[Federal Register Volume 81, Number 86 (Wednesday, May 4, 2016)]
[Rules and Regulations]
[Pages 26687-26692]
[FR Doc No: 2016-10385]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 610

[Docket No. FDA-2016-N-1170]

Standard Preparations, Limits of Potency, and Dating Period
Limitations for Biological Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Direct final rule.

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SUMMARY: The Food and Drug Administration (FDA or Agency or we) is
amending the general biological products standards relating to dating
periods and also removing certain standards relating to standard
preparations and limits of potency. FDA is taking this action to update
outdated requirements, and accommodate new and evolving technology and
testing capabilities, without diminishing public health protections.
This action is part of FDA's retrospective review of its regulations in
response to an Executive order. FDA is issuing these amendments
directly as a final rule because the Agency believes they are
noncontroversial and FDA anticipates no significant adverse comments.

DATES: This rule is effective September 16, 2016. Submit either
electronic or written comments on this direct final rule or its
companion proposed rule by July 18, 2016. If FDA receives no
significant adverse comments within the specified comment period, the
Agency intends to publish a document confirming the effective date of
the final rule in the Federal Register within 30 days after the comment
period on this direct final rule ends. If timely significant adverse
comments are received, the Agency will publish a document in the
Federal Register withdrawing this direct final rule within 30 days
after the comment period on this direct final rule ends.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2016-N-1170 for ``Standard Preparations, Limits of Potency, and
Dating Period Limitations for Biological Products.'' Received comments
will be placed in the docket and, except for those submitted as
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. If you do not
wish your name and contact information to be made publicly available,
you can provide this information on the cover sheet and not in the body
of your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, 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: Tami Belouin, 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:

I. Executive Summary

A. Purpose of Direct Final Rule

    FDA is issuing this direct final rule because revision and removal
of certain general biological products standards will update outdated
requirements and accommodate new and evolving technology and testing
capabilities without diminishing public health protections. FDA is
taking this action because the existing codified requirements are
duplicative of requirements that are also specified in biologics
license applications (BLAs) or are no longer necessary or appropriate
to help ensure the safety, purity, and potency of licensed biological
products.

B. Summary of the Major Provisions of the Direct Final Rule

    This direct final rule removes the requirements contained in Sec.
610.20 (21 CFR 610.20) from the regulations. FDA is taking this action
because the standard preparations listed in the regulation are
obsolete, no longer available, or described on a product specific basis
in BLAs. In addition, FDA believes that it is no longer necessary to
restrict the source of standard preparations to the Center for
Biologics Evaluation and Research (CBER), since

appropriate standard preparations can often be obtained from other
sources. Section 610.21 is removed because these potency limits are
either obsolete or best described on a product specific basis in the
BLA. Section 610.50 is amended to remove references to Sec. Sec.
610.20 and 610.21 and official potency tests and to reflect FDA's
updated approach to establishing dates of manufacture. Section 610.53
is amended to remove products no longer manufactured and products for
which dating information is identified in the BLA of each individual
product, and to reflect updated practices for the remaining products.

C. Legal Authority

    FDA is taking this action under the biological products provisions
of the Public Health Service Act (PHS Act), and the drugs and general
administrative provisions of the Federal Food, Drug, and Cosmetic Act
(the FD&C Act).

D. Costs and Benefits

    Because this direct final rule does not impose any additional
regulatory burdens, this regulation is not anticipated to result in any
compliance costs and the economic impact is expected to be minimal.

II. Direct Final Rulemaking

    In the document entitled ``Guidance for FDA and Industry: Direct
Final Rule Procedures,'' announced and provided in the Federal Register
of November 21, 1997 (62 FR 62466), FDA described its procedures on
when and how the Agency will employ direct final rulemaking. The
guidance may be accessed at: http://www.fda.gov/RegulatoryInformation/Guidances/ucm125166.htm. We have determined that this rule is
appropriate for direct final rulemaking because we believe that it
includes only noncontroversial amendments and we anticipate no
significant adverse comments. Consistent with our procedures on direct
final rulemaking, FDA is also publishing elsewhere in this issue of the
Federal Register a companion proposed rule proposing to amend the
general biological products standards relating to dating periods and to
remove those relating to standard preparations and limits of potency.
The companion proposed rule provides a procedural framework within
which the rule may be finalized in the event that the direct final rule
is withdrawn because of any significant adverse comments. The comment
period for the direct final rule runs concurrently with the companion
proposed rule. Any comments received in response to the companion
proposed rule will be considered as comments regarding the direct final
rule.
    We are providing a comment period on the direct final rule of 75
days after the date of publication in the Federal Register. If we
receive any significant adverse comments, we intend to withdraw this
direct final rule before its effective date by publication of a notice
in the Federal Register. A significant adverse comment is defined as a
comment that explains why the rule would be inappropriate, including
challenges to the rule's underlying premise or approach, or would be
ineffective or unacceptable without a change. In determining whether an
adverse comment is significant and warrants terminating a direct final
rulemaking, we will consider whether the comment raises an issue
serious enough to warrant a substantive response in a notice-and-
comment process. Comments that are frivolous, insubstantial, or outside
the scope of the rule will not be considered significant or adverse
under this procedure. A comment recommending a regulation change in
addition to those in this direct final rule would not be considered a
significant adverse comment unless the comment states why the rule
would be ineffective without the additional change. In addition, if a
significant adverse comment applies to part of this rule and that part
can be severed from the remainder of the rule (e.g., where, as here, a
direct final rule deletes several unrelated regulations), we may adopt
as final those provisions of the rule that are not the subject of the
significant adverse comment.
    If any significant adverse comments are received during the comment
period, FDA will publish, before the effective date of this direct
final rule, a document withdrawing the direct final rule. If we
withdraw the direct final rule, any comments received will be applied
to the proposed rule and will be considered in developing a final rule
using the usual notice-and-comment procedures.
    If FDA receives no significant adverse comments during the
specified comment period, FDA intends to publish a document confirming
the effective date within 30 days after the comment period ends.

