Blood Safety Summary - April 2001
DATE: May 30, 2001
TO: Interested Parties
FROM: Stephen D. Nightingale, MD
Executive Secretary, Advisory Committee on Blood Safety and Availability
SUBJECT: Summary of April 19 and 20, 2001 Meeting
The Advisory Committee on Blood Safety and Availability met for the fourteenth time on Thursday April 19 and Friday April 20, 2001. Present were Mr. Allen; Drs. Busch and Chamberland; Mr. Dalal; Drs. Davey and Epstein; COL Fitzpatrick; Drs. Gilcher, Gomperts, Guerra, Haas, Hoots, Klein, and Kuhn; Ms. Lipton; Dr. Lopes; Ms. Pahuja; Dr. Penner; Mr. Walsh; and Dr. Winkelstein. Also present were Dr. Nightingale, CAPT McMurtry, Dr. Silverman, and Ms. Wanamaker from the Office of Public Health and Science, and approximately 100 members of the public. In the absence of Dr. Caplan, Dr. Gomperts chaired the meeting.
On the first day of the meeting, the Advisory Committee considered what if any additional actions the Department should take to promote blood safety and availability throughout the world.
The first speaker was Dr. Jean Emmanuel, the Director of the Department of Blood Safety and Clinical Technology at the World Health Organization (WHO). Dr. Emmanuel described the structure and functions of WHO and its programs to promote blood safety and availability throughout the world. He then described striking disparities in the safety and availability of blood among nations with high, medium, and low human development indices. He identified the limited availability of volunteer donors, limited availability of appropriate laboratory support, inappropriate use of scarce blood resources, and weakness or lack of national blood transfusion services to support uniform practice standards and to provide adequate budget support as major challenges to be addressed. He described the educational programs WHO has developed for both producers and users of blood in developing countries, and the collaborations on the development and implementation of these programs between WHO and its regional offices, local governments, and nongovernmental agencies such as the International Federation of Red Cross and Red Crescent Societies, the International Society for Blood Transfusion, the World Federation of Hemophilia, and the American Association of Blood Banks.
Dr. Emmanuel then described structure and goals of the WHO Global Collaboration for Blood Safety (GCBS). While this body is independent of WHO, WHO provides a secretariat for it and a venue for its meetings. At these meetings, participants from governments and non-governmental organizations around the world can meet to promote collective actions by participants within the general framework of the WHO blood safety initiatives. The first formal meeting of the GCBS was in November 2000, and the next is planned for November 2001. Working groups that were established at the first meeting on frameworks for blood policy decisions, plasma production policies, quality assurance programs, and assistance for developing countries are meeting in the interim and will report their progress at the upcoming meeting.
In response to questions, Dr. Emmanuel discussed specific efforts of WHO to strengthen the blood "cold chain", issues related to centralization of blood laboratory testing services, appropriate technologies and appropriate operating characteristics for blood screening tests in developing countries, and the cost of blood safety technologies. He also addressed the possibilities of regional collaboration among countries in sub-Saharan Africa and within large nations such as India and China. He concluded his remarks by suggesting that well-coordinated representation by large countries at venues such as the GCBS would facilitate the process of formulating and implementing the recommendations made at these meetings.
Dr. Jose Ramiro Cruz of the Pan American Health Organization (PAHO) began his discussion by describing the diversity of the Americas and the diversity of blood safety and availability within it. He noted that many countries in Latin America collect only about one fifth of the blood that they need, at least by the standards of developed countries. He suggested that pressure to increase blood collections has increased already strong pressure to use paid or replacement donors. He described substantial variation in the use of paid versus volunteer donors, even between blood banks within the same city, and he noted that HIV seroprevalence could be over one thousand times higher in paid than in volunteer donors. He stated that one of PAHO'>s goals for blood safety is for each Latin American country to have at least 50% of its blood donors be volunteers by 2003.
