81 FR 40512 - Revisions to Exceptions Applicable to Certain Human Cells, Tissues, and Cellular and Tissue-Based Products

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 120 (June 22, 2016)

The Food and Drug Administration (FDA or Agency or we) is issuing this final rule to amend certain regulations regarding donor eligibility, including the screening and testing of donors of particular human cells, tissues, and cellular and tissue-based products (HCT/Ps), and related labeling. This final rule is in response to our enhanced understanding in this area and in response to comments from stakeholders regarding the importance of embryos to individuals and couples seeking access to donated embryos.

[Federal Register Volume 81, Number 120 (Wednesday, June 22, 2016)]
[Rules and Regulations]
[Pages 40512-40518]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2016-14721]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 1271

[Docket No. FDA-2014-N-1484]


Revisions to Exceptions Applicable to Certain Human Cells, 
Tissues, and Cellular and Tissue-Based Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA or Agency or we) is 
issuing this final rule to amend certain regulations regarding donor 
eligibility, including the screening and testing of donors of 
particular human cells, tissues, and cellular and tissue-based products 
(HCT/Ps), and related labeling. This final rule is in response to our 
enhanced understanding in this area and in response to comments from 
stakeholders regarding the importance of embryos to individuals and 
couples seeking access to donated embryos.

DATES: This rule is effective August 22, 2016.

ADDRESSES: For access to the docket to read background documents or 
comments received, go to http://www.regulations.gov and insert the 
docket number found in brackets in the heading of this final rule into 
the ``Search'' box and follow the prompts, and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Jessica T. Walker, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911.

SUPPLEMENTARY INFORMATION: 

Table of Contents

I. Executive Summary
    A. Purpose of the Final Rule
    B. Summary of the Major Provisions of the Final Rule
    C. Legal Authority
    D. Costs and Benefits
II. Background
    A. Need for the Regulation/History of This Rulemaking
    B. Summary of Comments to the Proposed Rule
    C. General Overview of the Final Rule
III. Legal Authority
IV. Comments on the Proposed Rule and FDA Response
    A. Introduction
    B. Description of General Comments and FDA Response

[[Page 40513]]

    C. Purpose and Scope of the Final Rule (Sec.  1271.1)
    D. Donor Screening (Sec.  1271.75)
    E. Exceptions From the Requirement of Determining Donor 
Eligibility (Sec.  1271.90)
    F. Labeling Requirements (Sec.  1271.370)
V. Effective Date
VI. Economic Analysis of Impacts
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. Federalism

I. Executive Summary

A. Purpose of the Final Rule

    FDA is issuing this final rule to amend certain regulations 
regarding donor eligibility, including the screening and testing of 
donors of particular HCT/Ps, and related labeling. We are finalizing 
these changes in response to our enhanced understanding in this area 
and in response to comments from stakeholders regarding the importance 
of embryos to individuals and couples seeking access to donated 
embryos.

B. Summary of the Major Provisions of the Final Rule

    FDA is amending existing regulations to provide additional 
flexibility to HCT/P establishments to make available for reproductive 
use embryos originally intended for reproductive use for a specific 
individual or couple when those embryos are subsequently intended for 
directed or anonymous donation. Specifically, this rulemaking 
redesignates the current Title 21 of the Code of Federal Regulations 
(CFR) 1271.90(b) (Sec.  1271.90(b)) to new Sec.  1271.90(c), and would 
insert a new Sec.  1271.90(b) entitled ``Exceptions for reproductive 
use'' to clarify that if an embryo was originally intended for 
reproductive use for a specific individual or couple, its use for 
directed or anonymous donation, would not be prohibited under Sec.  
1271.45(c), even when the applicable donor eligibility requirements 
under part 1271, subpart C, are not met. FDA also clarifies that we are 
not creating an exception for deficiencies that occurred in making the 
donor eligibility determination for either the oocyte donor or the 
semen donor as required under Sec.  1271.45(b), or for deficiencies in 
performing donor screening or testing, as required under Sec. Sec.  
1271.75, 1271.80, and 1271.85.
    The final rule also requires appropriate labeling for embryos that 
would describe the donor eligibility status of the individual donors 
whose gametes were used to form the embryo. The content of the labeling 
is not different from that required under current regulations. 
Consistent with current regulations, the intent of the labeling is to 
help ensure that physicians have specific and accurate information to 
provide to recipients for use in making informed medical decisions.

