Human Fetal Tissue: Acquisition for Federally Funded Biomedical Research
(Correspondence, 10/04/2000, GAO/GAO-01-65R).

This report focuses on the federal involvement in acquiring human fetal
tissue and how it is used in basic and preclinical research. Department
of Health and Human Services (HHS) officials reported that the National
Institute for Health (NIH) is the only federal agency under the Senate
Labor, HHS, and Education Subcommittee's jurisdiction that sponsors
research using human fetal tissue. According a GAO survey, 12,116 human
fetal tissue samples were acquired during fiscal years 1997 through 1999
for use in NIH-sponsored research. In fiscal year 1999, three fetal
tissue suppliers received federal funding. For therapeutic
transplantation research, the NIH Revitalization Act requires written
statements by the donor, the physician who obtained the tissue, and the
researcher receiving the tissue to ensure that the provisions of the law
are met. It also requires that all applicable and local laws must be
followed. The costs to acquire human fetal tissue were low. Principal
investigators reported that quality of tissue and compliance with
federal regulations were their primary criteria for choosing a human
fetal tissue supplier.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  GAO-01-65R
     TITLE:  Human Fetal Tissue: Acquisition for Federally Funded
	     Biomedical Research
      DATE:  10/04/2000
   SUBJECT:  Biomedical research
	     Research grants
	     Health research programs
	     Federal grants

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GAO-01-65R

Fetal Tissue Research United States General Accounting Office

Washington, DC 20548

October 4, 2000 The Honorable Arlen Specter Chairman The Honorable Tom
Harkin Ranking Minority Member Subcommittee on Labor, Health and Human

Services, and Education Committee on Appropriations United States Senate

The Honorable Bob Smith United States Senate

Subject: Human Fetal Tissue: Acquisition for Federally Funded Biomedical
Research Human fetal tissue is used in basic and preclinical biomedical
research to advance knowledge of basic biological processes and improve
research involving potential therapeutic approaches. It is also used in
therapeutic transplantation or clinical research that involves the
transplantation of human fetal tissue into patients for the cure or
amelioration of diseases and disorders. The study, analysis, or use of human
fetal tissue in biomedical research is considered by many medical
researchers to offer promise for treatment of disorders and diseases such as
Parkinson's disease, Alzheimer's disease, and diabetes.

You requested that we study the involvement of federal agencies under the
jurisdiction of the Senate Committee on Appropriations, Subcommittee on
Labor, Health and Human Services, and Education in the acquisition of human
fetal tissue for biomedical research. You specifically asked us to provide
information on (1) which federal agencies under the Subcommittee's
jurisdiction sponsor biomedical research using human fetal tissue, (2) the
number of human fetal tissue samples acquired annually, (3) the number of
central human fetal tissue supply organizations receiving federal funds, (4)
the costs associated with acquiring human fetal tissue, (5) how researchers
select and monitor human fetal tissue suppliers, (6) the extent to which
federal human fetal tissue acquisition policies adhere to federal law, and
(7) how federal agencies ensure that federally funded researchers comply
with human fetal tissue law.

To address these questions, we interviewed officials from the Department of
Health and Human Services (HHS) and the National Institutes of Health (NIH),
organizations that supply human fetal tissue for research, and selected
institutional review boards that are responsible for the oversight of
specific federally funded biomedical research

GAO- 01- 65R Fetal Tissue Research 2 grants involving human fetal tissue. To
gather information about the amount,

sources, and costs of human fetal tissue used in biomedical research, we
conducted a survey of NIH funded principal investigators for extramural and
intramural research using human fetal tissue in fiscal years 1997, 1998, and
1999. Finally, we reviewed the laws, regulations, and policies relevant to
human fetal tissue. We restricted our analysis to research projects that
directly received human fetal tissue. 1 We carried out our work between July
and September 2000 in accordance with generally accepted government auditing
standards.