Dr. Cruz then discussed screening of blood for infectious agents in Latin America. He noted that while testing for HIV was virtually universal, testing for hepatitis B and C was not. He described a PAHO program to evaluate and where necessary to help upgrade the performance of laboratories that do screen for infectious agents in blood. Dr. Cruz concluded his presentation with a discussion of hepatitis C infection in hemophiliacs in Latin America, where many are treated with cryopreciptiate, and the need reflected in these statistics for better screening of blood for infectious agents in the region.
In response to questions, Dr. Cruz discussed the need to educate the Latin American public about the need for volunteer blood donation, the conflicting pressures on the educated public whether to donate voluntarily or on behalf of a family member or friend, and the need for blood banks to become more donor-friendly. Dr. Cruz expressed his hope that a trend towards centralization of both blood collection and blood testing would address some of the concerns that he raised in his presentation, and he acknowledged that provision of services to donors who are found to have an infectious disease remains an unmet need. He said that two things the United States could do to support blood safety in Latin America would be to support screening of blood for all transmissible diseases, and not just HIV, and support the transfer of appropriate technology, such as standards for blood banks.
Dr. Mohammed El-Nageh of the International Consortium for Blood Safety then described the goals of his organization for the developing world. These are to support development, manufacture, and use of affordable and high quality tests for transfusion-transmissible diseases, and to promote quality assurance activities covering the whole spectrum of transfusion medicine. The obstacles Dr. El-Nageh has encountered include fragmentation of blood services within a region, lack of plans for regional self-sufficiency, an unsustainable supply of reagents and tests, inadequate regulation of blood products, no plans for recruitment of volunteer donors, insufficient funds, and lack of training opportunities for the staff. For these reasons, his organization prefers to initiate a project within a country where there is indigenous leadership and government support for it. Dr. El-Nageh encouraged the United States government to support training programs for professionals in developing countries in address economic as well as technical aspects of blood banking.
Dr. Eve Lackritz of CDC began her presentation by describing the LIFE (Leadership and Investment in Fighting the Epidemic) initiative against AIDS by the United States government in sub-Saharan Africa and the role of transfusion safety in that initiative. Dr. Lackritz then discussed clinical transfusion practice in sub-Saharan Africa. She presented data from one Kenyan district hospital where 21% of all children admitted had a hemoglobin less than 5%, and in whom the mortality was 18%. She said that children in sub-Saharan Africa receive about two-thirds of all blood transfusions, most commonly for malaria complicated by nutritional or other chronic anemia. At the Kenyan hospital previously cited, 21% of the children admitted received a blood transfusion. Most of the remaining transfusions given in sub-Saharan Africa are for anemia complicating pregnancy or delivery.
Dr. Lackritz noted that the observed prevalence of HIV in Kenyan blood donor populations in 1994 was 20%, and she estimated it to be higher now. Her own work indicated that 1 in 50 blood transfusions in Kenya transmitted HIV.
Dr. Lackritz summarized the needs to be addressed as follows. There must be an adequate supply of blood from low-risk donors. Donations must be tested for transmissible diseases, typing and cross-matches must be accurate, and essential equipment such as refrigerators must be reliable. Anemia in the community, particularly in children and women of child-bearing age, must be diagnosed and treated before it becomes life-threatening, and this will require strengthening of the public health infrastructure. Also, appropriate indications for transfusion must be followed. CDC will pursue these goals through the by working with communities directly and through partnerships with WHO as possible to implement standard practices and training programs appropriate for individual communities.
Dr. Lackritz noted that many immigrants to the United States donate blood, and that surveillance of pathogens encountered abroad would improve the performance of tests used to screen United States blood donors.
In the course of responding to a question about volunteer donations in countries with a high prevalence of HIV, Dr. Lackritz noted that the burst of blood donors who appeared in Kenya after the bombing of the United States embassy had a HIV prevalence of 2%, compared to a baseline donor prevalence of 7%.
Dr. Jay Epstein then reviewed FDA's involvement in international blood safety programs. FDA collaborates with regulatory agencies in developed countries in a variety of international policy groups, scientific collaborations, and workshops on development of reference reagents. FDA has regular meetings with its counterparts in many developed countries, and it participates in efforts to harmonize regulations among nations. FDA's regulation of blood products and plasma derivatives has served as a model for both the developed and the developing world; it also serves as de facto regulator for therapeutics manufactured in the United States and then exported. FDA also supports development of regulatory structures in emerging nations, and offers training opportunities, some sponsored by the Fogarty International Center at NIH, for regulators and scientists in these countries.