C. Legal Authority

    FDA has authority for this rulemaking under section 361 of the 
Public Health Service Act (PHS Act) (42 U.S.C. 264). Under section 361 
of the PHS Act, FDA may issue and enforce regulations necessary to 
prevent the introduction, transmission, or spread of communicable 
disease between the States or from foreign countries into the States.

D. Costs and Benefits

    Because this rule imposes no additional regulatory burdens, the 
costs associated with this rule are expected to be minimal.

II. Background

A. Need for the Regulation/History of This Rulemaking

    Under the authority of section 361 of the PHS Act, by delegation 
from the Surgeon General and the Secretary of Health and Human 
Services, FDA may make and enforce regulations necessary to prevent the 
introduction, transmission, or spread of communicable diseases. 
Communicable diseases include, but are not limited to, those 
transmitted by viruses, bacteria, fungi, parasites, and transmissible 
spongiform encephalopathy agents. Certain diseases are transmissible 
through implantation, transplantation, infusion, or transfer of HCT/Ps 
derived from donors infected with those diseases. To prevent the 
introduction, transmission, or spread of such communicable diseases, we 
consider it necessary to require establishments to take appropriate 
measures to prevent the use of HCT/Ps from infected donors. FDA 
regulates HCT/Ps intended for implantation, transplantation, infusion, 
or transfer into a human recipient under part 1271 that was issued 
under the authority of section 361 of the PHS Act. Part 1271 requires 
HCT/P establishments to screen and test donors for relevant 
communicable disease agents and diseases, to prepare and follow written 
standard operating procedures for the prevention of the spread of 
communicable diseases, and to maintain records. Part 1271 also requires 
that for most HCT/Ps, the donor must be determined to be eligible, 
based on the results of screening and testing for relevant communicable 
disease agents and diseases. In most cases, a donor who tests reactive 
for a particular communicable disease, or who possesses clinical 
evidence of, or risk factors for, communicable disease agents and 
diseases, would be considered ineligible, and HCT/Ps from that donor 
would not ordinarily be used.
    FDA has published three final rules that make up part 1271. In the 
Federal Register of January 19, 2001 (66 FR 5447), we published 
regulations requiring HCT/P establishments to register and list their 
HCT/Ps with FDA (registration final rule). In the Federal Register of 
May 25, 2004 (69 FR 29786), we published regulations requiring most 
donors to be tested and screened for relevant communicable disease 
agents and diseases (donor eligibility final rule). In the Federal 
Register of November 24, 2004 (69 FR 68612), we published regulations 
requiring certain HCT/P establishments to follow current good tissue 
practice (CGTP), which governs the methods used in, and the facilities 
and controls used for, the manufacture of HCT/Ps, recordkeeping, and 
the establishment of a quality program (CGTP final rule). These 
regulations apply to HCT/Ps recovered on or after May 25, 2005.
    As part of our ongoing effort to implement our framework for 
regulating HCT/Ps, in the Federal Register of May 25, 2005 (70 FR 
29949), we issued an interim final rule entitled ``Human Cells, 
Tissues, and Cellular and Tissue-Based Products; Donor Screening and 
Testing, and Related Labeling'' (2005 interim final rule), which had an 
effective date simultaneous with publication. This interim final rule 
was then adopted without change in the Federal Register of June 19, 
2007 (72 FR 33667), in the final rule entitled ``Human Cells, Tissues, 
and Cellular and Tissue-Based Products; Donor Screening and Testing, 
and Related Labeling'' (2007 final rule). The 2007 final rule amended 
regulations regarding the screening and testing of donors of HCT/Ps, 
timing of specimen collection, record retention requirements, and 
related labeling requirements in response to public comments concerning 
the importance of cryopreserved embryos to individuals seeking access 
to donated embryos. The 2007 final rule also added an exception to the 
donor eligibility requirements in Sec.  1271.90(a)(4) for cryopreserved 
embryos that, while originally exempt from the donor eligibility 
requirements because the donors were sexually intimate partners, are 
later intended for directed or anonymous donation.
    In recent years, industry and the medical community have expressed 
concerns that the exception added by

