors, not because of intellectual factors. Another important element is national pride and the sanctity of blood. Brazil wrote into its constitution that blood cannot be commercialized or exported, a reaction to abuses that took place 30 years ago. China has forbidden payment of blood donors as recently as two years ago on a national basis. Unfortunately, our current approaches to assist developing countries contribute to the feelings that I have just expressed. Whenever we talk about assistance to developing countries, we talk about technology. And I'm partially wrong because today I heard a lot of things from some of the people. Since it is easier to have a single contact point, we focus our efforts on government. We provide short-term financial assistance, we provide training in American institutions, and we provide equipment and supplies. Trainees come to the AABB meeting, look at the technology exhibit, and are mesmerized. They want it all. They return to their countries of origin and dream about setting up blood banks identical to those that they saw abroad. Some actually succeed in doing so. Then they realized that the system depends on the availability of qualified blood donors. This was not part of their training and was not mentioned by the local salesmen pitching technology wares. Trainees did not learn how to recruit volunteer blood donors. They did not learn how to create a sense of duty among the members of their community. They did not have resources to develop methods to deal with the frequent cultural barriers and myths about blood donation. In despair, they maintained their traditional replacement donors. Those are patients' friends, family members, or, not infrequently, individuals paid under the table to complete the blood donation quota required by the hospital where they are going to have surgery. The result is unfortunately clear. Every donor is a first-time donor, and a substantial portion of the collections is discarded because of test results. The situation is aggravated by the uncritical adoption of U.S. testing standards. For instance, Brazilian regulations require screening of all donors for hepatitis B core antibodies. Between 20 and 40 percent of the donors in the Amazon area are positive in the test. Between 10 and 20 percent in other areas of the country, the units are collected and discarded. Furthermore, overzealous regulators in Brazil require the performance of two different tests for HIV, Chagas, and syphilis. I would love to see these wasted resources diverted to donor recruitment efforts, leading to a stable base of loyal repeat donors. I must note that there are bright stars and that several Brazilian centers are focusing on volunteer donor recruitment and report great success. I believe that to some degree we bear responsibility for the confusion about blood safety standards around the world. Despite the communications and interaction between regulatory agencies and blood banking organizations among developed countries, we cannot agree among ourselves on procedures for the management of the safety of the blood supply. We are driven by fear, politics, and sometimes demagoguery. The examples that we give to the developing world are utterly embarrassing. There is no better example than the plethora of irrational measures adopted to prevent a theoretical risk of variant CJD by transfusion. England burns the plasma for every unit of blood it collects and buys plasma from the U.S. source plasma to fill its plasma fractionation plants. Portugal imports plasma for transfusion from Germany. Germany is considering discarding their plasma and obtaining it from other countries. And the two blood systems in Canada play a game of Chicken Little to see who will defer more donors to protect the blood supply. And in the U.S., a major blood banking organization decides that the recommendation of world actors on transmissible spongiform encephalopathies assembled by the Food and Drug Administration did not go far enough and wants to defer 6 to 9 percent of blood donors because of travel to Europe. This lack of coherence confuses everybody, including our own blood donors. ABC members want to contribute to the safety of the world blood supply and are ready to participate in every effort undertaken by HHS and by other blood banking organizations. ABC members believe that the department can support worldwide safety, and in answer to your questions, it can support by supporting harmonization of rational international standards in blood safety. We believe that an international committee on blood safety should attempt to reach consensus about rational safety measures. This could be done under the auspices of WHO, PAHO, ISPT, and must involve FDA and European regulatory agencies. HHS can support the activities, too, by supporting the role of FDA as the ultimate guardian of the safety of the U.S. supply and promoting consistent policies in our country; by supporting dissemination of expertise, for instance, by our military forces stationed abroad, DOD has the people and the knowledge to help communities develop effective blood programs; by publicly admitting that safety measures applied in the U.S. may not be appropriate for other countries, as, for instance, core antibodies to hepatitis B; by funding training programs in donor recruitment and retention at U.S. blood centers, particularly those that have a strong community base and are effective at recruiting donors; by promoting community-based recruitment efforts beyond government agencies through funding by organizations like World Bank and sister organizations; by direct support of PAHO and WHO efforts; by supporting the international activities of the Centers for Disease Control; and by increasing support for the NIH Fogarty program. I want to emphasize that ABC members are committed to blood safety at home and abroad. ABC members are also committed to the preservation of the supply of safe volunteer blood donors for all patients in need because no blood is a real risk, it is not a theoretical risk. I re-emphasize that we are ready to participate in your efforts. Thank you again for the opportunity to present our point of view. [Applause.] DR. GOMPERTS: Thank you, Dr. Bianco. Any questions? Yes, Dr. Epstein? DR. EPSTEIN: Well, Celso, you echoed Dr. Davey's earlier concern about the drive to high tech, and I just wonder what's your thought about the solution. DR. BIANCO: The solution is complex because whatever we try to do to address that, we are competing with a lot of messages that are reaching the same public and that confuse them. And they can show it. For instance, you go to many blood banks in any Latin American country, be it Mexico, Brazil, Argentina, every one of them has several pieces of apheresis equipment sitting there. Obviously no donors in the chair. They don't have the money for the software, the donors recruited, but every one of them has that piece of equipment. And this was sold to them not by us. They saw it. They have