Dr. Jeanne McDermott of the NIH then described in more detail the efforts funded through its Fogarty International Center (FIC) to support scientific research and training internationally in order to reduce disparities in global health. The core of the Fogarty program is sponsorship of both short and long-term training grants that are intended to promote locally appropriate research and researchers in developing countries. Dr. McDermott mentioned several blood safety-related programs throughout the world currently funded by FIC through grants to American universities, including one to be described later by Dr. Beyrer.
Dr. Celso Bianco of America's Blood Centers discussed the contributions of his organization's members to the training of transfusion medicine specialists throughout the world. He cited as examples the work of Dr. Paul Holland, the current president of the International Society for Blood Transfusion, and Dr. El-Najeh, whose work is based at the New York Blood Center. Dr.Bianco stated that developing countries have an almost uniform goal for their blood safety efforts, and that is to achieve the same level of safety that is found in the United States. He noted, however, that there are technologies or standards that are perhaps supportable in the United States but clearly not so in developing countries. Dr. Bianco warned against the inappropriate promotion and the subsidization of these technologies and standards. Instead, he recommended support for further efforts to promote volunteer donation and to achieve harmonization of "rational international standards" in blood safety.
Ms. Jan Lane of the American Red Cross (ARC) described the technical support her agency is committed to provide to the 113 other Red Cross societies throughout the world that are involved in blood banking. ARC also is a partner with CDC in the LIFE initiative described previously. ARC collaborates with PAHO not only to strengthen blood transfusion programs, but also to strengthen health care services that the transfusion programs support. Ms. Lane also mentioned support that ARC has provided directly through gifts of plasma derivatives to organizations that serve developing countries, and indirectly but no less importantly through scientific discovery at its Holland Laboratories.
Ms. Karen Lipton described the contributions of the American Association of Blood Banks (AABB) to the development of blood banking standards in the United States and throughout the world. She began by noting that 15% of AABB individual members and at least as many attendees at its national meeting come from outside the United States. She stated that the AABB fulfills its mission primarily by its educational programs and by standard-setting, accreditation, and inspection of blood banks and other laboratories that use related technologies, such as paternity testing services.
Ms. Lipton noted that, while AABB standards serve as a reference for the rest of the world, there are individual components perhaps not appropriate in all settings (she, like Dr. Bianco before her, cited hepatitis B core antibody testing as an example). In response, AABB standards are evolving beyond a simple delineation of technical and operational standards towards a quality management system that incorporates these standards. By restructuring its standards in this way, AABB has identified a framework for adapting its standards to the public health needs and resource limitations of individual countries or regions. AABB has worked with WHO and PAHO to implement this program, notably in the twenty-two countries that participate in the Caribbean Area Regional Standards and Accreditation Program. Ms. Lipton stressed the importance of working with local leadership during the establishment of region-specific standards. Ms. Lipton concluded by noting that these programs entailed substantial costs, and are in need of support beyond what can be provided solely by dues from AABB members.
Dr. Christopher Beyrer of Johns Hopkins University then described the involvement of one academic medical center, his own, in international blood safety initiatives. He began by noting that he represented several Hopkins colleagues who were currently in Chindu, China teaching a week-long intensive course in blood safety for all the provincial blood bank directors in China. The Hopkins efforts has been supported in part over the past 13 years by an AIDS International Training and Research Program (AITRP) grant from the Fogarty International Center. Recently, the National Heart, Lung, and Blood Institute (NHLBI) has sponsored supplemental AITRP grants specifically in the area of blood safety.