[[Page 40514]]

the 2007 final rule does not fully address the need for access to 
cryopreserved embryos. The stakeholders have raised concerns that the 
current regulations still unduly restrict the use of embryos that were 
originally intended for personal reproductive use, and therefore impose 
limitations on individuals and couples involved in family building. In 
response to these concerns, FDA published the proposed rule ``Revisions 
to Exceptions Applicable to Certain Human Cells, Tissues, and Cellular 
and Tissue-Based Products'' in the Federal Register of December 31, 
2014 (79 FR 78744). The proposed rule intended to increase access to 
embryos for reproductive use by expanding the current exceptions to the 
prohibitions on use under Sec.  1271.90, providing HCT/P establishments 
with the flexibility to make available any embryo originally formed for 
reproductive use for a specific individual or couple and now intended 
for reproductive use in a directed or anonymous donation, provided that 
specific criteria are met, including requirements for labeling.

B. Summary of Comments to the Proposed Rule

    We received approximately 10 comment letters on the proposed rule 
by the close of the comment period. We received comments from academia, 
professional organizations, and individuals. The comments were balanced 
between those expressing support for the proposed rule and those 
raising concerns about how the proposed exception will impact public 
health. They addressed the following topics: Purpose and scope of the 
final rule, donor screening, exceptions from the requirement of 
determining donor eligibility, and labeling requirements.

C. General Overview of the Final Rule

    FDA is adopting as final, without material change, the proposed 
rule to amend certain regulations regarding donor eligibility and 
related labeling.
    We are making revisions to the following FDA regulations:
1. Amendments to Sec.  1271.90
    Section 1271.90 sets forth exceptions where HCT/P establishments 
are not required to make a donor eligibility determination under Sec.  
1271.50 or to perform donor screening or testing under Sec. Sec.  
1271.75, 1271.80, and 1271.85. We are adding language to the exceptions 
listed in this section to provide clarity and update the regulation by 
allowing for an embryo originally intended for reproductive use for a 
specific individual or couple, to be subsequently used for directed or 
anonymous donation, even when the donor eligibility requirements under 
part 1271, subpart C are not met.
    We are amending Sec.  1271.90 as follows:
     Changing the heading of this section by deleting ``from 
the requirement of determining donor eligibility,'' and inserting 
``other'' before ``exceptions.'' The heading for Sec.  1271.90 will 
read ``Are there other exceptions and what labeling requirements 
apply?'' We made this change for clarity; the new heading will be more 
accurate.
     Changing Sec.  1271.90(a)(3) by replacing ``exempt'' with 
``excepted,'' which is the term used in the introductory title for this 
provision. Thus, this change will make the language more consistent. 
The beginning of Sec.  1271.90(a)(3) will read, ``Cryopreserved cells 
or tissue for reproductive use, other than embryos, originally excepted 
. . . .''
     Changing current Sec.  1271.90(a)(4) by replacing 
``exempt'' with ``excepted''.
     Redesignating current Sec.  1271.90(b) as Sec.  1271.90(c) 
and adding a new paragraph (b) to Sec.  1271.90.
     Changing newly designated Sec.  1271.90(c) by removing 
``paragraph (a)'' and adding in its place ``paragraphs (a) and (b)'' in 
the introductory text, revising Sec.  1271.90(c)(2) to replace 
``(b)(6)'' with ``(c)(6)'', and by adding ``recovery or'' before 
``cryopreservation'' in new Sec.  1271.90(c)(6) to clarify that some 
testing and screening activities may take place before recovery of the 
gametes, not just before cryopreservation of the embryos.
2. Section 1271.90(b)
    We are redesignating the current Sec.  1271.90(b) to Sec.  
1271.90(c), and adding a new Sec.  1271.90(b) entitled ``Exceptions for 
reproductive use.'' Under finalized Sec.  1271.90(b), an embryo 
originally intended for reproductive use for a specific individual or 
couple that is subsequently intended for directed or anonymous donation 
is excepted from the prohibition on use under Sec.  1271.45(c) even 
when the applicable donor eligibility requirements under part 1271, 
subpart C are not met. Accordingly, when an establishment fails to 
comply with applicable donor eligibility requirements under part 1271, 
subpart C, the establishment will not be prohibited from making 
available for reproductive use such embryos for reproductive purposes 
in accordance with this section. The exception from the prohibition on 
use does not create an exception for deficiencies that occurred in 
making the donor eligibility determination for either the oocyte donor 
or the semen donor as required under Sec.  1271.45(b), or for 
deficiencies in performing donor screening or testing, as required 
under Sec. Sec.  1271.75, 1271.80, and 1271.85.
    We note that the language we are adding to the exceptions currently 
listed in Sec.  1271.90 is additive. It creates an additional exception 
for the use of certain reproductive HCT/Ps that are not currently 
excepted, but it does not impact or restrict the exceptions currently 
provided for in the regulations.
3. Section 1271.90(c)
    Under Sec.  1271.90(c), HCT/P establishments must prominently label 
an HCT/P described in Sec.  1271.90(a) and (b). The labeling 
requirements are intended to help ensure that physicians have specific 
and accurate information to provide to recipients for use in making 
informed medical decisions.
    The nonsubstantive change to Sec.  1271.90(c)(2) clarifies that the 
labeling requirements contained in Sec.  1271.90(c)(2) do not apply to 
reproductive cells or tissue labeled in accordance with Sec.  
1271.90(c)(6). The change to Sec.  1271.90(c)(6) includes ``recovery 
or'' before the word ``cryopreservation''. Thus, the Sec.  
1271.90(c)(6) provision requires HCT/P establishments to prominently 
label an HCT/P described in Sec.  1271.90(a)(3) or (a)(4) with ``Advise 
recipient that screening and testing of the donor(s) were not performed 
at the time of recovery or cryopreservation of the reproductive cells 
or tissue, but have been performed subsequently'' for HCT/Ps described 
in Sec.  1271.90(a)(3) or (a)(4). This change is made to recognize that 
some testing and screening activities may take place even before 
recovery of HCT/Ps, not just before cryopreservation.
4. Amendment to Sec.  1271.370
    Section 1271.370 sets forth labeling requirements in addition to 
those that apply under Sec. Sec.  1271.55, 1271.60, 1271.65, and 
1271.90. Because, as discussed previously, this rule redesignates the 
current labeling requirements under Sec.  1271.90(b) to Sec.  
1271.90(c), we are amending Sec.  1271.370(b)(4) to revise the 
reference from Sec.  1271.90(b) to Sec.  1271.90(c).

