[Federal Register Volume 88, Number 225 (Friday, November 24, 2023)]
[Rules and Regulations]
[Pages 82252-82255]
[FR Doc No: 2023-25852]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 71

[Docket No. FAA-2023-1329; Airspace Docket No. 23-AEA-2]
RIN 2120-AA66

Establishment of United States Area Navigation (RNAV) Routes T-
440, T-455, T-457, T-459, and T-476, and Amendment of RNAV Routes T-
358, T-416, and T-445; Eastern United States

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Final rule.

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SUMMARY: This action establishes United States Area Navigation (RNAV)
routes T-440, T-455, T-457, T-459, and T-476, and amends RNAV routes T-
358, T-416, and T-445 in support of the FAA's Very High Frequency
Omnidirectional Range (VOR) Minimum Operational Network (MON) Program.
The purpose is to enhance the efficiency of the National Airspace
System (NAS) by transitioning from ground-based navigation aids to a
satellite-based navigation system.

DATES: Effective date 0901 UTC, January 25, 2024. The Director of the
Federal Register approves this incorporation by reference action under
1 CFR part 51, subject to the annual revision of FAA Order JO 7400.11
and publication of conforming amendments.

ADDRESSES: A copy of the Notice of Proposed Rulemaking (NPRM), all
comments received, this final rule, and all background material may be
viewed online at www.regulations.gov using the FAA Docket number.
Electronic retrieval help and guidelines are available on the website.
It is available 24 hours each day, 365 days each year.
    FAA Order JO 7400.11H, Airspace Designations and Reporting Points,
and subsequent amendments can be viewed online at www.faa.gov/air_traffic/publications/. You may also contact the Rules and
Regulations Group, Office of Policy, Federal Aviation Administration,
800 Independence Avenue SW, Washington, DC 20591; telephone: (202) 267-
8783.

FOR FURTHER INFORMATION CONTACT: Brian Vidis, Rules and Regulations
Group, Office of Policy, Federal Aviation Administration, 800
Independence Avenue SW, Washington, DC 20591; telephone: (202) 267-
8783.

SUPPLEMENTARY INFORMATION:

Authority for This Rulemaking

    The FAA's authority to issue rules regarding aviation safety is
found in Title 49 of the United States Code. Subtitle I, Section 106
describes the authority of the FAA Administrator. Subtitle VII,
Aviation Programs, describes in more detail the scope of the agency's
authority. This rulemaking is promulgated under the authority described
in Subtitle VII, Part A, Subpart I, Section 40103. Under that section,
the FAA is charged with prescribing regulations to assign the use of
the airspace necessary to ensure the safety of aircraft and the
efficient use of airspace. This regulation is within the scope of that
authority as it will expand the availability of RNAV routing in the
eastern United States and improve the efficient flow of air traffic
within the NAS by lessening the dependency on ground-based navigation.

History

    The FAA published a NPRM for Docket No. FAA-2023-1329 in the
Federal Register (88 FR 37177; June 7, 2023), proposing to establish 5
low-altitude RNAV routes and amend 3 low-altitude RNAV routes in
support of transitioning the NAS from a ground-based to a satellite-
based navigation. Interested parties were invited to participate in
this rulemaking effort by submitting written comments on the proposal
to the FAA. No comments were received.

Differences From the NPRM

    Subsequent to the NPRM, a minor amendment was made to the
geographic coordinates for the GABRS, NJ, Waypoint (WP). The GABRS, NJ,
WP was moved 1.25 nautical miles (NM) south from its proposed location
due to required route geometry and does not substantively alter the
proposed route of T-457. The GABRS, NJ, WP is updated from ``lat.
39[deg]38'15.91'' N, long. 075[deg]04'15.96'' W'' to ``lat.
39[deg]37'14.11'' N, long. 075[deg]03'20.87'' W.''

