[House Report 104-746]
[From the U.S. Government Publishing Office]
Union Calendar No. 392
104th Congress, 2nd Session - - - - - - - - House Report 104-746
PROTECTING THE NATION'S BLOOD SUPPLY FROM INFECTIOUS AGENTS: THE NEED
FOR NEW STANDARDS TO MEET NEW THREATS
__________
TENTH REPORT
by the
COMMITTEE ON GOVERNMENT
REFORM AND OVERSIGHT
together with
ADDITIONAL VIEWS
August 2, 1996.--Committed to the Committee of the Whole House on the
State of the Union and ordered to be printed
COMMITTEE ON GOVERNMENT REFORM AND OVERSIGHT
WILLIAM F. CLINGER, Jr.,
Pennsylvania, Chairman
BENJAMIN A. GILMAN, New York
DAN BURTON, Indiana
J. DENNIS HASTERT, Illinois
CONSTANCE A. MORELLA, Maryland
CHRISTOPHER SHAYS, Connecticut
STEVEN SCHIFF, New Mexico
ILEANA ROS-LEHTINEN, Florida
WILLIAM H. ZELIFF, Jr., New
Hampshire
JOHN M. McHUGH, New York
STEPHEN HORN, California
JOHN L. MICA, Florida
PETER BLUTE, Massachusetts
THOMAS M. DAVIS, Virginia
DAVID M. McINTOSH, Indiana
RANDY TATE, Washington
DICK CHRYSLER, Michigan
GIL GUTKNECHT, Minnesota
MARK E. SOUDER, Indiana
WILLIAM J. MARTINI, New Jersey
JOE SCARBOROUGH, Florida
JOHN B. SHADEGG, Arizona
MICHAEL PATRICK FLANAGAN, Illinois
CHARLES F. BASS, New Hampshire
STEVEN C. LaTOURETTE, Ohio
MARSHALL ``MARK'' SANFORD, South
Carolina
ROBERT L. EHRLICH, Jr., Maryland
CARDISS COLLINS, Illinois SCOTT L. KLUG, Wisconsin
HENRY A. WAXMAN, California
TOM LANTOS, California
ROBERT E. WISE, Jr., West Virginia
MAJOR R. OWENS, New York
EDOLPHUS TOWNS, New York
JOHN M. SPRATT, Jr., South Carolina
LOUISE McINTOSH SLAUGHTER, New York
PAUL E. KANJORSKI, Pennsylvania
GARY A. CONDIT, California
COLLIN C. PETERSON, Minnesota
KAREN L. THURMAN, Florida
CAROLYN B. MALONEY, New York
THOMAS M. BARRETT, Wisconsin
BARBARA-ROSE COLLINS, Michigan
ELEANOR HOLMES NORTON, District of Columbia
JAMES P. MORAN, Virginia
CARRIE P. MEEK, Florida
CHAKA FATTAH, Pennsylvania
BILL BREWSTER, Oklahoma
TIM HOLDEN, Pennsylvania
ELIJAH CUMMINGS, Maryland
------
BERNARD SANDERS, Vermont (Independent)
James L. Clarke, Staff Director
Kevin Sabo, General Counsel
Judith McCoy, Chief Clerk
Bud Myers, Minority Staff Director
_________________________________________________________________
Subcommittee on Human Resources and Intergovernmental Relations
CHRISTOPHER SHAYS, Connecticut,
Chairman
MARK E. SOUDER, Indiana
STEVEN SCHIFF, New Mexico
CONSTANCE A. MORELLA, Maryland
THOMAS M. DAVIS, Virginia
DICK CHRYSLER, Michigan
WILLIAM J. MARTINI, New Jersey
JOE SCARBOROUGH, Florida
MARSHALL ``MARK'' SANFORD, South
EDOLPHUS TOWNS, New York Carolina
TOM LANTOS, California
BERNARD SANDERS, Vermont (Ind.)
THOMAS M. BARRETT, Wisconsin
GENE GREEN, Texas
CHAKA FATTAH, Pennsylvania
HENRY A. WAXMAN, California
Ex Officio
WILLIAM F. CLINGER, Jr.,
CARDISS COLLINS, Illinois Pennsylvania
Lawrence Halloran, Staff Director
Anne Marie Finley, Professional
Staff Member
Thomas Costa, Clerk
Cheryl Phelps, Minority
Professional Staff
LETTER OF TRANSMITTAL
----------
House of Representatives,
Washington, DC, August 2, 1996.
Hon. Newt Gingrich,
Speaker of the House of Representatives,
Washington, DC.
Dear Mr. Speaker: By direction of the Committee on
Government Reform and Oversight, I submit herewith the
committee's tenth report to the 104th Congress.
William F. Clinger, Jr.,
Chairman.
C O N T E N T S
----------
Page
I. Executive summary................................................1
II. Background.......................................................3
III. Findings.........................................................9
IV. Recommendations.................................................23
VIEWS
Additional views of Hon. Carolyn B. Maloney...................... 27
Union Calendar No. 392
104th Congress Report
HOUSE OF REPRESENTATIVES
2nd Session 104-746
_______________________________________________________________________
PROTECTING THE NATION'S BLOOD SUPPLY FROM INFECTIOUS AGENTS: THE NEED
FOR NEW STANDARDS TO MEET NEW THREATS
_______
August 2, 1996.--Committed to the Committee of the Whole House on the
State of the Union and ordered to be printed
_______________________________________________________________________
Mr. Clinger, from the Committee on Government Reform and Oversight,
submitted the following
TENTH REPORT
together with
ADDITIONAL VIEWS
On July 25, 1996, the Committee on Government Reform and
Oversight approved and adopted a report entitled ``Protecting
the Nation's Blood Supply From Infectious Agents: The Need For
New Standards To Meet New Threats.'' The chairman was directed
to transmit a copy to the Speaker of the House.
I. Executive Summary
In the early 1980's, 10,000 hemophiliacs and 12,000 other
patients were infected with the human immunodeficiency virus
(HIV) through blood and blood products. Approximately 300,000
people were infected with the Hepatitis C virus (HCV), many of
whom have never been told of their exposure to infection.
The lessons of these tragedies compel greater vigilance and
higher regulatory standards to protect the Nation's blood
supply from emerging infectious agents and blood borne
pathogens.
Threats to blood safety are both natural and man-made, as
aggressive new infectious agents emerge and blood safety
practices evolve. As a result, substantial improvements are
needed in coordination between the Public Health Service (PHS)
agencies within the Department of Health and Human Services
(HHS), particularly the Food and Drug Administration (FDA), the
Centers for Disease Control and Prevention (CDC) and the
National Institutes of Health (NIH).
At the first of two subcommittee hearings on blood safety
issues, HHS Secretary Donna Shalala announced that the
Department's focus on blood safety issues will be expanded and
elevated, with the Assistant Secretary for Health charged to
improve the coordination and effectiveness of blood safety
policy.
Current FDA and CDC regulatory systems are not adequate to
meet the aggressive nature of emerging threats to blood safety.
Product recalls and notification regarding possible exposure to
blood borne pathogens are not well communicated to physicians,
pharmacists, patients or the public. Regulation of blood
collection, testing and the production of blood-derived
therapeutics is not well coordinated or consistently managed to
minimize known risks.
The public is not well served if patients are permitted to
believe there is no risk in blood transfusions or in the use of
blood derived therapies. While such risks are extremely small,
and the U.S. blood supply is safer than it has ever been,
greater efforts should be made to convey known risks to
consumers who may wish to minimize even those risks through the
use of alternative procedures or therapies.
Findings in brief
1. The blood supply is safer than it has ever been.
2. The blood supply continues to face new infectious
disease challenges.
3. In response to the recommendations of the Institute of
Medicine (IOM), HHS has begun to implement higher regulatory
standards to protect the Nation's blood supply from emerging
infectious diseases and blood borne pathogens.
4. The public is provided insufficient information on the
risks of blood and blood products.
5. The FDA has not effectively managed regulatory review of
blood issues, particularly its advisory committee on blood
safety issues, the Blood Products Advisory Committee (BPAC).
6. Despite a BPAC recommendation to the contrary, the FDA
took the first step toward closing the ``window period'' of
possible HIV transmission by licensing the p24 antigen test for
screening of donated blood.
7. Fifteen years after the AIDS virus emerged as a threat
to the blood supply, FDA still has not developed an effective
system for communicating blood product recalls to pharmacists,
doctors or patients.
8. The size of plasma pools for fractionated products can
increase the risk of infectious disease transmission.
Recommendations in brief
1. Congress should establish the Blood Safety Council and
the Advisory Committee on Blood Safety and Availability in
statute.
2. Congress should consider establishing an indemnification
system for individuals who suffer adverse consequences from the
use of blood and blood products.
3. HHS should take steps to ensure that the estimated
300,000 living recipients of blood and blood products who were
infected with Hepatitis C virus before 1990 are notified of
their potential infection so that they might seek diagnosis and
treatment.
4. HHS should disseminate more clinically useful
information to providers of care and to the public regarding
blood safety issues.
5. FDA should immediately develop an effective system of
recall notification for blood and plasma products.
6. FDA should immediately cease its practice of providing
advance notice of safety and compliance inspections to some
plasma fractionators.
7. Plasma fractionators should limit the size of plasma
pools, with pool sizes determined as much by public health risk
factors as by production economies of scale.
II. Background
Each year, approximately 4 million patients in the United
States receive transfusions of whole blood and blood components
derived from 20 million units of whole blood and blood
components.\1\ When receiving a transfusion, each of these
patients forms a very personal bond of trust with one or more
blood donors and with all those responsible for the collection,
processing, storage, distribution and administration of these
potentially lifesaving therapies.
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\1\ HIV and the Blood Supply: An Analysis of Crisis Decisionmaking,
Institute of Medicine, National Academy Press, 1995, p. 1 (``IOM
Report'').
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The advent of the era of antibiotics promoted a complacent
view among medical professionals and the Federal Government
that new, fatal, untreatable, infectious diseases were
afflictions of the past. Tragically, a new retrovirus, Human
Immunodeficiency Virus (HIV) which produced Acquired Immune
Deficiency Syndrome (AIDS), challenged that view when it
infected the U.S. blood supply in the early 1980's.