In brief, HHS officials reported that NIH is the only federal agency under
the Labor, HHS, and Education Subcommittee's jurisdiction that sponsors
research using human fetal tissue. On the basis of information supplied to
us by NIH, we estimate that NIH awarded approximately $17.0 million for 103
research grants using human fetal tissue in fiscal year 1999. Principal
investigators who responded to our survey acquired 12,116 human fetal tissue
samples in fiscal years 1997 through 1999 for use in NIHsponsored research.
NIH funded three central human fetal tissue suppliers to provide human fetal
tissue to biomedical researchers in fiscal year 1999. The costs of acquiring
human fetal tissue were generally low. In fiscal year 1999, 49 percent of
the principal investigators in our survey received human fetal tissue
without paying an acquisition fee. Among those who did pay an acquisition
fee, the average fee per sample was $80 in fiscal year 1999. The median
number of tissue samples received by principal investigators in fiscal year
1999 was 26. In fiscal year 1999, 62 percent of principal investigators
received human fetal tissue from central fetal tissue supply organizations,
31 percent from academic medical center hospitals, and 30 percent from
health clinics or physicians' offices. 2 The principal investigators
identified quality of the tissue supplier and a supplier's compliance with
relevant regulations as the primary criteria for selecting their human fetal
tissue suppliers. We found that federal human fetal tissue procurement
policies and guidance are consistent with federal law. Review boards that
are established at each institution performing HHSfunded biomedical research
have the primary responsibility for ensuring that the procedures for
acquiring human fetal tissue comply with federal, state, and local laws. The
Office for Human Research Protections (OHRP) is the HHS entity that oversees
the ongoing review practices of these institutional review boards.

1 This definition excludes (1) research involving human cord blood,
placenta, amniotic fluid, and chorionic villi; (2) research involving
derivatives of human fetal tissue such as human fetal cell cultures or human
fetal cell lines; (3) studies involving a collection of existing human fetal
tissue; and (4) pathology studies or autopsies.

2 Sum of percentages is greater than 100 because some principal
investigators had more than one supplier.

GAO- 01- 65R Fetal Tissue Research 3 BACKGROUND AND METHODOLOGY

The NIH Revitalization Act of 1993 (P. L. 103- 43) added two provisions to
the Public Health Service Act regarding the acquisition and use of human
fetal tissue. 3 The NIH Revitalization Act 4 prohibits a person from
knowingly acquiring or transferring human fetal tissue for valuable
consideration if the transfer affects interstate commerce. The statute
defines “valuable consideration” as excluding reasonable
payments associated with the transportation, implantation, processing,
preservation, quality control, or storage of human fetal tissue. For
therapeutic transplantation research, the NIH Revitalization Act requires
written statements by the donor, the physician who obtained the tissue, and
the researcher receiving the tissue to ensure that the provisions of the law
are met. It further requires that all applicable state and local laws must
be followed. 5

Because we found no central source of information about the amount of human
fetal tissue used for research or the number of human fetal tissue
suppliers, we conducted a survey of principal investigators for all NIH-
funded extramural and intramural research NIH reported to us as possibly
using human fetal tissue for fiscal years 1997, 1998, and 1999. In the
survey, we asked the principal investigators to identify (1) the number and
type of entities they selected to be human fetal tissue suppliers, (2) the
amount of tissue they received, (3) the number of shipments or acquisitions
they received, and (4) the direct and indirect costs associated with human
fetal tissue acquisition. We also asked principal investigators to identify
the relevant oversight bodies at their institution, to describe the policies
that exist at their institution regarding research using human fetal tissue,
and to explain how their institution ensures compliance with federal, state,
and local laws. We sent the survey instrument to all 160 of the
investigators identified for us by NIH as having a research grant that may
have involved the use of human fetal tissue for fiscal years 1997, 1998, and
1999. The survey was returned by 151 of the principal investigators, for a
response rate of 94 percent. Of those respondents, 93 acquired fetal tissue
for their research and completed the entire survey form, 47 told us that
their research did not use human fetal tissue or that they did not acquire
human fetal tissue in fiscal years 1997, 1998, and 1999, and 11 told us that
they did not directly acquire human fetal tissue but used tissue acquired by
another researcher included in our survey. 6

3 Prior to the enactment of the NIH Revitalization Act, the National Organ
and Transplantation Act of 1988 (P. L. 100- 607) expanded the definition of
“human organ” in the Public Health Service Act (42 U. S. C.
section 274e) to include human fetal organs and tissue. This act thus
prohibits the transfer of human organs, including human fetal tissue, for
valuable consideration for use in human therapeutic transplantation.

