81_FR_40632 81 FR 40512 - Revisions to Exceptions Applicable to Certain Human Cells, Tissues, and Cellular and Tissue-Based Products

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)

Page Range40512-40518
FR Document2016-14721

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 Issue 120 (Wednesday, June 22, 2016)
[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]


=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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



                                              40512              Federal Register / Vol. 81, No. 120 / Wednesday, June 22, 2016 / Rules and Regulations

                                                Authority: 15 U.S.C. 77e, 77f, 77g, 77h, 77j,          § 230.456    [Amended]                                 DEPARTMENT OF HEALTH AND
                                              77k, 77s, 77z–2, 77z–3, 77aa(25), 77aa(26),                                                                     HUMAN SERVICES
                                              77ddd, 77eee, 77ggg, 77hhh, 77iii, 77jjj,                ■ 9. Amend § 230.456 in paragraph
                                              77nnn, 77sss, 78c, 78i, 78j, 78j–3, 78l, 78m,            (c)(3) by removing ‘‘post-effective                    Food and Drug Administration
                                              78n, 78n–1, 78o, 78u–5, 78w, 78ll, 78 mm,                amendment or’’.
                                              80a–8, 80a–9, 80a–20, 80a–29, 80a–30, 80a–                                                                      21 CFR Part 1271
                                              31(c), 80a–37, 80a–38(a), 80a–39, 80b–11 and             PART 239—FORMS PRESCRIBED
                                              7201 et seq. 18 U.S.C. 1350; Sec. 953(b), Pub.           UNDER THE SECURITIES ACT OF 1933                       [Docket No. FDA–2014–N–1484]
                                              L. 111–203, 124 Stat. 1904; Sec. 102(a)(3),
                                              Pub. L. 112–106, 126 Stat. 309; and Sec.                                                                        Revisions to Exceptions Applicable to
                                              84001, Pub. L. 114–94, 129 Stat. 1312.                   ■ 10. The authority citation for part 239              Certain Human Cells, Tissues, and
                                                                                                       continues to read, in part, as follows:                Cellular and Tissue-Based Products
                                              *      *     *        *      *
                                                                                                         Authority: 15 U.S.C. 77c, 77f, 77g, 77h, 77j,
                                              § 229.1100       [Amended]                                                                                      AGENCY:   Food and Drug Administration,
                                                                                                       77s, 77z–2, 77z–3, 77sss, 78c, 78l, 78m, 78n,
                                                                                                                                                              HHS.
                                                                                                       78o(d), 78o–7 note, 78u–5, 78w(a), 78ll,
                                              ■  2. Amend § 229.1100 in paragraph (a)                                                                         ACTION:   Final rule.
                                                                                                       78mm, 80a–2(a), 80a–3, 80a–8, 80a–9, 80a–
                                              by removing ‘‘(§§ 229.1100 through                       10, 80a–13, 80a–24, 80a–26, 80a–29, 80a–30,
                                              229.1123)’’ and adding in its place                                                                             SUMMARY:    The Food and Drug
                                                                                                       80a–37, and Sec. 71003 and Sec. 84001, Pub.            Administration (FDA or Agency or we)
                                              ‘‘(§§ 229.1100 through 229.1125)’’.                      L. 114–94, 129 Stat. 1312, unless otherwise
                                                                                                                                                              is issuing this final rule to amend
                                              § 229.1104       [Amended]                               noted.
                                                                                                                                                              certain regulations regarding donor
                                                                                                       § 239.45    [Amended]                                  eligibility, including the screening and
                                              ■ 3. Amend § 229.1104 in paragraph
                                                                                                                                                              testing of donors of particular human
                                              (e)(2) by adding ‘‘in response to Rule
                                                                                                       ■  11. Amend Form SF–3 (referenced in                  cells, tissues, and cellular and tissue-
                                              15Ga–1’’ after ‘‘(as that term is defined
                                                                                                       § 239.45) in Note 2 of Notes to the                    based products (HCT/Ps), and related
                                              in Section 15G(a) of the Securities
                                                                                                       ‘‘Calculation of Registration Fee’’ Table              labeling. This final rule is in response
                                              Exchange Act of 1934)’’.
                                                                                                       (‘‘Fee Table’’) by removing ‘‘in a post-               to our enhanced understanding in this
                                              § 229.1105       [Amended]                               effective amendment to the registration                area and in response to comments from
                                                                                                       statement or’’.                                        stakeholders regarding the importance
                                              ■ 4. Amend § 229.1105 in paragraph                                                                              of embryos to individuals and couples
                                              (a)(3)(ii) by removing ‘‘135 days after’’                PART 249—FORMS, SECURITIES                             seeking access to donated embryos.
                                              and adding in its place ‘‘135 days of’’.                 EXCHANGE ACT OF 1934                                   DATES: This rule is effective August 22,
                                              § 229.1115       [Amended]                                                                                      2016.
                                                                                                       ■ 12. The authority citation for part 249              ADDRESSES: For access to the docket to
                                              ■  5. Amend § 229.1115 in Instruction 1                  continues to read, in part, as follows:                read background documents or
                                              to Item 1115 by removing ‘‘, 3 and 5 to                                                                         comments received, go to http://
                                                                                                          Authority: 15 U.S.C. 78a et seq. and 7201
                                              Item 1114’’ and adding in its place ‘‘and                et seq.; 12 U.S.C. 5461 et seq.; and 18 U.S.C.         www.regulations.gov and insert the
                                              4 to Item 1114(b)’’.                                     1350, unless otherwise noted.                          docket number found in brackets in the
                                                                                                                                                              heading of this final rule into the
                                              § 229.1125       [Amended]                               *      *      *       *      *                         ‘‘Search’’ box and follow the prompts,
                                              ■ 6. Amend Appendix to § 229.1125—                       § 249.308    [Amended]                                 and/or go to the Division of Dockets
                                              Schedule AL in Item 4(i) and Item 4(j)                                                                          Management, 5630 Fishers Lane, Rm.
                                              by removing all references to ‘‘loan’’ and               ■ 13. Amend Form 8–K (referenced in                    1061, Rockville, MD 20852.
                                              adding in their place ‘‘lease’’; and                     § 249.308) by amending Item 6.05 to                    FOR FURTHER INFORMATION CONTACT:
                                              removing all references to ‘‘loans’’ and                 remove ‘‘Form S–3 (17 CFR 239.13)’’                    Jessica T. Walker, Center for Biologics
                                              adding in their place ‘‘leases’’.                        and add in its place ‘‘Form SF–3 (17                   Evaluation and Research, Food and
                                                                                                       CFR 239.45)’’.                                         Drug Administration, 10903 New
                                              PART 230—GENERAL RULES AND                                                                                      Hampshire Ave., Bldg. 71, Rm. 7301,
                                              REGULATIONS, SECURITIES ACT OF                           § 249.312    [Amended]                                 Silver Spring, MD 20993–0002, 240–
                                              1933                                                                                                            402–7911.
                                                                                                       ■  14. Amend Form 10–D (referenced in
                                                                                                       § 249.312) by amending Item 1 in Part                  SUPPLEMENTARY INFORMATION:
                                              ■ 7. The authority citation for part 230
                                                                                                       I:                                                     Table of Contents
                                              continues to read, in part, as follows:
                                                                                                       ■ a. to remove all references to the                   I. Executive Summary
                                                Authority: 15 U.S.C. 77b, 77b note, 77c,
                                              77d, 77d note, 77f, 77g, 77h, 77j, 77r, 77s,             phrase ‘‘Item 1121(a) and (b)’’ and                       A. Purpose of the Final Rule
                                              77z–3, 77sss, 78c, 78d, 78j, 78l, 78m, 78n,              replacing them with the phrase ‘‘Item                     B. Summary of the Major Provisions of the
                                              78o, 78o–7 note, 78t, 78w, 78ll(d), 78mm,                1121(a), (b) and (c)’’; and                                  Final Rule
                                              80a–8, 80a–24, 80a–28, 80a–29, 80a–30, and                                                                         C. Legal Authority
                                                                                                       ■ b. to remove the phrase ‘‘17 CFR                        D. Costs and Benefits
                                              80a–37, and Pub. L. 112–106, sec. 201(a), 126
                                                                                                       229.1121(a) and (b)’’ and add in its                   II. Background
                                              Stat. 313 (2012), unless otherwise noted.
                                                                                                       place ‘‘17 CFR 1121(a), (b) and (c)’’.                    A. Need for the Regulation/History of This
                                              *      *     *        *      *                                                                                        Rulemaking
                                                                                                         Dated: June 16, 2016.
                                                                                                                                                                 B. Summary of Comments to the Proposed
                                              § 230.405    [Amended]                                   Brent J. Fields,
sradovich on DSK3TPTVN1PROD with RULES




