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. 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.
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.
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.
Hemophiliacs are dependent on clotting factor concentrates, concentrated amounts of the
deficient clotting proteins, made from the pooled plasma of up to 20,000 individuals. If
there is an infectious agent in the blood supply, it will be seen in the hemophiliac
population first.
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.
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 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.
CDC estimates that 290,000 (approximately 7%) of the 3.9 million Americans chronically
infected with HCV acquired their infection from transfusion. Most of these individuals
received transfusions prior to the availability of a screening test in 1990. 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.''
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.
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.''
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.''
CDC articulates its vision for the 21st century as ``Healthy People in a Healthy World
Through Prevention.''
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.''
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.
The CDC's Blood Donor Study, 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.
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 that AIDS funds should be redirected from supporting research related
to the safety of the blood supply after REDS funding expires in August 1998.
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.
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.
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 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.
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.''
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, appears to have eliminated the risk of HIV and
some forms of Hepatitis from antihemophilic factor products.
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.
Creutzfeldt-Jacob Disease (CJD) is a spongiform encepha lopathy 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.
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.
There is a theoretical risk that CJD can be transmitted via transfusion of blood or
blood products. CJD has been transmitted through tissue transplants such as dura mater and
corneas, by injections of human growth hormone pituitary extracts and during procedures
with contaminated surgical instruments.
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.''
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 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. If manufacturers determine that a plasma product is in short supply, they may
release the quarantined product with appropriate CJD labeling.
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. 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.
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.
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.''
Hepatitis C Virus (HCV)-an estimated 300,000 individuals 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.
Treatment of HCV is usually with interferon and approximately 12-15% of individuals
will clear the infection with the first treatment. 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.
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.
Hepatitis G Virus (HGV)-accounts for 0.3% if all acute viral hepatitis in the
United States. The virus is transmissible via blood transfusion and is present in the U.S.
volunteer blood donor population. ``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.
Parvovirus B19-is a common virus that has been implicated in a wide variety of
clinical conditions. Immunosuppressed individuals cannot destroy the virus, which limits
blood cell production leading to chronic anemia.
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.'' Because many hemophiliacs are infected with HIV and therefore immunosuppressed,
first-time exposure to Parvovirus via factor concentrate may present an additional health
risk.
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. 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.
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, although the rate of transmission is believed to be quite low.
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, Cytomegalovirus and Epstein Barr virus are also
occasionally transmitted through transfusion.
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. 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.
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. 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.
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.''
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, except the recommendation to create
a prospective compensation program for individuals harmed by blood and blood products,
similar to the National Vaccine Injury Compensation Program.
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.''
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.
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. 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.
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.
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.
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.''
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. 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. He concluded that ``a strong educational
program with frequent reinforcement will be needed before any significant reduction in
inappropriate use can be obtained.''
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. For three decades, the risk of contracting Hepatitis was considered a medically
acceptable risk with regard to use of blood and blood products. 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.
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. It appears that, little, if any information, is routinely provided to
patients regarding these options.
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.
However, the BPAC has not taken action on this issue.
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.
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.
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. One manufacturer submitted a 510(k) 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.
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.
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. 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.
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. The National Hemophilia
Foundation feels that FDA has not been open to consumer participation in blood safety
policy areas. 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.
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.''
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.
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 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.
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.
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.
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.
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.
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.''
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.''
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.
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. 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.
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."
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.
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. 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.
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. U.S. plasma collection
facilities conduct approximately 13 million plasmapheresis collection procedures annually
and provide 60 percent of the world's need for plasma. 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.
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 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.
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.
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.
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.
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.
The fewer donations from individual donors that go into a plasma pool, the safer that
pool will be. In addition, viral load has been reduced by companies 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.
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
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. Since blood borne
pathogens take years to manifest harm, not only do individuals have to overcome State
blood shield laws, but statutes of limitations as well.
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.
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. The Blood Safety
Committee has met bimonthly since December 1995 but no public statements have been made on
this issue.
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.
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.''
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.''
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. 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.
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 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.
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.''
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. It is used only by the CBER officials on a joint inspection with FDA
Office of Regulatory Affairs 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.
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.''
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.
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.
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