Incorporation by Reference

    United States Area Navigation Routes are published in paragraph
6011 of FAA Order JO 7400.11, Airspace Designations and Reporting
Points, which is incorporated by reference in 14 CFR 71.1 on an annual
basis. This document amends the current version of that order, FAA
Order JO 7400.11H, dated August 11, 2023, and effective September 15,
2023. FAA Order JO 7400.11H is publicly available as listed in the
ADDRESSES section of this document. These amendments will be published
in the next update to FAA Order JO 7400.11.

    FAA Order JO 7400.11H lists Class A, B, C, D, and E airspace areas,
air traffic service routes, and reporting points.

The Rule

    This action amends 14 CFR part 71 by establishing RNAV routes T-
440, T-455, T-457, T-459, and T-476, and amend RNAV routes T-358, T-
416, and T-445 in the eastern United States to support the VOR MON
Program and the transition of the NAS from ground-based navigation to
satellite-based navigation. The routes are described below.
    T-358: T-358 is an amended route that extends to the northeast
between the AVALO, NJ, WP and the Augusta, ME (AUG), VOR/Distance
Measuring Equipment (VOR/DME). T-358 overlays VOR Federal airway V-268
between the AVALO WP and the BURDY, MA, WP; and between the LBSTA, MA,
WP and the Augusta VOR/DME. The MOYRR, MD, WP name is replaced by the
HAMRR, MD, WP at the same location due to similar sounding WP names.
    T-416: T-416 is an amended route that moves the RIDNG, NJ, WP 1.83
NM southwest of its current location to align with a standard
instrument departure procedure.
    T-440: T-440 is a new route that extends from the Elmira, NY (ULW),
VOR/DME to the TALLI, PA, WP. T-440 overlays VOR Federal airway V-147
from the Elmira VOR/DME to the Wilkes-Barre, PA (LVZ), VOR/Tactical Air
Navigation (VORTAC); and VOR Federal airway V-116 from the Wilkes-Barre
VORTAC to the TALLI WP.
    T-445: T-445 is an amended route that removes the segment from the
Westminster, ME (EMI), VORTAC to the Harrisburg, PA (HAR), VORTAC.
Further, the Elmira, NY (ULW), VOR/DME replaces the STUBN, NY, WP.
    T-455: T-455 is a new route that extends from the Allentown, PA
(FJC), VORTAC to the WIGGZ, PA, WP. T-455 overlays VOR Federal airway
V-613 from the Allentown VORTAC to the Wilkes-Barre, PA (LVZ), VORTAC,
and overlays VOR Federal airway V-188 from the Wilkes-Barre VORTAC to
the Slate Run, PA (SLT), VORTAC.
    T-457: T-457 is a new route that extends from the JIIMS, NJ, WP to
the BOOCH, PA, WP.
    T-459: T-459 is a new route that extends from the JIIMS, NJ, WP to
the DOGGR, PA, WP.
    T-476: T-476 is a new route that extends from the TUNDR, MD, WP to
the WIMKA, NJ, WP.

Regulatory Notices and Analyses

    The FAA has determined that this regulation only involves an
established body of technical regulations for which frequent and
routine amendments are necessary to keep them operationally current.
It, therefore: (1) is not a ``significant regulatory action'' under
Executive Order 12866; (2) is not a ``significant rule'' under DOT
Regulatory Policies and Procedures (44 FR 11034; February 26, 1979);
and (3) does not warrant preparation of a regulatory evaluation as the
anticipated impact is so minimal. Since this is a routine matter that
only affects air traffic procedures and air navigation, it is certified
that this rule, when promulgated, does not have a significant economic
impact on a substantial number of small entities under the criteria of
the Regulatory Flexibility Act.