Dr. Beyrer then described specific programs Hopkins has established in China, India, and Laos. In each, Hopkins provides expertise from its School of Public Health in epidemiology and in infectious disease; from its basic science Departments such as Molecular Microbiology and Immunology; and from its clinical Departments, including Bioethics as well as Transfusion Medicine. In China, where current funding is about $100,000 per year, Hopkins provides an in-country "train-the-trainers" course once a year; some of those trained will receive fellowships for further study in the United States. In India, Hopkins is supporting the development of a model transfusion program in a single state. In Laos, Hopkins is supporting the development of training Laotian health professionals in Thailand, a neighboring country with a cognate language. Dr. Beyrer stressed the importance of ongoing relationships with former trainees, relocation grants, and support for attendance of former trainees to present their subsequent work at international scientific meetings.
Dr. Barbee Whitaker of the American Blood Resources Association (ABRA) and the Plasma Protein Therapeutics Association (PPTA) discussed the work of these organizations to develop standards for plasma and plasma product safety throughout the world. The international Quality Plasma Program (iQPP) program for plasma is built on a foundation of compliance with FDA standards and include such additional efforts as drug screening, and quarantine of donations until donor retesting. iQPP has been implemented in Western Europe and is currently being extended to Eastern Europe. She also described the Quality Standards of Excellence Assurance and Leadership (Q SEAL) program for plasma derivatives was recently developed by PPTA for use by all its members around the world.
Dr. Helen Lee of the University of Cambridge then discussed the development of tests and technologies appropriate for developing countries. She began by enumerating the economic disincentives to this development. These include limited ability of developing countries to pay for tests themselves, and for the industrial infrastructure in which most tests are developed; lack of economies of scale for rapid tests, which are used in units of 1 rather than, for example, 96 as in the case of microtiter plates; expensive and unreliable distribution channels; and competition from existing technologies.
Dr. Lee then described the technology of dipstick tests in some detail. Among the topics she mentioned were the use of thermostable enzymes used in PCR tests to produce the colors that indicate the result of dipstick tests. She used this topic to illustrate the challenges to development of these tests, and to illustrate how these challenges (in this case, the extreme environmental conditions under which tests in developing countries may be shipped, stored, or used) can be overcome.
Dr. Lee then discussed the goals of her own work, which is to make simple, rapid, and inexpensive dipstick tests available to the developing world. She defined simple as trainable in ten minutes, rapid as complete within 30 minutes, and inexpensive as less than $0.40 per unit. In addition, Dr. Lee requires that the test have a one year shelf life, use non-invasive samples such as saliva, urine, or fingerstick blood, and be able to be multiplexed - for example, as a single dipstick that tests for HIV, hepatitis B, and hepatitis C in blood donors. She noted that the construction of dipsticks adversely affects the sensitivity of tests, and described signal amplification strategies to compensate for this. She concluded by mentioning the possibility of using dipstick tests to prescreen donors and thereby avoid at least some of the costs of blood collection from unsuitable donors.
Dr. Jean-Pierre Alain then discussed the challenges to safe blood transfusion from the perspective of a physician practicing in a developing country. The first challenge he mentioned was the prevalence of transfusion-transmissible diseases in the donor population; this prevalence is roughly 100 times greater in the developing than in the developed world. He then mentioned the smaller size of blood banks in developing countries, and the absence of health insurance that makes cost an immediate patient concern and a constraint against expensive safety measures.
Dr. Alain discussed the benefits in developing countries of prescreening blood donors with rapid tests such as Dr. Lee had described. Dr. Alain noted that in his practice site in Africa, 78% of the budget is for supplies, and blood bags themselves comprise 30% of that cost. He estimated that a program that reduced the unnecessary use of blood bags by 20% could reduce total expenditures of a blood bank such as his by 13%. Dr. Alain also noted that rapid tests permit immediate counseling of donors in environments where there is little if any other chance to recall them. Dr. Alain also discussed the use of different rapid tests in sequence to improve the sensitivity and specificity to the level of an EIA test.
