Department of Health and Human Services 
OFFICE OF 
INSPECTOR GENERAL 
Oversight of Tissue Banking 
JANUARY 2001 
OEI-01-00-00441  OFFICE OF INSPECTOR GENERAL 
The mission of the Office of Inspector General (OIG), as mandated by Public Law 95-452, is to 
protect the integrity of the Department of Health and Human Services programs as well as the 
health and welfare of beneficiaries served by them.  This statutory mission is carried out through a 
nationwide program of audits, investigations, inspections, sanctions, and fraud alerts.  The 
Inspector General informs the Secretary of program and management problems and recommends 
legislative, regulatory, and operational approaches to correct them. 
Office of Evaluation and Inspections 
The Office of Evaluation and Inspections (OEI) is one of several components of the Office of 
Inspector General.  It conducts short-term management and program evaluations (called 
inspections) that focus on issues of concern to the Department, the Congress, and the public.  The 
inspection reports provide findings and recommendations on the efficiency, vulnerability, and 
effectiveness of departmental programs. 
OEI's Boston Office prepared this report under the direction of Mark R. Yessian, Ph.D., Regional 
Inspector General.  Principal OEI staff included: 
BOSTON  HEADQUARTERS 
Russell W. Hereford, Ph.D., Project Leader  Alan Levine, Program Specialist