                                                                                                                                                                    Rule
                                                                                                       Secretary.                                                C. General Overview of the Final Rule
                                              ■ 8. Amend § 230.405 in paragraph (1)(i)
                                                                                                       [FR Doc. 2016–14730 Filed 6–21–16; 8:45 am]            III. Legal Authority
                                              of the definition of an Ineligible issuer,                                                                      IV. Comments on the Proposed Rule and FDA
                                              by removing the phrase ‘‘General                         BILLING CODE 8011–01–P                                       Response
                                              Instruction I.A.4 of Form S–3’’ and                                                                                A. Introduction
                                              adding in its place ‘‘General Instruction                                                                          B. Description of General Comments and
                                              I.A.2 of Form SF–3’’                                                                                                  FDA Response



                                         VerDate Sep<11>2014    16:06 Jun 21, 2016   Jkt 238001   PO 00000   Frm 00036   Fmt 4700   Sfmt 4700   E:\FR\FM\22JNR1.SGM   22JNR1


                                                               Federal Register / Vol. 81, No. 120 / Wednesday, June 22, 2016 / Rules and Regulations                                         40513

                                                C. Purpose and Scope of the Final Rule                labeling is to help ensure that                        communicable disease, or who
                                                   (§ 1271.1)                                         physicians have specific and accurate                  possesses clinical evidence of, or risk
                                                D. Donor Screening (§ 1271.75)                        information to provide to recipients for               factors for, communicable disease
                                                E. Exceptions From the Requirement of                 use in making informed medical                         agents and diseases, would be
                                                   Determining Donor Eligibility (§ 1271.90)
                                                F. Labeling Requirements (§ 1271.370)
                                                                                                      decisions.                                             considered ineligible, and HCT/Ps from
                                              V. Effective Date                                                                                              that donor would not ordinarily be
                                                                                                      C. Legal Authority                                     used.
                                              VI. Economic Analysis of Impacts
                                              VII. Analysis of Environmental Impact                      FDA has authority for this rulemaking                  FDA has published three final rules
                                              VIII. Paperwork Reduction Act of 1995                   under section 361 of the Public Health                 that make up part 1271. In the Federal
                                              IX. Federalism                                          Service Act (PHS Act) (42 U.S.C. 264).                 Register of January 19, 2001 (66 FR
                                                                                                      Under section 361 of the PHS Act, FDA                  5447), we published regulations
                                              I. Executive Summary                                                                                           requiring HCT/P establishments to
                                                                                                      may issue and enforce regulations
                                              A. Purpose of the Final Rule                            necessary to prevent the introduction,                 register and list their HCT/Ps with FDA
                                                                                                      transmission, or spread of                             (registration final rule). In the Federal
                                                FDA is issuing this final rule to
                                                                                                      communicable disease between the                       Register of May 25, 2004 (69 FR 29786),
                                              amend certain regulations regarding
                                                                                                      States or from foreign countries into the              we published regulations requiring most
                                              donor eligibility, including the
                                                                                                      States.                                                donors to be tested and screened for
                                              screening and testing of donors of
                                                                                                                                                             relevant communicable disease agents
                                              particular HCT/Ps, and related labeling.                D. Costs and Benefits                                  and diseases (donor eligibility final
                                              We are finalizing these changes in                                                                             rule). In the Federal Register of
                                                                                                        Because this rule imposes no
                                              response to our enhanced                                                                                       November 24, 2004 (69 FR 68612), we
                                                                                                      additional regulatory burdens, the costs
                                              understanding in this area and in                                                                              published regulations requiring certain
                                                                                                      associated with this rule are expected to
                                              response to comments from                                                                                      HCT/P establishments to follow current
                                                                                                      be minimal.
                                              stakeholders regarding the importance                                                                          good tissue practice (CGTP), which
                                              of embryos to individuals and couples                   II. Background                                         governs the methods used in, and the
                                              seeking access to donated embryos.                                                                             facilities and controls used for, the
                                                                                                      A. Need for the Regulation/History of
                                              B. Summary of the Major Provisions of                   This Rulemaking                                        manufacture of HCT/Ps, recordkeeping,
                                              the Final Rule                                                                                                 and the establishment of a quality
                                                                                                         Under the authority of section 361 of               program (CGTP final rule). These
                                                 FDA is amending existing regulations                 the PHS Act, by delegation from the                    regulations apply to HCT/Ps recovered
                                              to provide additional flexibility to HCT/               Surgeon General and the Secretary of                   on or after May 25, 2005.
                                              P establishments to make available for                  Health and Human Services, FDA may                        As part of our ongoing effort to
                                              reproductive use embryos originally                     make and enforce regulations necessary                 implement our framework for regulating
                                              intended for reproductive use for a                     to prevent the introduction,                           HCT/Ps, in the Federal Register of May
                                              specific individual or couple when                      transmission, or spread of                             25, 2005 (70 FR 29949), we issued an
                                              those embryos are subsequently                          communicable diseases. Communicable                    interim final rule entitled ‘‘Human
                                              intended for directed or anonymous                      diseases include, but are not limited to,              Cells, Tissues, and Cellular and Tissue-
                                              donation. Specifically, this rulemaking                 those transmitted by viruses, bacteria,                Based Products; Donor Screening and
                                              redesignates the current Title 21 of the                fungi, parasites, and transmissible                    Testing, and Related Labeling’’ (2005
                                              Code of Federal Regulations (CFR)                       spongiform encephalopathy agents.                      interim final rule), which had an
                                              1271.90(b) (§ 1271.90(b)) to new                        Certain diseases are transmissible                     effective date simultaneous with
                                              § 1271.90(c), and would insert a new                    through implantation, transplantation,                 publication. This interim final rule was
                                              § 1271.90(b) entitled ‘‘Exceptions for                  infusion, or transfer of HCT/Ps derived                then adopted without change in the
                                              reproductive use’’ to clarify that if an                from donors infected with those                        Federal Register of June 19, 2007 (72 FR
                                              embryo was originally intended for                      diseases. To prevent the introduction,                 33667), in the final rule entitled
                                              reproductive use for a specific                         transmission, or spread of such                        ‘‘Human Cells, Tissues, and Cellular
                                              individual or couple, its use for directed              communicable diseases, we consider it                  and Tissue-Based Products; Donor
                                              or anonymous donation, would not be                     necessary to require establishments to                 Screening and Testing, and Related
                                              prohibited under § 1271.45(c), even                     take appropriate measures to prevent                   Labeling’’ (2007 final rule). The 2007
                                              when the applicable donor eligibility                   the use of HCT/Ps from infected donors.                final rule amended regulations
                                              requirements under part 1271, subpart                   FDA regulates HCT/Ps intended for                      regarding the screening and testing of
                                              C, are not met. FDA also clarifies that                 implantation, transplantation, infusion,               donors of HCT/Ps, timing of specimen
                                              we are not creating an exception for                    or transfer into a human recipient under               collection, record retention
                                              deficiencies that occurred in making the                part 1271 that was issued under the                    requirements, and related labeling
                                              donor eligibility determination for                     authority of section 361 of the PHS Act.               requirements in response to public
                                              either the oocyte donor or the semen                    Part 1271 requires HCT/P                               comments concerning the importance of
                                              donor as required under § 1271.45(b), or                establishments to screen and test donors               cryopreserved embryos to individuals
                                              for deficiencies in performing donor                    for relevant communicable disease                      seeking access to donated embryos. The
                                              screening or testing, as required under                 agents and diseases, to prepare and                    2007 final rule also added an exception
                                              §§ 1271.75, 1271.80, and 1271.85.                       follow written standard operating                      to the donor eligibility requirements in
                                                 The final rule also requires                         procedures for the prevention of the                   § 1271.90(a)(4) for cryopreserved
                                              appropriate labeling for embryos that                   spread of communicable diseases, and                   embryos that, while originally exempt
sradovich on DSK3TPTVN1PROD with RULES