III. Background

    On January 18, 2011, President Barack Obama issued Executive Order
13563, ``Improving Regulation and Regulatory Review'' (76 FR 3821,
January 21, 2011). One of the provisions in the Executive Order
requires Agencies to consider how best to promote the retrospective
analysis of rules that may be outmoded, ineffective, insufficient, or
excessively burdensome, and to modify, streamline, expand, or repeal
them in accordance with what has been learned (76 FR 3821 at 3822). As
one step in implementing the Executive Order, FDA published a notice in
the Federal Register of April 27, 2011 (76 FR 23520) entitled
``Periodic Review of Existing Regulations; Retrospective Review Under
E.O. 13563.'' In that notice, FDA announced that it was conducting a
review of existing regulations to determine, in part, whether they can
be made more effective in light of current public health needs and to
take advantage of, and support, advances in innovation that have
occurred since those regulations took effect. As part of this
initiative, FDA is updating outdated regulations as specified in this
rule.
    FDA's general biological products standards in part 610 are
intended to help ensure the safety, purity, and potency of biological
products administered to humans. The revision and removal of certain
general biological products standards are designed to update outdated
requirements and accommodate new and evolving manufacturing and control
testing technology. The rule provides manufacturers of biological
products with flexibility, as appropriate, to employ advances in
science and technology as they become available, without diminishing
public health protections.

A. Sections 610.20 and 610.21

    Standard preparations are generally used to perform lot release
testing or other specific product characterization assays. Under the
current standard preparations, Sec.  610.20, FDA requires specific
standard preparations to be used for a small number of the biological
products FDA regulates unless a modification is permitted under Sec.
610.9. Specifically, according to current Sec.  610.20 Standard
preparations, standard preparations, made available by CBER, are
required to be used in the testing of potency or opacity of certain
biological products, mostly biological products that were initially
licensed several decades ago. Most of these standard preparations
requirements are now obsolete, because either CBER no longer provides
the listed standard preparations, or the specific biological products
are no longer manufactured, or both. In addition, standard preparations
to help ensure the safety, purity, and potency of particular biological
products can often be obtained from sources other than CBER now,
including international sources, or can be

developed internally by the applicant. Thus, FDA believes it is no
longer necessary to specify CBER as the source of standard preparations
in Sec.  610.20. For these reasons, FDA is removing Sec.  610.20.
Consistent with current practice and BLAs, CBER will continue to make
and supply standard preparations when appropriate, as well as continue
to collaborate with external organizations in the development and
assessment of physical standard preparations for biological products.
    Under the current Sec.  610.21 Limits of potency, FDA specifies
minimal potency limits to be met for the antibodies and antigens
listed. However, most of the biological products subject to the
specified potency limits are no longer manufactured. In addition, for
those that are still manufactured, or for anyone wanting to manufacture
the listed products, FDA's updated practice is to have the potency
limit also be specified in the BLA. For this reason, FDA is removing
Sec.  610.21. As a result of removing Sec. Sec.  610.20 and 610.21,
part 610, subpart C is removed and reserved.
    In addition to sometimes being duplicative of information provided
in the BLA and unnecessarily restrictive regarding the source of
standard preparations, the codification by regulation of many of the
standard preparations and limits of potency for certain biological
products sometimes does not keep abreast of technological advances in
science related to manufacturing and testing. For many years, because
of the potential for impeding scientific progress, FDA has not codified
additional specific standard preparations and limits of potency for
licensed biological products, but instead the standards are established
in the BLA. Failure to conform to applicable standards established in
the license is grounds for revocation under Sec.  601.5(b)(1)(iv) (21
CFR 601.5(b)(1)(iv)). Notwithstanding the changes in this rule, FDA
will continue to require that each biological product meet standards to
assure that the product is safe, pure, and potent, and will continue to
require that each lot demonstrate conformance with the standards
applicable to that product (see Sec.  610.1) through appropriate
testing. Therefore, we expect that standard preparations and potency
limits will be established in the BLA and may be changed only in
accordance with regulations for reporting post-approval changes (see
Sec.  601.12). Furthermore, no lot of any licensed product may be
released by the manufacturer prior to the completion of tests for
conformity with standards applicable to such product (see Sec.  610.1).
    FDA is therefore amending its regulations to remove Sec. Sec.
610.20 and 610.21 because appropriate standard preparations and potency
limits for any listed product are specified during the licensing
process on a product specific basis. The removal of Sec. Sec.  610.20
and 610.21 will also increase regulatory flexibility by allowing
industry and FDA to more readily use and incorporate current scientific
technology and other appropriate reference materials in the manufacture
and regulation of licensed biological products.