Elizabeth A. Robboy, M.M.H.S, Program Analyst

Maria E. Maddaloni, M.A., Program Analyst

China D. Eng, M.P.H., Program Analyst

To obtain copies of this report, please call the Boston Regional Office at 617-565-1050. 
Reports are also available on the World Wide Web at our home page address: 
http://www.hhs.gov/oig/oei  E X E C U T I V E   S U M M A R Y  
PURPOSE 
To provide a profile of the current external oversight system for tissue banking, and to 
identify limitations in that system. 
BACKGROUND 
Human tissue is an important resource for medical treatment.  For example, it is used in 
burn treatment, reconstructive surgery, cancer care, and heart valve replacement. 
Tissue from one donor can be processed into many forms and used to treat many people. 
The exact number of donors is not known, but it is growing.  In 1999, more than 20,000 
donors provided cadaveric tissue, up from perhaps 6,000 donors in 1994.  It is estimated 
that tissue banks distributed more than 750,000 allografts for transplantation in 1999. 
Human tissue can transmit disease.  In the early 1990's two events raised major concerns. 
First, HIV was transmitted from one infected donor to several recipients of organs and 
unprocessed tissues.  Second, investigators from the Food and Drug Administration 
(FDA) found instances of domestic suppliers accepting foreign tissue that had not been 
tested or screened; in one case the FDA found tissue that tested positive for Hepatitis B. 
These concerns led FDA to issue an interim final rule in December 1993.  FDA modified 
this regulation and reissued it as a new rule, effective in January 1998.  It requires that 
tissue banks screen and test donors and that they maintain the appropriate records.  The 
rule also provides for FDA inspections of tissue banks and retention, recall, and 
destruction of tissue that doesnt comply with these requirements. 
This report responds to a request from the Secretary of Health and Human Services, 
asking the Office of Inspector General to examine the oversight system for tissue banking. 
We analyzed available data related to tissue banking, and we reviewed regulations, laws, 
and standards.  We interviewed staff from FDA, from 30 tissue banks, and from 
associations representing various sectors of the tissue banking industry. 
In this report, we use the term tissue banks to refer to entities involved in procuring, 
processing, storing, and distributing tissue.  We use the term tissue to refer to skin, heart 
valves, and musculoskeletal tissue such as bone, cartilage, ligaments, and tendons.  Our 
report does not address eyes and reproductive tissue. 
PROFILE OF TISSUE BANKING OVERSIGHT 
Oversight of tissue banking takes place at three levels: 
C  The Food and Drug Administration focuses on preventing transmission of 
Oversight of Tissue Banking  i  OEI-01-00-00441  communicable disease by requiring donor screening and testing.  FDA has conducted 188 
inspections of 118 tissue banks since 1993.  The agency has proposed two regulations and 
is developing a third that would expand its oversight of tissue banking.  These regulations 
would require registration of all tissue banks, expanded screening and testing, and use of 
good tissue practices, akin to good manufacturing practices. 
C	 The American Association of Tissue Banks (AATB) conducts a voluntary accreditation 
program.  While AATB currently accredits 58 tissue banks, we identified another 90 that 
are not accredited.  Accreditation addresses not only donor screening and testing 
practices, but operational and organizational aspects, such as qualifications of tissue bank 
personnel and banks safety practices, equipment testing, facilities, labeling, and quality 
assurance programs. 
C	 New York and Florida are the only two States to license and inspect tissue banks.  In 
addition to screening and testing, these States require banks to report adverse incidents. 
They also address areas such as tissue procurement processes, tracking practices, 
emergency procedures, equipment standards, conflict of interest, community involvement, 
labeling standards, laboratory testing, and disposition of unused tissue.  A few States, 
including California, Georgia, and Maryland, require tissue banks to be licensed by the 
State. 
LIMITATIONS IN TISSUE BANKING OVERSIGHT 
No new cases of disease transmission through human tissue have been identified since the 
FDAs 1993 regulation.  This absence of new cases points to significant strengths and 
accomplishments in the current system which has focused on preventing the spread of 
communicable disease.  Nevertheless, in the course of this limited inquiry, we identified 
situations that show the need for continued vigilance and monitoring.  For example, FDA 
inspectors have found serious deficiencies in tissue banks screening and testing practices. 
Banks have failed to meet basic standards of the AATB and been denied accreditation. 
States have received notification of adverse incidents involving tissue. 
The rapid development of the tissue banking field means that traditional oversight methods 
may not keep pace with growth and changes in the industry.  Consequently, thoughtful 
consideration needs to be given to the nature of any oversight approach. 
Below, we outline limitations and vulnerabilities in current approaches, and we offer a 
combination of options that, taken singularly or in combination, could provide a way of 
enhancing oversight of the tissue banking field. 
FDA oversight 
Some tissue banks have never been inspected by FDA.  We found at least 36 tissue 
banks that have never been inspected, out of 154 tissue establishments that we were able 
to identify.  FDA has indicated that regulation of tissue banks is an unfunded mandate, and 
that in order to carry out these inspections, the agency has had to borrow resources 
Oversight of Tissue Banking  ii  OEI-01-00-00441  from other programs, such as blood and plasma. 
FDA lacks a prescribed cycle for reinspection of tissue banks.  Of 118 tissue banks 
that FDA has inspected, 68 have been inspected only once.  Due to limited resources, the 
agency has had to establish a priority list for followup inspections.  The first priority is 
reinspection of firms whose previous inspection was classified as Official Action Indicated, 
the most serious level of deficiency. 
The number and location of tissue banks are unknown.  Information is lacking about 
the number of tissue banks in operation and the products they produce and distribute. 
FDA has proposed a regulation to require tissue banks to register and list their products. 
The regulation would address directly this limitation in knowledge about tissue banking. 
The scope of FDAs current regulation is limited.  Because the agencys current 
regulation focuses on donor screening and testing to prevent transmission of HIV-1 and  -
2 and Hepatitis B and C, other important aspects of tissue bank quality are not monitored. 
Until FDAs good tissue practices rule is finalized, tissue banks have no external 
requirements for quality and handling of tissue if they are not accredited by AATB or 
licensed by New York or Florida.  Of the 154 tissue banks we identified, 67 are neither 
accredited by AATB nor inspected by Florida or New York. 
Private accreditation 
Many banks do not seek AATB accreditation.  AATB accredits 58 tissue banks. 
However, we identified 90 tissue banks that are not accredited.  These banks are under no 
obligation to meet the standards or policies set by the association.  For many tissue banks 
there is no real incentive to seek accreditation.  There are a number of ways to encourage 
private accreditation of tissue banks.  For example, FDA could provide technical advice 
and information that could be used in developing standards.  FDA also could consider in 
what areas, if any, the agency could accept accreditation as showing compliance with FDA 
regulations.  In such a case, legislation would be needed. 
State oversight 
Only two States inspect tissue banks.  In many ways, these inspections go beyond FDA 
requirements; yet the inspections are limited to banks that conduct business in Florida and 
New York.  Other States could give consideration as to whether they wish to regulate 
tissue banking and, if so, how they would coordinate with other entities to limit 
redundancy and regulatory burden. 
Information on supply and availability of tissue 
Concerns about shortages.  There is no national system for tracking the availability of 
tissue.  Two recent surveys by industry representatives raised concerns that skin may not 
be available when needed for treating burn victims.  However, some shortcomings in these 
studies suggest that additional research is warranted to examine the extent and 
implications of shortages of tissues. 
Oversight of Tissue Banking  iii  OEI-01-00-00441  RECOMMENDATIONS 
The Food and Drug Administration should expedite the publication of its 
regulatory agenda that requires registration of tissue banks, enhanced donor 
suitability screening and testing, and the use of good tissue practices. 
At present, FDA is able to inspect only those banks that it knows about.  Requiring 
registration of all tissue banks would ensure that the agency has a comprehensive list of 
tissue banks as a first step in assuring their compliance with standards. 
In addition, many tissue banks are neither accredited by the AATB nor licensed and 
inspected by New York or Florida.  Those banks that are not accredited or inspected do 
not have to meet any standards beyond the current FDA minimum requirements that they 
screen and test tissue donors for HIV and hepatitis. 
FDA should set a realistic, yet aggressive, date by which it would complete an 
initial inspection of all tissue banks. 
This could be accomplished under FDAs existing regulatory authority.  Establishing a 
baseline of information will provide a minimum level of assurance that tissue banks are 
meeting basic public health and safety standards to prevent transmission of communicable 
diseases. 
FDA should determine an appropriate minimum cycle for tissue bank inspections. 
This, too, could be accomplished under FDAs existing regulatory authority.  A minimum 
cycle for inspections would help ensure that tissue banks are meeting standards on an 
ongoing basis. 
FDA should work with States and with professional associations that have 
inspection and accreditation programs to determine in what areas, if any, 
oversight activities could be coordinated. 
FDA, the industry, and the States with regulatory programs could benefit from examining 
where standards are in agreement, as well as areas in which standards might conflict. 
Following such an examination, determination could be made of whether formal 
partnership or other arrangements would be appropriate to maximize the effectiveness of 
the oversight process.  Such arrangements could require enactment of legislation. 
COMMENTS ON THE REPORT 
We received comments on a draft of this report from the Department of Health and 
Human Services.  They are supportive of our findings and recommendations.  The full text 
is included in Appendix B. 
Our work in tissue banking continues.  We will maintain an active watch on how the tissue 
banking community responds to the concerns that we have raised. 
Oversight of Tissue Banking  iv  OEI-01-00-00441  T A B L E  O F  C O N T E N T S  
EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  i

INTRODUCTION  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

PROFILE OF OVERSIGHT FOR TISSUE BANKING

FDA oversight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

AATB accreditation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

State regulation  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

LIMITATIONS IN TISSUE BANKING OVERSIGHT 
FDA oversight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Private accreditation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  9

