[Federal Register: March 12, 2007 (Volume 72, Number 47)]
[Rules and Regulations]
[Page 10922-10925]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr12mr07-7]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 1271
[Docket No. 2006N-0051]
RIN 0910-AF65
Health Resources and Services Administration
42 CFR Part 121
Blood Vessels Recovered With Organs and Intended for Use in Organ
Transplantation
AGENCIES: Food and Drug Administration, Health Resources and Services
Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) and the Health
Resources and Services Administration (HRSA) are amending their
regulations to include as part of an organ those blood vessels
recovered with the organ that are intended for use in organ
transplantation (HRSA regulation); and to exclude such blood vessels
from the definition of human cells, tissues, or cellular or tissue-
based products (HCT/Ps) (FDA regulation). The purpose of this final
rule is to amend the regulations so that blood vessels recovered with
organs and intended for use in organ transplantation, and labeled as
such, are governed by the regulations pertaining to organs. The
regulation of other recovered blood vessels remains unchanged. We (HRSA
and FDA) believe that this change will eliminate the burden resulting
from an organ procurement organization's efforts to comply with both
FDA and HRSA rules with respect to blood vessels (FDA jurisdiction) and
organs (HRSA jurisdiction).
DATES: This rule is effective on April 11, 2007.
FOR FURTHER INFORMATION CONTACT:
For information regarding FDA's rule: Denise S[aacute]nchez, Center
for Biologics Evaluation and Research (HFM-17), Food and Drug
Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-
1448, 301-827-6210.
For information regarding HRSA's rule: Jim Burdick, Division of
Transplantation, Healthcare Systems Bureau, Health Resources and
Services Administration (HRSA), 5600 Fishers Lane, rm. 12C-06,
Rockville, MD 20857, 301-443-7577.
SUPPLEMENTARY INFORMATION:
I. Introduction
HRSA oversees transplantation of organs through the Organ
Procurement and Transplantation Network (OPTN), which sets policies
related to the procurement, transplantation, and allocation of human
organs (see 42 CFR part 121). FDA currently regulates blood vessels.
However, FDA does not regulate vascularized human organs (see 21 CFR
1270.3(j)(4) and 1271.3(d)(1)). FDA's jurisdiction over blood vessels
intended for use in organ transplantation overlaps with HRSA's
oversight of the OPTN.
There is a routine practice of recovering blood vessels intended
for use in organ transplantation during organ procurement and using
such blood vessels to connect donor organ and recipient vessels. Blood
vessels intended for use in organ transplantation are recovered with
human organs by Organ Procurement Organizations (OPOs) and stored for
use at transplant centers. Both OPOs and transplant centers are already
subject to HRSA oversight because of their organ procurement and
transplantation activities. The application of both HRSA and FDA
regulatory requirements to these facilities in relation to organs and
blood vessels procured for use in organ transplantation is not
supported by a need for such dual oversight. In order to avoid the
duplication of efforts and reduce the burden on affected facilities,
this final rule transfers from FDA to HRSA jurisdiction over blood
vessels intended and labeled for use in organ transplantation. This
final rule does not affect the regulation of blood vessels intended for
transplantation that do not involve organ transplantation. Jurisdiction
over such blood vessels remains with FDA.
Under this final rule, blood vessels labeled and intended solely
for use in organ transplantation will be subject to HRSA requirements
in 42 CFR part 121 and any enforceable OPTN policies established under
42 CFR part 121. To be regulated under HRSA requirements, such blood
vessels intended for use in organ transplantation must be labeled ``For
use in organ transplantation only.'' However, they are not required to
be attached to the organ(s), transplanted simultaneously with such
organ(s) to the same recipient, or transplanted with the organ(s) from
the same donor. For example, occasionally blood vessels not used
immediately for the transplantation of a donated organ are stored for a
number of days and subsequently used to modify the organ transplant in
the same recipient or to accomplish transplantation in the
[[Page 10923]]
recipient of an organ from a different donor. Such blood vessels
intended and labeled for use in organ transplantation may be used in
these ways when the use is consistent with HRSA requirements.