Environmental Review

    The FAA has determined that this action of establishing RNAV routes
T-440, T-455, T-457, T-459, and T-476, and amend RNAV routes T-358, T-
416, and T-445 in the eastern United States, to provide additional RNAV
routing within the NAS in support of transitioning it from ground-based
to satellite-based navigation, qualifies for categorical exclusion
under the National Environmental Policy Act (42 U.S.C. 4321 et seq.)
and its implementing regulations at 40 CFR part 1500, and in accordance
with FAA Order 1050.1F, ``Environmental Impacts: Policies and
Procedures,'' paragraph 5-6.5a, which categorically excludes from
further environmental impact review rulemaking actions that designate
or modify classes of airspace areas, airways, routes, and reporting
points (see 14 CFR part 71, Designation of Class A, B, C, D, and E
Airspace Areas; Air Traffic Service Routes; and Reporting Points); and
paragraph 5-6.5b, which categorically excludes from further
environmental impact review ``Actions regarding establishment of jet
routes and Federal airways (see 14 CFR 71.15, Designation of jet routes
and VOR Federal airways) . . .''. As such, this airspace action is not
expected to cause any potentially significant environmental impacts. In
accordance with FAA Order 1050.1F, paragraph 5-2 regarding
Extraordinary Circumstances, the FAA has reviewed this action for
factors and circumstances in which a normally categorically excluded
action may have a significant environmental impact requiring further
analysis. Accordingly, the FAA has determined that no extraordinary
circumstances exist that warrant preparation of an environmental
assessment or environmental impact study.

Lists of Subjects in 14 CFR Part 71

    Airspace, Incorporation by reference, Navigation (air).

The Amendment

    In consideration of the foregoing, the Federal Aviation
Administration amends 14 CFR part 71 as follows:

PART 71--DESIGNATION OF CLASS A, B, C, D, AND E AIRSPACE AREAS; AIR
TRAFFIC SERVICE ROUTES; AND REPORTING POINTS

0
1. The authority citation for 14 CFR part 71 continues to read as
follows:

    Authority:  49 U.S.C. 106(f), 106(g), 40103, 40113, 40120; E.O.
10854, 24 FR 9565, 3 CFR, 1959-1963 Comp., p.389.

Sec.  71.1  [Amended]

0
2. The incorporation by reference in 14 CFR 71.1 of FAA Order JO
7400.11H, Airspace Designations and Reporting Points, dated August 11,
2023, and effective September 15, 2023, is amended as follows:

Paragraph 6011 United States Area Navigation Routes.

* * * * *

T-358 Martinsburg, WV (MRB) to Augusta, ME (AUG) [Amended]

Martinsburg, WV (MRB)                           VORTAC                         (Lat. 39[deg]23'08.06'' N, long. 077[deg]50'54.08'' W)
CPTAL, MD                                       WP                             (Lat. 39[deg]32'16.02'' N, long. 077[deg]41'55.65'' W)
TWIRK, MD                                       WP                             (Lat. 39[deg]34'36.70'' N, long. 077[deg]12'44.75'' W)
HAMRR, MD                                       WP                             (Lat. 39[deg]30'03.42'' N, long. 076[deg]56'10.84'' W)
DANII, MD                                       WP                             (Lat. 39[deg]17'46.42'' N, long. 076[deg]42'19.36'' W)
OBWON, MD                                       WP                             (Lat. 39[deg]11'54.69'' N, long. 076[deg]32'04.84'' W)
SWANN, MD                                       WP                             (Lat. 39[deg]09'05.28'' N, long. 076[deg]13'43.94'' W)
Smyrna, DE (ENO)                                VORTAC                         (Lat. 39[deg]13'53.93'' N, long. 075[deg]30'57.49'' W)
AVALO, NJ                                       WP                             (Lat. 39[deg]16'54.52'' N, long. 074[deg]30'50.75'' W)
MANTA, NJ                                       WP                             (Lat. 39[deg]54'07.01'' N, long. 073[deg]32'31.63'' W)
ORCHA, NY                                       WP                             (Lat. 40[deg]54'55.46'' N, long. 072[deg]18'43.64'' W)