                                              would describe the donor eligibility                    to maintain records. Part 1271 also                    from the donor eligibility requirements
                                              status of the individual donors whose                   requires that for most HCT/Ps, the donor               because the donors were sexually
                                              gametes were used to form the embryo.                   must be determined to be eligible, based               intimate partners, are later intended for
                                              The content of the labeling is not                      on the results of screening and testing                directed or anonymous donation.
                                              different from that required under                      for relevant communicable disease                         In recent years, industry and the
                                              current regulations. Consistent with                    agents and diseases. In most cases, a                  medical community have expressed
                                              current regulations, the intent of the                  donor who tests reactive for a particular              concerns that the exception added by


                                         VerDate Sep<11>2014   16:06 Jun 21, 2016   Jkt 238001   PO 00000   Frm 00037   Fmt 4700   Sfmt 4700   E:\FR\FM\22JNR1.SGM   22JNR1


                                              40514            Federal Register / Vol. 81, No. 120 / Wednesday, June 22, 2016 / Rules and Regulations

                                              the 2007 final rule does not fully                      subsequently used for directed or                      donor or the semen donor as required
                                              address the need for access to                          anonymous donation, even when the                      under § 1271.45(b), or for deficiencies in
                                              cryopreserved embryos. The                              donor eligibility requirements under                   performing donor screening or testing,
                                              stakeholders have raised concerns that                  part 1271, subpart C are not met.                      as required under §§ 1271.75, 1271.80,
                                              the current regulations still unduly                       We are amending § 1271.90 as                        and 1271.85.
                                              restrict the use of embryos that were                   follows:                                                 We note that the language we are
                                              originally intended for personal                           • Changing the heading of this                      adding to the exceptions currently listed
                                              reproductive use, and therefore impose                  section by deleting ‘‘from the                         in § 1271.90 is additive. It creates an
                                              limitations on individuals and couples                  requirement of determining donor                       additional exception for the use of
                                              involved in family building. In response                eligibility,’’ and inserting ‘‘other’’ before          certain reproductive HCT/Ps that are not
                                              to these concerns, FDA published the                    ‘‘exceptions.’’ The heading for § 1271.90              currently excepted, but it does not
                                              proposed rule ‘‘Revisions to Exceptions                 will read ‘‘Are there other exceptions                 impact or restrict the exceptions
                                              Applicable to Certain Human Cells,                      and what labeling requirements apply?’’                currently provided for in the
                                              Tissues, and Cellular and Tissue-Based                  We made this change for clarity; the                   regulations.
                                              Products’’ in the Federal Register of                   new heading will be more accurate.
                                                                                                         • Changing § 1271.90(a)(3) by                       3. Section 1271.90(c)
                                              December 31, 2014 (79 FR 78744). The
                                              proposed rule intended to increase                      replacing ‘‘exempt’’ with ‘‘excepted,’’                   Under § 1271.90(c), HCT/P
                                              access to embryos for reproductive use                  which is the term used in the                          establishments must prominently label
                                              by expanding the current exceptions to                  introductory title for this provision.                 an HCT/P described in § 1271.90(a) and
                                              the prohibitions on use under § 1271.90,                Thus, this change will make the                        (b). The labeling requirements are
                                              providing HCT/P establishments with                     language more consistent. The                          intended to help ensure that physicians
                                              the flexibility to make available any                   beginning of § 1271.90(a)(3) will read,                have specific and accurate information
                                              embryo originally formed for                            ‘‘Cryopreserved cells or tissue for                    to provide to recipients for use in
                                              reproductive use for a specific                         reproductive use, other than embryos,                  making informed medical decisions.
                                              individual or couple and now intended                   originally excepted . . . .’’                             The nonsubstantive change to
                                              for reproductive use in a directed or                      • Changing current § 1271.90(a)(4) by               § 1271.90(c)(2) clarifies that the labeling
                                              anonymous donation, provided that                       replacing ‘‘exempt’’ with ‘‘excepted’’.                requirements contained in
                                              specific criteria are met, including                       • Redesignating current § 1271.90(b)                § 1271.90(c)(2) do not apply to
                                              requirements for labeling.                              as § 1271.90(c) and adding a new                       reproductive cells or tissue labeled in
                                                                                                      paragraph (b) to § 1271.90.                            accordance with § 1271.90(c)(6). The
                                              B. Summary of Comments to the                              • Changing newly designated                         change to § 1271.90(c)(6) includes
                                              Proposed Rule                                           § 1271.90(c) by removing ‘‘paragraph                   ‘‘recovery or’’ before the word