CDC Director David Satcher testified at the November 2,
1995 subcommittee hearing that:
In the past few decades, many of the best scientific
minds in the country expected infectious diseases to be
eliminated as a public health problem in the United
States. As recent events have shown, these
pronouncements were premature. Infectious diseases
remain the leading cause of death worldwide and among
the most important causes of death in the United
States.
In addition, we are faced increasingly with new and
re-emerging infectious disease challenges. At home, we
have seen the re-emergence of a public health scourge,
tuberculosis; recent outbreaks of food and waterborne
illnesses, such as those caused by E. Coli 0157.H7 and
cryptosporidiosis; and the emergence of a new hanta
virus. On a global front, the worldwide HIV/AIDS
epidemic is now in its fifteenth year. We recently
witnessed an epidemic of plague in India; diphtheria
outbreaks in the New Independent States of the former
Soviet Union; and the frightening re-emergence of the
Ebola virus in Zaire.
To meet the challenges posed by infectious diseases
and to reduce their potential threat to safety of the
blood supply, a strong public health capacity is needed
at both the Federal and State levels. At the Federal
level, CDC, the National Institutes of Health (NIH),
and the Food and Drug Administration (FDA) provide our
first line of defense in ensuring that the Nation's
blood supply and products made from blood are free of
infectious agents.
The U.S. blood supply is currently safer than it has
ever been but the HIV experience in the early 1980's
and the more recent experience with Hepatitis C virus
(HCV) transmission from intravenous immunoglobulin
illustrate the need for continued vigilance regarding
unrecognized, uncharacterized, and new threats to the
blood supply.\2\
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\2\ Protecting the Nation's Blood Supply from Infectious Agents:
New Standards to Meet New Threats, 104th Cong., 1st Sess., p. 105
(1995) (``HRIR hearings'') (statement of Dr. David Satcher).
Threats to blood safety are first detected in those who
regularly rely on blood derived therapies. They serve as a
``human shield'' or early warning system for the presence of
infectious agents in the blood supply. For example, persons
with severe hemophilia are exposed to more blood products from
more blood donors than any other patient group.\3\ Hemophiliacs
\4\ are dependent on clotting factor concentrates, concentrated
amounts of the deficient clotting proteins, made from the
pooled plasma of up to 20,000 individuals.\5\ If there is an
infectious agent in the blood supply, it will be seen in the
hemophiliac population first.
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\3\ July 16, 1996 letter from Stephen Bajardi, executive director,
National Hemophilia Foundation to HRIR Subcommittee staff (in
subcommittee files).
\4\ Individuals with a hereditary deficiency of coagulation Factors
VIII or IX. Dorland's Medical Dictionary, 28th edition, 1994.
\5\ IOM Report, p. 1.
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Hemophilia is a lifelong, hereditary blood clotting
disorder which primarily, but not exclusively, affects males.
In addition, there are an additional 25,200 men and women in
the United States who rely heavily on multiple infusions of
blood and plasma protein products, according to estimates
provided by the NIH Office of Rare Diseases and the National
Heart, Lung, and Blood Institute.\6\
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\6\ NIH correspondence with the HRIR Subcommittee, July 16, 1996
(in subcommittee files).
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In the early 1980's, 10,000 people with hemophilia, fully
50% of all U.S. hemophiliacs at the time, as well as 12,000 \7\
other transfusion recipients, were infected with HIV through
blood products prior to 1985, when a screening test was
implemented that could detect HIV antibodies in donated blood.
Many also unknowingly infected their spouses and children
before learning of their own infections.
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\7\ IOM Report, p. 1.
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CDC estimates that 290,000 (approximately 7%) of the 3.9
million Americans chronically infected with HCV acquired their
infection from transfusion.\8\ Most of these individuals
received transfusions prior to the availability of a screening
test in 1990.\9\ The Institute of Medicine report described HCV
infection as ``often silent, is one of the major causes of
cirrhosis, hepatocellular carcinoma, or both, in the United
States, and is a common precipitant of liver failure
necessitating liver transplantation.'' \10\
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\8\ CDC correspondence with HRIR Subcommittee, July 18, 1996 (in
subcommittee files).
\9\ Testimony of Assistant Secretary Philip Lee, HRIR hearings, p.
29.
\10\ IOM Report, p. 86.
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In 1992, Representative Porter Goss (R-FL), Senator Edward
Kennedy (D-MA), and Senator Bob Graham (D-FL) asked HHS
Secretary Donna Shalala to investigate the role of the
Government in the transmission of HIV to hemophiliacs. HHS in
turn commissioned the National Academy of Sciences' Institute
of Medicine (IOM) to review the situation and make prospective
recommendations to assure greater safety in the blood supply
from emerging and re-emerging infectious agents. The resulting
report ``HIV and the Blood Supply: An Analysis of Crisis
Decisionmaking'' was released on July 13, 1995.
The IOM concluded that HHS failed to recognize that the
blood supply was not immune to a new infectious agent, HIV,
about which there was substantial scientific uncertainty.
Furthermore, a lack of leadership on the part of the FDA, CDC,
NIH and the blood collection and plasma fractionation
industries resulted in a pattern of decisionmaking
characterized by adoption of the most limited public health
responses. These inadequate responses did not contain the
spread of HIV through the blood supply and opportunities to
prevent primary and secondary infections were missed, with
particularly tragic consequences for the bleeding disorders
community.\11\
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\11\ IOM Report, p. 208-209.
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Other factors were also at work that resulted in the
infection of large numbers of blood and blood product
recipients. ``Many of our blood banking centers were created
over 40 years ago as small community volunteer programs and
were ill-equipped to respond to the HIV threat. Industry on the
other hand, failed to respond for other reasons, notably a lack
of medically knowledgeable management and emphasis on profit
with a need to maintain productivity in a competitive market.''
\12\
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\12\ Testimony of Dr. John Penner, p. 48.
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THE ROLE OF THE FOOD AND DRUG ADMINISTRATION (FDA)
The Food and Drug Administration derives its authority to
regulate biologic drugs, ``any virus, therapeutic serum, toxin,
antitoxin, vaccine, blood, blood component or derivative,
allergenic product, or analogous product . . . applicable to
the prevention, treatment, or cure of diseases or injuries of
man . . .'' from the 1902 Virus Act. It is the oldest law
currently administered by FDA (P.L. No. 57-244, 32 Stat. 328
(1902); 42 U.S.C. 262 (1982)), predating the Federal Food, Drug
and Cosmetic Act of 1906.
FDA helps ensure the safety of the Nation's blood supply by
minimizing the risk of infectious disease transmission and
other hazards while maintaining an adequate supply. FDA
oversees all phases of blood preparation and manufacture from
donor screening and selection and testing to product
collection, processing, labeling, and storage. FDA's Center for
Biologics Evaluation and Research (CBER) licenses blood
establishments that ship blood products in interstate commerce
and inspects these establishments and more than 2,500
registered intrastate blood establishments.
THE ROLE OF THE CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC)
The Centers for Disease Control and Prevention (CDC) is the
Federal agency responsible for disease and injury prevention.
CDC's mission is to promote health and quality of life by
preventing and controlling disease, injury, and disability. The
agency's name was expanded to include ``prevention'' through
``The Preventative Health Amendments of 1992.'' \13\ CDC
articulates its vision for the 21st century as ``Healthy People
in a Healthy World Through Prevention.'' \14\
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\13\ P.L. 102-531.
\14\ CDC Priorities Paper, April 1995.
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CDC evaluates public health problems by applying a four
step scientific analysis: define the problem, identify risk
factors, develop and test prevention strategies, and implement
nationwide prevention programs. CDC conducts its programs in
collaboration with State and local health departments, national
and community-based organizations, academia, business, and
labor.
The CDC uses its nationwide surveillance system of State
public health officers to identify and monitor blood-borne
diseases. CDC believes that its epidemiological investigations
alerted the Federal Government to the presence of HIV in the
blood supply, even though a screening test did not become
available until 1985. Dr. Satcher testified that CDC estimates
``over 700,000 lives were saved because of the epidemiological
investigations that were able to show that there was something
being transmitted through the blood supply and other means.''
\15\
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\15\ Protecting the Nation's Blood Supply from Infectious Agents:
New Standards to Meet New Threats, 104th Cong., 1st Sess., testimony of
CDC Director David Satcher, HRIR hearings, p. 105; and For a Healthy
Nation: Returns on Investment in Public Health, Centers for Disease
Control and Prevention, p. 29-30.
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The CDC also conducts a Hemophilia Monitoring Project which
monitors infectious agents in the hemophilia population. The
CDC maintains an internal working group on blood safety, which
coordinates blood safety issues and evaluates any new or
potential threats to the blood supply through the National
Center for Infectious Diseases (NCID). NCID's mission is to
``prevent illness, disability, and death caused by infectious
diseases in the United States and around the world.'' It is
noteworthy that there is no specific mention of blood in the
NCID list of priorities.\16\
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\16\ Major NCID Prevention Activities, FY 1995, National Center for
Infectious Diseases, Centers for Disease Control and Prevention.
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The CDC's Blood Donor Study,\17\ in conjunction with the
Red Cross, selected blood banks, and selected local public
health departments around the country, has been interviewing
HIV-positive donors at 20 regional centers since 1988 to
evaluate their risk factors for HIV-1, in order to determine
their motivations for donating. This will allow investigators
to estimate the length of time between infection and detection
of antibodies in individuals who subsequently convert to HIV
positive status, as well as the current risk of HIV
transmission from blood transfusions.
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\17\ Official title ``An evaluation of the behavioral, donation
history and laboratory characteristics of US blood donors infected with
human immunodeficiency virus (HIV).'' CDC communication with HRIR
Subcommittee, July 17, 1996 (in subcommittee files).
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Each month, CDC publishes the HIV/AIDS Surveillance Report,
which contains the cumulative number of AIDS cases reported to
CDC, as well as new cases. The data are broken down into
various exposure categories, including transfusion recipients
of HIV-infected blood.