B. Sections 610.50 and 610.53

    A biological product is expected to remain stable and retain its
identity, strength, quality, and purity for a period of time after
manufacture when it is properly stored. The dating period limitations
regulations provided at Sec. Sec.  610.50 and 610.53 specify how the
date of manufacture for biological products will be determined, when
the dating begins, and dating periods for certain biological products.
The existing Sec.  610.50 prescribes how the date of manufacture is
determined for biological products and relies in part upon Sec. Sec.
610.20 and 610.21 or official standards of potency (i.e., a specific
test method described in regulation). With the removal of Sec. Sec.
610.20 and 610.21 for reasons described in this document, FDA is
revising Sec.  610.50 to reflect FDA's updated approach to establishing
dates of manufacture.
    In addition, current Sec.  610.50(b) does not provide FDA or
applicants with flexibility to consider the variety of manufacturing
situations and technologies that exist today and which may occur in the
future. Since 1977, when the regulation was last amended, new methods
of manufacture and testing often associated with new biological
products have been developed. The revisions to Sec.  610.50 provided in
this direct final rule therefore allow additional manufacturing
activities other than those currently listed to be used to determine
the date of manufacture.
    Under the revised regulation, the date of manufacture must be
identified in the approved BLA. FDA recommends that applicants discuss
a suitable date of manufacture with FDA during late clinical
development and propose a date of manufacture in the BLA. We consider
the underlying science and manufacturing process testing methods in
determining the date of manufacture for each specific product. The
approved BLA will specify how the date of manufacture is determined. A
paragraph is being added, Sec.  610.50(c), specifying how the date of
manufacture for Whole Blood and blood components is determined. This
will assist in complying with the dating periods prescribed for Whole
Blood and blood components in the revised table in redesignated Sec.
610.53(b).
    The current table at Sec.  610.53(c) lists dating periods,
manufacturer's storage periods, and storage conditions for many
biological products. The table in Sec.  610.53(c) (which is
redesignated as Sec.  610.53(b)) is revised to remove products where
storage conditions and dating periods are established to help ensure
the continued safety, potency, and purity of each individual product,
based upon information submitted in the relevant BLA. The dating period
and storage conditions for these products will be identified in the
BLA. The table in Sec.  610.53(c) is also revised to delete those
products that are no longer manufactured. We are retaining those
products, specifically Whole Blood and blood components, whose dating
periods are based upon data relating to the anticoagulant or
preservative solution in the product, usage, clinical experience,
laboratory testing, or further processing. The list is updated to
include currently licensed Whole Blood and blood component products
with their applicable storage temperatures and dating periods.
    In listing the dating periods for Whole Blood and blood component
products, we took into account existing regulations, guidance
documents, package inserts for solutions used for manufacture or
storage of Whole Blood and blood components, and operator instruction
manuals for devices used in the manufacture of Whole Blood and blood
component products. Because we understand from these materials that
these dating periods are in current use, and because blood
establishments can request an exception under Sec.  640.120 (21 CFR
640.120), we do not anticipate significant objections to codifying this
information. Similarly, we are removing Sec.  610.53(d) because it is
duplicative of Sec.  640.120. In addition, we recognize that future
scientific understanding and new technology, such as the implementation
of pathogen reduction technology or the approval of extended storage
systems, could affect what dating periods would be necessary, as a
scientific matter, for Whole Blood and blood components. For this
reason, the rule allows for changes to the dating periods specified in
Sec.  610.53(b) when the dating period is otherwise specified in the
instructions for use by the blood collection, processing, and storage
system approved or cleared for such use by FDA.

    In conclusion, the amendments to the regulations provided by this
rule are designed to be consistent with updated practices in the
biological product industry and to remove unnecessary or outdated
requirements. FDA is taking this action as part of our continuing
effort to reduce the burden of unnecessary regulations on industry and
to revise outdated regulations to provide flexibility without
diminishing public health protection. Given the additional flexibility
provided by these revised regulations, FDA does not anticipate that
applicants for licensed biological products will need to revise
information in BLAs in order to conform to the revised regulations.