                                                 We received approximately 10                         (a)’’ and adding in its place ‘‘paragraphs             ‘‘cryopreservation’’. Thus, the
                                              comment letters on the proposed rule by                 (a) and (b)’’ in the introductory text,                § 1271.90(c)(6) provision requires HCT/
                                              the close of the comment period. We                     revising § 1271.90(c)(2) to replace                    P establishments to prominently label
                                              received comments from academia,                        ‘‘(b)(6)’’ with ‘‘(c)(6)’’, and by adding              an HCT/P described in § 1271.90(a)(3) or
                                              professional organizations, and                         ‘‘recovery or’’ before ‘‘cryopreservation’’            (a)(4) with ‘‘Advise recipient that
                                              individuals. The comments were                          in new § 1271.90(c)(6) to clarify that                 screening and testing of the donor(s)
                                              balanced between those expressing                       some testing and screening activities                  were not performed at the time of
                                              support for the proposed rule and those                 may take place before recovery of the                  recovery or cryopreservation of the
                                              raising concerns about how the                          gametes, not just before                               reproductive cells or tissue, but have
                                              proposed exception will impact public                   cryopreservation of the embryos.                       been performed subsequently’’ for HCT/
                                              health. They addressed the following                    2. Section 1271.90(b)                                  Ps described in § 1271.90(a)(3) or (a)(4).
                                              topics: Purpose and scope of the final                                                                         This change is made to recognize that
                                                                                                         We are redesignating the current                    some testing and screening activities
                                              rule, donor screening, exceptions from
                                                                                                      § 1271.90(b) to § 1271.90(c), and adding               may take place even before recovery of
                                              the requirement of determining donor
                                                                                                      a new § 1271.90(b) entitled ‘‘Exceptions               HCT/Ps, not just before
                                              eligibility, and labeling requirements.
                                                                                                      for reproductive use.’’ Under finalized                cryopreservation.
                                              C. General Overview of the Final Rule                   § 1271.90(b), an embryo originally
                                                FDA is adopting as final, without                     intended for reproductive use for a                    4. Amendment to § 1271.370
                                              material change, the proposed rule to                   specific individual or couple that is                     Section 1271.370 sets forth labeling
                                              amend certain regulations regarding                     subsequently intended for directed or                  requirements in addition to those that
                                              donor eligibility and related labeling.                 anonymous donation is excepted from                    apply under §§ 1271.55, 1271.60,
                                                We are making revisions to the                        the prohibition on use under                           1271.65, and 1271.90. Because, as
                                              following FDA regulations:                              § 1271.45(c) even when the applicable                  discussed previously, this rule
                                                                                                      donor eligibility requirements under                   redesignates the current labeling
                                              1. Amendments to § 1271.90                              part 1271, subpart C are not met.                      requirements under § 1271.90(b) to
                                                 Section 1271.90 sets forth exceptions                Accordingly, when an establishment                     § 1271.90(c), we are amending
                                              where HCT/P establishments are not                      fails to comply with applicable donor                  § 1271.370(b)(4) to revise the reference
                                              required to make a donor eligibility                    eligibility requirements under part 1271,              from § 1271.90(b) to § 1271.90(c).
                                              determination under § 1271.50 or to                     subpart C, the establishment will not be
                                              perform donor screening or testing                      prohibited from making available for                   III. Legal Authority
sradovich on DSK3TPTVN1PROD with RULES




                                              under §§ 1271.75, 1271.80, and 1271.85.                 reproductive use such embryos for                         FDA is issuing this final rule under
                                              We are adding language to the                           reproductive purposes in accordance                    the authority of section 361 of the PHS
                                              exceptions listed in this section to                    with this section. The exception from                  Act (42 U.S.C. 264). Under section 361
                                              provide clarity and update the                          the prohibition on use does not create                 of the PHS Act, FDA may issue and
                                              regulation by allowing for an embryo                    an exception for deficiencies that                     enforce regulations necessary to prevent
                                              originally intended for reproductive use                occurred in making the donor eligibility               the introduction, transmission, or
                                              for a specific individual or couple, to be              determination for either the oocyte                    spread of communicable disease


                                         VerDate Sep<11>2014   16:06 Jun 21, 2016   Jkt 238001   PO 00000   Frm 00038   Fmt 4700   Sfmt 4700   E:\FR\FM\22JNR1.SGM   22JNR1


                                                               Federal Register / Vol. 81, No. 120 / Wednesday, June 22, 2016 / Rules and Regulations                                         40515