THE ROLE OF THE NATIONAL INSTITUTES OF HEALTH (NIH)
NIH is the primary agency of the Federal Government charged
with the conduct and support of biomedical and behavioral
research. It also has major roles in research training, health
information dissemination, and health services research. The
National Heart, Lung, and Blood Institute (NHLBI), one of the
NIH Institutes, is the principal Federal funding agency for
research on blood.
NHLBI sponsors REDS (Retrovirus Epidemiology Donor Study),
an extensive project to determine the current and ongoing
prevalence of human retroviruses, as well as Hepatitis C and
other emerging viruses and infectious agents in blood donors.
REDS also was designed to determine outcomes of specific non-
HIV infections in affected donors and recipients.
Because REDS can study repeat blood donors, it can
determine the retroviral infection rate. So far, REDS
investigators have found a greater incidence of non-HIV
retroviral infection in blood donors than they had expected.
The researchers are also examining why individuals who know
they have risk factors for retroviral infection continue to
donate blood.
A major advantage of the study is its large repository of
samples collected from blood donors. As new tests for blood-
borne infections are developed, it will be possible to screen
the stored samples to provide better information on currently
known retroviruses and on other uncharacterized infectious
agents. However, the Office of AIDS Research recently
recommended \18\ that AIDS funds should be redirected from
supporting research related to the safety of the blood supply
after REDS funding expires in August 1998.\19\
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\18\ Report of the NIH AIDS Research Program Evaluation Working
Group of the Office of AIDS Research Advisory Council, March 13, 1996.
\19\ April 30, 1996 NHLBI correspondence with subcommittee staff
(in subcommittee files); and Report of the NIH AIDS Research Program
Evaluation, Natural History, Epidemiology, and Prevention Research Area
Review Panel Findings and Recommendations of the Office of AIDS
Research Advisory Council, June 7, 1996.
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NIH also conducts ongoing research to improve blood banking
operations and blood safety, such as development of methods to
destroy infectious agents in blood components and development
of physician guidelines for the appropriate use of blood
products. In FY 95, NHLBI awarded $182,892,000 in extramural
grants through the Blood Diseases and Resources program on
basic and applied research into diseases which require
treatment with blood products.
In 1987, the NHLBI launched a broad education effort by
establishing the National Blood Resources Education Program
(NBREP), which was tasked with dissemination of information
about the blood supply to more than 30 national organizations
with interests in blood donation, transfusion, and public
education. NBREP had two goals: to ensure an adequate supply of
safe blood to meet the Nation's needs, and to ensure that blood
components are transfused only when therapeutically
appropriate. This program was phased out in FY 1994 because
NHLBI officials felt that many of the educational materials
being developed duplicated materials developed by the blood
banking community.\20\
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\20\ HRIR Subcommittee staff conference call with Sandra Lindsay,
NHLBI Office of Legislative Affairs, July 16, 1996 (notes in
subcommittee files).
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THE HRIR SUBCOMMITTEE INVESTIGATION
The Committee on Government Reform and Oversight's
Subcommittee on Human Resources and Intergovernmental Relations
(HRIR) initiated an investigation into the safety of the blood
supply in April 1995. The subcommittee sought assurance that
the U.S. Department of Health and Human Services' Public Health
Service (PHS) agencies, particularly the Food and Drug
Administration, are aggressively maintaining safeguards to
detect emerging infectious agents and eliminate blood-borne
pathogens from the Nation's blood supply.
Hearings were held on October 12, 1995 and November 2,
1995. HHS Secretary Donna E. Shalala announced HHS' response to
the IOM report recommendations at the October 12th hearing. The
perspectives of consumers, clinicians, and the blood collection
and plasma fractionation industries on blood safety were also
heard in testimony at these hearings.
In addition, FDA supplied approximately 44,000 pages of
documents requested by the subcommittee on the following dates:
June 6, 1995; July 5, 1995; July 20, 1995; July 21, 1995;
August 30, 1995; September 12, 1995; September 21, 1995;
October 5, 1995; October 6, 1995; December 8, 1995; March 25,
1996; April 5, 1996; May 6, 1996; May 24, 1996; June 3, 1996;
June 5, 1996; and June 6, 1996.
Interviews and/or conference calls were conducted with FDA
personnel on the following dates: August 8, 1995; September 8,
1995; November 7, 1995; November 30, 1995; March 6, 1996; March
26, 1996; April 4, 1996; April 8, 1996; April 9, 1996; April
18, 1996; April 29, 1996 (two meetings); May 10, 1996; May 16,
1996; May 24, 1996; and July 17, 1996 (two conference calls).
NIH supplied requested documents to the subcommittee on the
following dates: September 28, 1995; October 3, 1995; October
31, 1995; January 22, 1996; and April 30, 1996.
Interviews and/or conference calls were conducted with NIH
personnel on the following dates: October 2, 1995; October 6,
1995; and July 17, 1996.
CDC supplied documents to the subcommittee on December 27,
1995.
Interviews and/or conference calls were conducted with CDC
personnel on the following dates: September 20, 1995; October
31, 1995; and February 13, 1996.
HHS Office of the Inspector General (OIG) supplied
documents to the subcommittee on April 18, 1996; April 24,
1996; and May 2, 1996. OIG staff briefed the subcommittee on
April 30, 1996.
Interviews and/or conference calls were conducted with HHS
personnel on the following dates: September 18, 1995; September
26, 1995; and December 8, 1995.
An interview was conducted with Health Resources and
Services Administration (HRSA) personnel on October 5, 1995.
Interviews and/or conference calls were conducted with
American Association of Blood Banks (AABB) personnel on the
following dates: June 27, 1995; July 27, 1995; October 30,
1995; and April 25, 1996.
Interviews and/or conference calls were conducted with
American Red Cross (ARC) personnel on the following dates: June
28, 1995; October 31, 1995; February 9, 1996; February 14,
1996: March 1, 1996; and April 3, 1996.
Interviews and/or conference calls were conducted with
American Blood Resources Association (ABRA) and/or ABRA member
companies on the following dates: August 3, 1995; August 24,
1995; September 20, 1995; September 21, 1995; October 3, 1995;
October 13, 1995; October 19, 1995; October 24, 1995; October
25, 1995; October 26, 1995 (ABRA); October 26, 1995 (ABRA
member company); October 27, 1995; October 30, 1995 (ABRA
member company); October 30, 1995 (ABRA member company);
October 30, 1995 (ABRA member company); March 20, 1996; April
23, 1996; and May 8, 1996.
An interview was conducted with International Plasma
Products Industry Association (IPPIA) personnel on May 6, 1996.
Interviews and/or conference calls were conducted with
National Hemophilia Foundation (NHF) personnel on the following
dates: September 6, 1995; October 24, 1995; December 13, 1995;
and March 20, 1996.
Interviews and/or conference calls were conducted with
Council of Community Blood Centers (CCBC) personnel on the
following dates: August 8, 1995; September 7, 1995; and October
30, 1995.
The subcommittee staff also participated in the September
22, 1995 Institute of Medicine Forum on Blood Safety and
Availability and the ABRA Annual Plasma Forum on June 14, 1996.
The hearing records, documents and interviews of the
subcommittee's investigation serve as the basis for the
findings and recommendations of this oversight report.
III. Findings
1. The blood supply is safer than it has ever been
The U.S. blood supply is currently safer than it has ever
been, due largely to a blood safety system enforced by FDA
which consists of five layers: donor screening, blood testing,
donor deferral, inventory management to insure that products
have been thoroughly tested and that donation records have been
verified, and mandatory investigation and reporting by blood
establishments to FDA of any accidents and errors relating to
these safeguards. Blood establishments are also required to
correct any system deficiencies that are found.\21\
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\21\ Testimony of Dr. Kathryn Zoon, HRIR hearings, p. 88.
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Better screening tests for viruses, such as HIV and
Hepatitis, and viral inactivation measures have increased the
margins of safety for many blood products since the 1980's.
However, after infection with HIV, there is a period of time
known as a ``window'' in which infection may be present but
antibodies to the virus have not been produced in sufficient
quantity for detection. This window can last up to 6 months in
some individuals, but is usually about 20 days. Antigens \22\
appear and can be detected sooner, reducing the window by 10
days or more. Donated blood from persons infected with HIV, who
do not yet exhibit antibodies to the virus, may be able to
transmit the disease to others.
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\22\ Molecules that stimulate the production of antibodies. ``IOM
Report'' definition, p. 305-6.
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FDA believes, ``Reducing the window period further reduces
the chances that HIV-contaminated blood will enter the blood
supply and infect recipients of transfused blood or other blood
products.'' \23\
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\23\ FDA Talk Paper ``FDA Takes Steps To Increase Safety of U.S.
Blood Supply,'' August 10, 1995.
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FDA issued guidance to the blood industry on August 8, 1995
recommending testing of blood donors within 3 months after the
licensure of the first HIV antigen test kit. FDA approved the
first application for licensure of the antigen tests on March
14, 1996.
The use of viral inactivation measures in plasma products,
such as the addition of solvent detergents and/or heat
treatments,\24\ appears to have eliminated the risk of HIV and
some forms of Hepatitis from antihemophilic factor
products.\25\
---------------------------------------------------------------------------
\24\ IOM Report, p. 92.
\25\ IOM Report, p. 78.
---------------------------------------------------------------------------
2. The blood supply continues to face new infectious disease challenges
NIH held a consensus conference on infectious agents in the
blood supply in January 1995. Several emerging threats to the
blood supply were identified. The report of that conference
also discusses the criteria to evaluate, detect and eliminate
emerging blood-borne agents.\26\
---------------------------------------------------------------------------
\26\ NIH consensus statement Infectious Disease Testing for Blood
Transfusions, January 9-11, 1995.
---------------------------------------------------------------------------
Creutzfeldt-Jacob Disease (CJD) is a spongiform
encephalopathy \27\ caused by a prion, a newly identified,
infectious protein. It is noteworthy that prions are not
bacteria, viruses, or parasitic agents. Prion diseases of
humans may incubate for 30 years or more.\28\ CJD can only be
diagnosed with certainty on autopsy of the brain. There is
concern that consumption of Bovine Spongiform Encephalopathy
(BSE) or ``Mad Cow Disease'' infected beef could produce a
variant form of CJD (vCJD) in humans.\29\
---------------------------------------------------------------------------
\27\ A rare, untreatable and fatal neurological disease; S.B.