4 Section 112 of the NIH Revitalization Act, adding section 498B of the
Public Health Service Act (42 U. S. C. section 289g- 1). 5 For a fuller
description of this provision, see section 111 of the NIH Revitalization
Act, adding section

498A of the Public Health Service Act, 42 U. S. C. section 298g- 1. 6 One
hundred nineteen of the principal investigators received NIH grants in
fiscal year 1999 (the remainder received funds only in fiscal years 1997 or
1998). For those with fiscal year 1999 grants the response rate was 97
percent; 68 acquired human fetal tissue in fiscal year 1999, 39 reported
that they

GAO- 01- 65R Fetal Tissue Research 4 FEDERALLY FUNDED BIOMEDICAL

RESEARCH USING HUMAN FETAL TISSUE HHS officials told us that NIH is the only
federal agency under the Labor, HHS, and Education Appropriations bill that
sponsors biomedical research using human fetal tissue. Separately, the
Centers for Disease Control and Prevention told us that it does not conduct
research using human fetal tissue. On the basis of information supplied to
us by NIH, we estimate that NIH awarded to our survey respondents
approximately $17.0 million for 103 research projects that used human fetal
tissue in fiscal year 1999. 7 The researchers who responded to our survey
collectively received $12.3 million in funding for extramural research at
universities and research institutions, $3.2 million in funding for NIH
intramural research, and $1.5 million for central human fetal tissue supply
organizations.

NUMBER AND SOURCES OF TISSUE SAMPLES ACQUIRED The NIH- sponsored biomedical
researchers who responded to our survey acquired an average of roughly 4,000
samples of human fetal tissue in each year from fiscal years 1997 to 1999
(see table 1). We defined a tissue sample as a separate amount of tissue, or
a single piece of tissue, in one vial. In fiscal year 1999, researchers
received 4,147 samples in 1,878 shipments or acquisitions. The median number
of tissue samples received by principal investigators in fiscal year 1999
was 26.

Table 1: Human Fetal Tissue Samples Acquired, by Fiscal Year

Fiscal year Number of fetal tissue samples

1997 3,676 1998 4,293 1999 4,147

Total 12,116

The principal investigators we surveyed received human fetal tissue most
often from central tissue suppliers. Among principal investigators who
identified their sources for human fetal tissue in fiscal year 1999, 62
percent received human fetal tissue from central tissue suppliers, 31
percent from academic medical center hospitals, and 30

did not use human fetal tissue in their research or that they did not
receive human fetal tissue in fiscal year 1999, and 9 reported that they did
not directly acquire human fetal tissue but used tissue acquired by another
researcher we surveyed. In addition to data from the 68 researchers who
acquired tissue in fiscal year 1999, our analyses for that year also
included data from 10 researchers with NIH grants for only fiscal years 1997
and/ or 1998 who told us that they also acquired human fetal tissue in
fiscal year 1999.

7 This total was calculated by summing the grant funding amounts we received
from NIH for survey respondents who told us that their research used human
fetal tissue in fiscal year 1999. This total probably is slightly
understated, however, because some of the researchers who did not respond to
our survey may have used human fetal tissue.

GAO- 01- 65R Fetal Tissue Research 5 percent from health clinics. 8 Fifty
four percent of all of the human fetal tissue

samples received by the NIH- sponsored researchers we surveyed came from
central tissue suppliers in fiscal year 1999. Likewise, 34 percent of the
tissue samples came from health clinics and 10 percent from academic medical
centers.

CENTRAL TISSUE SUPPLY ORGANIZATIONS NIH sponsors three central human fetal
tissue supply organizations. The Birth Defects Laboratory at the University
of Washington is funded by NIH for the sole purpose of providing human fetal
tissue to federally funded biomedical researchers. While most of the
laboratory's funds are provided by NIH, it also charges researchers a small
fee for the human fetal tissue samples it collects, prepares, and
distributes. The laboratory distributed 2,869 human fetal tissue samples and
collected $52,035 in fees directly from researchers in fiscal year 1999. NIH
provided a grant award of $346,743 to maintain the laboratory's capabilities
in fiscal year 1999. NIH also funds the Brain and Tissue Banks for
Developmental Disorders at the University of Maryland and the University of
Miami School of Medicine/ Children's Hospital of Orange County primarily to
serve as suppliers of human nonfetal tissue for the study of developmental
disorders, but both banks also supply a relatively small amount of human
fetal tissue to biomedical researchers. In fiscal year 1999, NIH funds
totaled $563,823 for the University of Maryland Bank and $574,643 for the
University of Miami Bank. The University of Maryland Bank provided 195 human
fetal tissue samples to investigators in fiscal year 1999, and the
University of Miami Bank provided approximately 40 samples between March 1
and August 31, 1999.