State oversight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Lack of information on supply and availability  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

RECOMMENDATIONS  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  11

APPENDICES 
A:  Safety and quality problems  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

B:  Comments from the Department of Health and Human Services . . . . . . . . . . . . . . .  14

C:  Endnotes  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Oversight of Tissue Banking  OEI-01-00-00441  I N T R O D U C T I O N  
PURPOSE 
To provide a profile of the current external oversight system for tissue banking, and to 
identify limitations in that system. 
BACKGROUND 
Transplantation of Human Tissue 
Human tissue is an important resource for medical treatment.  Physicians and dentists use 
cadaveric human tissue for a variety of medical purposes.  Donated skin can meet critical 
needs in healing burn victims and in reconstructive surgery.  Donated bone can be 
implanted to replace cancerous bone; it can be used in knee and hip replacements and for 
spinal surgery; and it can be processed into powder for use in dental surgery.  Donated 
heart valves can replace defective valves in young children, saving their lives. 
The exact number of tissue donors in this country is not known.  It is clear, though, that 
the numbers are increasing.  In 1999, more than 20,000 donors provided cadaveric tissue, 
up from perhaps 6,000 donors in 1994. 
Initial Concerns about Disease Transmission 
Human tissue is capable of transmitting disease.  Tissue from one donor can be implanted 
into many different people.  Thus, if a donor has a communicable disease, using that tissue 
places multiple recipients at risk.  It is estimated that tissue banks distributed more than 
750,000 allografts for transplantation in 1999. 
In the early 1990's two events occurred that raised concerns about disease transmission 
through tissue donation.  First, HIV was transmitted to a number of recipients of organs 
and unprocessed tissues from an infected donor.  Second, investigators from the Food and 
Drug Administration (FDA) found instances in which domestic suppliers were accepting 
foreign tissue that had not been adequately tested or screened; in one of these cases the 
FDA found tissue that tested positive for Hepatitis B. 
Since these initial two cases, no other cases have been identified.  However, without 
proper screening and testing, these problems could reemerge.  As we discuss below, FDA 
continues to uncover deficiencies in the course of its inspections of tissue banks. 
Limited Federal Oversight of Tissue Banking 
Tissue banks procure, process, store, and distribute human tissue.  Federal regulation of 
tissue banking focuses on donor screening and testing to prevent the introduction, 
transmission, and spread of HIV-1 and -2, and Hepatitis B and C.1  By way of contrast, 
organ procurement organizations (OPOs) must meet statutory requirements about their 
organization and operation; they are regulated and certified by the Health Care Financing 
Oversight of Tissue Banking  1  OEI-01-00-00441  Administration.  Furthermore, the procurement and allocation of human organs are 
governed by Federal statute and are administered through a contract with the Health 
Resources and Services Administration (HRSA).  Likewise, legislation authorizes the 
operation of a national bone marrow donor registry, also administered under contract with 
HRSA. 
Recent Concerns about Tissue Banking 
Several press reports in the Spring of 2000, appearing in the Orange County Register and 
the Chicago Tribune, raised concerns about tissue banking, including the extent to which 
the performance of the industry was monitored.  Several members of Congress expressed 
their concerns to the Secretary of Health and Human Services.  The Secretary asked the 
Office of Inspector General to examine two aspects of the tissue banking industry: 
consent for donation and the external oversight structure.  This report responds to the 
second of those requests.  Our companion report, Informed Consent in Tissue Donation: 
Expectations and Reality (OEI-01-00-00440), addresses consent for donation. 
This Inquiry 
This report provides a profile of the oversight structure for tissue banks.  We also identify 
limitations of current oversight efforts and steps that could be taken to address those 
limitations. 
Throughout this report, we use the term tissue banks to refer to entities involved in 
procuring, processing, storing, and distributing tissue.  We use the term tissue to refer to 
skin, heart valves, and musculoskeletal tissue such as bone, cartilage, ligaments, and 
tendons.  Our report does not address eyes and reproductive tissue. 
METHODOLOGY 
Our inquiry is based on data analysis, document reviews, an observational visit, and 
interviews.  We analyzed data from FDAs Program Operations Data System which tracks 
information about FDA inspection activity across the nation.  Our analysis examines this 
data from December 15, 1993 (following the issuance of the interim rule on tissue 
banking) through the end of Fiscal Year 2000.2  Our analysis includes only tissue banks 
involved in procuring, processing, storing, and distributing tissues such as skin, heart 
valves, and musculoskeletal tissue.  We do not include establishments that are involved in 
eye banking, or hospitals and laboratories inspected under the FDA tissue compliance 
program.3 
We also reviewed pertinent FDA documents and inspection reports from the central office 
and from 3 of the 20 FDA district offices.  We conducted interviews with FDA staff at 
both the central and district offices. 
We reviewed AATB standards and accompanied an inspector on an accreditation visit to a 
tissue bank.  We reviewed documents and data from the AATB and interviewed officials 
and staff from the association.  We conducted interviews with senior staff from 
Oversight of Tissue Banking  2  OEI-01-00-00441  30 organizations involved in obtaining, processing, and distributing human tissue. 
We also interviewed officials and reviewed data, statutes, and regulations from New York, 
Florida, California, Georgia, and Maryland. 
We conducted this study in accordance with the Quality Standards for Inspections issued 
by the Presidents Council on Integrity and Efficiency. 
Oversight of Tissue Banking  3  OEI-01-00-00441  P R O F I L E   O F   O V E R S I G H T  