Prusiner ``The Prion Diseases,'' Scientific American, January 1995, p.
48; and statement of Dr. Ronald Gilcher, HRIR hearings, p. 56.
\28\ Ibid, p. 51.
\29\ Ibid, p. 48.
---------------------------------------------------------------------------
There is a theoretical risk that CJD can be transmitted via
transfusion of blood or blood products.\30\ CJD has been
transmitted through tissue transplants such as dura mater \31\
and corneas, by injections of human growth hormone pituitary
extracts and during procedures with contaminated surgical
instruments.\32\
---------------------------------------------------------------------------
\30\ FDA's Summary of Meeting (via Conference Call) of
Transmissible Spongiform Encephalopathies Advisory Committee, July 2,
1996 (in subcommittee files).
\31\ ``The outermost, toughest, and most fibrous of the three
membranes (meninges) covering the brain and spinal cord, Dorland's
Medical Dictionary, 28th edition, 1994.
\32\ See supra note 27, p. 49.
---------------------------------------------------------------------------
FDA stated in November 1994, ``there has never been a
reported case of transmission of CJD by blood or plasma
products, and it is not known whether CJD can be transmitted by
blood. However . . . it is prudent to withdraw the (blood of
the infected donor and the plasma products made from it) at
this time.'' \33\
---------------------------------------------------------------------------
\33\ FDA Talk Paper, ``Voluntary Market Withdrawal of Blood
Products,'' Nov. 17, 1994.
---------------------------------------------------------------------------
FDA requires that if a blood or plasma donor meets any of
the following qualifications, all in-date blood components and
plasma derivatives should be withdrawn and quarantined and
consignees \34\ notified: a diagnosis of CJD is discovered via
post-donation information; a donor has a family member with a
diagnosis of CJD; a donor has received human pituitary-derived
hormones, including growth hormone; or a donor has received a
dura mater transplant.\35\ If manufacturers determine that a
plasma product is in short supply, they may release the
quarantined product with appropriate CJD labeling.
---------------------------------------------------------------------------
\34\ Consignees are hospitals, pharmacies, etc., which may have
received the affected products, not the patient recipient.
\35\ FDA Summary of Meeting (via conference call) of Transmissible
Spongiform Encephalopathies Advisory Committee, July 2, 1996 (in
subcommittee files).
---------------------------------------------------------------------------
In the past 7 years, more than 20 reported cases of CJD
have been confirmed in blood donors in the United States, with
some level of product recall.\36\ The American Red Cross has
overseen three major withdrawals since November 1994, that
together involved more than 200 lots of blood. Each lot has the
potential to transfuse or be manufactured into products for
1,000 to 10,000 patients. Bayer, Baxter/Highland, and Sandoz
have also withdrawn plasma products and albumin due to CJD
affected donors.\37\
---------------------------------------------------------------------------
\36\ Ibid; and July 17, 1996 conference call with Dr. Joseph
Fratantoni, FDA, and HRIR Subcommittee staff (notes in subcommittee
files).
\37\ American Red Cross Press Release ``American Red Cross
Announces Precautionary Voluntary Withdrawal of Plasma Derivative
Products,'' June 6, 1996.
---------------------------------------------------------------------------
Also in June 1995, NIH, and the American Red Cross began a
collaborative study to determine whether CJD could be
transmitted by blood and blood products. Results will not be
available until after February or March 1997.\38\
---------------------------------------------------------------------------
\38\ Conference call with Dr. Paul McCurdy, NHLBI, July 17, 1996
(notes in subcommittee files).
---------------------------------------------------------------------------
In April 1995, the American Red Cross, in collaboration
with the CDC and the New York Blood Center initiated a long-
term investigational lookback study to evaluate the
transmission of CJD through blood components. The ARC reports
that ``no cases of CJD have been identified among the
recipients of blood from donors who subsequently developed CJD,
but long-term surveillance of these recipients continues.''
\39\
---------------------------------------------------------------------------
\39\ See supra note 37.
---------------------------------------------------------------------------
Hepatitis C Virus (HCV)--an estimated 300,000 individuals
\40\ are still alive who acquired HCV infection through blood
and blood products prior to 1990 because a screening test for
donated blood was not available. Most of these individuals do
not know of their infection. A screening test for HCV became
available in 1990.
---------------------------------------------------------------------------
\40\ Testimony of Assistant Secretary Philip Lee, HRIR hearings, p.
29.
---------------------------------------------------------------------------
Treatment of HCV is usually with interferon \41\ and
approximately 12-15% of individuals will clear the infection
with the first treatment.\42\ There is some evidence that
individuals with HCV who do not respond to the first treatment
may be able to clear the infection with a second round of
treatment, or with higher dosages of interferon or combinations
of drugs. Many infected persons do not develop symptoms.
Others, however, will develop severe cirrhosis of the liver,
which will require a liver transplant or be fatal.
---------------------------------------------------------------------------
\41\ The only FDA approved drug to treat HCV.
\42\ HRIR Subcommittee conference call with Teresa L. Wright, M.D.,
Associate Professor of Medicine, University of California, San
Francisco, July 17, 1996 (notes in subcommittee files).
---------------------------------------------------------------------------
The February 1994 transmission of Hepatitis C virus to
patients who received immune globulin intravenous (IGIV)
products illustrates the need for continued vigilance regarding
unrecognized, uncharacterized and new threats to the blood
supply. These were the first reported cases of Hepatitis C
infection from licensed IGIV products and prompted withdrawal
of the products from the world market.\43\
---------------------------------------------------------------------------
\43\ Testimony of Dr. Satcher, HRIR hearings, p. 105; and FDA
February 25, 1994 Talk Paper, Immune Globulin Intravenous Removed From
World Market.
---------------------------------------------------------------------------
Hepatitis G Virus (HGV)--accounts for 0.3% if all acute
viral hepatitis in the United States.\44\ The virus is
transmissible via blood transfusion and is present in the U.S.
volunteer blood donor population.\45\ ``The association of the
virus with chronic liver disease and its presence in patients
with dual infections due to HBV or HCV is irrefutable,''
reported Howard C. Thomas, M.D., of St. Mary's Hospital in
London.\46\
---------------------------------------------------------------------------
\44\ Testimony of Dr. Satcher, HRIR hearings, p. 106.
\45\ J. Linnen, et al. ``Molecular Cloning and Disease Association
of Hepatitis G Virus: A Transfusion-Transmissible Agent,'' Science,
271, p. 505, 1996.
\46\ American Association of Blood Banks Newsletter, Nov. 1994.
---------------------------------------------------------------------------
Parvovirus B19--is a common virus that has been implicated
in a wide variety of clinical conditions.\47\ Immunosuppressed
individuals cannot destroy the virus, which limits blood cell
production leading to chronic anemia.
---------------------------------------------------------------------------
\47\ A genus of viruses that infect mammals and birds. Human
parvoviruses cause aplastic crisis in patients with hemolytic anemia or
sickle cell disease, spontaneous abortion and fetal death. Persistent
infection in immunocompromised patients can lead to chronic bone marrow
failure. Dorland's Medical Dictionary, 28th edition, 1994.
---------------------------------------------------------------------------
Parvovirus B19 ``is being increasingly recognized as an
important human pathogen, and has been established as the cause
of `aplastic crisis' in patients with sickle cell disease.''
\48\ Because many hemophiliacs are infected with HIV and
therefore immunosuppressed, first-time exposure to Parvovirus
via factor concentrate may present an additional health risk.
---------------------------------------------------------------------------
\48\ E.A. Lowenthal, A. Wills, P.D. Emanuel, R. Player and J.T.
Prachal, Sickle Cell Acute Chest Syndrome Associated with Parvovirus
B19 Infection: Case Series and Review, American Journal of Hematology
51, 207, 1996.
---------------------------------------------------------------------------
Chagas' Disease--(also called American trypanosomiasis) is
an infection caused by the parasite Trypanosoma cruzi and
transmitted to humans primarily by the reduviid bug. It is a
major cause of illness and death among poor people in
developing countries and is endemic in almost all Latin
American countries. In most cases, Chagas' disease is a mild
illness. In immunocompromised individuals, however, the disease
can be severe or fatal.
If detected early enough, drug treatment can shorten the
acute phase and decrease mortality, but it is only partially
effective in curing the disease. Without treatment, infected
individuals remain chronically infected for their lifetime.
Chagas' has been transmitted through blood and blood
products.\49\ Since this disease is not endemic to the United
States, affected individuals would be unlikely to receive an
accurate and prompt diagnosis. There is growing concern that
with increasing immigration to the United States from Latin
American countries, transfusion could become the primary means
of transmission in this country. This concern is heightened by
the fact that many infected individuals are asymptomatic,
chronic carriers.
---------------------------------------------------------------------------
\49\ Testimony of Dr. Ronald Gilcher, HRIR hearings, p. 58.
---------------------------------------------------------------------------
American Red Cross studies prove Chagas' disease is present
in the Los Angeles/Orange Counties blood donor population. The
on-going study, which began in April 1994, has found that 1 in
10,000 donations overall in this region is confirmed positive
for Trypanosoma cruzi,\50\ although the rate of transmission is
believed to be quite low.
---------------------------------------------------------------------------
\50\ ``Evaluation of Blood Donor Screening Strategies for
Trypsanosoma Cruzi in Los Angeles. E.J. Read, D.A. Leiby, A.A. Pan,
R.J. Stumpf, R.Y. Dodd, paper presented at the November 9-15, 1995 AABB
Convention, San Diego, CA.
---------------------------------------------------------------------------
Bacterial contamination--bacterial contamination of
transfused blood products is a well-recognized source of
sepsis, often due to improper preparation of the venipuncture
site at the time of blood collection as well as improper
screening of ill donors.
About 10%-15% of blood product recipients experience an
adverse reaction and 1% experience a serious side effect.
Approximately 30 people die each year in the United States as a
direct result of blood product transfusion. This estimate may
be conservative because transfusion reactions can mimic common
post-surgical or intensive care problems. The delayed effects
associated with the infectious process may be another reason
for under-reporting of blood product transfusion reactions. One
example is the transmission of Yersinia Enterocolitica, a
gastrointestinal microbe from a blood donor which multiplies in
stored blood.