                                              between the States or from foreign                      eligibility, screening, and testing of                 establishments take appropriate
                                              countries into the States. It is important              donors of reproductive cells. One                      measures to prevent the use of HCT/Ps
                                              to recognize that HCT/Ps recovered in                   suggestion was that FDA’s donor                        from donors infected with
                                              one State may be sent to another for                    eligibility, screening, and testing                    communicable diseases. Part 1271
                                              processing, and then shipped for use                    requirements closely parallel American                 requires HCT/P establishments to screen
                                              throughout the United States, or                        Society of Reproductive Medicine/                      and test donors for relevant
                                              beyond. FDA has been involved in                        Society for Assisted Reproductive                      communicable disease agents and
                                              many recalls where HCT/Ps processed                     Technology guidelines.                                 diseases, and to maintain records. Part
                                              in a single establishment have been                        (Response) FDA acknowledges and                     1271 also requires for most HCT/Ps that
                                              distributed in many States. In any event,               appreciates the supportive comments.                   the donor must be determined to be
                                              intrastate transactions affecting                       We appreciate the interest in additional               eligible, based on the results of
                                              interstate communicable disease                         guidance for the screening and testing of              screening and testing for relevant
                                              transmission may also be regulated                      donors of reproductive cells. We                       communicable disease agents and
                                              under section 361 of the PHS Act. (See                  continue to review existing regulations                diseases. We have retained the qualifier
                                              Louisiana v. Mathews, 427 F. Supp. 174,                 with respect to providing additional                   ‘‘when possible’’ in § 1271.90(a)(4) to
                                              176 (E.D. La. 1977); Independent Turtle                 guidance or modifying these regulations                provide HCT/P establishments with the
                                              Farmers of Louisiana, Inc. v. United                    as appropriate, in the future.                         flexibility to make available any
                                              States of America, et al., 2010 U.S. Dist.                 (Comment 2) One comment asked if                    embryos originally formed for
                                              LEXIS 31117). This final rule                           the final rule would be applied                        reproductive use for a specific
                                              incorporates changes in response to our                 retrospectively to embryos formed and                  individual or couple and now intended
                                              enhanced understanding of the uses of                   cryopreserved on or after May 25, 2005.                for reproductive use in a directed or
                                              certain types of HCT/Ps in specific                        (Response) Yes, the final rule applies              anonymous donation, provided that
                                              situations and in response to comments                  to embryos formed and cryopreserved                    specific criteria are met, including
                                              from stakeholders regarding the                         on or after May 25, 2005.                              requirements for labeling.
                                              importance of embryos to individuals                    C. Purpose and Scope of the Final Rule                    The final rule provides for the
                                              and couples seeking access to donated                   (§ 1271.1)                                             continued applicability of labeling
                                              embryos.                                                                                                       requirements for embryos intended for
                                                                                                         (Comment 3) One comment noted that                  reproductive use that would be
                                              IV. Comments on the Proposed Rule                       preventing the spread of communicable                  excepted from the prohibition on use.
                                              and FDA Response                                        disease protects the population and the                The rule requires prominent labeling
                                                                                                      family receiving the donation. Two                     that describes the donor eligibility
                                              A. Introduction                                         comments suggested that the proposed                   status of the individual donors whose
                                                We received approximately 10                          rule conflicts with FDA regulations that               gametes were used to form the embryo.
                                              comment letters on the proposed rule by                 serve to prevent the introduction,                     The required labeling will provide
                                              the close of the comment period, each                   transmission, and spread of                            information to the treating physician to
                                              containing one or more comments on                      communicable disease. One comment                      permit discussion of the potential risks
                                              one or more issues. We received                         expressed concern that the proposed                    of communicable disease with the
                                              comments from academia, professional                    rule appears to relax the testing                      recipient.
                                              organizations, and individual                           requirements for donors and conflicts
                                              consumers.                                              with the PHS Act, specifically section                 D. Donor Screening (§ 1271.75)
                                                We describe and respond to the                        361, that provides FDA with the                           (Comment 4) Some of the comments
                                              comments in sections IV.B through IV.F.                 authority to make and enforce                          expressed concern about the risk of
                                              We have numbered each comment to                        regulations ‘‘to prevent the introduction,             accepting an unscreened donation.
                                              help distinguish among different                        transmission, or spread of                             Another comment noted that eligibility
                                              comments. We have grouped similar                       communicable diseases from foreign                     of the HCT/P donor must be assessed
                                              comments together under the same                        countries into the States or possessions,              prior to usage to ensure the safety of
                                              number, and, in some cases, we have                     or from State or possession into any                   recipients, their offspring, and the
                                              separated different issues discussed in                 other State or possession’’ (42 U.S.C.                 public as a whole; and furthermore,
                                              the same comment and designated them                    264(a)). This commenter’s interpretation               ensuring the proper screening of the
                                              as distinct comments for purposes of                    of the proposed rule is that it removes                donor’s HCT/P enables the control of
                                              our responses. The number assigned to                   the requirement for reproductive tissue                the spread of disease.
                                              each comment is purely for                              donors to be tested, and only requires                    (Response) We agree that the proper
                                              organizational purposes and does not                    reproductive tissue donor testing ‘‘when               screening of HCT/P donors minimizes
                                              signify the comment’s value or                          possible.’’ According to the comment,                  the risk of introducing, transmitting, or
                                              importance or the order in which the                    FDA seems to posit informed consent as                 spreading communicable diseases. As
                                              comments were received.                                 an adequate response to the health risks               stated in the proposed rule, we consider
                                                                                                      faced by recipients of donated embryos.                it necessary to require establishments to
                                              B. Description of General Comments                      The commenter would like FDA to                        take appropriate measures to prevent
                                              and FDA Response                                        strike the qualifier ‘‘when possible’’                 the use of HCT/Ps from infected donors.
                                                Several comments made general                         from the text of the proposed rule                     Part 1271 requires HCT/P
                                              remarks supporting the proposed rule                    because the commenter believes this                    establishments to screen and test donors
                                              without focusing on a particular                        approach would provide a greater level                 for relevant communicable disease
sradovich on DSK3TPTVN1PROD with RULES




                                              proposed provision. In the following                    of protection to the recipient than the                agents and diseases, and to maintain
                                              paragraphs, we discuss and respond to                   proposed rule and preserve FDA’s                       records. Part 1271 also requires, for
                                              such general comments.                                  intention of relaxing the current donor                most HCT/Ps, that donor be determined
                                                (Comment 1) There were several                        eligibility regulations in the interest of             to be eligible, based on the results of
                                              comments that were in support of the                    family building.                                       screening and testing for relevant
                                              proposed rule and suggested that we                        (Response) As stated previously, we                 communicable disease agents and
                                              provide even more guidance on donor                     consider it necessary that                             diseases. In most cases, a donor who


                                         VerDate Sep<11>2014   16:06 Jun 21, 2016   Jkt 238001   PO 00000   Frm 00039   Fmt 4700   Sfmt 4700   E:\FR\FM\22JNR1.SGM   22JNR1