F O R   T I S S U E   B A N K I N G  
Oversight of tissue banking occurs at three levels.  At the Federal level, the Food and 
Drug Administration (FDA) has primary responsibility to set and enforce standards to 
ensure the safety of tissue.  Within the industry, the American Association of Tissue Banks 
(AATB) operates a voluntary accreditation program.  At the State level, two States  
New York and Florida   license and inspect tissue banks.  Below we provide a 
description of each of these activities. 
Food and Drug Administration 
FDAs regulation of tissue dates to December 1993.  Operating under its public health 
authority, the agency issued an interim final regulation in response to evidence about 
transmission of HIV to recipients of organs and unprocessed tissues from an infected 
donor.4  In a second case, FDA inspectors found imported foreign tissue that tested 
positive for Hepatitis B.  In July 1997, the FDA reissued this rule with minor 
modifications, and the new rule became effective January 26, 1998.5 
The FDA requires that tissue banks must ensure that donor screening and infectious 
disease testing are performed for HIV -1 and -2 and for Hepatitis B and C.  Tissue banks 
must maintain and make available to FDA inspectors records that document screening and 
testing for each donor of human tissue.  FDA has the authority to order the retention, 
recall, and destruction of tissue that doesnt comply with these requirements. 
FDA has conducted 188 inspections of 118 tissue banks since 1993.  In more than half of 
these inspections, FDA inspectors found deficiencies that needed correction.  FDA issued 
26 notices of official action  the most serious level of deficiency, in which the agency 
requires the bank to take corrective actions.  In 72 other inspections, FDA issued a notice 
recommending that the bank take voluntary actions to meet the requirements.6 
FDA is in the process of expanding its oversight of tissue banking.  Regulations to expand 
that authority, however, have not yet been finalized.  The components of  expanded FDA 
oversight strategy comprise three regulations: 
C	 Registration of all tissue banks.  This proposed regulation would require tissue banks to 
register with FDA and list their products.  The proposed regulation would apply to 
establishments engaged in recovery, screening, testing, processing, storage, labeling, 
packaging, or distribution of human cellular or tissue-based products.7 
C	 Expanded screening and testing for communicable diseases.  This proposed regulation 
would require donor screening and testing for diseases such as Human T-lymphotropic 
viruses (HTLV) and syphilis, and donor screening for Creutzfeld-Jakob Disease (CJD).8 
Oversight of Tissue Banking  4  OEI-01-00-00441  C	 Standards for good tissue practices.  These standards, akin to good manufacturing 
practices required of medical device pharmaceutical manufacturers, would cover areas 
such as proper handling, processing, and tracking of tissue.9 
American Association of Tissue Banks 
AATB currently accredits 58 cadaveric tissue banks.10  Tissue banks perform a variety of 
functions.  Of these 58 banks, 54 retrieve tissue, 34 process tissue, and 56 store and 
distribute tissue; 51 of these banks retrieve musculoskeletal tissues, 37 retrieve 
cardiovascular tissues, and 20 retrieve skin.  Five banks are for-profit (three tissue 
processors, one tissue distributor, and one retrieval agency).  The other 53 accredited 
banks are non-profit organizations.  Eleven banks are OPOs.  The number of donors 
recovered by accredited banks has grown substantially, from 6,132 donors in 1994 to 
17,725 donors in 1999. 
AATBs standards are consistent with, but go beyond, FDA's requirements.  For example, 
in addition to screening and testing for HIV and hepatitis, AATB requires that tissue 
banks test for HTLV and screen for CJD.  The standards also address operational and 
organizational issues.  These areas include qualifications of tissue bank personnel and 
technical issues, such as safety practices, equipment testing, facilities, labeling, and quality 
assurance. 
Accreditation involves a review of a banks written procedures and an on-site inspection. 
Since 1997, AATB has used contract inspectors to conduct accreditation visits.11  Since 
1997, an average of five new banks have sought accreditation each year. 
A bank receives one of four recommendations.  Banks that show no deficiencies receive 
immediate accreditation.  A bank with minor deficiencies receives Level A accreditation, 
meaning that it must submit to AATB a written plan to correct the deficiencies found 
during the inspection.  A bank with more serious deficiencies receives Level B 
accreditation, which means that it must take corrective action and be reviewed again 
through an on-site inspection.  Finally, a bank could be denied accreditation outright. 
Accreditation is given for a three-year period, at the end of which the bank is subject to 
another review, including an on-site inspection.  Since 1986, AATB has accredited a total 
of 98 tissue banks; 19 banks have been denied accreditation.12 
State Regulation 
New York and Florida are the only two States that operate oversight programs requiring 
that tissue banks be licensed and inspected.  A few States, including California, Georgia, 
and Maryland, require that banks be licensed, either as tissue banks or as laboratories. 
New Yorks licensure law dates to 1990.13  Currently, the State licenses 13 allogeneic 
tissue banks located in New York and 36 located out-of-State.14  New York inspects both 
in-State and out-of-State banks prior to initial licensure and every two years thereafter. 
Oversight of Tissue Banking  5  OEI-01-00-00441  Banks are licensed along two dimensions.  One is a functional dimension: whether the 
bank procures or processes tissue.  The second dimension relates to the type of tissue 
which the bank works with  cardiovascular, musculoskeletal, or skin.  A bank may be 
licensed for any or all tissues and functions.  At present, 29 banks are licensed to procure 
and 9 to process cardiovascular tissue; 39 to procure and 20 to process musculoskeletal 
tissue; and 33 to procure and 19 to process skin. 
Licensure requires an initial application and on-site survey.  Banks do not pay a fee for 
licensure.  Tissue banks must disclose ownership and key staff.  Banks must update this 
information annually and report statistics on procurement, processing, and distribution. 