Mr. Rajen Dalal then presented his perspective on international blood safety issues. He felt that the United States' standards for safety and availability could, for the most part, serve as standards for other countries as well. In particular, he felt that high performance blood safety technology could be provided to all countries, and that educational and regulatory infrastructures could be established, once a political consensus to pay for them has emerged. He noted the presence most developing countries of a small, private markets for safe blood that meets the highest safety standards; these comprise roughly ten percent of the total market. He contrasted these markets to the public markets in developing countries. In the public markets, collaboration with organizations such as WHO and PAHO can improve market efficiency. Mr. Dalal referred to the need for patent protection in these public markets.. Finally, he agreed with other speakers that technology without infrastructure is an inadequate response to the problem of blood safety.
After discussion by the Advisory Committee of these issues Dr. Penner moved and Dr. Guerra seconded the following recommendations:
The Advisory Committee recognizes the importance of international issues in blood safety and availability and its importance to public health in the United States. The Advisory Committee endorses the present activities of government agencies in this area and supports the enhancement of these activities. Specifically, the Advisory Committee encourages the Department of Health and Human Services to foster research, training, and standard setting activities in international blood safety, including development and transfer of appropriate technologies for the developing world.
The Advisory Committee supports the establishment of a mechanism to identify priorities and coordinate the exchange of information and activities among government and appropriate non-government agencies in the United States. This effort should include appropriate linkages with international organizations and ongoing monitoring of these issues.
The recommendations were approved unanimously. The meeting was then adjourned until the following day.
On the second day of the meeting, the Advisory Committee considered what the Department's current and future actions should be under its Blood Action Plan to monitor the availability of blood products in the United States.
Ms. Marian Sullivan of the National Blood Data Resource Center (NBDRC) described her organization's mission and then introduced Dr. James Greer, who reviewed the data on the blood supply that NBDRC had collected under contract with the National Heart, Lung, and Blood Institute (NHLBI). This contract initiated the blood supply monitoring activities proposed in the DHHS/ FDA Blood Action Plan.
NBDRC has recruited 26 blood centers that are a representative sample - and comprise 34% - of all blood centers in the United States that collect over 25,000 units of blood annually. (Dr. Greer estimated from prior data that there are 28 blood establishments that collect less than this amount). Dr. Greer described seasonal variation in collections and corresponding, but smaller, seasonal variations in inventories of blood products; much of this latter variation occurred in the northeast region of the country and in the very largest blood centers. Dr. Greer anticipated that more robust analyses of seasonal variations and overall trends would be forthcoming after the second year of this data collection effort concludes in December 2001.
Dr. Edward Wallace of NBDRC then reviewed past efforts, many of them his own, to monitor the blood supply, and the operational challenges that had to be overcome. He noted that both actual transfusions and units collected had declined in the United States between 1987 and 1997, but that the margin between collections and transfusions had declined by roughly 50%. He then noted that both collections and transfusions had increased by about 10% between 1997 and 1999, without change in the margin between them. He concluded his remarks by discussing the need to collect data on utilization of blood by Diagnosis Related Groups (DRGs), and the need to study variation in utilization of blood by DRGs.
In response to questions, Dr. Wallace observed that variations in supply were somewhat seasonal, but variations in demand was also driven by changes in medical practice. He cited a recent article (Jeffries LC, Sachis BS, Young DS: Blood transfusion costs by diagnosis related groups in 60 university hospitals in 1009. Transfusion 2001; 41:522-9) to suggest that monitoring trends in claims for the relatively few DRGs that account for the most blood use might help predict future increases in demand for blood. Dr. Greer suggested that the concentration of hospitals in the northeast might explain relatively greater inventory fluctuations in that region, although his sample includes only seven northeast hospitals. Ms. Sullivan stated that almost two-thirds of the $190,000 cost of the current NBDRC monthly supply monitoring is for compensation of blood centers. Dr. Wallace stated that in his view the elasticity of the blood supply was substantial in the short run, for example after disasters, but uncertain in the long run, because of such factors as aging and contraction of the current donor population.
Dr. Richard Lewis of FDA stated that while assuring the availability of products is not strictly a part of FDA's mission, availability does impact on decisions about safety of products in the context of their use, and safety decisions are within FDA's mandate. For example, FDA has a medical necessity policy to evaluate products in times of shortage. He noted that the Department's responses to the supply section of the DHHS/FDA Blood Action Plan have included the monitoring of the blood supply previously described; a workshop on best recruiting practices; scientific review of the donor history questionnaire; and development of guidances on computer-assisted and self-administered donor questionnaires, donations by individuals with hemochromatosis, and incentives.
