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.
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