III. Legal Authority

    FDA is issuing this final rule under the authority of section 361 
of the PHS Act (42 U.S.C. 264). Under section 361 of the PHS Act, FDA 
may issue and enforce regulations necessary to prevent the 
introduction, transmission, or spread of communicable disease

[[Page 40515]]

between the States or from foreign countries into the States. It is 
important to recognize that HCT/Ps recovered in one State may be sent 
to another for processing, and then shipped for use throughout the 
United States, or beyond. FDA has been involved in many recalls where 
HCT/Ps processed in a single establishment have been distributed in 
many States. In any event, intrastate transactions affecting interstate 
communicable disease transmission may also be regulated under section 
361 of the PHS Act. (See Louisiana v. Mathews, 427 F. Supp. 174, 176 
(E.D. La. 1977); Independent Turtle Farmers of Louisiana, Inc. v. 
United States of America, et al., 2010 U.S. Dist. LEXIS 31117). This 
final rule incorporates changes in response to our enhanced 
understanding of the uses of certain types of HCT/Ps in specific 
situations and in response to comments from stakeholders regarding the 
importance of embryos to individuals and couples seeking access to 
donated embryos.

IV. Comments on the Proposed Rule and FDA Response

A. Introduction

    We received approximately 10 comment letters on the proposed rule 
by the close of the comment period, each containing one or more 
comments on one or more issues. We received comments from academia, 
professional organizations, and individual consumers.
    We describe and respond to the comments in sections IV.B through 
IV.F. We have numbered each comment to help distinguish among different 
comments. We have grouped similar comments together under the same 
number, and, in some cases, we have separated different issues 
discussed in the same comment and designated them as distinct comments 
for purposes of our responses. The number assigned to each comment is 
purely for organizational purposes and does not signify the comment's 
value or importance or the order in which the comments were received.