According to testimony, Babesiosis,\51\ Cytomegalovirus
\52\ and Epstein Barr virus \53\ are also occasionally
transmitted through transfusion.\54\
---------------------------------------------------------------------------
\51\ A tick born parasite, statement of Dr. Ronald Gilcher, HRIR
hearings, p. 56.
\52\ A herpes virus, Dorland's Medical Dictionary, 28th edition,
1994.
\53\ ``A virus of the genus Lymphocryptovirus that causes
infectious mononucleosis. Also called human herpesvirus 4.'' Dorland's
Medical Dictionary, 28th edition, 1994.
\54\ Statement of Dr. Ronald Gilcher, HRIR hearings, p. 56.
---------------------------------------------------------------------------
Unfortunately, many infectious agents are transmitted by
blood and may not be discovered until weeks, months or years
after the transfusion.
The CDC's most significant concerns are with the challenges
of new infectious agents of which we are now unaware, so that
uncharacterized threats to the blood supply are detected as
soon as possible.\55\ The American Association of Blood Banks
(AABB) is also convinced that it is critical to be vigilant
with respect to unknown infectious agents in the blood
supply.\56\
---------------------------------------------------------------------------
\55\ Testimony of Dr. David Satcher, HRIR hearings, p. 104.
\56\ Testimony of Karen Lipton, AABB, HRIR hearings, p. 150.
---------------------------------------------------------------------------
Other infectious agents such as HIV-1 and II, and Hepatitis
B and C, still continue to be transmitted through blood product
transfusions, although at a very low rate. Hepatitis A virus
outbreaks have recently been reported in clotting factor
concentrates for the first time in the United States.\57\ The
presence of HIV O variant has been documented recently in the
United States, and current screening tests for donated blood
must be modified to detect it.\58\
---------------------------------------------------------------------------
\57\ Morbidity and Mortality Weekly Report, Centers for Disease
Control, January 19, 1996, Vol. 45, No. 2.
\58\ FDA Talk Paper, ``First Group O HIV Infection Reported in the
United States,'' July 5, 1996.
---------------------------------------------------------------------------
Assistant Secretary for Health Philip Lee testified that
``the level of scientific uncertainty in the early and mid-
1980's was very great. There was disagreement among the
scientists and the physicians on a number of these issues. And
that same problem we face today. I mean, the scientific
uncertainty.'' \59\
---------------------------------------------------------------------------
\59\ Testimony of Dr. Philip Lee, HRIR hearings, p. 23.
---------------------------------------------------------------------------
3. In response to the recommendations of the Institute of Medicine
(IOM), HHS has begun to implement higher regulatory standards
to protect the Nation's blood supply from emerging infectious
diseases and blood borne pathogens
The IOM presented its report to HHS on July 13, 1995. HHS
Secretary Donna E. Shalala created a task force of Public
Health Service agencies to evaluate the recommendations and
develop an implementation plan.
At the subcommittee's October 12, 1995 hearing, Secretary
Shalala announced that HHS accepted all of the recommendations
put forth by IOM,\60\ except the recommendation to create a
prospective compensation program for individuals harmed by
blood and blood products,\61\ similar to the National Vaccine
Injury Compensation Program.
---------------------------------------------------------------------------
\60\ IOM Report, p. 13.; and statement of Secretary Shalala, HRIR
hearings, p. 17-18.
\61\ Representative Porter Goss (R-FL) introduced a retrospective
compensation bill in the 104th Congress, H.R. 1023 ``The Ricky Ray
Hemophilia Relief Fund Act'' to compensate hemophiliacs who acquired
AIDS through blood and blood products prior to 1987. The bill would
authorize a $1 billion trust fund to provide payments of $125,000 to
HIV-infected hemophiliacs, their survivors, and infected family
members.
---------------------------------------------------------------------------
HHS will create a Blood Safety Committee consisting of the
CDC Director, NIH Director and the FDA Commissioner. The
committee will be chaired by the Assistant Secretary for
Health. The committee will be advised by the Advisory Council
on Blood Safety and Availability, which will include
representatives of industry, consumers, scientific experts, and
ethicists.
The Secretary views the Advisory Council as ``a forum in
which to examine broad public health and societal implications
of blood safety issues. These include availability, informed
consent, social choice, the allocation of research resources,
and the impact of economic factors on availability.'' \62\
---------------------------------------------------------------------------
\62\ Testimony of Secretary Shalala, HRIR hearings, p. 10.
---------------------------------------------------------------------------
According to HHS, the Blood Safety Committee will provide a
high level forum for decisionmaking, priority setting, and
interagency coordination on an ongoing basis, as well as
facilitating rapid and effective responses to new developments.
It will be convened to bring broad-based input from the
consumer sector, medical care providers, legal and ethical
experts, and blood products service organizations and related
industries to consider broader societal concerns around blood
safety that cannot be resolved through the evaluation of
scientific data alone.\63\
---------------------------------------------------------------------------
\63\ Minutes of the Blood Safety Committee, January 17, 1996, U.S.
Department of Health and Human Services, p. 3.
---------------------------------------------------------------------------
The FDA's Blood Products Advisory Committee (BPAC) will
provide expert scientific advice to the FDA on regulatory
matters relating to the blood supply and human tissues for
transplantation, which are areas under FDA's regulatory
authority.\64\ BPAC input will be sought when there is
controversy over the applicable scientific standard,
interpretation of clinical trial data, or when outside
expertise is needed on manufacturing and supply issues in order
to support FDA regulatory decisions. The BPAC also provides FDA
with public input on regulatory policy development in these
areas.\65\
---------------------------------------------------------------------------
\64\ Ibid.
\65\ Minutes of the Blood Safety Committee meeting, U.S. Department
of Health and Human Services, January 17, 1996.
---------------------------------------------------------------------------
Following the Secretary's October 12, 1995 announcement of
the creation of the Blood Safety Committee at the hearing, the
committee met on December 11, 1995, January 17, 1996, April 24,
1996 and June 11, 1996. Agenda issues have not been released
and no appointments have yet been announced to the Advisory
Council on Blood Safety and Availability.
From the documents provided by HHS to the HRIR
Subcommittee, the PHS agencies appear to use the committee for
exchange of information on blood safety issues on a bimonthly
basis. The meeting is chaired by Assistant Secretary for Health
Dr. Philip Lee and is attended by agency heads and their
deputies as voting members. Additional PHS staff are included
as required.\66\
---------------------------------------------------------------------------
\66\ Ibid.
---------------------------------------------------------------------------
The Advisory Council is scheduled to meet two times each
year and have 18 voting members, as well as non-voting ex
officio representatives of the PHS agencies.\67\
---------------------------------------------------------------------------
\67\ Ibid.
---------------------------------------------------------------------------
4. The public is provided insufficient information on the risks of
blood and blood products
Federal, State and local public health officials, as well
as physicians and other health care providers, must evaluate
the inevitable risks in the use of blood and blood-derived
therapies. Those risks, however small, must then be
communicated to patients in time, and in a form, to be useful
in their consideration of alternative, less risky, treatment
options.
Dr. John A. Penner, a professor of medicine and pathology
at Michigan State University, testified that the ``public has
long enjoyed the sense that blood provided through the best of
intentions by volunteers, their neighbors in the communities,
is not only life-saving but essentially risk-free. . . .
Although the public and health care workers have been
disillusioned by events over the past 15 years, they still
unrealistically expect and demand complete, safe, and risk-free
blood and blood products.'' \68\
---------------------------------------------------------------------------
\68\ Testimony of Dr. John Penner, HRIR hearings, p. 48.
---------------------------------------------------------------------------
He believes that physicians have also left the burden of
knowledgeable use of blood products to others and have avoided
careful evaluation of these products.\69\ Dr. Penner feels that
transfusion education is critically needed by most physicians.
He conducted a study, funded by NIH, which attempted to alter
physician practices in relation to the use of blood products.
While physicians decreased the number of blood products
transfused, they failed to improve ``the appropriateness of
their ordering practices and often administered concentrates
unnecessarily when platelet levels were decreased, but not to a
degree that would require support'' with blood products.\70\ He
concluded that ``a strong educational program with frequent
reinforcement will be needed before any significant reduction
in inappropriate use can be obtained.'' \71\
---------------------------------------------------------------------------
\69\ Ibid.
\70\ J.A. Penner, R.G. Brigham, Intervention/Education to Improve
Hemostatic Product Use, Final Progress Report for National Heart, Lung
& Blood Institute, Grant #HL33922-05, submitted 2/92.
\71\ Testimony of John Penner, M.D., HRIR hearings, p. 52.
---------------------------------------------------------------------------
According to testimony, the degree to which a patient is
informed of the risks associated with blood products also
varies from geographic location and from physician to
physician.\72\ For three decades, the risk of contracting
Hepatitis was considered a medically acceptable risk with
regard to use of blood and blood products.\73\ If Hepatitis had
not been tolerated as a medically acceptable risk, available
technologies to kill Hepatitis virus could have also killed the
unknown HIV present in the blood supply, greatly reducing the
exposure of blood product users to HIV.\74\
---------------------------------------------------------------------------
\72\ Patricia De Filippi, HRIR hearings, p. 65.
\73\ Statement of Corey Dubin, HRIR hearings, p. 40.
\74\ Ibid, p. 44; and IOM Report, p. 93-94.
---------------------------------------------------------------------------
Patients have a number of autologous (self-donation)
options to reduce use of donated and pooled blood products.
These options include: preoperative donation of blood products,
intraoperative salvage of red blood cells, postoperative
salvage of blood from surgical wound drainage.\75\ It appears
that, little, if any information, is routinely provided to
patients regarding these options.
---------------------------------------------------------------------------
\75\ Statement of Ronald Gilcher, M.D., HRIR hearings, p. 59.
---------------------------------------------------------------------------
5. The FDA has not effectively managed regulatory review of blood
issues, particularly its advisory committee on blood safety
issues, the Blood Products Advisory Committee (BPAC)
A test for HCV became available for screening blood donors
in 1990. At that time, an estimated 300,000 persons were still
alive who had been infected through blood products and were
unaware of their infection. Treatment options were available.