                                              40516            Federal Register / Vol. 81, No. 120 / Wednesday, June 22, 2016 / Rules and Regulations

                                              tests reactive for a particular                         determination for either the oocyte                    implantation; however, we decline to
                                              communicable disease, or who                            donor or the semen donor as required                   make the suggested change. As stated in
                                              possesses clinical evidence of, or risk                 under § 1271.45(b), or for deficiencies in             the preamble of the proposed rule, the
                                              factors for, a communicable disease                     performing donor screening or testing,                 proposed labeling requirements are
                                              agent and disease, would be considered                  as required under §§ 1271.75, 1271.80,                 based on the expectation that a
                                              ineligible, and cells or tissues from that              and 1271.85.                                           physician will be closely involved in
                                              donor would not ordinarily be used.                        We note that the change we are                      the decision to use an embryo and the
                                                (Comment 5) A few comments                            making to the exceptions currently                     recognition that physicians are under
                                              expressed the belief that the proposed                  listed in § 1271.90 is additive. It creates            legal and ethical obligations that require
                                              rule will allow for better genetic                      an additional exception for the use of                 them to discuss the risks of
                                              profiling. One of those comments stated                 certain reproductive HCT/Ps that are not               communicable disease transmission
                                              that labeling will make it easier to                    currently excepted, but it does not                    stemming from the use of HCT/Ps. FDA
                                              identify particular genotypes for                       impact or restrict the exceptions                      relies on physicians to meet these
                                              research. Another comment stated that                   currently provided for in the                          obligations when discussing procedures
                                              genetically profiling all donors and to                 regulations.                                           involving HCT/Ps with recipients.
                                              the extent possible all embryos will                       (Comment 7) One comment                             Further, we expect that a recipient
                                              reduce the risk of recipients of embryos                recommends that the term ‘‘embryos                     would be fully informed of the risks
                                              giving birth to children with serious                   formed for autologous use’’ not be used                involved in using an embryo for
                                              genetic disorders. The commenter asked                  in conjunction with embryos. The                       reproductive purposes as finalized
                                              FDA to require establishments to                        commenter reasons that after a sperm or                under § 1271.90(b) even when the donor
                                              genetically screen all donors and the                   oocyte form an embryo, the embryo                      eligibility requirements under part 1271,
                                              embryo when possible.                                   should not be considered autologous,                   subpart C are not met.
                                                (Response) These comments address a                   given the definition at § 1271.3(a).                      (Comment 9) One comment suggested
                                              topic that is outside the scope of this                    (Response) We agree with the                        that while a labeling requirement that is
                                              rulemaking.                                             comment and are not adopting, as part                  tiered according to the risks may
                                                                                                      of the final rule, the term ‘‘embryos                  mitigate the risks, it does not go far
                                              E. Exceptions From the Requirement of                   formed for autologous use’’. Likewise,
                                              Determining Donor Eligibility                                                                                  enough in abolishing the risks.
                                                                                                      we are not adopting, as part of the final                 (Response) As described under
                                              (§ 1271.90)                                             rule, the reference to § 1271.90(a)(1) in              proposed § 1271.90(c)(2) through (6), an
                                                 (Comment 6) One comment sought                       § 1271.90(a)(4).                                       embryo originally intended for
                                              transparency as to which embryos are                                                                           reproductive use for a specific
                                              excepted and requested specific                         F. Labeling Requirements (§ 1271.370)
                                                                                                                                                             individual or couple that is
                                              examples of how the rule provides                          (Comment 8) Several comments were                   subsequently intended for directed or
                                              additional flexibility to make embryos                  in support of labeling because it allows               anonymous donation must be labeled as
                                              available for directed and anonymous                    the physician to fully discuss the risks               applicable. We acknowledge that the
                                              donation. Specifically, the commenter                   of any communicable disease and it                     labeling requirement will not abolish all
                                              asked whether donation would be                         allows the patient to make a fully                     risks of implanting those embryos.
                                              allowed when the embryo was                             informed decision. One commenter                       Rather, as stated in the proposed rule,
                                              originally intended for transfer to a                   noted that factors affecting decisions of              the required labeling would provide
                                              sexually intimate partner, where one of                 an HCT/P recipient may outweigh the                    information to the treating physician to
                                              the gamete providers (either a directed                 expert advice of medical doctors.                      permit discussion of the potential risks
                                              or anonymous donor) would be                            Another comment referenced                             of communicable diseases with the
                                              considered ineligible based on screening                § 1271.90(c)(6) of the proposed rule                   recipient. Our expectation is that the
                                              and testing.                                            (embryo labeling requirements) that                    recipient will become fully informed of
                                                 (Response) The rulemaking provides                   states establishments are required to                  the risk when the donor eligibility
                                              additional flexibility to make embryos                  ‘‘advise recipients that screening and                 requirements under part 1271, subpart C
                                              available when there have been changes                  testing of the donor(s) were not                       are not met, so that the recipient can
                                              in the original plans for use of the                    performed at the time of recovery or                   make a well informed decision about
                                              embryos. Under finalized § 1271.90(b),                  cryopreservation of the reproductive                   receiving the embryo.
                                              an embryo originally intended for                       cells or tissues, but have been
                                              reproductive use for a specific                         performed subsequently.’’ The comment                  V. Effective Date
                                              individual or couple that is                            further states that ‘‘Description of the                 This rule is effective August 22, 2016.
                                              subsequently intended for directed or                   Proposed Rule’’ provides that these
                                              anonymous donation is excepted from                     labeling requirements are ‘‘based on the               VI. Economic Analysis of Impacts
                                              the prohibition on use under                            expectation that a physician will be                      We have examined the impacts of the
                                              § 1271.45(c) even when the applicable                   closely involved in the decision of the                final rule under Executive Order 12866,
                                              donor eligibility requirements under                    embryo and the recognition that                        Executive Order 13563, the Regulatory
                                              part 1271, subpart C are not met.                       physicians are under legal and ethical                 Flexibility Act (5 U.S.C. 601–612), and
                                              Accordingly, when an establishment                      obligations that require them to discuss               the Unfunded Mandates Reform Act of
                                              fails to comply with applicable donor                   the risks of communicable disease                      1995 (Pub. L. 104–4). Executive Orders
                                              eligibility requirements under part 1271,               transmission stemming from the use of                  12866 and 13563 direct us to assess all
                                              subpart C, the establishment will not be                HCT/Ps.’’ The comment asked that FDA                   costs and benefits of available regulatory
sradovich on DSK3TPTVN1PROD with RULES




                                              prohibited from making available for                    revise the rule to expressly require                   alternatives and, when regulation is
                                              reproductive use such embryos for                       establishments to counsel recipients on                necessary, to select regulatory
                                              reproductive purposes in accordance                     the risk of disease.                                   approaches that maximize net benefits
                                              with this section. The exception from                      (Response) We agree that the                        (including potential economic,
                                              the prohibition on use does not create                  recipients should be fully informed                    environmental, public health and safety,
                                              an exception for deficiencies that                      about the risk of communicable disease                 and other advantages; distributive
                                              occurred in making the donor eligibility                before accepting an embryo for                         impacts; and equity). We have


                                         VerDate Sep<11>2014   16:06 Jun 21, 2016   Jkt 238001   PO 00000   Frm 00040   Fmt 4700   Sfmt 4700   E:\FR\FM\22JNR1.SGM   22JNR1


                                                               Federal Register / Vol. 81, No. 120 / Wednesday, June 22, 2016 / Rules and Regulations                                             40517