B. Description of General Comments and FDA Response

    Several comments made general remarks supporting the proposed rule 
without focusing on a particular proposed provision. In the following 
paragraphs, we discuss and respond to such general comments.
    (Comment 1) There were several comments that were in support of the 
proposed rule and suggested that we provide even more guidance on donor 
eligibility, screening, and testing of donors of reproductive cells. 
One suggestion was that FDA's donor eligibility, screening, and testing 
requirements closely parallel American Society of Reproductive 
Medicine/Society for Assisted Reproductive Technology guidelines.
    (Response) FDA acknowledges and appreciates the supportive 
comments. We appreciate the interest in additional guidance for the 
screening and testing of donors of reproductive cells. We continue to 
review existing regulations with respect to providing additional 
guidance or modifying these regulations as appropriate, in the future.
    (Comment 2) One comment asked if the final rule would be applied 
retrospectively to embryos formed and cryopreserved on or after May 25, 
2005.
    (Response) Yes, the final rule applies to embryos formed and 
cryopreserved on or after May 25, 2005.

C. Purpose and Scope of the Final Rule (Sec.  1271.1)

    (Comment 3) One comment noted that preventing the spread of 
communicable disease protects the population and the family receiving 
the donation. Two comments suggested that the proposed rule conflicts 
with FDA regulations that serve to prevent the introduction, 
transmission, and spread of communicable disease. One comment expressed 
concern that the proposed rule appears to relax the testing 
requirements for donors and conflicts with the PHS Act, specifically 
section 361, that provides FDA with the authority to make and enforce 
regulations ``to prevent the introduction, transmission, or spread of 
communicable diseases from foreign countries into the States or 
possessions, or from State or possession into any other State or 
possession'' (42 U.S.C. 264(a)). This commenter's interpretation of the 
proposed rule is that it removes the requirement for reproductive 
tissue donors to be tested, and only requires reproductive tissue donor 
testing ``when possible.'' According to the comment, FDA seems to posit 
informed consent as an adequate response to the health risks faced by 
recipients of donated embryos. The commenter would like FDA to strike 
the qualifier ``when possible'' from the text of the proposed rule 
because the commenter believes this approach would provide a greater 
level of protection to the recipient than the proposed rule and 
preserve FDA's intention of relaxing the current donor eligibility 
regulations in the interest of family building.
    (Response) As stated previously, we consider it necessary that 
establishments take appropriate measures to prevent the use of HCT/Ps 
from donors infected with communicable diseases. Part 1271 requires 
HCT/P establishments to screen and test donors for relevant 
communicable disease agents and diseases, and to maintain records. Part 
1271 also requires for most HCT/Ps that the donor must be determined to 
be eligible, based on the results of screening and testing for relevant 
communicable disease agents and diseases. We have retained the 
qualifier ``when possible'' in Sec.  1271.90(a)(4) to provide HCT/P 
establishments with the flexibility to make available any embryos 
originally formed for reproductive use for a specific individual or 
couple and now intended for reproductive use in a directed or anonymous 
donation, provided that specific criteria are met, including 
requirements for labeling.
    The final rule provides for the continued applicability of labeling 
requirements for embryos intended for reproductive use that would be 
excepted from the prohibition on use. The rule requires prominent 
labeling that describes the donor eligibility status of the individual 
donors whose gametes were used to form the embryo. The required 
labeling will provide information to the treating physician to permit 
discussion of the potential risks of communicable disease with the 
recipient.