In addition to meeting FDA requirements to screen and test for HIV and hepatitis, New 
York requires banks to test for HTLV and syphilis.  New York also requires tissue banks 
to meet specific standards for each type of tissue   musculoskeletal, cardiovascular, and 
skin   that the bank procures, processes, or stores.  These standards relate to donor 
qualifications, tissue retrieval processes, laboratory testing, and disposal of unused tissue. 
Banks must report any adverse incidents to the State.  Since 1991, the State has received 
8 reports from cardiovascular, 13 from musculoskeletal, and 6 from skin banks. 
Floridas law was enacted in 199215 at the urging of the States OPO, tissue banking, and 
eye banking community.  Florida currently licenses 20 cadaveric tissue banks; 9 are 
located in Florida and 11 are based in other States.  Another 2 banks have submitted 
applications that are now under review.  The State inspects both in-State and out-of-State 
tissue banks prior to initial licensure and every two years thereafter. 
Florida requires tissue banks to pay an initial application fee of $1,000 and an annual fee 
of  0.25 percent of gross Florida revenues, with a minimum of $1,000 and a maximum of 
$35,000.  The fees go to a State trust fund used for operating the licensure program, the 
State donation advisory committee, a donor registry, and donor education programs. 
Applicants must disclose the banks ownership, as well as information on equipment and 
donor selection and testing criteria.  Florida requires tissue banks to comply with current 
FDA regulations.  The surveying standards also address tissue tracking practices, 
emergency procedures, equipment standards, procurement processes, conflict of interest 
policies, community involvement, and labeling standards. 
Florida requires tissue banks to report within 24 hours adverse events that could affect 
tissue recipients medical conditions.  Only three such incidents have been reported in the 
programs history. 
Oversight of Tissue Banking  6  OEI-01-00-00441  L I M I T A T I O N S   I N   O V E R S I G H T  
O F   T I S S U E   B A N K S  
Todays tissue banking system is complex and rapidly changing.  Tissue is processed into 
new forms and products that are put to a variety of important medical uses.  New 
technologies using human tissue emerge constantly.  No new cases of disease transmission 
through human tissue have been identified since 1993.  This absence points to significant 
strengths and accomplishments in the current oversight system which has focused on 
preventing the spread of communicable disease.16 
However, continued vigilance and monitoring are needed:  FDA inspectors have found 
deficiencies in tissue banks screening and testing practices.  Banks have failed to meet 
basic standards of the AATB and been denied accreditation.  States have received 
notification of adverse incidents involving tissue.  Appendix A describes some safety 
problems that FDA inspectors have identified during inspection visits and adverse events 
that have been reported to the State agencies.  These problems include distribution of 
tissue from donors who tested reactive for hepatitis, bacterial contamination of tissue, and 
repeat testing of donors as a way of qualifying their tissue as suitable for transplantation. 
In the course of this limited inquiry, we identified some important vulnerabilities and 
limitations in the current tissue banking oversight structure.  Rapid developments and 
innovation in the tissue banking field mean that traditional oversight methods have not 
kept pace with growth and changes in the industry.  Under these circumstances, thoughtful 
consideration needs to be given to the nature of any oversight approach. 
Below, we outline limitations and vulnerabilities in the current approaches, and we offer a 
combination of options that, taken singularly or in combination, could provide a way of 
enhancing oversight of the tissue banking field. 
FDA oversight 
Some tissue banks have never been inspected by FDA. 
We developed a list of 154 tissue banks, based on data from three FDA district offices, 
AATB, Florida, and New York.  We found that FDA had never inspected 36 (23 percent) 
of these banks.  In addition to the 154 banks we identified, there are likely others that 
operate in States without licensing programs.17 
FDA has indicated that regulation of tissue banks is an unfunded mandate.  In order to 
carry out these inspections, the agency has had to borrow resources from other programs, 
such as blood and plasma. 
FDA lacks a prescribed cycle for reinspection of tissue banks. 
FDA staff told us that their goal is to inspect tissue banks once every two years, but there 
is no required minimum cycle for these inspections.18  Of 118 tissue banks that the agency 
Oversight of Tissue Banking  7  OEI-01-00-00441  has inspected, 68 have been inspected only once since the FDA began its tissue program in 
late 1993. 
FDAs compliance program acknowledges that there are insufficient resources to 
accomplish biennial inspections of all banks.  As a consequence, the agency has established 
a priority list for followup inspections.  The first priority for the program is reinspection of 
firms whose last inspection was classified as Official Action Indicated.  This classification 
is the most serious level of deficiency, in which the agency requires the bank to take 
corrective actions.19 
The number and location of tissue banks are unknown. 
Information is lacking about the number of tissue banks in operation, and the types of 
tissue products that they produce.  This lack of information limits the confidence with 
which assurances can be made that the supply of tissue is safe.  These unknown tissue 
banks are likely to be new entities that may be in the early stages of operation.  This 
situation does not inspire confidence that these banks are meeting basic standards of 
safety. 
The FDA has issued a proposed regulation20 calling for registration of tissue banks and 
listing of their products.  Such a regulation would address directly this current limitation in 
knowledge about tissue banking. 
The current scope of FDAs regulations is limited. 
The agencys current regulations focus on preventing transmission of communicable 
disease.  The regulations require tissue banks to conduct some donor screening and 
testing, to prepare and follow written procedures, and to maintain records.  The 