Sandy Point, RI (SEY)                           VOR/DME                        (Lat. 41[deg]10'02.77'' N, long. 071[deg]34'33.91'' W)
BURDY, MA                                       WP                             (Lat. 41[deg]57'19.14'' N, long. 070[deg]57'07.45'' W)
HAVNS, OA                                       WP                             (Lat. 42[deg]17'55.00'' N, long. 070[deg]27'42.00'' W)
GRGIO, MA                                       WP                             (Lat. 42[deg]35'09.36'' N, long. 070[deg]33'54.40'' W)
LBSTA, MA                                       WP                             (Lat. 42[deg]48'00.00'' N, long. 070[deg]36'48.70'' W)
MESHL, ME                                       WP                             (Lat. 43[deg]19'12.07'' N, long. 070[deg]09'48.03'' W)
Augusta, ME (AUG)                               VOR/DME                        (Lat. 44[deg]19'12.07'' N, long. 069[deg]47'47.63'' W)

                                                                     * * * * * * *
T-416 Smyrna, NJ (ENO) to PREPI, OA [Amended]

Smyrna, NJ (ENO)                                VORTAC                         (Lat. 39[deg]13'53.93'' N, long. 075[deg]30'57.49'' W)
TEBEE, NJ                                       WP                             (Lat. 39[deg]30'13.97'' N, long. 075[deg]19'37.19'' W)
LULOO, NJ                                       WP                             (Lat. 39[deg]36'35.96'' N, long. 075[deg]12'57.43'' W)
RIDNG, NJ                                       WP                             (Lat. 39[deg]43'56.08'' N, long. 075[deg]07'12.86'' W)
ALBEK, NJ                                       WP                             (Lat. 39[deg]46'39.92'' N, long. 074[deg]54'25.99'' W)
Coyle, NJ (CYN)                                 VORTAC                         (Lat. 39[deg]49'02.42'' N, long. 074[deg]25'53.85'' W)
PREPI, OA                                       WP                             (Lat. 39[deg]48'41.06'' N, long. 073[deg]15'40.70'' W)

                                                                     * * * * * * *
T-440 Elmira, NY (ULW) to TALLI, PA [New]

Elmira, NY (ULW)                                VOR/DME                        (Lat. 42[deg]05'38.96'' N, long. 077[deg]01'29.30'' W)
WLKES, PA                                       WP                             (Lat. 41[deg]16'22.57'' N, long. 075[deg]41'21.60'' W)
TALLI, PA                                       WP                             (Lat. 41[deg]19'01.60'' N, long. 075[deg]06'43.17'' W)

                                                                     * * * * * * *
T-445 Harrisburg, PA (HAR) to AIRCO, NY [Amended]

Harrisburg, PA (HAR)                            VORTAC                         (Lat. 40[deg]18'08.06'' N, long. 077[deg]04'10.41'' W)
Selinsgrove, PA (SEG)                           VOR/DME                        (Lat. 40[deg]47'27.09'' N, long. 076[deg]53'02.55'' W)
LYKOM, PA                                       WP                             (Lat. 41[deg]20'18.75'' N, long. 076[deg]46'30.30'' W)
Elmira, NY (ULW)                                VOR/DME                        (Lat. 42[deg]05'38.96'' N, long. 077[deg]01'29.32'' W)
BEEPS, NY                                       WP                             (Lat. 42[deg]49'13.26'' N, long. 076[deg]59'04.84'' W)
Rochester, NY (ROC)                             VOR/DME                        (Lat. 43[deg]07'04.65'' N, long. 077[deg]40'22.06'' W)
AIRCO, NY                                       WP                             (Lat. 43[deg]12'36.66'' N, long. 078[deg]28'57.00'' W)

                                                                     * * * * * * *
T-455 Allentown, PA (FJC) to WIGGZ, PA [New]

Allentown, PA (FJC)                             VORTAC                         (Lat. 40[deg]43'36.07'' N, long. 075[deg]27'17.08'' W)
WLKES, PA                                       WP                             (Lat. 41[deg]16'22.57'' N, long. 075[deg]41'21.60'' W)
LYKOM, PA                                       WP                             (Lat. 41[deg]20'18.75'' N, long. 076[deg]46'30.30'' W)
WIGGZ, PA                                       WP                             (Lat. 41[deg]30'51.00'' N, long. 077[deg]58'52.00'' W)