D. Donor Screening (Sec.  1271.75)

    (Comment 4) Some of the comments expressed concern about the risk 
of accepting an unscreened donation. Another comment noted that 
eligibility of the HCT/P donor must be assessed prior to usage to 
ensure the safety of recipients, their offspring, and the public as a 
whole; and furthermore, ensuring the proper screening of the donor's 
HCT/P enables the control of the spread of disease.
    (Response) We agree that the proper screening of HCT/P donors 
minimizes the risk of introducing, transmitting, or spreading 
communicable diseases. As stated in the proposed rule, we consider it 
necessary to require establishments to take appropriate measures to 
prevent the use of HCT/Ps from infected donors. Part 1271 requires HCT/
P establishments to screen and test donors for relevant communicable 
disease agents and diseases, and to maintain records. Part 1271 also 
requires, for most HCT/Ps, that donor be determined to be eligible, 
based on the results of screening and testing for relevant communicable 
disease agents and diseases. In most cases, a donor who

[[Page 40516]]

tests reactive for a particular communicable disease, or who possesses 
clinical evidence of, or risk factors for, a communicable disease agent 
and disease, would be considered ineligible, and cells or tissues from 
that donor would not ordinarily be used.
    (Comment 5) A few comments expressed the belief that the proposed 
rule will allow for better genetic profiling. One of those comments 
stated that labeling will make it easier to identify particular 
genotypes for research. Another comment stated that genetically 
profiling all donors and to the extent possible all embryos will reduce 
the risk of recipients of embryos giving birth to children with serious 
genetic disorders. The commenter asked FDA to require establishments to 
genetically screen all donors and the embryo when possible.
    (Response) These comments address a topic that is outside the scope 
of this rulemaking.

E. Exceptions From the Requirement of Determining Donor Eligibility 
(Sec.  1271.90)

    (Comment 6) One comment sought transparency as to which embryos are 
excepted and requested specific examples of how the rule provides 
additional flexibility to make embryos available for directed and 
anonymous donation. Specifically, the commenter asked whether donation 
would be allowed when the embryo was originally intended for transfer 
to a sexually intimate partner, where one of the gamete providers 
(either a directed or anonymous donor) would be considered ineligible 
based on screening and testing.
    (Response) The rulemaking provides additional flexibility to make 
embryos available when there have been changes in the original plans 
for use of the embryos. Under finalized Sec.  1271.90(b), an embryo 
originally intended for reproductive use for a specific individual or 
couple that is subsequently intended for directed or anonymous donation 
is excepted from the prohibition on use under Sec.  1271.45(c) even 
when the applicable donor eligibility requirements under part 1271, 
subpart C are not met. Accordingly, when an establishment fails to 
comply with applicable donor eligibility requirements under part 1271, 
subpart C, the establishment will not be prohibited from making 
available for reproductive use such embryos for reproductive purposes 
in accordance with this section. The exception from the prohibition on 
use does not create an exception for deficiencies that occurred in 
making the donor eligibility determination for either the oocyte donor 
or the semen donor as required under Sec.  1271.45(b), or for 
deficiencies in performing donor screening or testing, as required 
under Sec. Sec.  1271.75, 1271.80, and 1271.85.
    We note that the change we are making to the exceptions currently 
listed in Sec.  1271.90 is additive. It creates an additional exception 
for the use of certain reproductive HCT/Ps that are not currently 
excepted, but it does not impact or restrict the exceptions currently 
provided for in the regulations.
    (Comment 7) One comment recommends that the term ``embryos formed 
for autologous use'' not be used in conjunction with embryos. The 
commenter reasons that after a sperm or oocyte form an embryo, the 
embryo should not be considered autologous, given the definition at 
Sec.  1271.3(a).
    (Response) We agree with the comment and are not adopting, as part 
of the final rule, the term ``embryos formed for autologous use''. 
Likewise, we are not adopting, as part of the final rule, the reference 
to Sec.  1271.90(a)(1) in Sec.  1271.90(a)(4).