                                              developed a comprehensive Economic                      originally intended for reproductive use               Order and, consequently, a federalism
                                              Analysis of Impacts that assesses the                   for a specific individual or couple,                   summary impact statement is not
                                              impacts of the final rule. We believe that              while continuing to emphasize the                      required.
                                              this final rule is not a significant                    applicability of the donor eligibility
                                                                                                                                                             List of Subjects in 21 CFR Part 1271
                                              regulatory action as defined by                         screening and testing requirements for
                                              Executive Order 12866.                                  individual gamete donors. The final rule                  Biologics, Drugs, Human cells and
                                                 The Regulatory Flexibility Act                       will provide HCT/P establishments with                 tissue-based products, Medical devices,
                                              requires us to analyze regulatory options               the flexibility to make embryos                        Reporting and recordkeeping
                                              that would minimize any significant                     originally intended for reproductive use               requirements.
                                              impact of a rule on small entities.                     for a specific individual or couple now                   Therefore, under the Public Health
                                              Because the costs associated with this                  available for directed or anonymous                    Service Act and under authority
                                              rule are expected to be minimal, we                     donation, provided that specific criteria              delegated to the Commissioner of Food
                                              certify that the rule will not have a                   are met. Consistent with current                       and Drugs, 21 CFR part 1271 is
                                              significant economic impact on a                        regulations, the labeling requirements                 amended as follows:
                                              substantial number of small entities.                   will help ensure that physicians have
                                                 The Unfunded Mandates Reform Act                     specific and accurate information to                   PART 1271—HUMAN CELLS, TISSUES,
                                              of 1995 (section 202(a)) requires us to                 provide to recipients for use in making                AND CELLULAR AND TISSUE–BASED
                                              prepare a written statement, which                      informed medical decisions. Because                    PRODUCTS
                                              includes an assessment of anticipated                   this rule imposes no additional
                                              costs and benefits, before issuing ‘‘any                regulatory burdens, the costs associated               ■ 1. The authority citation for part 1271
                                              rule that includes any Federal mandate                  with this rule are expected to be                      continues to read as follows:
                                              that may result in the expenditure by                   minimal.                                                 Authority: 42 U.S.C. 216, 243, 263a, 264,
                                              State, local, and tribal governments, in                                                                       271.
                                              the aggregate, or by the private sector, of             VII. Analysis of Environmental Impact
                                              $100,000,000 or more (adjusted                            We have determined under 21 CFR                      ■ 2. In § 1271.90:
                                              annually for inflation) in any one year.’’              25.30(h) that this action is of a type that            ■ a. Revise the heading;
                                              The current threshold after adjustment                  does not individually or cumulatively                  ■ b. Revise paragraph (a)(3) introductory
                                              for inflation is $146 million, using the                have a significant effect on the human                 text;
                                              most current (2015) Implicit Price                      environment. Therefore, neither an                     ■ c. Revise paragraph (a)(4);
                                              Deflator for the Gross Domestic Product.                environmental assessment nor an                        ■ d. Redesignate paragraph (b) as
                                              This final rule would not result in an                  environmental impact statement is                      paragraph (c);
                                              expenditure in any year that meets or                   required.                                              ■ e. Add a new paragraph (b);
                                              exceeds this amount.                                                                                           ■ f. Revise newly designated paragraph
                                                 This rule amends certain regulations                 VIII. Paperwork Reduction Act of 1995                  (c) introductory text;
                                              regarding donor eligibility and labeling                   The labeling requirements contained                 ■ g. Revise newly designated paragraph
                                              related to the screening and testing of                 in this final rule are not subject to                  (c)(2); and
                                              donors of particular HCT/Ps. The final                  review by the Office of Management and                 ■ h. Revise newly designated paragraph
                                              rule will provide additional flexibility                Budget (OMB) because they do not                       (c)(6).
                                              to HCT/P establishments to make                         constitute a ‘‘collection of information’’                The revisions and additions read as
                                              available for reproductive use embryos                  under the Paperwork Reduction Act of                   follows:
                                              originally intended for reproductive use                1995 (the PRA) (44 U.S.C 3501–3520).
                                                                                                                                                             § 1271.90 Are there other exceptions and
                                              for a specific individual or couple and                 Rather, the requirement to label HCT/Ps                what labeling requirements apply?
                                              subsequently intended for directed or                   in accordance with the final rule is a
                                              anonymous donation. Specifically, the                   ‘‘public disclosure of information                        (a) * * *
                                              final rule will clarify that if an embryo               originally supplied by the Federal                        (3) Cryopreserved cells or tissue for
                                              was originally intended for reproductive                government to the recipient for the                    reproductive use, other than embryos,
                                              use for a specific individual or couple,                purpose of disclosure to the public’’ (5               originally excepted under paragraphs
                                              its use for directed or anonymous                       CFR 1320.3(c)(2)). Therefore, FDA                      (a)(1) or (a)(2) of this section at the time
                                              donation would not be prohibited under                  concludes that these requirements in                   of donation, that are subsequently
                                              § 1271.45 (c), even when the applicable                 this document are not subject to review                intended for directed donation,
                                              donor eligibility requirements under                    by OMB because they do not constitute                  provided that:
                                              part 1271, subpart C are not met. This                  a ‘‘collection of information’’ under the              *      *     *      *     *
                                              exception from prohibition for use                      PRA.                                                      (4) A cryopreserved embryo,
                                              would not create an exception for                                                                              originally excepted under paragraph
                                              deficiencies that occurred in making the                IX. Federalism                                         (a)(2) of this section at the time of
                                              donor eligibility determination for                       We have analyzed this final rule in                  recovery or cryopreservation, that is
                                              either the oocyte donor or the semen                    accordance with the principles set forth               subsequently intended for directed or
                                              donor as required under § 1271.45(b), or                in Executive Order 13132. FDA has                      anonymous donation. When possible,
                                              for deficiencies in performing donor                    determined that the rule does not                      appropriate measures should be taken to
                                              screening or testing, as required under                 contain policies that have substantial                 screen and test the semen and oocyte
                                              §§ 1271.75, 1271.80, and 1271,85. The                   direct effects on the States, on the                   donors before transfer of the embryo to
                                              final rule also requires appropriate                    relationship between the National                      the recipient.
sradovich on DSK3TPTVN1PROD with RULES




                                              labeling that describes the donor                       Government and the States, or on the                      (b) Exceptions for reproductive use.
                                              eligibility status of the individual                    distribution of power and                              An embryo originally intended for
                                              donors whose gametes were used to                       responsibilities among the various                     reproductive use for a specific
                                              form the embryo.                                        levels of government. Accordingly, we                  individual or couple that is
                                                 This rule will provide greater                       conclude that the rule does not contain                subsequently intended for directed or
                                              accommodation of individuals and                        policies that have federalism                          anonymous donation for reproductive
                                              couples wanting access to embryos                       implications as defined in the Executive               use is excepted from the prohibition on


                                         VerDate Sep<11>2014   16:06 Jun 21, 2016   Jkt 238001   PO 00000   Frm 00041   Fmt 4700   Sfmt 4700   E:\FR\FM\22JNR1.SGM   22JNR1