II. Background
In the Federal Register of May 12, 2006, we published a direct
final rule and a companion proposed rule (71 FR 27606 and 27649,
respectively) to revise HRSA's definition of ``organ'' to include blood
vessels recovered from an organ donor during the same recovery
procedure of such organ(s) and intended and labeled for use in organ
transplantation; and to exclude such blood vessels from FDA's
definition of human cells, tissues, or cellular or tissue-based
products (HCT/Ps) (21 CFR 1271.3(d)). The direct final rule amended the
regulations so that blood vessels intended and labeled for use in organ
transplantation were under the same regulatory scheme as organs,
thereby making blood vessels intended and labeled for use in organ
transplantation readily available to meet organ transplant needs. Such
direct final rule would become effective unless we received significant
adverse comment. We published a companion proposed rule to provide a
procedural framework within which the rule could be finalized in the
event we received any significant adverse comments regarding the direct
final rule, and the direct final rule had to be withdrawn.
We received comments from health care professionals and a nonprofit
organization. Among the comments received, one comment fully supported
the rulemaking. Another comment concerned the use and tracking of blood
vessels recovered from a deceased organ donor but not transplanted with
the recovered organ, and questioned the transfer of regulatory
responsibility for such blood vessels from FDA to HRSA. Another comment
suggested that the rulemaking distinguish between organ transplant
recipients based on the type of their organ donor (living, nonrelated;
living, related; or deceased) and use these distinctions to define who
may receive the blood vessels addressed in the rulemaking. The comments
received and our responses to the comments are discussed in section IV
of this document. Because we received significant adverse comment in
response to the rulemaking, we published a notice in the Federal
Register of September 14, 2006 (71 FR 54198), withdrawing the direct
final rule.
III. Highlights of the Final Rule
To transfer from FDA to HRSA jurisdiction over blood vessels
intended for use in organ transplantation, the final rule amends 21 CFR
1271.3(d), 42 CFR 121.2, and 42 CFR 121.7 as follows:
A. 21 CFR 1271.3(d)
21 CFR 1271.3(d) defines HCT/Ps as ``articles containing or
consisting of human cells or tissues that are intended for
implantation, transplantation, infusion, or transfer into a human
recipient.'' In the definition, we also exclude certain articles from
the definition of HCT/Ps. This final rule adds Sec. 1271.3(d)(8),
excluding from the definition of HCT/Ps blood vessels intended for use
in organ transplantation. The rule excludes such blood vessels intended
for use in organ transplantation only when they are labeled as ``For
use in organ transplantation only,'' to distinguish such vessels from
blood vessels not intended for use in organ transplantation. By
labeling such blood vessels ``For use in organ transplantation only,''
we expect that they will not be used for other purposes. Under the
final rule, blood vessels intended for other uses remain subject to 21
CFR part 1271.
B. 42 CFR 121.2
Under 42 CFR 121.2, ``Organ'' means a human kidney, liver, heart,
lung, or pancreas. This final rule adds to that definition ``Blood
vessels recovered from an organ donor during the recovery of such
organ(s) are considered part of an organ with which they are procured
for purposes of this Part if the vessels are intended for use in organ
transplantation and labeled `For use in organ transplantation only'.''
Blood vessels intended for use in organ transplantation are required to
be in compliance with HRSA provisions for donor screening and testing.
The labeling provision is required in order for such blood vessels to
fall under this regulatory program. Any OPTN labeling policies, whether
voluntary or enforceable, supplement this requirement.
C. 42 CFR 121.7
In 42 CFR 121.7, we are redesignating paragraph (e) as paragraph
(f), and adding a new paragraph (e). Under 42 CFR 121.7(e), a blood
vessel intended for use in organ transplantation is subject to the
allocation requirements under 42 CFR part 121 and enforceable OPTN
policies pertaining to the organ with which the blood vessel is
procured. These provisions apply until the transplant center receiving
the organ determines that the blood vessel is not needed for the
transplantation of that organ. This allocation priority assures that
vessels that may be necessary for the immediate transplantation of the
organs with which they are recovered are made available for that use
prior to being diverted to other organ transplant uses.
IV. Comments on the Proposed Rule and HRSA and FDA Responses
(Comment 1) One comment supported the proposed rule. The comment
stated that the Organ Procurement and Transplantation Network/United
Network for Organ Sharing (OPTN/UNOS) Board of Directors has approved a
policy to provide guidance for the recovery, use, and storage of
deceased donor vascular allografts. The comment also stated that the
OPTN/UNOS policy does not result in undue burden to the transplant
community and is consistent with the provisions of the proposed rule.