F. Labeling Requirements (Sec.  1271.370)

    (Comment 8) Several comments were in support of labeling because it 
allows the physician to fully discuss the risks of any communicable 
disease and it allows the patient to make a fully informed decision. 
One commenter noted that factors affecting decisions of an HCT/P 
recipient may outweigh the expert advice of medical doctors. Another 
comment referenced Sec.  1271.90(c)(6) of the proposed rule (embryo 
labeling requirements) that states establishments are required to 
``advise recipients that screening and testing of the donor(s) were not 
performed at the time of recovery or cryopreservation of the 
reproductive cells or tissues, but have been performed subsequently.'' 
The comment further states that ``Description of the Proposed Rule'' 
provides that these labeling requirements are ``based on the 
expectation that a physician will be closely involved in the decision 
of the embryo and the recognition that physicians are under legal and 
ethical obligations that require them to discuss the risks of 
communicable disease transmission stemming from the use of HCT/Ps.'' 
The comment asked that FDA revise the rule to expressly require 
establishments to counsel recipients on the risk of disease.
    (Response) We agree that the recipients should be fully informed 
about the risk of communicable disease before accepting an embryo for 
implantation; however, we decline to make the suggested change. As 
stated in the preamble of the proposed rule, the proposed labeling 
requirements are based on the expectation that a physician will be 
closely involved in the decision to use an embryo and the recognition 
that physicians are under legal and ethical obligations that require 
them to discuss the risks of communicable disease transmission stemming 
from the use of HCT/Ps. FDA relies on physicians to meet these 
obligations when discussing procedures involving HCT/Ps with 
recipients. Further, we expect that a recipient would be fully informed 
of the risks involved in using an embryo for reproductive purposes as 
finalized under Sec.  1271.90(b) even when the donor eligibility 
requirements under part 1271, subpart C are not met.
    (Comment 9) One comment suggested that while a labeling requirement 
that is tiered according to the risks may mitigate the risks, it does 
not go far enough in abolishing the risks.
    (Response) As described under proposed Sec.  1271.90(c)(2) through 
(6), an embryo originally intended for reproductive use for a specific 
individual or couple that is subsequently intended for directed or 
anonymous donation must be labeled as applicable. We acknowledge that 
the labeling requirement will not abolish all risks of implanting those 
embryos. Rather, as stated in the proposed rule, the required labeling 
would provide information to the treating physician to permit 
discussion of the potential risks of communicable diseases with the 
recipient. Our expectation is that the recipient will become fully 
informed of the risk when the donor eligibility requirements under part 
1271, subpart C are not met, so that the recipient can make a well 
informed decision about receiving the embryo.

V. Effective Date

    This rule is effective August 22, 2016.

VI. Economic Analysis of Impacts

    We have examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct us 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). We 
have

[[Page 40517]]

developed a comprehensive Economic Analysis of Impacts that assesses 
the impacts of the final rule. We believe that this final rule is not a 
significant regulatory action as defined by Executive Order 12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because the costs associated with this rule are expected to 
be minimal, we certify that the rule will not have a significant 
economic impact on a substantial number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before issuing ``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 $146 
million, using the most current (2015) Implicit Price Deflator for the 
Gross Domestic Product. This final rule would not result in an 
expenditure in any year that meets or exceeds this amount.
    This rule amends certain regulations regarding donor eligibility 
and labeling related to the screening and testing of donors of 
particular HCT/Ps. The final rule will provide additional flexibility 
to HCT/P establishments to make available for reproductive use embryos 
originally intended for reproductive use for a specific individual or 
couple and subsequently intended for directed or anonymous donation. 
Specifically, the final rule will clarify that if an embryo was 
originally intended for reproductive use for a specific individual or 
couple, its use for directed or anonymous donation would not be 
prohibited under Sec.  1271.45 (c), even when the applicable donor 
eligibility requirements under part 1271, subpart C are not met. This 
exception from prohibition for use would not create an exception for 
deficiencies that occurred in making the donor eligibility 
determination for either the oocyte donor or the semen donor as 
required under Sec.  1271.45(b), or for deficiencies in performing 
donor screening or testing, as required under Sec. Sec.  1271.75, 
1271.80, and 1271,85. The final rule also requires appropriate labeling 
that describes the donor eligibility status of the individual donors 
whose gametes were used to form the embryo.
    This rule will provide greater accommodation of individuals and 
couples wanting access to embryos originally intended for reproductive 
use for a specific individual or couple, while continuing to emphasize 
the applicability of the donor eligibility screening and testing 
requirements for individual gamete donors. The final rule will provide 
HCT/P establishments with the flexibility to make embryos originally 
intended for reproductive use for a specific individual or couple now 
available for directed or anonymous donation, provided that specific 
criteria are met. Consistent with current regulations, the labeling 
requirements will help ensure that physicians have specific and 
accurate information to provide to recipients for use in making 
informed medical decisions. Because this rule imposes no additional 
regulatory burdens, the costs associated with this rule are expected to 
be minimal.