IV. Highlights of the Direct Final Rule

    FDA is revising the general biological products standards relating
to dating periods and removing certain standard preparations and limits
of potency. These changes are designed to remove unnecessary or
outdated requirements, and accommodate new and evolving technology and
testing capabilities without diminishing public health protections. FDA
is issuing these revisions directly as a final rule because the Agency
believes they include only noncontroversial amendments and FDA
anticipates no significant adverse comments.
    FDA is removing Sec.  610.20 because the standard preparations
listed are obsolete or no longer available; standard preparations to
ensure the safety, purity, and potency of a product can best be
determined on a product specific basis; and standard preparations may
be obtained from other sources. Applicants for biological product
licenses currently identify standard preparations in the BLA, and the
proposed standard preparations and their purpose are reviewed by FDA
during the regulatory process. The standard preparations may include
standard preparations developed by the applicant as well as appropriate
standard preparations that can be obtained from other sources.
Consistent with current practice, CBER will continue to make and supply
standard preparations when appropriate, as well as continue to
collaborate with external organizations in the development and
assessment of physical standard preparations for licensed biological
products.
    We are removing Sec.  610.21 because these potency limits are best
described in the BLAs on a product specific basis. Applicants for
biological product licenses already identify standards for potency to
help ensure the safety, purity, and potency of the product within their
BLA, and the proposed standards are reviewed by FDA during the
regulatory process. The use of a potency limit is suitably described in
the specific product's BLA and allows for its continued and appropriate
use in the absence of Sec.  610.21.
    We are revising Sec.  610.50 by making a minor amendment to the
section heading, removing the current language, redesignating Sec.
610.53(b) as Sec.  610.50(a) with edits, revising Sec.  610.50(b), and
adding new Sec.  610.50(c). Current Sec.  610.53(b), which applies to
all biological products, has been moved to Sec.  610.50(a) and edits
have been made for better organization and clarification. Section
610.50(b) is being revised and Sec.  610.50(c) is being added to
clarify how the date of manufacture is set for purposes of determining
the dating period for general biological products and for Whole Blood
and blood components, respectively.
    We are amending the section heading of Sec.  610.53 to reflect that
it only addresses dating periods for Whole Blood and blood components.
We are revising Sec.  610.53(a) since this section only applies to the
dating periods for Whole Blood and blood components. We are
redesignating Sec.  610.53(c) as Sec.  610.53(b) and revising the text
to provide an explanation on using the table and to correspond with 21
CFR 606.121(c)(7). We are revising the text and table to eliminate
those products for which storage periods, storage conditions, and
dating periods are better established by data submitted in the BLA, and
to delete those products which are no longer manufactured. The dating
period and storage conditions for these products are identified in the
BLA. We are including an updated list of Whole Blood and blood
component products with their applicable storage temperatures and
dating periods, which are based upon available information, including
data relating to the anticoagulant or preservative solution in the
product, usage, clinical experience, laboratory testing, or further
processing. The table contains a list of storage temperatures and
dating periods for Whole Blood and blood components that FDA has
reviewed and determined to be necessary to help ensure the safety,
potency, and purity of these products. In listing the dating periods
for the Whole Blood and blood component products, we took into account
existing guidance documents, package inserts for solutions used for
manufacture or storage of Whole Blood and blood components, and
operator instruction manuals for devices used in the manufacture of
Whole Blood and blood component products. We are redesignating Sec.
610.53(c) as Sec.  610.53(b) and removing all products regulated by
FDA's Center for Drug Evaluation and Research (CDER) from the table.
Finally, we are removing Sec.  610.53(d) because it is duplicative of
Sec.  640.120.

V. Legal Authority

    FDA is issuing this rule under the biological products provisions
of the PHS Act (42 U.S.C. 216, 262, 263, 263a and 264) and the drugs
and general administrative provisions of the FD&C Act (21 U.S.C. 321,
331, 351, 352, 353, 355, 360, 360c, 360d, 360h, 360i, 371, 372, 374,
and 381). Under these provisions of the PHS Act and the FD&C Act, we
have the authority to issue and enforce regulations designed to ensure
that biological products are safe, pure, and potent, and prevent the
introduction, transmission, and spread of communicable disease.

VI. Economic Analysis of Impacts

    We have examined the impacts of the direct final rule under
Executive Order 12866, Executive Order 13563, and 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 believe that this direct 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 direct final rule is removing regulations and
revising regulations to be consistent with updated practice, we certify
that this direct final 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 $144
million, using the most current (2014) Implicit Price Deflator for the
Gross Domestic Product. This direct final rule would not result

in an expenditure in any year that meets or exceeds this amount.

VII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.31(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. Federalism

    We have analyzed this direct 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.

IX. Paperwork Reduction Act of 1995

    This direct final rule contains collections of information that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3520). The
collections of information in part 610 have been approved under OMB
control number 0910-0338. The removal of Sec.  610.53(d) impacts OMB
control number 0910-0338. We are removing Sec.  610.53(d) because it is
duplicative of Sec.  640.120, which is also approved under the same
collection of information. While there is no net change in the burden
estimate, the current approved collection of information will be
updated to reflect this removal. The actions taken by this direct final
rule do not create a substantive or material modification to this
approved collection of information. Therefore, FDA concludes that OMB
has already approved this information collection and the requirements
in this document are not subject to additional review by OMB.

List of Subjects in 21 CFR Part 610

    Biologics, Labeling, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR part 610 is amended as follows:

PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS

0
1. The authority citation for part 610 continues to read as follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c,
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a,
264.

Subpart C [Removed and Reserved]

0
2. Remove and reserve subpart C, consisting of Sec. Sec.  610.20 and
610.21.

0
3. Revise Sec.  610.50 to read as follows:

Sec.  610.50  Date of manufacture for biological products.

    (a) When the dating period begins. The dating period for a product
must begin on the date of manufacture as described in paragraphs (b)
and (c) of this section. The dating period for a combination of two or
more products must be no longer than the dating period of the component
with the shortest dating period.
    (b) Determining the date of manufacture for biological products
other than Whole Blood and blood components. The date of manufacture
for biological products, other than Whole Blood and blood components,
must be identified in the approved biologics license application as one
of the following, whichever is applicable: The date of:
    (1) Potency test or other specific test as described in a biologics
license application or supplement to the application;
    (2) Removal from animals or humans;
    (3) Extraction;
    (4) Solution;
    (5) Cessation of growth;
    (6) Final sterile filtration of a bulk solution;
    (7) Manufacture as described in part 660 of this chapter; or
    (8) Other specific manufacturing activity described in a biologics
license application or supplement to the biologics license application.
    (c) Determining the date of manufacture for Whole Blood and blood
components. (1) The date of manufacture for Whole Blood and blood
components must be one of the following, whichever is applicable:
    (i) Collection date and/or time;
    (ii) Irradiation date;
    (iii) The time the red blood cell product was removed from frozen
storage for deglycerolization;
    (iv) The time the additive or rejuvenation solution was added;
    (v) The time the product was entered for washing or removing plasma
(if prepared in an open system);
    (vi) As specified in the instructions for use by the blood
collection, processing, and storage system approved or cleared for such
use by FDA; or
    (vii) As approved by the Director, Center for Biologics Evaluation
and Research, in a biologics license application or supplement to the
application.
    (2) For licensed Whole Blood and blood components, the date of
manufacture must be identified in the approved biologics license
application or supplement to the application.