The FDA's BPAC considered whether patients who received the HCV
infected units should be notified of their exposure on all of
the following dates: Oct. 31, 1989; Jan. 17-18, 1991; Sept. 26-
27, 1991; March 12-13, 1992; March 25-26, 1993; Dec. 2-3, 1993;
and Dec. 15-16, 1994.\76\ However, the BPAC has not taken
action on this issue.
---------------------------------------------------------------------------
\76\ BPAC minutes (in subcommittee files).
---------------------------------------------------------------------------
Nevertheless, Subcommittee Chairman Shays received a
commitment from Secretary Shalala and Assistant Secretary for
Health Philip Lee at the October 12th hearing that HCV
notification would be the first issue considered by the new
Advisory Council on Blood Safety and Availability.\77\
---------------------------------------------------------------------------
\77\ Testimony of Dr. Lee, HRIR hearings, p. 29-30.
---------------------------------------------------------------------------
In another area, the BPAC again failed to reach a final
decision on an important public health issue. In March 1994,
the National Hemophilia Foundation (NHF) recommended to BPAC
that manufacturers of plasma products update their product
package inserts to include the risks of Parvovirus B19 and
Hepatitis A attendant to use of these products. The issue was
again considered in March 1996 but no decision was ever made.
The National Hemophilia Foundation believes that specific
warnings of possible infectious disease transmission via
clotting factor concentrates, although needed to ensure
informed treatment decisions, are not on the package insert
because the BPAC has been unable to make a decision on the
matter.\78\
---------------------------------------------------------------------------
\78\ National Hemophilia Foundation's June 6, 1996 correspondence
with HRIR Subcommittee (in subcommittee files).
---------------------------------------------------------------------------
According to testimony, FDA is also not working effectively
with manufacturers to expedite the development of new screening
tests and viral inactivation techniques for blood product
sterilization.\79\ One manufacturer submitted a 510(k) \80\
application for a Chagas' disease screening test as a medical
device to FDA's Center for Devices and Radiological Health
(CDRH), at the suggestion of FDA in November 1995. The company
had already received approval of a 510(k) for diagnostic
testing in 1994. In November 1995, FDA informed the company
that the screening indication required filing a Product
Licensing Application (PLA) with the Center for Biologics
Evaluation and Research (CBER). As a result of this confused
regulatory system, to date there is still no approved Chagas
disease screening test for donated blood and plasma.
---------------------------------------------------------------------------
\79\ Statement of Patricia De Filippi, National Hemophilia
Foundation, p. 40.
\80\ Section 510 of the Federal Food, Drug, and Cosmetic Act
requires the filing of a premarket notification by a manufacturer prior
to initial marketing of a device or prior to marketing a device with a
new intended use, or a modified device (42 Fed. Reg. 42,520, 42,528
(1977); 21 C.F.R. 807.81.
---------------------------------------------------------------------------
Questions have also been raised by consumer groups about
the agency's selection of agenda items for BPAC meetings,
drafting of questions which must be voted upon after BPAC
deliberation, the comprehensiveness and impartiality of the
background information FDA sends to committee members, and the
criteria used to select BPAC members.\81\
---------------------------------------------------------------------------
\81\ Response of the National Hemophilia Foundation to the Task
Force on Blood Safety Report, HRIR hearings, p. 80; and July 2, 1996
letter of complaint about BPAC from Keith Waterbrook, director of
Health Services, Jeffrey Goodman Special Care Clinic, Los Angeles, CA
to Subcommittee Chairman Christopher Shays (in subcommittee files).
---------------------------------------------------------------------------
According to NHF, the FDA's policies and procedures for
BPAC structure, organization, and the methods used for making
decisions regarding its membership are tightly controlled by
agency officials.\82\ After the reorganization of the BPAC in
the Fall of 1995, the HRIR Subcommittee discovered that only
one of the current BPAC members was nominated by individuals or
organizations outside FDA. In fact, FDA officials chose at
least one individual now serving on the BPAC who was not
nominated to represent an organization over other equally
qualified individuals who had been nominated by that very
organization.\83\
---------------------------------------------------------------------------
\82\ Response of the National Hemophilia Foundation to the Task
Force on Blood Safety Report, HRIR hearings, p. 80.
\83\ BPAC nomination documents delivered to HRIR Subcommittee on
Feb. 20, 1996 in response to Feb. 1, 1996 HRIR Subcommittee document
request (in subcommittee files).
---------------------------------------------------------------------------
There are a number of critical sectors, such as consumers
who are heavy users of blood products and their treating
physicians, which believe they have not had and still do not
have input into blood policy decisions at the Federal
level.\84\ The National Hemophilia Foundation feels that FDA
has not been open to consumer participation in blood safety
policy areas.\85\ One hemophiliac consumer, who is also a
physician, was added to the BPAC in 1994. A second consumer was
added to the committee in 1995. In 1996, there are only two
voting consumers and one non-voting consumer on the BPAC, which
has 17 members.
---------------------------------------------------------------------------
\84\ Statement of Dr. John Penner, HRIR hearings, p. 52.; statement
of Patricia De Filippi, HRIR hearings, p. 40; statement of Corey Dubin,
HRIR hearings, p. 46; and statement of Dr. Ronald Gilcher, HRIR
hearings, p. 58.
\85\ Response for the record of the National Hemophilia Foundation
to the Task Force on Blood Safety Report, HRIR hearings, p. 77.
---------------------------------------------------------------------------
Representative Porter Goss (R-FL) has introduced a bill
H.R. 1021, ``The Blood Products Advisory Committee Act of
1995'' to require at least one-third of BPAC voting members to
be consumers. He believes this bill will ``rearrange what was
clearly a conflict of interest, a too-close-for-comfort
situation, between people who were making the decisions about
protecting the blood supply and the people who were producing
the products that were being used.'' \86\
---------------------------------------------------------------------------
\86\ Testimony of Representative Porter Goss, HRIR hearings, p. 31.
---------------------------------------------------------------------------
In addition, testimony indicates that the failure by FDA to
appoint treating physicians to the BPAC results in the absence
of a critical perspective of medical professionals treating
heavy consumers of blood products. As a result, treating
physicians have not been able to educate their patients and the
public about the risks and benefits of blood products.\87\
---------------------------------------------------------------------------
\87\ Statement of John Penner, M.D., HRIR hearings, p. 52.
---------------------------------------------------------------------------
On three occasions recently, FDA acknowledged problems in
the operation of the BPAC.
The FDA went around the BPAC and sought regulatory advice
from an ad hoc committee on CJD in 1995.
FDA's BPAC first met to discuss the potential risk of CJD
transmission through blood in December 1994, voting 14 to 1 in
favor of withdrawing blood components collected from donors who
subsequently developed CJD. But calling the CJD risk
theoretical and expressing concern about possibly creating
shortages of plasma products, the committee voted against the
recall of plasma derivatives despite impassioned pleas from
hemophiliac representatives. BPAC voted 9 to 4 in favor of
indefinite lookback \88\ and informing recipients of blood
components from blood donors who subsequently developed CJD.
However, the committee voted 10 to 4 against such notification
of plasma derivative recipients.
---------------------------------------------------------------------------
\88\ Locating the recipients of infected blood after they have been
transfused.
---------------------------------------------------------------------------
On June 22, 1995 FDA convened the ad hoc Special Advisory
Panel on CJD. The panel endorsed the recommendations made at
BPAC's December 1994 meeting to recall blood components made
from blood donors who developed CJD and to notify recipients.
However, the panel also recommended withdrawal of plasma
derivatives from plasma donors who subsequently developed CJD
and notification of recipients of these products.
In August 1995 FDA Commissioner Kessler asked 11 of the 13
members of the BPAC to resign due to perceived potential
conflicts of interest involving their employment in regulated
establishments such as hospital blood banks and regional blood
centers. The Commissioner's action followed much criticized
BPAC decisions on CJD and p24 antigen testing.\89\
---------------------------------------------------------------------------
\89\ See recommendation 6.
---------------------------------------------------------------------------
In addition, the subcommittee has learned that the FDA does
not manage its inspection responsibilities for the blood
industry in the same manner as the agency approaches other
regulated industries. The agency requests production schedules
from some plasma fractionation companies prior to scheduling
annual or biennial domestic biologic establishment inspections.
The request for production schedules would serve to notify a
firm of an impending inspection. Except in exceptional
circumstances, FDA operates on a system of unannounced
inspections of all other regulated industries.\90\
---------------------------------------------------------------------------
\90\ FDA briefing with HRIR Subcommittee staff, May 24, 1996 (notes
in subcommittee files). See also FDA Field Management Directive, 3/4/
88.
---------------------------------------------------------------------------
In FY 95, FDA's CBER personnel performed 47 inspections.
Production schedules were requested from one manufacturer for a
period of less than 3 months; from nine manufacturers for a
period of 3 to 6 months; from two manufacturers for a period of
1 year and four manufacturers were asked for production
schedules of unknown duration. In FY 95, CBER performed a total
of six annual/biennial inspections of domestic plasma
derivative manufacturers and requested production schedules for
3 to 6 months for two inspections.\91\ Furthermore, FDA does
not maintain records of these requests for production schedules
and was unable to provide a complete assessment of this
practice to the subcommittee staff.
---------------------------------------------------------------------------
\91\ June 3, 1996 FDA document delivery to HRIR Subcommittee (in
subcommittee files).
---------------------------------------------------------------------------
6. Despite a BPAC recommendation to the contrary, the FDA took the
first step toward closing the ``window period'' of possible HIV
transmission by licensing the p24 antigen test for screening of
donated blood
After infection with HIV, there is a period of time known
as a ``window'' in which infection may be present but
antibodies to the virus have not yet been produced in
sufficient quantity to be detected by blood screening tests.
This window can last up to 6 months in some individuals, but is
usually about 20 days. Antigens appear and can be detected
sooner than antibodies, reducing the window by 10 days or more.