regulations provide for FDA inspection of tissue banks, quarantine of imported tissue, and 
retention, recall, and destruction of tissue that doesnt comply with the regulations. 
The current regulations, however, do not monitor other important aspects of tissue bank 
quality.  FDA has proposed a regulation expanding donor suitability and testing 
requirements, and is developing a regulation on good tissue practices, akin to good 
manufacturing practices required of medical device pharmaceutical manufacturers.  Until 
that regulation is finalized, tissue banks have limited requirements for quality and handling 
of tissue if they are not accredited by AATB or licensed by New York or Florida. 
We were unable to document the extent to which banks that are neither AATB-accredited 
nor licensed in New York or Florida are involved in recovering tissue.  The number, 
however, is likely to be substantial.  For example, of the 154 tissue banks we identified, 67 
are neither accredited by AATB nor licensed by New York or Florida. 
Oversight of Tissue Banking  8  OEI-01-00-00441  Private accreditation 
Many banks do not seek AATB accreditation. 
At present, 58 tissue banks have AATB accreditation.  Yet we identified another 90 banks 
that are not accredited.  These banks are under no obligation to meet the standards or 
policies set by the AATB.21 
Unaccredited banks include both large and small operations.  For example, the countrys 
largest processor of heart valves has never sought accreditation.  Some OPOs that operate 
tissue banks are not accredited by AATB.  Other unaccredited banks are small entities in 
the early stages of operations and do not yet feel that they can comply with the standards. 
For many tissue banks there is no real incentive to seek accreditation.  Hospitals and 
physicians regularly purchase tissue from unaccredited banks.  The cost of accreditation 
may present a major barrier for smaller banks.  For other banks, already subject to 
inspection by FDA and State authorities, a third inspection may seem burdensome.22 
A number of steps could be taken to encourage a role for private accreditation of tissue 
banks.  For example, FDA could provide technical advice and information that could be 
used in developing standards.  FDA could also consider in what areas, if any, the agency 
could accept accreditation as showing compliance with FDA inspection regulations.  To 
implement such a change, legislation would likely be needed. 
State oversight 
Only two States inspect tissue banks. 
In many ways, these inspections go beyond FDA requirements.  The State initiatives 
provide an important aspect of quality assurance.  Yet the inspections are limited to banks 
that conduct business in Florida and New York.  Those banks may be small, local entities 
that operate within each State, or they may be large national operations that are based 
elsewhere and that either process or distribute tissue in New York or Florida.  For 
example, 15 of the 20 banks licensed in Florida also are licensed in New York, and 14 are 
accredited by the AATB; 29 of the banks licensed in New York have AATB accreditation. 
A few States, including California, Georgia, and Maryland, require tissue banks to be 
licensed by the State, either as tissue banks or as laboratories. 
Other States could give consideration as to whether they wish to regulate tissue banking, 
and, if so, how they would coordinate with other entities to limit redundancy and 
regulatory burden. 
Information on supply and availability of tissue 
There is no national system for tracking the availability of tissue and where there may be a 
shortage.  Each bank maintains its own inventory and distribution records.  Concerns have 
been raised that some tissues, such as skin, may be in short supply, and that donated 
Oversight of Tissue Banking  9  OEI-01-00-00441  skin is processed into products that may be used for procedures that are not medically 
indicated.  It is not clear how much tissue goes for such cosmetic uses; because physicians 
and patients determine how these products actually are used, tissue banks that 
manufacture them do not have that information.23 
Recent concerns about shortages of skin have led to two surveys related to its availability. 
A survey of burn centers, conducted by the American Burn Association (ABA), found that 
32 percent of respondents had delayed or altered treatment over the past year, and about 
half reported that they had difficulty obtaining allograft skin.  The AATB survey found 
that banks recovered skin from over 6,000 donors in 1999.  It also found that banks 
generally can meet the local need for skin, but when skin is requested by facilities outside 
their local area, meeting those requests is more problematic.  Only 3 of 20 banks supplying 
cryo-preserved skin, and only 3 of 12 banks supplying fresh skin, can always meet 
requests from outside of their local area. 
These initial surveys suggest that further research may be warranted to examine the extent 
and implications of a potential shortage of tissues.  They provide the first systematic 
information about tissue supply and availability.  The two associations deserve great credit 
for collecting and publicizing these data.  However, there are limitations related to the 
source and specificity of information obtained.  For example, the AATB respondents were 
accredited banks only; the ABA data do not allow one to determine if any patient actually 
was unable to obtain skin needed in a surgical procedure.  These shortcomings and the 
limitations of an initial survey can easily be overcome in future refinements. 
Oversight of Tissue Banking  10  OEI-01-00-00441  R E C O M M E N D A T I O N S  
The Food and Drug Administration should expedite the publication of its 
regulatory agenda that requires registration of tissue banks, enhanced donor 
suitability screening and testing, and the use of good tissue practices. 
The FDA has been the lead agency within the Department of Health and Human Services 
for oversight of tissue banking.  The FDAs current regulatory program focuses on 
preventing transmission of HIV and hepatitis by requiring that tissue banks test and screen 
donors to detect these conditions. 
FDA has proposed and is refining three regulations that will enhance oversight of tissue 
banking.  That regulatory agenda would require registration of all tissue banks, expanded 
screening and testing, and use of good tissue practices, akin to good manufacturing 