(Response) We appreciate the supportive comment. One of our reasons
for the proposed rule is to eliminate the burden of dual oversight, by
FDA and HRSA, of those blood vessels used in organ transplantation. The
policy discussed in the comment is OPTN/UNOS Policy 5.7.\1\ OPTN/UNOS
Policy 5.7 addresses practices for blood vessel recovery, storage, and
transplant by transplant centers and OPOs. The policy will only be
implemented once this final rule goes into effect.
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\1\ See http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.optn.org/PoliciesandBylaws2/policies/pdfs/policy_17.pdf.
(FDA and HRSA have verified the Web site address,
but the agencies are not responsible for subsequent changes to the
Web site after this document publishes in the Federal Register).
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(Comment 2) One comment stated that patients would be better
protected under the existing regulatory scheme. The comment questioned
the safety of transplanting blood vessels recovered from a deceased
organ donor into third party recipients who received organs from other
donors. The comment explained that use of blood vessels in these
recipients poses disease transmission and human leukocyte antigen (HLA)
sensitization risks that jeopardize patient safety. The comment also
stated that the OPTN and organ transplant programs lack adequate
tracking and traceability mechanisms for such blood vessels.
(Response) We acknowledge that the use of blood vessels poses
disease transmission and HLA sensitization risks in third party
recipients. The intent of this rule is to facilitate the successful
completion of life-saving organ transplants in medical procedures
[[Page 10924]]
where the vasculature of the donated organ is inadequate, or to salvage
a graft that would otherwise be lost. It is up to the organ transplant
surgeon to assess the risks and benefits of, and alternatives to, using
a particular vessel to accomplish or modify an organ transplant.
Moreover, the risks of disease transmission and HLA sensitization would
apply even if FDA retained jurisdiction over these blood vessels as
HCT/Ps. FDA regulations, like HRSA policies, reduce, but cannot
entirely eliminate, the risk of disease transmission, and FDA tissue
regulations do not address HLA sensitization. In addition, the OPTN has
long-established mechanisms for tracking of organs from the donor to
the recipient, which require the reporting of transplant outcomes. HRSA
intends to monitor the use and outcomes of these vessels used in organ
transplantation, and to work with the OPTN to modify policies governing
their use as needed.
(Comment 3) One comment suggested that the rulemaking should
distinguish between organ recipients based on the type of their organ
donor (living, nonrelated; living, related; or deceased) and use these
distinctions to define the types of transplant recipients who may
receive these vessels for organ transplant use. The comment asked
whether a surgeon may use vessels from a deceased donor to repair a
thrombosed renal artery in the recipient of a living donor kidney.
(Response) We decline to make these suggested changes to the
rulemaking. The language in 42 CFR 121.7(e) establishes a priority
allocation for use of vessels with organs from the same donor. If
vessels are not needed for this use, the rule does not preclude vessels
recovered from deceased donors and labeled ``For use in organ
transplantation only'' from being transplanted into recipients of
organs from living donors, either to perform the initial transplant of
the organ or to later modify the organ transplant. The situation
described in the comment would be an example of the use of such vessels
to modify a transplant.
V. Legal Authority
We are issuing these regulations under the authority of the
National Organ Transplant Act as amended (NOTA) and section 361 of the
Public Health Service Act (the PHS Act). NOTA authorizes HRSA, by
delegation from the Secretary, to issue regulations governing the
operation of the OPTN. NOTA, as amended, also authorizes the Secretary
to define human organs to be covered by the OPTN. Section 374 of the
PHS Act specifically states, ``[t]he term `organ' means the human
kidney, liver, heart, lung, pancreas, and any other human organ (other
than corneas and eyes) specified by the Secretary by regulation.* *
*.'' (42 U.S.C. Sec. 274b(d)(2)) (emphasis supplied). Accordingly,
HRSA is issuing this regulation to modify the definition of ``organ,''
and to make blood vessels labeled and intended for use in the
transplantation of organs subject to regulations governing the
operation of the OPTN. Extending the definition of organs governed by
HRSA in 42 CFR 121.2 to add blood vessels recovered with organs that
are intended for use in organ transplantation, and labeled as such,
furthers the Secretary's charge under NOTA.
Under the authority of section 361 of the PHS Act delegated to the
Commissioner of FDA, the Department of Health and Human Services may
make and enforce regulations necessary to prevent the introduction,
transmission, or spread of communicable diseases between the States or
from foreign countries into the States. This modification of FDA's
existing regulation reflects FDA's re-evaluation of the level of
regulation that is necessary to prevent disease transmission involving
blood vessels intended for use in organ transplantation.