Reduction of the window period by 10 days is estimated to
result in detection of up to 20 infected (antigen positive/
antibody negative) donation cases per year which would be
missed using only the antibody tests. Since each donation
collected undergoes separation into at least two units, antigen
testing could prevent up to 40 individuals from exposure to
HIV-tainted blood products each year. That in turn could
prevent transmission via sexual contact or other high-risk
behavior to an additional estimated 1.7 individuals per
infected recipient. As a result, at least 68 individuals per
year could be protected from HIV infection through licensing of
antigen tests as a screening tool.
On June 23, 1995, the FDA's Blood Products Advisory
Committee (BPAC) recommended against routine HIV-1 antigen
screening of blood donor units. At the October 12th hearing,
Corey Dubin, a voting member of BPAC at the time, described the
BPAC deliberation process on antigen testing as a ``discussion
centered on whether this was the best expenditure of the
shrinking monies for AIDS. The BPAC, dominated by blood
bankers, was clearly in violation of its mandate regarding the
safety of the blood supply. I do not believe that it is the job
of the FDA and its BPAC to be considering how AIDS dollars are
spent and then basing what should be a purely safety driven
decision on that economic analysis.'' \92\
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\92\ Statement of Corey Dubin, HRIR hearings, p. 45.
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On July 12, 1995 Subcommittee Chairman Shays wrote to FDA
Commissioner David A. Kessler urging him not to accept the
BPAC's decision but to approve the immediate licensing of HIV-1
antigen tests for the screening of the Nation's blood supply.
Shays pointed out that antigen testing would further close
the window of potential infection in recipients of blood and
blood products, a goal which was consistent with remarks made
by Commissioner Kessler at a September 26, 1994 NIH conference.
Dr. Kessler said he believed that as a public health agency the
FDA has ``an obligation to foster the development of new
technologies, especially if these technologies hold the promise
of a blood supply that is even safer. This is especially true
for detecting HIV--the AIDS virus. We need to close the
window.'' \93\
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\93\ September 26, 1994 NIH Conference on the Feasibility of
Genetic Technology to Close the HIV Window in Donor Screening.
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Subcommittee Chairman Shays was also concerned that failure
to license antigen testing for donor screening would make it
unlikely that any company would pursue RNA technology which
could close the window completely within 5 years. On August 8,
1995 Dr. Kessler announced FDA guidance to industry
recommending use of the new p24 antigen screening kits within
90 days of the first kit's licensure by FDA.\94\
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\94\ August 8, 1995 CBER memo to all registered blood and plasma
establishments.
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Also in August 1995, FDA requested the resignations of most
of the BPAC members who were affiliated with regulated entities
such as hospital blood banks. FDA did not however, increase the
voting role of consumers most affected by blood safety
decisions.
The Product Licensing Applications (PLAs) for the short
duration p24 HIV-1 antigen tests were filed in 1990 but not
approved until 1996.
7. Fifteen years after the AIDS virus emerged as a threat to the blood
supply, FDA still has not developed an effective system for
communicating blood product recalls or viral outbreaks to
pharmacists, doctors or patients
FDA has the authority to request a manufacturer to recall a
product if it poses a risk to public health.\95\ Failure by a
manufacturer to voluntarily recall a product when requested to
do so by FDA can result in the seizure of the violative product
and or suspension of the manufacturer's license. That in turn
could shut down the manufacturer's operations and destroy
public confidence in the product, damaging the market for the
product.
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\95\ 21 C.F.R. 7.11.
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FDA regulations require that manufacturers of recalled
products notify each of the firm's ``directed accounts'' about
the recall. The regulation doesn't define ``accounts'' and
states that ``where appropriate . . . the direct account should
in turn notify its customers who received the product about the
recall.'' \96\
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\96\ 21 C.F.R. 7.49; presentation of Glenn Pierce, M.D., National
Hemophilia Foundation, to BPAC, March 15, 1996 (in subcommittee files);
and HRIR Subcommittee conference call with FDA CBER personnel, July 17,
1996 (notes in subcommittee files).
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Even when the provider of the recalled product notifies a
patient of the recall, the notification of the patient by the
manufacturers and treating hospitals varies a great deal.
Patricia De Filippi, the parent of a hemophiliac, testified
that the medical center providing a recalled product did not
inform her for 6 months of the recall, during which time her
son consumed a 6 month supply of the recalled product in home
therapy.\97\
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\97\ Statement of Patricia De Filippi, p. 38.
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In addition to notification of consumers and providers of
contaminated products, there are also disputes about
nomenclature used for market withdrawal and recall
notification. The term ``field exchange'' has been used by
plasma concentrate manufacturers to describe actions referred
to as recalls by the FDA in its enforcement report.\98\ Terms
such as field exchange have no basis in statute or in FDA
regulations, yet the agency has apparently permitted
manufacturers of biologic products to utilize these terms in a
practice for biological products that is not permitted for
drugs, devices or foods.
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\98\ FDA January 16, 1996 Talk Paper ``Factor VIII and Factor IX
Products Associated with Hepatitis A Transmission,'' and NHF March 11,
1996 press release ``Alpha Therapeutic Corporation Conducts `Field
Exchange' of Lots of Alphanine SD . . . Due to Possible Transmission of
Hepatitis A Virus.''
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8. The size of plasma pools for fractionated products can increase the
risk of infectious disease transmission
In the United States, there are over 400 FDA-licensed
plasma collection facilities and 5 principal pharmaceutical
firms engaged in plasma fractionation.\99\ U.S. plasma
collection facilities conduct approximately 13 million
plasmapheresis collection procedures annually and provide 60
percent of the world's need for plasma.\100\ Plasmapheresis, a
method of collecting plasma from the donor instead of whole
blood, increases the plasma yield from each donor and can
reduce the number of donors in each pool of plasma from which
products are manufactured.\101\
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\99\ Plasma fractionation is the separation of plasma into its
major proteins. Since the production of antihemophilic factor (a.k.a.
clotting factor concentrates) requires donations from thousands of
donors, these donations are pooled into a large batch for further
processing. IOM Report, p. 311.
\100\ Testimony of James Reilly, American Blood Resources
Association, HRIR hearings, p. 181-182.
\101\ Testimony of Dr. Bruce Evatt, CDC, HRIR hearings, p. 117.
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Source plasma is the non cellular fluid portion of blood
that is used as a raw material in the production of plasma-
based therapies. These products are used in the treatment and
diagnosis of conditions such as cardiac surgery, immune
disorders, hemophilia, burns, trauma, and to provide protection
against Hepatitis B, Rh disease and tetanus.
These products are made with the pooled plasma of up to
60,000 \102\ people for some products. Some potential donors
have HIV, Hepatitis and other infectious diseases. Therefore,
manufacturers attempt to reduce the viral load of the initial
plasma prior to manufacturing, creating a greater safety
margin.\103\
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\102\ HRIR conference call with FDA CBER personnel, July 17, 1996
(notes in subcommittee files).
\103\ Testimony of Dr. Thomas Waytes, Immuno-U.S., HRIR hearings,
p. 226.
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But some virus gets through the donor screening process,
and viral inactivation procedures such as heat treatments,
pasteurization and solvent detergents are used in an effort to
kill the remaining viruses in the pool.
Therefore, donor pool size is equivalent to risk. Reduction
in pool size reduces the number of donors to which a recipient
of fractionated products is exposed. The fewer the donors to
which a recipient is exposed, the less the risk.\104\
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\104\ Testimony of Dr. Bruce Evatt, CDC, HRIR hearings, p. 119.
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First time donors present the greatest risk to the plasma
and blood supply. Ninety-five percent of plasma donations which
test positive for HIV or Hepatitis B or C come from first time
donors who do not return to make a second donation within 3
months.\105\
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\105\ Testimony of Mark Phillip, Immuno, HRIR hearings, p. 216.
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Some companies have used this information to develop
manufacturing approaches to enhance the safety of pooled plasma
products. In 1994, Immuno-U.S. (``Immuno''), a producer of
plasma products, established a first-time donor applicant
rejection system. Under this policy, the company destroys all
plasma from first time donors who do not return to make a
second donation within 3 months and undergo a second round of
viral testing. This eliminates the chance that a donor in the
window period of hepatitis or HIV infection is donating only
for the screening test results.
Immuno has also instituted an inventory hold for 3 months
in which units of plasma from first time donors which have been
screened and found suitable for production are placed on hold
for 90 days. If the donor is found to be reactive to screening
tests on a subsequent donation or if the donor does not return
to donate again with the 90 day period, the previous plasma is
destroyed. This is to eliminate the possibility of a window
case of Hepatitis or HIV, where the donor may have donated only
to get tested for an infectious agent. Ninety-seven percent of
plasma units collected by Immuno are followed by at least one
additional donation by the same donor and thus have the benefit
of this inventory hold follow-up.\106\
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\106\ Testimony of Dr. Mark Philip, Immuno-U.S., HRIR hearings, p.
219.
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Immuno reports that as a result of the 3-month inventory
hold, the company removed and destroyed 8 times more
potentially risky plasma than would have been removed without
the benefit of this program. The inventory hold program results
in removal and destruction of almost 1% of the plasma collected
by Immuno which otherwise would be acceptable for use by FDA
standards. However, this has resulted in greater costs of
production.\107\
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\107\ Testimony of Dr. Mark Philip, Immuno-U.S., HRIR hearings, p.
217.
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The fewer donations from individual donors that go into a
plasma pool,\108\ the safer that pool will be.\109\ In
addition, viral load has been reduced by companies \110\ which
locate centers in pleasant and supportive environments, with
child care. These provisions in turn encourage frequent,
regular donation by desirable, low-risk donors in communities
with low incidence of infectious disease.
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\108\ Through utilization of repeat donors, where the donors are
clearly identified and monitored very closely.
\109\ Testimony of Dr. Bruce Evatt, CDC, HRIR hearings, p. 117.
\110\ Immuno testified that the company has seen an 88% decrease
the last 5 years in viral marker rates for HIV among the donor
population, with similar rate reductions for Hepatitis B and C.
Testimony of Dr. Mark Philip, Immuno-U.S., HRIR hearings, p. 215.