In addition, some researchers obtained human fetal tissue from private,
nonprofit central tissue supply organizations that did not directly receive
federal funds. In their responses to our survey, the principal investigators
who received tissue from these sources most frequently obtained tissue from
Advanced Bioscience Resources, Incorporated (Alameda, California), and the
Albert Einstein College of Medicine Human Fetal Tissue Repository (New York,
New York).

COSTS OF ACQUIRING HUMAN FETAL TISSUE The direct acquisition fees for human
fetal tissue were low. In fiscal year 1999, 49 percent of the respondents to
our survey did not pay any acquisition fees for the human fetal tissue they
received. Among those who paid acquisition fees in fiscal year 1999,
investigators reported an average fee of $80 per human fetal tissue sample,
with a minimum fee of $2 and a maximum fee of $214. In addition, tissue
acquisition fees varied substantially among the different sources identified
in our survey. Only one of the researchers who received human fetal tissue
from academic medical centers paid an acquisition fee ($ 12). More than
four- fifths of the researchers who received tissue from health clinics paid
no fee. The fees per sample of human fetal tissue from health clinics ranged
from $2 to $75, with an average of $22. In contrast,

8 Sum of percentages is greater than 100 because some principal
investigators had more than one supplier. Three percent of these respondents
did not categorize their tissue source.

GAO- 01- 65R Fetal Tissue Research 6 78 percent of the researchers receiving
human fetal tissue from a central tissue

supplier paid an acquisition fee–- those fees ranged from $5 to $214
per sample, with investigators paying an average fee of $96. 9

Second, some of the principal investigators who completed our survey had
additional expenses for transporting, processing, preserving, storing, and
ensuring the quality of human fetal tissue specimens, even if they paid
nothing to acquire the tissue. For all of the principal investigators who
responded to our survey, total expenditures for acquiring human fetal tissue
in fiscal year 1999 totaled approximately $359,000, including both tissue
acquisition fees and these other expenses (see table 2). This total includes
about $142,000 in acquisition fees, $80,000 in shipping and transportation
costs, and $135,000 in other internal laboratory costs for processing,
preserving, storing, and ensuring quality. 10

Table 2: Total Costs Related to Acquiring Human Fetal Tissue, Fiscal Year
1999

Cost category Number of investigators incurring cost

Average annual cost per investigator

Total for all investigators

Acquisition fee 40 (51%) $3,554 $142,144 Shipping and transportation costs

42 (54%) $1,914 $80,405 Other direct costs 9 (11%) a $176 $1,580 Internal
costs 13 (17%) b $10,350 $134,550

Total $358,679

a Two respondents who said that they had other direct costs but did not
provide a cost figure are not included. b Seven respondents who said that
they had internal costs but did not provide a cost figure are not

included. CRITERIA FOR SELECTING HUMAN FETAL TISSUE SUPPLIERS In response to
an open- ended question on our survey, principal investigators reported that
quality of tissue and compliance with federal regulations were their primary
criteria for choosing a human fetal tissue supplier. Overall, 55 percent of
the respondents who received human fetal tissue in fiscal year 1999 told us
that they

9 Twelve percent of researchers who obtained human fetal tissue from central
supply organizations paid no fee. Ten percent of researchers who identified
central supply organizations as the entity that supplied their tissue did
not tell us whether or not they paid an acquisition fee.

10 Shipping and transportation costs include any costs associated with
transporting tissue samples from the supplier to the researcher by any
means, including by personal delivery or commercial shipping company, and
shipping supplies such as sample containers or sterile media provided by the
researcher. Other direct costs include renting space at a supplier's
facility, in- kind services or donations of staff time or supplies to the
tissue supplier, and any other financial considerations to the tissue
supplier. Internal costs are any costs researchers may have incurred as a
result of acquiring fetal tissue that they would not have otherwise, such as
equipment for storing the tissue.