                                                                     * * * * * * *
T-457 JIMMS, NJ to BOOCH, PA [New]

JIIMS, NJ                                       WP                             (Lat. 39[deg]32'15.62'' N, long. 074[deg]58'01.72'' W)
GABRS, NJ                                       WP                             (Lat. 39[deg]37'14.11'' N, long. 075[deg]03'20.87'' W)
RIDNG, NJ                                       WP                             (Lat. 39[deg]43'56.08'' N, long. 075[deg]07'12.86'' W)
BOJID, PA                                       WP                             (Lat. 40[deg]03'20.87'' N, long. 075[deg]12'16.25'' W)
BOOCH, PA                                       WP                             (Lat. 40[deg]14'09.24'' N, long. 075[deg]16'08.52'' W)

                                                                     * * * * * * *
T-459 JIIMS, NJ to DOGGR, PA [New]

JIIMS, NJ                                       WP                             (Lat. 39[deg]32'15.62'' N, long. 074[deg]58'01.72'' W)
LULOO, NJ                                       WP                             (Lat. 39[deg]36'35.96'' N, long. 075[deg]12'57.43'' W)
DOGGR, PA                                       WP                             (Lat. 40[deg]08'12.25'' N, long. 075[deg]27'07.50'' W)

                                                                     * * * * * * *
T-476 TUNDR, MD to WIMKA, NJ [New]

TUNDR, MD                                       WP                             (Lat. 38[deg]44'37.73'' N, long. 076[deg]15'38.97'' W)
FILRO, MD                                       WP                             (Lat. 38[deg]57'51.42'' N, long. 075[deg]56'45.51'' W)
TWANE, MD                                       WP                             (Lat. 39[deg]10'57.10'' N, long. 075[deg]57'34.19'' W)
EYEUP, MD                                       WP                             (Lat. 39[deg]18'30.83'' N, long. 075[deg]51'56.10'' W)
COHLE, DE                                       WP                             (Lat. 39[deg]20'26.55'' N, long. 075[deg]34'36.79'' W)
WIMKA, NJ                                       WP                             (Lat. 39[deg]25'22.02'' N, long. 075[deg]08'32.67'' W)

* * * * *

    Issued in Washington, DC, on November 16, 2023.
Karen L. Chiodini,
Acting Manager, Rules and Regulations Group.
[FR Doc. 2023-25852 Filed 11-22-23; 8:45 am]
BILLING CODE 4910-13-P


From:
Jones, DonnaLee<EMAIL_ADDRESS>Sent:
Thursday, November 12, 2015 1:36 PM
To:
David Ailor<EMAIL_ADDRESS>Cc:
Raymond, Gabrielle<EMAIL_ADDRESS>French, Chuck<EMAIL_ADDRESS>McLamb, Marguerite<EMAIL_ADDRESS>Subject:
RE: Donna Lee: Can you send me the latest versions of ICR Enclosures 1 and 2? DCA

Hi. Sorry it took so long today, but I wanted these to be up-to-date for our purposes also. Nothing has changed in the enclosures from technical perspective from the last time you saw the Enclosure 2 tables and also Enclosure 1. However, I've updated the schedule in both documents, which I believe I sent you in an email, and the methods in the body of Enclosure 2 now match the revised Table 1-B, which you also have seen. I also just received the CBI project # so I added that.

I wanted to send you all before the meeting the examples of the data sheet files which we will be providing for facilities to use to respond to the ICR. I've labelled these "Examples", since as the ICR changes so will the data sheets. We are looking at whether the Enclosure 2 data sheets are sufficient for the methods recently added, so that revision will happen soon.
_____________________________________________________________
Regards,
Donna Lee Jones, Ph.D.
Senior Technical Advisor, Metals Sector
U. S. Environmental Protection Agency
Office of Air Quality Planning and Standards
Sector Policies and Programs Division / Metals & Inorganic Chemicals Group (D 243-02)
Research Triangle Park, NC  27711  Tele:<PHONE_NUMBER>  Fax<PHONE_NUMBER>
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
"Reasonableness never fails to be appreciated."  - anon.