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IV. Recommendations
1. Congress should establish the Blood Safety Committee and the
Advisory Committee on Blood Safety and Availability in statute
The IOM Report states that the Blood Safety Director should
be at the level of a deputy assistant secretary or higher, and
should not be a representative of any single PHS agency in
order to be effective in coordinating the various agencies of
the PHS. The Clinton administration's appointment of the
Assistant Secretary for Health as the Blood Safety Director
would not obligate this or any future administration to
maintain this structure or continue to implement the IOM
recommendations.
The roles and responsibilities of the Blood Safety Council,
National Advisory Committee and the BPAC should be defined
clearly to ensure greater coordination and to ensure that the
BPAC confines its decisions to scientific matters under the
jurisdiction of FDA.
2. Congress should consider establishing an indemnification system for
individuals who suffer adverse consequences from the use of
blood and blood products \111\
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\111\ Statement of Secretary Shalala, HRIR hearings, p. 17.
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Potential injury from blood, blood products, and blood
derivatives continues to be a reality for all people who must
use these products in the course of medical treatment. Since
1985, clotting factor products have been treated with viral
inactivation measures which have virtually eliminated the
threat of HIV.
Blood components from individual donors, however, are not
virally inactivated and may transmit infectious diseases. Since
it is impossible to make the blood 100 percent safe, society
needs to examine effective avenues for compensating those
parties who will be injured as result of the inherent
imperfections in the blood supply, however small, including
alternative dispute mechanisms and no-fault compensation
programs as a means to achieve better and more efficient
resolutions of claims resulting from transfusion-related
injuries.
The solution may be the enactment of a blood and blood
products compensation trust fund that would give consumers
needed recourse in most legal settings.\112\ Since blood borne
pathogens take years to manifest harm, not only do individuals
have to overcome State blood shield laws,\113\ but statutes of
limitations as well.
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\112\ IOM Report, p. 13.
\113\ The blood shield laws were enacted by 47 States in the 1950's
and 1960's to exempt blood and blood products from ``strict liability
or implied warranty claims on the basis that blood and blood products
provide a service, not a sale.'' IOM Report, p. 49.
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Experience to date suggests that development of such a
program involves resolution of many complex issues, including
development of sufficient funding mechanisms and obtaining the
cooperation of both Government and private insurers to support
an alternative to the traditional tort system, such as the
National Vaccine Compensation Program.\114\
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\114\ Statement of Karen Shoos Lipton, HRIR hearings, p. 131;
statement of Dr. Toby Simon, HRIR hearings, p. 140.
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3. HHS should take steps to ensure that the estimated 300,000 living
recipients of blood and blood products who were infected with
Hepatitis C virus before 1990 are notified of their potential
infection so that they might seek diagnosis and treatment
Dr. Lee and Secretary Shalala agreed at the October 12
hearing to place the HCV notification issue first on the agenda
of the Blood Safety Committee.\115\ The Blood Safety Committee
has met bimonthly since December 1995 but no public statements
have been made on this issue.
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\115\ Testimony of Dr. Philip Lee and Secretary Shalala, HRIR
hearings, p. 29-30.
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HHS has informed the subcommittee staff that the Blood
Safety Committee has approved but not yet implemented an
outreach plan to medical providers that will identify patients
at risk and provide testing, treatment and counseling
recommendations. The committee will also identify a model for
outreach to affected consumers who would not be in regular
contact with a medical provider.\116\
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\116\ HRIR Subcommittee staff meeting with Marc Smolonsky, Office
of the HHS Assistant Secretary for Legislation, June 4, 1996 and
conference call of June 5, 1996 (notes in subcommittee files).
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4. HHS should disseminate more clinically useful information to
providers of care and to the public regarding blood safety
issues
Recommendation 13 of the IOM report states that, ``The
Department of Health and Human Services should convene an
expert panel to inform the providers of care and the public
about the risks associated with blood and blood products, about
alternatives to using them, and about treatments that have the
support of the scientific record.'' \117\
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\117\ IOM Report, p. 232.
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The HHS' Secretary's Task Force agreed: ``that this type of
clinically useful information should be communicated as it
becomes available. As issues of importance arise, the PHS Blood
Safety Committee and the Advisory Council on Blood Safety and
Availability will evaluate the government's communications
efforts, including the activities of the Agency for Health Care
Policy and Research and its clinical guidelines program, to
determine what additional efforts are needed.'' \118\
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\118\ Report to the Secretary--Task Force on Blood Safety, HRIR
hearings, p. 21.
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HHS should develop a standardized informed consent document
to be given to patients prior to transfusion, outlining the
risks and benefits of blood and blood product transfusion.\119\
Patients should be made aware of all options to reduce use of
donated and pooled blood products, as well as other non-blood
based products such as recombinant products which would reduce
the risk of transmitting blood borne pathogens.
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\119\ Statement of Patricia De Filippi, p. 40; testimony of Dr.
John Penner, p. 48-49.
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In addition, FDA should promptly require plasma
fractionators to provide adequate and appropriately updated
warning labels for plasma products to ensure that patients are
informed of the risks to which they may be exposed through use
of these products, whether or not the BPAC is able to reach
consensus on this matter.
FDA should also work with plasma fractionators to develop
appropriate labeling to include von Willebrand \120\ disease
indications for intermediate purity hemophilia products
developed for hemophilia treatment. These hemophilia products
are currently used off-label for treatment of severe von
Willebrand disease.
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\120\ An inherited bleeding disorder affecting 500,000 persons in
the United States (half of whom are women) caused by absent or
insufficient levels of glycoprotein in the blood. March 5, 1996 letter
from National Hemophilia Foundation President Stephen Bajardi to
Subcommittee Chairman Shays (in subcommittee files).
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Dr. John Penner testified that ``most of the patients with
severe von Willebrand disease are receiving these products as
their only means of controlling hemorrhagic episodes. In my
practice, I allow surgery to be performed on such patients,
despite the fact that I am unsure of the quality and the
content of the product that I have ordered. The potential for
serious complications exists under these conditions and surely
requires a solution that must be addressed by the FDA.'' \121\
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\121\ Statement of Dr. John Penner, HRIR hearings, p. 53; and March
5, 1996 letter from National Hemophilia Foundation President Stephen
Bajardi to Subcommittee Chairman Shays (in subcommittee files).
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5. FDA should immediately develop an effective system of recall
notification for blood and plasma products
A system should be developed and enforced by FDA for
notifying consumers and health care providers about potential
threats to blood products from infectious diseases, not only
manufacturers' directed accounts. An effective recall system
would require manufacturers undertaking voluntary withdrawals
and recalls to utilize consistent language for these
procedures, so that the impact on directed accounts and
consumers is fully realized.
An effective recall communication system would ensure that
consumers, as well as manufacturers directed accounts, are
promptly advised of identified hazardous products in order that
they may discontinue use and reduce their risks of exposure.
6. FDA should immediately cease its practice of providing advance
notice of safety and compliance inspections to some plasma
fractionators
This practice is inconsistent with FDA's inspection
practices for other industries regulated by FDA.\122\ It is
used only by the CBER officials on a joint inspection with FDA
Office of Regulatory Affairs \123\ personnel (ORA), only in
some cases, and is not documented when used. This practice may
appear to companies as favoritism for competing firms and could
affect consumer and industry confidence in the agency's
enforcement practices.
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\122\ HRIR Subcommittee interview with FDA, May 24, 1996 (notes in
subcommittee files).
\123\ FDA field inspection personnel.
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7. Plasma fractionators should limit the size of plasma pools, with
pool sizes determined as much by public health risk factors as
by production economies of scale
The IOM report stated that ``reducing risks by smaller
pools would not eliminate risk. Indeed, a substantial pool is
necessary to assure the efficacy of some plasma derivatives and
reduce certain risks in others. But maintaining these levels
could be accomplished while reducing pool sizes by a factor of
20. The critical point to this example is that because FDA
promoted no changes in pooling practices, it faces in 1995 the
same dilemma concerning Creutzfeldt-Jakob disease that it faced
in 1983-84 concerning AIDS.'' \124\
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\124\ IOM Report, p. 165 and p. 222.
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A reduction in plasma pool size could make product recalls
easier and also minimize the potentially disruptive effect of
product withdrawal and recalls on supply of plasma
products.\125\
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\125\ Testimony of Dr. Thomas Waytes, Immuno-U.S., HRIR hearings,
p. 224.
ADDITIONAL VIEWS OF HON. CAROLYN B. MALONEY
I applaud the Subcommittee on Human Resources and
Intergovernmental Relations for its in-depth report entitled
``Protecting the Nation's Blood Supply from Infectious Agents:
The Need for New Standards to Meet New Threats.'' Chairman
Shays and ranking Democrat Ed Towns have done an outstanding
job on the series of hearings held in the Fall of 1995 and in
the preparation of the report.
The report raises important and complex scientific, public
health and safety issues. It is heartening, indeed, that the
committee has found that the Nation's blood supply is safer
than it has ever been. This is due in no small measure to the
cooperation of government regulators and the Nation's blood
suppliers and blood derivative manufacturers. At the same time
we all agree that safety is an important concern and continued
vigilance is necessary. With more HIV-infected people than any
other state--20% of the Nation's total AIDS cases--the safety
of our Nation's blood supply is of critical importance to my
constituents in New York.
The report urges the Congress to consider establishing an
indemnification system for individuals who suffer adverse
consequences from the use of blood and blood derivatives. While
I agree that Congress should continue to review the underlying
causes that produce such a recommendation, it does not appear
that the hearing records support the suggestion that the
National Vaccine Compensation Program (NVCP) be used as a model
for such a system. It does not appear that the true costs of
such a ``prospective'' system have been calculated and weighed.
The additional costs imposed on vaccine products for the NVCP
are spread over millions of users for products that are
themselves modest in cost. Coverage of blood and blood
derivatives with such a system, considering the vastly smaller
user population, could result in substantial additional costs
being passed through to users. This could result in fewer
hemophiliacs and other chronic disease sufferers being able to
afford these life-giving and lifesaving products and therapies.
The alternative would seem to be the use of a taxpayer funded
initiative which would give us all some pause. This issue
should be given further consideration before Congress takes any
legislative action.
Again, I applaud the subcommittee for its work in this
area. I agree that we must remain vigilant in our efforts to
insure the safety of our Nation's blood supply and look forward
to working with the subcommittee in the years ahead to pursue
this shared goal.
-