0
4. Revise Sec.  610.53 to read as follows:

Sec.  610.53  Dating periods for Whole Blood and blood components.

    (a) General. Dating periods for Whole Blood and blood components
are specified in the table in paragraph (b) of this section.
    (b) Table of dating periods. In using the table in this paragraph,
when a product in column A is stored at the storage temperature
prescribed in column B, storage of a product must not exceed the dating
period specified in column C, unless a different dating period is
specified in the instructions for use by the blood collection,
processing and storage system approved or cleared for such use by FDA.
Container labels for each product must include the recommended storage
temperatures.

Whole Blood and Blood Components Storage Temperatures and Dating Periods
------------------------------------------------------------------------
              A                         B                     C
------------------------------------------------------------------------
           Product             Storage temperature      Dating period
------------------------------------------------------------------------
                               Whole Blood
------------------------------------------------------------------------
ACD, CPD, CP2D..............  Between 1 and 6       21 days from date of
                               [deg]C.               collection.

CPDA-1......................  do \1\..............  35 days from date of
                                                     collection.
------------------------------------------------------------------------
                             Red Blood Cells
------------------------------------------------------------------------
ACD, CPD, CP2D..............  Between 1 and 6       21 days from date of
                               [deg]C.               collection.
CPDA-1......................  do..................  35 days from date of
                                                     collection.
Additive solutions..........  do..................  42 days from date of
                                                     collection.
Open system.................  do..................  24 hours after
(e.g., deglycerolized,                               entering bag.
 washed).
Deglycerolized in closed      do..................  14 days after
 system with additive                                entering bag.
 solution added.
Irradiated..................  do..................  28 days from date of
                                                     irradiation or
                                                     original dating,
                                                     whichever is
                                                     shorter.
Frozen......................  -65 [deg]C or colder  10 years from date
                                                     of collection.
------------------------------------------------------------------------
                                Platelets
------------------------------------------------------------------------
Platelets...................  Between 20 and 24     5 days from date of
                               [deg]C.               collection.
Platelets...................  Other temperatures    As specified in the
                               according to          instructions for
                               storage bag           use by the blood
                               instructions.         collection,
                                                     processing and
                                                     storage system
                                                     approved or cleared
                                                     for such use by
                                                     FDA.
------------------------------------------------------------------------
                                 Plasma
------------------------------------------------------------------------
Fresh Frozen Plasma.........  -18 [deg]C or colder  1 year from date of
                                                     collection.
Plasma Frozen Within 24       do..................  1 year from date of
 Hours After Phlebotomy.                             collection.
Plasma Frozen Within 24       do..................  1 year from date of
 Hours After Phlebotomy Held                         collection.
 at Room Temperature Up To
 24 Hours After Phlebotomy.
Plasma Cryoprecipitate        do..................  1 year from date of
 Reduced.                                            collection.
Plasma......................  do..................  5 years from date of
                                                     collection.
Liquid Plasma...............  Between 1 and 6       5 days from end of
                               [deg]C.               Whole Blood dating
                                                     period.
Source Plasma (frozen         -20 [deg]C or colder  10 years from date
 injectable).                                        of collection.
Source Plasma Liquid          10 [deg]C or colder.  According to
 (injectable).                                       approved biologics
                                                     license
                                                     application.
Source Plasma                 Temperature           10 years from date
 (noninjectable).              appropriate for       of collection.
                               final product.
Therapeutic Exchange Plasma.  -20 [deg]C or colder  10 years from date
                                                     of collection.
------------------------------------------------------------------------
                          Cryoprecipitated AHF
------------------------------------------------------------------------
Cryoprecipitated AHF........  -18 [deg]C or colder  1 year from date of
                                                     collection of
                                                     source blood or
                                                     from date of
                                                     collection of
                                                     oldest source blood
                                                     in pre-storage
                                                     pool.
------------------------------------------------------------------------
                            Source Leukocytes
------------------------------------------------------------------------
Source Leukocytes...........  Temperature           In lieu of
                               appropriate for       expiration date,
                               final product.        the collection date
                                                     must appear on the
                                                     label.
------------------------------------------------------------------------
\1\ The abbreviation ``do.'' for ditto is used in the table to indicate
  that the previous line is being repeated.

    Dated: April 27, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-10385 Filed 5-3-16; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register Volume 80, Number 174 (Wednesday, September 9, 2015)]
[Rules and Regulations]
[Pages 54248-54252]
[FR Doc No: 2015-22030]

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

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2015-0143; FRL-9932-06]

Propylene Glycol Monomethyl Ether; Exemption from the Requirement
of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of propylene glycol monomethyl ether (PGME;
CAS No. 107-98-2) when used as an inert ingredient under 40 CFR 180.910
as a solvent in pesticide formulations which include pre-and post-
harvest use on crops. Syngenta Crop Protection submitted a petition to
EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting
establishment of an exemption from the requirement of a tolerance. This
regulation eliminates the need to establish a maximum permissible level
for residues of PGME.