read the articles. They saw it at AABB, and they can show it to the people that walk through their service. But it doesn't contribute to the local thing. I think that the best thing is still education, and a lot of the education has to be not them coming to us only and seeing what we do, but us going to them and learning what our issues are, what the problems are, and being able to participate with them in the resolution of those issues. DR. GOMPERTS: Thank you. Other questions? [No response.] DR. GOMPERTS: Okay. Thank you. We'll move on to Dr. Lane, American Red Cross. MS. LANE: With all due respect, it's not "doctor," simply a master's. What can I say? But I am joined by our physician colleague, Dr. Roger Dodd, and our chief medical officer, Dr. Rebecca Haley. And I work daily for a doctor, Dr. Bernadine Healy. So thank you. First of all, one of the things we've talked about during break is we want to thank you for this forum. It has been energizing to hear from the various components who are involved in the international activities, and we'd like to share with you some of the efforts that we've been able to undertake through our unique position as a member of the International Red Cross movement. Our congressional charter of 1905 calls upon the Red Cross to play a leading role in providing humanitarian assistance through an international system. Much of this effort is coordinated with our Red Cross and Red Cross sister societies around the world; 113 of those societies are involved in some aspect of blood banking in their home countries. At the multilateral, bilateral, and individual level, we have collaborated in a number of ways to responding to requests for knowledge sharing and technology transfer. At the 27th International Conference of the Red Cross and Red Cross Societies in Geneva in late 1999, the Red Cross pledged to take a proactive role in sharing our technological expertise in blood quality assurance with other Red Cross societies, and this assistance will continue as resources allow and will be coordinated to complement our other international and regional priorities. Presently, we're engaged in a number of activities in the Americas and in Eastern Europe, and we are expanding efforts into Africa and Asia. With regard to our collaborative efforts--or multilateral efforts, I should say, we have been involved in a number of public health and AIDS education and awareness initiatives around the world, which will, through a collateral effect, improve the safety of the blood supply in those countries that are hit hardest by the AIDS epidemic. We have joined forces with the Centers for Disease Control in 14 African countries and in India through the Leadership and Investment in Fighting the Epidemic, or the LIFE Initiative that you may have heard about. At the clinical level, the LIFE program aims to change blood collection and screening processes in targeted countries to help ensure a safe blood supply and reduce the HIV incidence rates. We've also collaborated with PAHO in its development of regional blood safety initiatives that are aimed at improving the efficiencies of the laboratories that act as the screening centers, help develop the national quality assurance programs, and establish external performance evaluation programs, and, most importantly, as we've heard repeatedly, promote voluntary, non-remunerated blood donation. But Dr. Lackritz focused this morning on one of those key areas, which is preventing the need for transfusion in the first place. And how do you strengthen primary health care in the vulnerable groups of women and children? In late 1999, we joined with PAHO in a Healthy Children Goal 2002 program aimed at some of these primary health care initiatives. As you probably know, 200,000 children under the age of five die every year in the region covered by PAHO. We are working with a minimal--it's a $6 million investment in ten countries in that region to go for the community-based programs, to identify and work with local health care providers to help them address, as my international services colleagues keep trying to get me to remember it, the DAMMM diseases: diarrhea, acute respiratory, malnutrition, malaria, and measles. And that program is going quite well, and I think it's one of those, as Dr. Lackritz identified it, practical opportunities that we have with improving blood safety and availability. We've also been involved in a number of bilateral relationships to improve blood safety and availability. Through the World Hemophilia Federation, about a year ago we donated $1 million of anti-hemophiliac factor to be used through the American Red Cross Cares 2000 program, and that will be used worldwide. We've also recently donated a year's supply of albumin to a not-for-profit organization in Nicaragua, and that is geared to help burn victims in a large hospital there which receives over 1,000 pediatric burn cases a year. One of the major strengths of the Red Cross movement is the ability to take a developed society and work side by side with a less developed society and help them build capacity, through staff interchanges and, again, technology transfer and knowledge sharing. And in those areas, we've been in a number of places: Jamaican Red Cross, working with a Together We Can program, targeting teens and young adults through HIV prevention, ultimately helping us to build a group of safe donors. We've also partnered with the Tropical Disease Institute at Ohio University to improve blood safety in Ecuador. And we're working alongside our sister societies in Honduras, Egypt, China, and the Ukraine. And, lastly, of course, as you've heard, and I think as Dr. Bianco was saying, it's those individual relationships that we have with blood banking colleagues throughout the world, and certainly Dr. Dodd and others at Holland Laboratory have been for years working on a one-to-one basis. So, again, I thank you for the opportunity to share with you some of the efforts we've been involved in. We're certainly energized and looking forward to see what comes out of the forum as far as future initiatives. [Applause.] DR. GOMPERTS: Thank you. Any questions for Ms. Lane? [No response.] DR. GOMPERTS: Well, thank you very much. MS. LANE: Thank you. DR. NIGHTINGALE: Just a procedural note. It is now about three minutes to 12:00. If we begin promptly at 1 o'clock, we will be beginning one hour after the stated time on the agenda, but exactly when I hoped we would be able to begin. If we begin at 1:00, we will do everything we can to get out of here at 4:30, which is at the time when the discourses of this sort start to degrade. [Laughter.] DR. NIGHTINGALE: If you could please be back here at 1 o'clock, we will continue and have a productive day, and I thank everybody for their contributions so far. [Whereupon, at 11:56 p.m., the meeting recessed, to reconvene at 1:00 p.m., this same day.] 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.]
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