GAO- 01- 65R Fetal Tissue Research 7 selected a tissue supplier on the basis
of the qualifications and reliability of its staff,

its reputation for high- quality work, or other reasons indicating a
preference for a high- quality supplier. Forty- four percent of these 1999
respondents told us that the supplier's compliance with federal and state
laws, or its nonprofit status, was an important reason for their selection.
Thirty- seven percent told us that the location of the tissue supplier was
important (21 percent told us that the tissue supplier was part of their
institution). Fewer respondents (29 percent) selected a tissue supplier
simply because appropriate human fetal tissue was available there. Finally,
9 percent of those who received human fetal tissue in fiscal year 1999 told
us that the low cost of the tissue was a factor in their selection of a
supplier.

HUMAN FETAL TISSUE POLICIES AND GUIDANCE The NIH Revitalization Act of 1993
places limits on the procurement of human fetal tissue. The statute bars
anyone from knowingly acquiring, receiving, or transferring human fetal
tissue for valuable consideration if the transfer affects interstate
commerce. For therapeutic transplantation research, it further bars directed
donations of human fetal tissue and payment of valuable consideration for
costs associated with terminating a pregnancy. Each of these prohibitions
carries criminal penalties, including fines and imprisonment. Because these
provisions do not require implementing regulations, 11 NIH addresses the
importance it attaches to these statutory requirements and the criminal
penalties that the prohibitions carry through guidance to its grantee
researchers. In its forthcoming policy statement on “Research on Human
Fetal Tissue,” NIH emphasizes that “the scientific and ethical
challenges associated with research utilizing human fetal tissues make it
imperative that researchers and their institutions be clearly aware of and
in compliance with federal requirements,” especially those that carry
criminal penalties.

INSTITUTIONAL REVIEW BOARDS Except for research conducted at its own
facilities, NIH does not directly oversee the conduct of research using
human fetal tissue. Instead, under the regulations regarding the protection
of human subjects, institutional review boards oversee HHSfunded research
using human fetal tissue. 12 These review boards are required at all
institutions conducting HHS- supported research. The boards are responsible
for approving research proposals before studies begin and for periodically
reviewing studies after they are under way to ensure compliance with
relevant regulations for the protection of human subjects. OHRP is the HHS
entity responsible for ensuring that the institutional review boards are
conducting the appropriate reviews of HHSfunded research using human fetal
tissue. Before grant funds are distributed, the grantee institution submits
an “assurance” to OHRP. The assurance is a written

11 In addition, although not directly addressing the procurement of human
fetal tissue, NIH regulations specifically require that
“activities” involving these materials must be in accordance
with any applicable state or local laws (45 C. F. R. section 46.210). 12
Almost all of our survey respondents identified the institutional review
board at their institution as

the body responsible for oversight of their research.

GAO- 01- 65R Fetal Tissue Research 8 statement of an institution's
requirements for its institutional review board and

human- subject protections. If the institution receives only one grant from
HHS, a single project assurance is submitted to OHRP. If the institution
receives many HHS grants, a multiple project assurance is submitted. In the
assurance, the institution states that the research will be conducted in
compliance with applicable federal, state, and local laws. Institutions are
required to renew multiple project assurances every 5 years after an initial
period of 3 years. Continuing reviews of the HHS- funded projects are
conducted annually by the institutional review boards. 13

NIH's Office of Intramural Research periodically reviews each intramural
investigator using fetal tissue to confirm that they are complying with the
relevant requirements.

AGENCY COMMENTS NIH and OHRP officials reviewed a draft this report. They
provided technical comments, which we incorporated where appropriate.

---- We will make copies of this letter available to those who are
interested on request. Major contributors to this report were Martin T.
Gahart, Emily J. Rowe, Jenny C. Chen, Lisanne Bradley, and Stefanie Weldon.
Please contact me at (202) 512- 7119 if you have any questions.

Janet Heinrich Director, Health Care - Public Health Issues

(201089) 13 Our review did not evaluate the effectiveness of institutional
review board oversight. We previously reported that NIH- sponsored
investigators conducting therapeutic human fetal tissue transplantation
research were in compliance with federal laws and regulations. See NIH-
Funded Research: Therapeutic Human Fetal Tissue Transplantation Projects
Meet Federal Requirements( GAO/ HEHS- 9761, Mar. 10, 1997).
*** End of document. ***