DATES: This regulation is effective September 9, 2015. Objections and
requests for hearings must be received on or before November 9, 2015,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2015-0143, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334,
1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays. The telephone number for the Public
Reading Room is<PHONE_NUMBER>, and the telephone number for the OPP
Docket is<PHONE_NUMBER>. Please review the visitor instructions and
additional information about the docket available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Susan Lewis, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone
number:<PHONE_NUMBER>; email address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:

     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2015-0143 in the subject line on the first
page of your submission. All objections and requests for a hearing must
be in writing, and must be received by the Hearing Clerk on or before
November 9, 2015. Addresses for mail and hand delivery of objections
and hearing requests are provided in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing (excluding any Confidential Business Information (CBI)) for
inclusion in the public docket. Information not marked confidential
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without
prior notice. Submit the non-CBI copy of your objection or hearing
request, identified by docket ID number EPA-HQ-OPP-2015-0143, by one of
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be CBI or other
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC
20460-0001.
     Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.html.

Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at http://www.epa.gov/dockets.

II. Petition for Exemption

    In the Federal Register of April 6, 2015 (80 FR 18327) (FRL-9924-
00), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C.
346a, announcing the filing of a pesticide petition inert ingredient
(PP IN-10775) by Syngenta Crop Protection, P.O. Box 18300, Greensboro,
NC 27409, The petition requested that 40 CFR 180.910 be amended by
establishing an

exemption from the requirement of a tolerance for residues of PGME (CAS
No. 107-98-2) when used as an inert ingredient as a solvent in
pesticide formulations applied to pre- and post-harvest use on crops.
That document referenced a summary of the petition prepared by Syngenta
Crop Protection, the petitioner, which is available in the docket,
http://www.regulations.gov. There were no comments received in response
to the notice of filing.

III. Inert Ingredient Definition

    Inert ingredients are all ingredients that are not active
ingredients as defined in 40 CFR 153.125 and include, but are not
limited to, the following types of ingredients (except when they have a
pesticidal efficacy of their own): Solvents such as alcohols and
hydrocarbons; surfactants such as polyoxyethylene polymers and fatty
acids; carriers such as clay and diatomaceous earth; thickeners such as
carrageenan and modified cellulose; wetting, spreading, and dispersing
agents; propellants in aerosol dispensers; microencapsulating agents;
and emulsifiers. The term ``inert'' is not intended to imply
nontoxicity; the ingredient may or may not be chemically active.
Generally, EPA has exempted inert ingredients from the requirement of a
tolerance based on the low toxicity of the individual inert
ingredients.

IV. Aggregate Risk Assessment and Determination of Safety

    Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement for a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) of FFDCA defines
``safe'' to mean that ``there is a reasonable certainty that no harm
will result from aggregate exposure to the pesticide chemical residue,
including all anticipated dietary exposures and all other exposures for
which there is reliable information.'' This includes exposure through
drinking water and in residential settings, but does not include
occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to
give special consideration to exposure of infants and children to the
pesticide chemical residue in establishing a tolerance and to ``ensure
that there is a reasonable certainty that no harm will result to
infants and children from aggregate exposure to the pesticide chemical
residue. . . .''
    EPA establishes exemptions from the requirement of a tolerance only
in those cases where it can be clearly demonstrated that the risks from
aggregate exposure to pesticide chemical residues under reasonably
foreseeable circumstances will pose no appreciable risks to human
health. In order to determine the risks from aggregate exposure to
pesticide inert ingredients, the Agency considers the toxicity of the
inert in conjunction with possible exposure to residues of the inert
ingredient through food, drinking water, and through other exposures
that occur as a result of pesticide use in residential settings. If EPA
is able to determine that a finite tolerance is not necessary to ensure
that there is a reasonable certainty that no harm will result from
aggregate exposure to the inert ingredient, an exemption from the
requirement of a tolerance may be established.
    Consistent with FFDCA section 408(c)(2)(A), and the factors
specified in FFDCA section 408(c)(2)(B), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for PGME including exposure
resulting from the exemption established by this action. EPA's
assessment of exposures and risks associated with PGME follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered their
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. Specific information on the studies received and the nature
of the adverse effects caused by PGME as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies are discussed in this unit.
    PGME exhibits low acute toxicity by the oral, dermal, and
inhalation routes. PGME is not a skin sensitizer or skin irritant and
was only slightly irritating to the eye. In repeat dose inhalation
studies ranging from 11 days to six months in duration, NOAELs of 300
parts per million (ppm) and higher were seen in rats, mice, rabbits,
guinea pigs and monkeys. Effects observed included sedation, hepatic
changes and a decrease in body weight gain. Oral NOAELs of 459.5
milligram/kilogram/day (mg/kg/day) and 919 mg/kg/day were observed in
rat studies lasting 13 and 5 weeks, respectively. Observations included
central nervous system (CNS) effects at very high doses (above limit
dose of 1,000 mg/kg/day), enlarged livers and weight loss. In a
reproduction study conducted via the inhalation route, offspring
effects seen at 3,000 ppm appear to be related to decreased maternal
body weight and secondary to general toxicity and nutritional stress.
Decreased maternal body weight was also noted at the next lower dose.
NOAELs in this study were 300 ppm for adults and 1,000 ppm for
offspring. Studies with rats, mice, and rabbits showed that PGME was
not a developmental toxicant (two inhalation and three gavage studies).
Weight-of-evidence indicates that PGME is not genotoxic or
carcinogenic. In a 2-year bioassay, there were no statistically
significant increases in any tumor type in rats and mice.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA
identifies toxicological points of departure (POD) and levels of
concern to use in evaluating the risk posed by human exposure to the
pesticide. For hazards that have a threshold below which there is no
appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which the NOAEL and the LOAEL are identified.
Uncertainty/safety factors are used in conjunction with the POD to
calculate a safe exposure level--generally referred to as a population-
adjusted dose (PAD) or a reference dose (RfD)--and a safe margin of
exposure (MOE). For non-threshold risks, the Agency assumes that any
amount of exposure will lead to some degree of risk. Thus, the Agency
estimates risk in terms of the probability of an occurrence of the
adverse effect expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
    No acute adverse effect level has been selected for PGME. The
chronic NOAEL of 459.5 mg/kg/day was based on CNS effects at very high
doses, enlarged livers and weight loss in a 13 week oral study in rats.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to PGME, EPA considered