practices. 
This proposed agenda is important for at least two reasons.  First, at present FDA is able 
to inspect only those banks that it knows about.  Requiring registration of all tissue banks 
would ensure that the agency has a comprehensive list of those banks that are in operation, 
as a first step in assuring their compliance with standards. 
Second, many tissue banks are neither accredited by the American Association of Tissue 
Banks nor licensed and inspected by New York or Florida.  Those banks that are not 
accredited or inspected do not have to meet any standards beyond the current FDA 
minimum requirements that they screen and test tissue donors for HIV and hepatitis. 
Within its existing regulatory authority, FDA should take two steps to enhance 
oversight of tissue banking: 
FDA should set a realistic, yet aggressive, date by which it would complete an initial 
inspection of all tissue banks. 
As we show above, more than one of every five tissue banks has never been inspected.  As 
we also note, the agency has indicated that regulation of tissue banks is an unfunded 
mandate, and that it has had to borrow resources from other programs to carry out current 
inspections.  Nevertheless, we believe that it is important to establish a baseline of 
information.  Such information would provide a minimum level of assurance that tissue 
banks are meeting basic public health and safety standards to prevent transmission of 
communicable disease. 
FDA should determine an appropriate minimum cycle for tissue bank inspections. 
A minimum cycle for inspections would help ensure that tissue banks are meeting 
standards on an ongoing basis.  As we note above, FDA has established a priority list for 
Oversight of Tissue Banking  11  OEI-01-00-00441  followup inspections to maximize available resources.  We believe, however, that some 
minimum cycle, which the agency would determine, is important to ensure that tissue 
banks are subject to ongoing oversight. 
FDA should work with States and with professional associations that have 
inspection and accreditation programs to determine in what areas, if any, 
oversight activities could be coordinated. 
We recognize that resource constraints can put pressure on an agencys capacity to 
conduct inspections and reviews of tissue banks.  In addition, we recognize that multiple 
inspection visits can place a strain on a tissue banks operations.  We believe that FDA, 
the industry, and the States with regulatory programs could benefit from examining where 
standards are in agreement, as well as places in which standards might conflict. 
Following such an examination, determination could be made of whether formal 
partnership or other arrangements would be appropriate to maximize the effectiveness of 
the oversight process.  Such arrangements could require that legislation be enacted. 
COMMENTS ON THE REPORT 
We received comments on a draft of this report from the Department of Health and 
Human Services.  They are supportive of our findings and recommendations.  The full text 
is included in Appendix B. 
Our work in tissue banking continues.  We will maintain an active watch on how the tissue 
banking community responds to the concerns that we have raised. 
Oversight of Tissue Banking  12  OEI-01-00-00441  AAPPPPEENNDDIIXX  AA 
Examples of Safety and Quality Problems 
Found in Tissue Banking 
C	 Routine acceptance of tissue for further manufacturing without accompanying records 
from procurement agency documenting that donors serum specimen had been tested and 
found negative. 
C	 Confirmatory testing repeated until negative result was obtained for Hepatitis B surface 
antigen and Hepatitis C antibody, as a means of potentially qualifying donors as suitable 
for transplantation. 
C	 Acceptance of foreign tissue with donor records not translated into English and without 
documented medical/ social histories. 
C	 Lack of adequate controls to assure product sterility.  Lack of standard operating 
procedures to prevent cross contamination of human tissue during manufacture. 
C	 Failure to assure tissue was quarantined until all infectious disease testing and donor 
screening reviewed by a responsible official, and donor found to be free of risk factors for/ 
clinical evidence of Hepatitis B and C or HIV-1 and -2. 
C	 Errors in calculating a donor's serodilution status.  In retrospect, tissue bank determined 
that the tissue should not have been accepted because of indicators recorded on medical/ 
social history. 
C	 Tissue bank notified that a donor had been incarcerated in the year prior to his death, nine 
months after tissue was tested, processed, and distributed. 
C	 Distribution and implantation of soft tissue grafts from a single donor with possible 
bacterial contamination. The grafts came from a donor with no evidence of risk for HIV 
or hepatitis (confirmed through serological testing).  Contamination appears to have 
occurred either at recovery or during processing. 
C	 Positive test for the Hepatitis C antibody found by distributor, even though others who had 
handled the tissue had found negative test results. 
C  Tissue processing errors, such as use of expired processing reagents. 
C	 Release and distribution of tissue from donors who tested repeatedly reactive for Hepatitis 
B surface antigen. 
C	 Improper donor testing by the tissue banks contract lab for HIV, Hepatitis C antibody, 
and Hepatitis B surface antigen. 
C  Culture-positive tissue or tissue lots distributed, then recalled. 
C  Adverse reaction in a heart valve recipient. 
From actual problems found by FDA inspectors and 
adverse event reports to States 
Oversight of Tissue Banking  13  OEI-01-00-00441   Comments from the 
APPENDIX B 
Department of Health and Human Services 
Oversight of Tissue Banking  14  OEI-01-00-00441  APPENDIX C 
Endnotes 
1.  The FDA issued these regulations under the legal authority of section 361 of the Public Health 
Service Act.  This section authorizes the Secretary to make and enforce regulations judged 
necessary to prevent the introduction, transmission, or spread of communicable diseases. 
2.  Since we obtained the FY 2000 data from FDA, seven additional inspections have been 
entered into the PODS data system.  Because we cannot tell whether these are tissue banks as we 
define them here, or eye banks or some other type of establishment, we do not include these seven 
banks in our analysis. 