VII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.30(h) 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.

VIII. Paperwork Reduction Act of 1995

    The labeling requirements contained in this final rule are not 
subject to review by the Office of Management and Budget (OMB) because 
they do not constitute a ``collection of information'' under the 
Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C 3501-3520). Rather, 
the requirement to label HCT/Ps in accordance with the final rule is a 
``public disclosure of information originally supplied by the Federal 
government to the recipient for the purpose of disclosure to the 
public'' (5 CFR 1320.3(c)(2)). Therefore, FDA concludes that these 
requirements in this document are not subject to review by OMB because 
they do not constitute a ``collection of information'' under the PRA.

IX. Federalism

    We have analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has 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, we conclude 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.

List of Subjects in 21 CFR Part 1271

    Biologics, Drugs, Human cells and tissue-based products, Medical 
devices, Reporting and recordkeeping requirements.

    Therefore, under the Public Health Service Act and under authority 
delegated to the Commissioner of Food and Drugs, 21 CFR part 1271 is 
amended as follows:

PART 1271--HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED 
PRODUCTS

0
1. The authority citation for part 1271 continues to read as follows:

    Authority:  42 U.S.C. 216, 243, 263a, 264, 271.


0
2. In Sec.  1271.90:
0
a. Revise the heading;
0
b. Revise paragraph (a)(3) introductory text;
0
c. Revise paragraph (a)(4);
0
d. Redesignate paragraph (b) as paragraph (c);
0
e. Add a new paragraph (b);
0
f. Revise newly designated paragraph (c) introductory text;
0
g. Revise newly designated paragraph (c)(2); and
0
h. Revise newly designated paragraph (c)(6).
    The revisions and additions read as follows:


Sec.  1271.90  Are there other exceptions and what labeling 
requirements apply?

    (a) * * *
    (3) Cryopreserved cells or tissue for reproductive use, other than 
embryos, originally excepted under paragraphs (a)(1) or (a)(2) of this 
section at the time of donation, that are subsequently intended for 
directed donation, provided that:
* * * * *
    (4) A cryopreserved embryo, originally excepted under paragraph 
(a)(2) of this section at the time of recovery or cryopreservation, 
that is subsequently intended for directed or anonymous donation. When 
possible, appropriate measures should be taken to screen and test the 
semen and oocyte donors before transfer of the embryo to the recipient.
    (b) Exceptions for reproductive use. An embryo originally intended 
for reproductive use for a specific individual or couple that is 
subsequently intended for directed or anonymous donation for 
reproductive use is excepted from the prohibition on

[[Page 40518]]

use under Sec.  1271.45(c) even when the applicable donor eligibility 
requirements under subpart C of this part are not met. Nothing in this 
paragraph creates an exception for deficiencies that occurred in making 
the donor eligibility determination for either the oocyte donor or the 
semen donor as required under Sec.  1271.45(b), or for deficiencies in 
performing donor screening or testing, as required under Sec. Sec.  
1271.75, 1271.80, and 1271.85.
    (c) Required labeling. As applicable, you must prominently label an 
HCT/P described in paragraphs (a) and (b) of this section as follows:
* * * * *
    (2) ``NOT EVALUATED FOR INFECTIOUS SUBSTANCES,'' unless you have 
performed all otherwise applicable screening and testing under 
Sec. Sec.  1271.75, 1271.80, and 1271.85. This paragraph does not apply 
to reproductive cells or tissue labeled in accordance with paragraph 
(c)(6) of this section.
* * * * *
    (6) ``Advise recipient that screening and testing of the donor(s) 
were not performed at the time of recovery or cryopreservation of the 
reproductive cells or tissue, but have been performed subsequently,'' 
for paragraphs (a)(3) or (a)(4) of this section.


Sec.  1271.370  

0
3. Amend Sec.  1271.370(b)(4) by removing ``Sec.  1271.90(b)'' and by 
adding in its place ``Sec.  1271.90(c)''.

    Dated: June 16, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-14721 Filed 6-21-16; 8:45 am]
 BILLING CODE 4164-01-P