Mr. Jan Bult of the Plasma Products Therapeutics Association (PPTA) described the three-year experience of his association in collecting and disseminating information about the availability of plasma derivatives and their recombinant analogs. He began by noting that PPTA had announced its commitment to this activity at the Advisory Committee meeting on April 27, 1998. The data consist of monthly (recently increased to twice monthly) release, inventory, and distribution of albumin, recombinant Factor VIII, high purity Factor VIII, intravenous immunoglobulins, intermediate purity Factor VIII, high purity Factor IX, and Factor IX complex. Mr. Bult noted that, because of antitrust law, data is collected by an independent third party, and PPTA releases data on a particular product to the public if three or more manufacturers provided data; however, all data is provided in confidence to FDA. Mr. Bult then emphasized two constraints on the projection of future demand: the antitrust laws, and the obvious point that unpredictable events that affect production are, by definition, unpredictable.
Dr. Mark Weinstein of FDA reiterated Dr. Lewis's point that product availability is in his agency's view a safety issue. FDA hopes that monitoring inventory and distribution of plasma derivatives will help it distinguish spot shortages from the beginning of a severe crisis in product availability, and thereby assist decisions about allocating agency resources to review of a product or licensure of a facility; weighing the risk to the public health of the potential shortage versus the risk of a regulatory issue under consideration; and choosing among regulatory options that might affect product availability.
Dr. Weinstein then noted that the publicly available data provided by PPTA over the past three years had not always reflected the consumer and distributor perception of availability, for example in September 2000. He suggested that more frequent and even real-time data reporting of both aggregate and individual company data - particularly of anticipated production shortfalls - would be more useful to FDA for the purposes previously noted. Dr. Weinstein indicated that timely information on product availability within the distribution chain, for example fulfillment time for orders and changes in the location and characteristics of end users, would also be helpful. He warned, however, that premature public disclosure of this information, in addition to raising legal issues, might promote speculation and hoarding of products and thereby exacerbate product shortages.
Mr. Patrick Schmidt of FFF Enterprises then discussed efficient allocation of a limited supply of therapeutic products from the perspective of a distributor. He presented a hypothetical example of how arbitrary allocation schemes might exacerbate shortages. He described efficient allocation under such circumstances as an art. He defined that art as the use of rapidly changing information on both the quantity of product at each stage of the distribution pipeline and the structure of the pipeline itself. He proposed that this tracking data is critical to the measurement and monitoring of demand for a therapeutic product. His recommendation to the Advisory Committee was that real-time lot tracking systems be established for any product anticipated to be in short supply..
The Advisory Committee then heard comments from an invited panel of consumer representatives.
Mr. Jason Bablak of the Immune Deficiency Foundation presented a strategy for management of product shortages based on the experience of the immune deficient community in responding to the shortage of immunoglobulins that developed in late 1997. The first step in this strategy is to identify an emergency supply of product for those in greatest need. The second is to encourage the development of prioritization protocols to assure that available product is distributed in the medically most appropriate manner. The third is to document the extent of the shortage and its impact on the affected population, and bring this information to the attention of the government. The fourth is to monitor existing supplies. The fifth is to identify additional sources of product.
Mr. Bablak recommended an enhancement of the current monitoring system for plasma derivatives that would support real-time modeling of demand, and more timely communication of production and distribution issues by manufacturers to consumers. He recognized the legal issues that constrain competitive manufacturers from sharing projections of future demand, and he described efforts of his own patient service organization to develop these projections.
Mr. Val Bias of the National Hemophilia Foundation complemented the PPTA and the FDA for their past efforts to develop and publish supply data, but he emphasized that these efforts had been insufficient to manage the acute shortage of recombinant Factor VIII that was currently confronting the hemophilia community. He urged that all manufacturers, and not just some as at present, provide production information to the PPTA-sponsored data collection program. He requested that this information include worldwide distribution of product, and not just product released to the United States market. He asked that information be obtained from distributors as well as manufacturers on the availability of products. Finally, he asked that manufacturers make available information about the amount of product at the various stages of their manufacturing processes, so that the adequacy of future supplies could be assessed.