exposure under the proposed exemption from the requirement of a
tolerance. EPA assessed dietary exposures from PGME in food as follows:
    An acute dietary risk assessment was not conducted because no
endpoint of concern following a single exposure was identified in the
available studies. A chronic dietary exposure assessment was completed
and performed using the Dietary Exposure Evaluation Model DEEM-
FCID\TM\, Version 3.16.which includes food consumption information from
the U.S. Department of Agriculture's National Health and Nutrition
Examination Survey, ``What We Eat In America'', (NHANES/WWEIA). This
dietary survey was conducted from 2003 to 2008. In the absence of
actual residue data, the inert ingredient evaluation is based on a
highly conservative model that assumes that the residue level of the
inert ingredient would be no higher than the highest established
tolerance for an active ingredient on a given commodity. Implicit in
this assumption is that there would be similar rates of degradation
between the active and inert ingredient (if any) and that the
concentration of inert ingredient in the scenarios leading to these
highest of tolerances would be no higher than the concentration of the
active ingredient. The model assumes 100 percent crop treated (PCT) for
all crops and that every food eaten by a person each day has tolerance-
level residues. A complete description of the general approach taken to
assess inert ingredient risks in the absence of residue data is
contained in the memorandum entitled ``Alkyl Amines Polyalkoxylates
(Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water)
Dietary Exposure and Risk Assessments for the Inerts'' (D361707, S.
Piper, 2/25/09) and can be found at http://www.regulations.gov in
docket ID number EPA-HQ-OPP-2008-0738.
    2. Dietary exposure from drinking water. For the purpose of the
screening level dietary risk assessment to support this request for an
exemption from the requirement of a tolerance for PGME, a conservative
drinking water concentration value of 100 parts per billion (ppb) based
on screening level modeling was used to assess the contribution to
drinking water for the chronic dietary risk assessments for parent
compound. These values were directly entered into the dietary exposure
model.
    3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., textiles (clothing and diapers), carpets, swimming
pools, and hard surface disinfection on walls, floors, tables). The
highest exposures to consumers are likely to be associated with the use
of paints and varnishes that contain PGME with some small dermal
exposures possible. Inhalation exposures to relatively high
concentrations of PGME are believed to be self-limiting due to the
irritant effects of the chemical. Based on this residential exposure
assessment, exposure to PGME would be low (less than 2 mg/kg/day). This
level of exposure would be two orders of magnitude below that which
would be of concern for PGME.
    4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
    EPA has not found PGME to share a common mechanism of toxicity with
any other substances, and PGME does not appear to produce a toxic
metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has assumed that PGME does not have a
common mechanism of toxicity with other substances. For information
regarding EPA's efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the Food Quality
Protection Act Safety Factor (FQPA SF). In applying this provision, EPA
either retains the default value of 10X, or uses a different additional
safety factor when reliable data available to EPA support the choice of
a different factor.
    2. Prenatal and postnatal sensitivity. Studies in laboratory
animals indicate that PGME is not a developmental toxicant when
administered via inhalation or ingestion. Developmental studies
conducted in rats and rabbits with PGME administered via inhalation
showed no developmental toxicity in the rabbit and developmental delays
(delayed sternebral ossification) in the rat but only in the presence
of maternal toxicity. In oral developmental studies in rats, mice, and
rabbits, developmental delays were seen only in the rat fetuses at the
highest dose tested.
    3. Conclusion. Based on this information there is no concern for
increased sensitivity to infants and children to PGME when used as an
inert ingredient in pesticide formulations. For the same reason, a
safety factor analysis has not been used to assess risk to PGME and,
therefore, the additional safety factor for the protection of infants
and children is also unnecessary.
    EPA has determined that reliable data show the safety of infants
and children would be adequately protected if the FQPA SF were reduced
to 1X. That decision is based on the following findings:
    i. The toxicity database for PGME is complete.
    ii. There is a clinical signs of neurotoxicity observed at very
high oral doses. However, there are no concern at this time because the
clinical signs were observed at or above limit doses. Therefore there
is no need for a developmental neurotoxicity study or additional UFs to
account for neurotoxicity.
    iii. There is no evidence that PGME results in increased
susceptibility in in utero rats or rabbits in the prenatal
developmental studies or in young rats in the 2-generation reproduction
study.
    iv. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed based
on 100% CT and model estimates from the use of PGME in pesticidal
formulations resulting in chronic dietary exposure estimates for food
and drinking water below the Agency's level of concern. EPA made
conservative (protective) assumptions in the ground and surface water
modeling used to assess exposure to PGME in drinking water. EPA used
similarly conservative assumptions to assess postapplication exposure
of children as well as incidental oral exposure of toddlers. These
assessments will not underestimate the exposure and risks posed by
PGME.