VI. Analysis of Impacts
FDA and HRSA have examined the impacts of the final rule under
Executive Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-
612), and the Unfunded Mandates Reform Act of 1995 (Public Law 104-4).
Executive Order 12866 directs agencies to assess all costs and benefits
of available regulatory alternatives and, when regulation is necessary,
to select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). The agencies believe
that this final rule is not a significant regulatory action under the
Executive order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because the agencies do not expect that the transfer
from FDA to HRSA of jurisdiction over the blood vessels described in
the rule will result in substantial changes in the way transplant
hospitals and OPOs procure, store, and transplant such blood vessels,
FDA and HRSA certify that the final rule will not have a significant
economic impact on a substantial number of small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $122 million, using the most current (2005) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
final rule to result in any 1-year expenditure that would meet or
exceed this amount.
VII. The Paperwork Reduction Act of 1995
This final rule contains no collections of information. Therefore,
clearance by OMB under the Paperwork Reduction Act of 1995 is not
required.
VIII. Environmental Impact
FDA and HRSA have determined under 21 CFR 25.30(j) that this action
is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required.
IX. Federalism
FDA and HRSA have analyzed this final rule in accordance with the
principles set forth in Executive Order 13132. FDA and HRSA have
determined that the rule does not contain policies that have
substantial direct effects on the States, on the relationship between
the National Government and the States, or on the distribution of power
and responsibilities among the various levels of government.
Accordingly, FDA and HRSA have concluded that the rule does not contain
policies that have federalism implications as defined in the Executive
order and, consequently, a federalism summary impact statement is not
required.
X. Effective Date
This final rule is effective on April 11, 2007.
List of Subjects
21 CFR Part 1271
Biologics, Communicable diseases, Drugs, HIV/AIDS, Human cells,
tissues, and cellular and tissue-based products, Medical devices,
Reporting and recordkeeping requirements.
[[Page 10925]]
42 CFR Part 121
Healthcare, Hospitals, Reporting and recordkeeping requirements.
0
Therefore, under the Public Health Service Act and under authority
delegated to the Commissioner of Food and Drugs and to the
Administrator, Health Resources and Services Administration, 21 CFR
part 1271 and 42 CFR part 121 are amended as follows:
21 CFR Chapter I
PART 1271--HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED
PRODUCTS
0
1. The authority citation for 21 CFR part 1271 continues to read as
follows:
Authority: 42 U.S.C. 216, 243, 263a, 264, 271.
0
2. Section 1271.3 is amended by adding paragraph (d)(8) to read as
follows:
Sec. 1271.3 How does FDA define important terms in this part?
* * * * *
(d) * * *
(8) Blood vessels recovered with an organ, as defined in 42 CFR
121.2, that are intended for use in organ transplantation and labeled
``For use in organ transplantation only.''
* * * * *
42 CFR Chapter I
PART 121--ORGAN PROCUREMENT AND TRANSPLANTATION NETWORK
0
3. The authority citation for 42 CFR part 121 continues to read as
follows:
Authority: Sections 215, 371-376 of the Public Health Service
Act (42 U.S.C. 216, 273-274d); and sections 1102, 1106, 1138, and
1871 of the Social Security Act (42 U.S.C. 1302, 1306, 1320b-8 and
1395hh).
0
4. Section 121.2 is amended by adding a sentence at the end of the
definition of ``Organ'' to read as follows:
Sec. 121.2 Definitions
* * * * *
Organ * * * Blood vessels recovered from an organ donor during the
recovery of such organ(s) are considered part of an organ with which
they are procured for purposes of this part if the vessels are intended
for use in organ transplantation and labeled ``For use in organ
transplantation only.''
* * * * *
0
5. Section 121.7 is amended by redesignating paragraph (e) as paragraph
(f) and by adding paragraph (e) to read as follows:
Sec. 121.7 Identification of organ recipient.
* * * * *
(e) Blood vessels considered part of an organ. A blood vessel that
is considered part of an organ under this part shall be subject to the
allocation requirements and policies pertaining to the organ with which
the blood vessel is procured until and unless the transplant center
receiving the organ determines that the blood vessel is not needed for
the transplantation of that organ.
* * * * *
Dated: December 8, 2006.
Elizabeth M. Duke,
Administrator, Health Resources and Services Administration.
Dated: February 2, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy, Food and Drug Administration.
[FR Doc. 07-1131 Filed 3-9-07; 8:45 am]
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