Mr. Bias described the impact of the current shortage of recombinant factor VIII on the hemophilia community. He observed that the products of different manufacturers were not therapeutically identical to individual patients. He noted that parents who had deferred having children until recombinant products were available now had to face the prospect of treating those children with plasma-derived products. He pointed out that the surgical procedures in hemophiliacs that were being delayed because of product shortages were major ones, such as joint replacements that were necessary for patients if they were to get on with their lives. He urged the Advisory Committee to make strong recommendations that more and more timely data on supply be collected so that product shortages could be more effectively addressed, and perhaps even permanently resolved.
Ms. Nancy Buelow of the Alpha-1 Foundation discussed the concerns of a community served by only a single manufacturer of a single product, and one that had been unable to prevent recurrent shortages of that product. She described why, and how strongly, her community viewed availability of therapeutic products as a safety issue. She urged expedited review by FDA of alternative products, and alternative delivery systems for those products, for her community.
Ms. Jan Hamilton of the Hemophilia Federation of America also urged that additional data on supply and distribution of plasma derivatives be obtained and made available to the public. She particularly urged that more information about product in the manufacturing pipeline, and on the status of that pipeline, be made available, and that more information be made available about domestic versus international distribution of products. She noted, as had Mr. Bias before her, that there were substantial concerns in the patient community over this issue. Ms. Hamilton expressed hope that the timely provision of this information might limit the impact of product shortages on patients. She also expressed concern that patients who had to revert from recombinant to plasma-based therapies during the current shortage might not be permitted by their insurers to resume use of the more expensive recombinant products after current shortage is resolved.
Ms. Hamilton noted that the hemophilia community was a user of blood products as well as plasma derivatives, and she supported recommendations made by other speakers to promote blood availability. In addition, she requested further efforts be made to improve the efficiency of the blood distribution system, and the sharing of information about blood product availability.
The Advisory Committee next heard from representatives of the blood industry.
Ms. Jacqueline Fredrick of the American Red Cross (ARC) addressed the question of where responsibility resides for ensuring an adequate blood supply, and the role of the federal government. She identified the role of the FDA in assuring the safety of the blood supply, the role of the NIH and CDC in studying blood borne pathogens and how to prevent their transmission through the blood supply, and the role of the Health Care Financing Administration (HCFA) in assuring adequate reimbursement for blood products. However, Ms. Fredrick stated that the ARC does not believe that it is the role of the federal government to routinely monitor the availability of the transfusible blood supply, but rather a role of the private sector.
Ms. Fredrick noted that blood availability had in the past been based on a supply-driven model, and the result was seasonal shortages that had grown worse as the population has aged and the need for blood has increased. She stated that the ARC was now instituting a need-driven management system that will enable it to plan for and pinpoint where specific blood products are needed and where potential shortages may occur, so that its daily collections from some 500 sites can best serve the immediate and projected needs of the some 3000 hospitals that it serves.
In the discussion that followed, Ms. Lipton asked Ms. Fredrick if the ARC would be willing to share its projections of blood demand with policy makers. Ms. Fredrick responded that the best place to obtain information about the impact of a proposed policy would be those institutions that would have to implement that policy. Dr. Nightingale observed that projections by businesses of future demand for their products were recognized by the government as trade secrets and entitled to protection as such, but he asked Ms. Fredrick if anything in her statements denied the need of the government to have access to these projections in the event of a compelling national interest, and if that interest might include a perception by the public that a blood shortage was immanent. Ms. Fredrick responded that the ARC had always shared its information, but she challenged those who would demand access to this data to accept responsibility to act on it. Dr. Lopes asked Ms. Fredrick if she thought that blood donors would assume that data about their donations would be available to the Public Health Service; Ms. Fredrick responded that she had no information on this.