3. When eye banks, hospitals, and other establishments falling under the FDA tissue establishment 
compliance program are included, the total number of inspections rises to 363 inspections of 251 
establishments.  These additional establishments include 79 eye banks,  29 hospitals, and 25 
establishments, such as laboratories, that we classified as other entities. 
4.  21 C.F.R., Parts 16 and 1270, added at 58 Fed. Reg. 65,514, December 14, 1993. 
5.  21 C.F.R., Parts 16 and 1270, added at 62 Fed. Reg. 40,429, July 29, 1997. 
6.  Our analysis includes only those banks we identified as banks involved with procuring, 
processing, storing, and distributing skin, heart valves, and musculoskeletal tissue. 
7.  Proposed regulation at 63 Fed. Reg. 26,744, May 14, 1998. 
8.  Proposed regulation at 64 Fed. Reg. 52,696, September 30, 1999. 
9.  This proposed regulation has not yet been published. 
10.  The total number of AATB-accredited banks is actually 71; 11 of these are reproductive 
tissue banks, and 2 are based in Canada.  In our analysis we use only cadaveric tissue banks 
located in the United States. 
11. When AATB began inspecting banks in 1986, the association relied on volunteer staff from 
member banks to conduct inspections.  The accreditation inspectors working with AATB since 
1997 are former staff from FDA or the National Institutes of Health, who have experience in 
facility inspection.  Using outside inspectors has helped to formalize the process and make it more 
professional.  The contract inspectors are trained in audit and evaluation methodologies, and they 
have had years of experience in inspecting facilities.  A second important difference is that the 
professional inspectors do not have any relationships with the banks they are inspecting; thus, they 
may be more objective in their evaluation. 
Oversight of Tissue Banking  15  OEI-01-00-00441  APPENDIX C 
12. Of the 19 banks, 8 were denied accreditation following Level B inspections.  Five more failed 
to complete the process which requires a one-year waiting period after a bank receives a Level B 
accreditation.  Inspections of four banks were aborted because of obvious non-compliance, and 
the inspections were not completed.  Two banks would have been recommended for denial, but 
because current accreditation had expired, they withdrew from the process. 
13.  New York Public Health Law, Article 43-B, Sections 4364-4366; New York Code of Rules 
and Regulations, Title 10, Part 52.  New York also licenses other types of tissue banks, such as 
hematopoietic progenitor cell banks, eye banks, semen banks, and tissue transplantation facilities. 
14.  New York actually licenses 60 tissue banks for procuring, processing, or storing skin, 
musculoskeletal, and cardiovascular tissue.  Of these, 7 New York banks and 4 out-of-State banks 
procure or process autogeneic bone or infant foreskin, which are non-cadaveric tissues. 
15.  Florida Statutes, Title 29, Chapter 381.6021-381.6025; Florida Administrative Code, 59A 
(Health Facility and Agency Licensing), Chapter 59A-1 Certification of Organ Procurement 
Organizations, Tissue Banks, and Eye Banks. 
16.  It is important to recognize, however, that there are no requirements to track recipients of 
tissue.  It is possible that cases of disease transmission could have occurred, but have never been 
reported to the tissue bank or to any government authorities. 
17.  The three FDA field offices are located in Dallas, Los Angeles, and Buffalo.  We recognize 
that the number of banks we identify here (154) differs from the 148 banks we discuss below in 
the potential AATB universe.  FDA can inspect any individual establishment involved in tissue 
banking; AATB accreditation applies to an entire organization.  Thus, for example, a tissue bank 
that has a main office and two satellite offices would have one accreditation from AATB  but 
FDA inspections could be conducted at each of the three different offices. 
18.  In contrast, blood banks, mammography facilities, and medical device firms must be inspected 
every two years. 
19.  Food and Drug Administration, Compliance Program Guidance Manual  Compliance 
Program 7341.002 - Inspection of Tissue Establishments, November 3, 1999, part II, page 4. 
The priorities for inspection of tissue banks are: 
1.  Firms whose last inspection was classified OAI (official action indicated). 
2.  Firms about which FDA has received surveillance information indicating there is a 
potential violation of 21 CFR 1270. 
3.  Laboratories that perform required viral marker testing for tissue banks. 
4.  Firms which have never been inspected and which are known to lack accreditation by a 
standard setting organization such as the American Association of Tissue Banks. 
5.  Firms which have never been inspected. 
6.  Firms whose last inspection was classified as VAI (voluntary action indicated). 
Oversight of Tissue Banking  16  OEI-01-00-00441  APPENDIX C 
20.  63 Fed. Reg. 26,744, May 14, 1998. 
21.  We recognize that the number of banks we identify here (148) differs from the 154 banks we 
discuss above in the potential FDA universe.  FDA can inspect any individual establishment 
involved in tissue banking; AATB accreditation applies to an entire organization.  Thus, for 
example, a tissue bank that has a main office and two satellite offices would have one 
accreditation from AATB  but FDA inspections could be conducted at each of the three 
different offices. 
22.  AATB accreditation contrasts sharply with the situation for hospitals, where accreditation by 
the Joint Commission on Accreditation of Health Care Organizations (JCAHO) carries a definite 
benefit.  Hospitals that receive accreditation are deemed to meet Federal requirements for 
certification as Medicare providers.  Thus, hospitals have a very strong incentive to achieve that 
status. 
23.  The American Medical Associations policy provides a useful framework for considering the 
differences between cosmetic and reconstructive surgery.  That policy states that cosmetic 
surgery is performed to reshape normal structures of the body in order to improve the patient's 
appearance and self-esteem.  Reconstructive surgery is performed on abnormal structures of the 
body, caused by congenital defects, developmental abnormalities, trauma, infection, tumors or 
disease.  It is generally performed to improve function, but may also be done to approximate a 
normal appearance.  (Policy H-475.992) 
Oversight of Tissue Banking  17  OEI-01-00-00441