E. Aggregate Risks and Determination of Safety

    Determination of safety section. EPA determines whether acute and
chronic dietary pesticide exposures are safe by comparing aggregate
exposure estimates to the acute PAD (aPAD) and chronic

PAD (cPAD). For linear cancer risks, EPA calculates the lifetime
probability of acquiring cancer given the estimated aggregate exposure.
Short-, intermediate-, and chronic-term risks are evaluated by
comparing the estimated aggregate food, water, and residential exposure
to the appropriate PODs to ensure that an adequate MOE exists.
    1. Acute risk. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. No adverse effect resulting from a single oral exposure
was identified and no acute dietary endpoint was selected. Therefore,
PGME is not expected to pose an acute risk.
    2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
PGME from food and water will utilize 15.4% of the cPAD for children 1-
2 years old, the population group receiving the greatest exposure.
Based on the explanation in this unit, regarding residential use
patterns, chronic residential exposure to residues of PGME is not
expected.
    3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).
    PGME may be used as an inert ingredient in pesticide products that
are registered for uses that could result in short-term residential
exposure, and the Agency has determined that it is appropriate to
aggregate chronic exposure through food and water with short-term
residential exposures to PGME.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water,
and residential exposures are below EPA's level of concern for PGME
based on highly conservative assumptions made regarding residential and
dietary exposures to PGME as described in Unit IV. Section C.
    4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level).
    PGME may be used as an inert ingredient in pesticide products that
are registered for uses that could result in intermediate-term
residential exposure, and the Agency has determined that it is
appropriate to aggregate chronic exposure through food and water with
short-term residential exposures to PGME.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined intermediate-term food,
water, and residential exposures are below EPA's level of concern for
PGME based on highly conservative assumptions made regarding
residential and dietary exposures to PGME as described in Unit IV.
Section C.
    5. Aggregate cancer risk for U.S. population. Based on the lack of
evidence of carcinogenicity in two adequate rodent carcinogenicity
studies, PGME is not expected to pose a cancer risk to humans.
    6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, or to infants and children from aggregate
exposure to PGME residues.

V. Other Considerations

A. Analytical Enforcement Methodology

    An analytical method is not required for enforcement purposes since
the Agency is establishing an exemption from the requirement of a
tolerance without any numerical limitation.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint United Nation Food
and Agriculture Organization/World Health Organization food standards
program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
    The Codex has not established a MRL for PGME.

VI. Conclusions

    Therefore, an exemption from the requirement of a tolerance is
established under 40 CFR 180.910 for PGME (CAS No. 107-98-2) when used
as an inert ingredient (as a solvent) in pesticide formulations applied
to crops, post-harvest.

VII. Statutory and Executive Order Reviews

    This action establishes a tolerance under FFDCA section 408(d) in
response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled ``Regulatory Planning and
Review'' (58 FR 51735, October 4, 1993). Because this action has been
exempted from review under Executive Order 12866, this action is not
subject to Executive Order 13211, entitled ``Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use'' (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
``Protection of Children from Environmental Health Risks and Safety
Risks'' (62 FR 19885, April 23, 1997). This action does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it require any
special considerations under Executive Order 12898, entitled ``Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations'' (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis
of a petition under FFDCA section 408(d), such as the tolerance in this
final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.), do not apply.
    This action directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled ``Federalism'' (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
``Consultation and Coordination with Indian Tribal Governments'' (65 FR
67249, November 9, 2000) do not apply to this action. In addition, this
action does not impose any enforceable duty or contain any unfunded
mandate as

described under Title II of the Unfunded Mandates Reform Act (UMRA) (2
U.S.C. 1501 et seq.).
    This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act (NTTAA) (15 U.S.C. 272 note).

VIII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.),
EPA will submit a report containing this rule and other required
information to the U.S. Senate, the U.S. House of Representatives, and
the Comptroller General of the United States prior to publication of
the rule in the Federal Register. This action is not a ``major rule''
as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

    Dated: August 17, 2015.
Susan Lewis,
Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority:  21 U.S.C. 321(q), 346a and 371.

0
2. In Sec.  180.910, add alphabetically the following inert ingredient
to the table to read as follows:

Sec.  180.910  Inert ingredients used pre- and post-harvest; exemptions
from the requirement of a tolerance.

* * * * *

------------------------------------------------------------------------
        Inert ingredients                Limits               Uses
------------------------------------------------------------------------

                              * * * * * * *
Propylene glycol monomethyl       none...............  solvent.
 ether (CAS No. 107-98-2).

                              * * * * * * *
------------------------------------------------------------------------

[FR Doc. 2015-22030 Filed 9-8-15; 8:45 am]
 BILLING CODE 6560-50-P