                                              40518            Federal Register / Vol. 81, No. 120 / Wednesday, June 22, 2016 / Rules and Regulations

                                              use under § 1271.45(c) even when the                    consequences for not meeting the                       Health and Human Services. Section
                                              applicable donor eligibility                            medical loss ratio threshold. The final                2718(a) of the PHSA requires a health
                                              requirements under subpart C of this                    regulations reflect the enactment of a                 insurance issuer to submit a report for
                                              part are not met. Nothing in this                       technical correction to section 833(c)(5)              each plan year to the Secretary of the
                                              paragraph creates an exception for                      of the Internal Revenue Code by the                    Department of Health and Human
                                              deficiencies that occurred in making the                Consolidated and Further Continuing                    Services concerning the percentage of
                                              donor eligibility determination for                     Appropriations Act of 2015. The final                  total premium revenue, after accounting
                                              either the oocyte donor or the semen                    regulations affect Blue Cross and Blue                 for collections or receipts for risk
                                              donor as required under § 1271.45(b), or                Shield organizations, and certain other                adjustment and risk corridors and
                                              for deficiencies in performing donor                    organizations involved in providing                    payments of reinsurance, that the issuer
                                              screening or testing, as required under                 health insurance.                                      expends: (1) On reimbursement for
                                              §§ 1271.75, 1271.80, and 1271.85.                       DATES: Effective Date: These regulations               clinical services provided to enrollees
                                                 (c) Required labeling. As applicable,                are effective on June 22, 2016.                        under such coverage; (2) for activities
                                              you must prominently label an HCT/P                       Applicability Date: For the date of                  that improve health care quality; and (3)
                                              described in paragraphs (a) and (b) of                  applicability, see § 1.833–1(e).                       on all other non-claims costs, excluding
                                              this section as follows:                                FOR FUTHER INFORMATION CONTACT:
                                                                                                                                                             federal and state taxes and licensing or
                                              *      *     *     *    *                               Rebecca L. Baxter, at (202) 317–6995                   regulatory fees.
                                                 (2) ‘‘NOT EVALUATED FOR                                                                                        Section 2718(b) of the PHSA requires
                                                                                                      (not a toll-free number).
                                                                                                                                                             that a health insurance issuer offering
                                              INFECTIOUS SUBSTANCES,’’ unless                         SUPPLEMENTARY INFORMATION:                             group or individual health insurance
                                              you have performed all otherwise
                                                                                                      Background                                             coverage, with respect to each plan year,
                                              applicable screening and testing under
                                                                                                                                                             provide an annual rebate to each
                                              §§ 1271.75, 1271.80, and 1271.85. This                    This Treasury decision contains final                enrollee under such coverage, on a pro
                                              paragraph does not apply to                             regulations that amend 26 CFR part 1                   rata basis, if the ratio of the amount of
                                              reproductive cells or tissue labeled in                 under section 833 of the Internal                      the premium revenue the issuer
                                              accordance with paragraph (c)(6) of this                Revenue Code (the Code). Section 833(a)                expends on costs for reimbursement for
                                              section.                                                provides that Blue Cross and Blue                      clinical services provided to enrollees
                                              *      *     *     *    *                               Shield organizations, and certain other                under such coverage and for activities
                                                 (6) ‘‘Advise recipient that screening                organizations involved in providing                    that improve health care quality to the
                                              and testing of the donor(s) were not                    health insurance as described in section               total amount of premium revenue
                                              performed at the time of recovery or                    833(c), are entitled to: (1) Treatment as              (excluding federal and state taxes and
                                              cryopreservation of the reproductive                    stock insurance companies for purposes                 licensing or regulatory fees and after
                                              cells or tissue, but have been performed                of sections 831 through 835 (related to                accounting for payments or receipts for
                                              subsequently,’’ for paragraphs (a)(3) or                taxation of non-life insurance                         risk adjustment, risk corridors, and
                                              (a)(4) of this section.                                 companies generally); (2) a special                    reinsurance under sections 1341, 1342,
                                                                                                      deduction determined under section                     and 1343 of the Affordable Care Act (42
                                              § 1271.370                                              833(b); and (3) computation of unearned                U.S.C. 18061, 18062, and 18063)) for the
                                              ■ 3. Amend § 1271.370(b)(4) by                          premium reserves under section                         plan year is less than a prescribed
                                              removing ‘‘§ 1271.90(b)’’ and by adding                 832(b)(4) based on 100 percent, and not                percentage. Section 2718(b)(1)(B)(ii) of
                                              in its place ‘‘§ 1271.90(c)’’.                          80 percent, of unearned premiums for                   the PHSA provides that beginning on
                                                Dated: June 16, 2016.
                                                                                                      purposes of determining ‘‘insurance                    January 1, 2014, the medical loss ratio
                                                                                                      company taxable income’’ under section                 computed under section 2718(b) of the
                                              Leslie Kux,
                                                                                                      832.                                                   PHSA shall be based on expenses and
                                              Associate Commissioner for Policy.                        Section 833(c)(5) was added to the                   premium revenues for each of the
                                              [FR Doc. 2016–14721 Filed 6–21–16; 8:45 am]             Code by section 9016 of the Patient                    previous three years of the plan.
                                              BILLING CODE 4164–01–P                                  Protection and Affordable Care Act                        The Department of Health and Human
                                                                                                      (Pub. L. 111–148, 124 Stat. 119) (the                  Services published in the Federal
                                                                                                      Affordable Care Act), effective for                    Register (75 FR 74864) an interim final
                                              DEPARTMENT OF THE TREASURY                              taxable years beginning after December                 rule under section 2718 of the PHSA on
                                                                                                      31, 2009. Section 833(c)(5), as enacted                December 1, 2010, an interim final rule
                                              Internal Revenue Service                                by the Affordable Care Act, provided                   and final rule on December 7, 2011 (76
                                                                                                      that section 833 did not apply to any                  FR 76596 and 76574), and a final rule
                                              26 CFR Part 1                                           organization unless the organization’s                 on May 16, 2012 (77 FR 28790). These
                                              [TD 9772]                                               medical loss ratio (MLR) for the taxable               rules implementing section 2718 of the
                                                                                                      year was at least 85 percent. For                      PHSA are codified at 45 CFR part 158
                                              RIN 1545–BN15                                           purposes of section 833, an                            (HHS Regulations).
                                              Modification of Treatment of Certain                    organization’s MLR was its percentage                     On December 6, 2010, the Treasury
                                              Health Organizations                                    of total premium revenue expended on                   Department and the IRS published
                                                                                                      reimbursement for clinical services                    Notice 2010–79 (2010–49 I.R.B. 809),
                                              AGENCY:  Internal Revenue Service (IRS),                provided to enrollees under its policies               which provided interim guidance and
                                              Treasury.                                               during such taxable year (as reported                  transitional relief to organizations under
                                              ACTION: Final regulations.                              under section 2718 of the Public Health                section 833(c)(5). The interim guidance
sradovich on DSK3TPTVN1PROD with RULES




                                                                                                      Service Act (42 U.S.C. 300gg–18)).                     applied to an organization’s first taxable
                                              SUMMARY:  This document contains final                    Section 2718 of the Public Health                    year beginning after December 31, 2009.
                                              regulations that provide guidance to                    Service Act (PHSA) was added by                           The interim guidance provided that
                                              Blue Cross and Blue Shield                              section 1001 and amended by section                    for purposes of determining whether an
                                              organizations, and certain other                        10101 of the Affordable Care Act.                      organization’s percentage of total
                                              organizations, on computing and                         Section 2718 of the PHSA is                            premium revenue expended on
                                              applying the medical loss ratio and the                 administered by the Department of                      reimbursement for clinical services


                                         VerDate Sep<11>2014   16:06 Jun 21, 2016   Jkt 238001   PO 00000   Frm 00042   Fmt 4700   Sfmt 4700   E:\FR\FM\22JNR1.SGM   22JNR1



Document Created: 2016-06-22 01:06:02
Document Modified: 2016-06-22 01:06:02
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionRules and Regulations
ActionFinal rule.
DatesThis rule is effective August 22, 2016.
ContactJessica 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.
FR Citation81 FR 40512 
CFR AssociatedBiologics; Drugs; Human Cells and Tissue-Based Products; Medical Devices and Reporting and Recordkeeping Requirements

2024 Federal Register | Disclaimer | Privacy Policy
USC | CFR | eCFR