Dr. Christopher Hillyer of Emory University spoke on behalf of the American Association of Blood Banks in support of government funding from a specific designated office for the collection and dissemination of usable, accessible, and unfettered real-time data on blood utilization as well as blood collection. He deplored the lack of sufficient data to answer such basic questions as whether the amount of blood collected drives the amount transfused, of if utilization would be higher if more blood were collected. He stressed a particular need for more information regarding the effect of hospital ordering and inventory practices on the blood supply.
Dr. Celso Bianco of America's Blood Centers opened his remarks by expressing his concern about the fragility of the blood supply, and his appreciation that this concern is shared by the government. He then expressed his support for an adequately funded data collection effort that would provide meaningful information to both the public and the operators of the blood system. He suggested that the unit of reporting the blood supply should be days of supply of a particular product, such as O negative blood, and he proposed a three day supply as a benchmark for this measure. Dr. Bianco suggested that monitoring include unfilled orders and the time until their fulfillment or cancellation would be another measure of the capacity of the blood supply to meet demand.
In the public comment period that followed, Ms. Lisa Halpern of Hemonetics Corporation encouraged the government to support and indeed lead the effort to recruit a new generation of blood donors. Mr. Derrick Robertson spoke on behalf of a coalition of Hemophilia Treatment Centers to support additional efforts to monitor the supply of plasma derivatives and their recombinant analogs. He raised a question from his constituency of why increased participation in the recombinant clotting factor market had not appeared to solve the problem of availability of these products. Dr. Alan Williams of FDA suggested that monitoring of the supply side of the blood system include monitoring of the effectiveness of campaigns to recruit and retain new donors. He also requested support for research on factors that motivate volunteer donors, and support for rapid surveys to provide data necessary to gauge the impact of proposed donor deferral strategies. Dr. Dennis Goldfinger of Cedars-Sinai Medical Center emphasized the severity of the current blood shortage and expressed the doubt that the system could absorb an additional loss of some seven percent of donors. He stated that blood centers would need more money to compensate for this loss of donors, and he challenged the government to find a mechanism to pay for the increased costs necessary to deliver a safe and adequate blood supply.
Following a short break, the Advisory Committee discussed the issue. Dr. Haas had been asked to comment on the measurement of demand for blood products from an economist's perspective. He discussed how the market for blood products differs from an ideal market. He noted that the government plays many roles in this non-ideal market to protect the consumer. He pointed out, however, the potential for these roles to conflict with each other. As an example, he cited the antitrust protections that could impede public access to information about projections of demand and projections of capacity to meet demand.
Dr. Kuhn had also been asked to comment. He focused his comments on the market for plasma derivatives. Dr. Kuhn emphasized the importance of monitoring the distribution chain as well as the production facilities for blood products. He also emphasized the need to obtain information on demand from the end-users of products rather than from the producers of these products, because the end-users could identify the specific indication for use of the product, and use by indication could be used to project future demand for various products.
Following discussion of these and related points, Dr. Davey proposed and Dr. Gilcher seconded the following motion:
Whereas patient access to a safe and available blood supply is a public health priority, the Advisory Committee recommends that the Secretary of Health and Human Services and the Congress:
A. Ensure that an appropriate office within the Department has the responsibility to facilitate the gathering and dissemination of national blood collection, distribution and utilization data, and the development of analytic models to predict shortages. Moreover, adequate federal dollars should be provided to support collection, analysis and distribution of these critical public health data.
Specifically, the following actions should be addressed:
Assign responsibility for this activity.
Support programs to develop the data, and ensure that the data collected are available to the public.
Encourage collaboration of blood collection centers for the purpose of identifying and addressing areas of short supply of blood and blood products.
Encourage collaboration of plasma manufacturers for the purpose of identifying and addressing areas of short supply of plasma products and their recombinant analogs.
B. Support a program of public and physician education designed to improve blood and blood product donation and utilization throughout the United States, and encourage support for such programs through the Department of Health and Human Services.
The motion was approved unanimously. The meeting was then adjourned at 3:03 PM.
This summary was approved by the Acting Chairman, Dr. Gomperts, on May 30, 2001.