<< EXAMPLE-Coke-Enclosure-1-Questionnaire Answer File_Part_I-X_10.6.15.xlsx >>
<< EXAMPLE-Master-Emission Test Template-11-12-DLJ.xlsx >>
<< new-CLEAN-EPA-V4-11-12-15-Coke ICR-Enclosure 2-DRAFT-8-20-15-DLJ.doc >>
<< CLEAN-EPA-V2-11-12-15-Coke ICR Intro-Enclosure I-DRAFT-08-20-15.docx >>

From: David Ailor<EMAIL_ADDRESS>Sent: Wednesday, November 11, 2015 1:18 PM
To: Jones, DonnaLee<EMAIL_ADDRESS>Subject: Donna Lee: Can you send me the latest versions of ICR Enclosures 1 and 2? DCA

David C. Ailor, P.E.
President
American Coke and Coal Chemicals Institute
25 Massachusetts Avenue, N.W.
Suite 800
Washington, D.C. 20001
Phone:<PHONE_NUMBER>
eFax.:<PHONE_NUMBER>
<EMAIL_ADDRESS>www.accci.org


[Federal Register Volume 76, Number 47 (Thursday, March 10, 2011)]
[Rules and Regulations]
[Pages 13083-13084]
[FR Doc No: 2011-5057]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 71

[Docket No. FAA-2011-0024; Airspace Docket No. 11-ASW-1]
RIN 2120-AA66

Amendment to VOR Federal Airway V-358; TX

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Final rule; technical amendment.

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SUMMARY: This action amends a final rule published by the FAA in the
Federal Register, that inadvertently extended VOR Federal airway V-358
to the wrong end point. This action reflects the correct end point and
coincides with the FAA's aeronautical database.

DATES: Effective date 0901 UTC, May 5, 2011. The Director of the
Federal Register approves this incorporation by reference action under
1 CFR part 51, subject to the annual revision of FAA Order 7400.9 and
publication of conforming amendments.

FOR FURTHER INFORMATION CONTACT: Colby Abbott, Airspace, Regulations
and ATC Procedures Group, Office of Airspace Services, Federal Aviation
Administration, 800 Independence Avenue, SW., Washington, DC 20591;
telephone:<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Background

    On October 16, 2000, the FAA published a final rule in the Federal
Register amending thirteen Federal airways in the vicinity of Dallas/
Fort Worth, TX (65 FR 61087). That action simplified the airway
structure and enhanced the management of aircraft operations in the
area. VOR Federal airway V-358 was one of the thirteen airways included
in the rule, changing its end point from Will Rogers, OK to Waco, TX.
    On October 2, 2001, the FAA published a final rule in the Federal
Register realigning a portion of V-358 to prevent instrument flight
rules (IFR) aircraft navigating on the airway from encroaching on the
newly established Prohibited Area 49 (P-49), Crawford, TX (66 FR
50101). The realignment around P-49 was necessary to assist the United
States Secret Service in providing security for the President of the
United States and preventing IFR aircraft from flying through P-49.
However, the airway description contained in the rule inadvertently
extended the V-358 end

point from Waco, TX, back to Will Rogers, OK.
    On October 26, 2009, the FAA published a third final rule in the
Federal Register amending the V-358 airway description (74 FR 54896).
That rule renamed the Lampasas, TX, VHF omnidirectional range/tactical
air navigation (VORTAC) to Gooch Springs, TX, VORTAC. This was done to
avoid confusion since the Lampasas VORTAC and Lampasas Airport both
shared the same name and location identifier, but were not co-located.
Again, the airway end point error was over looked and V-358 was
published with an end point as Will Rogers, OK, instead of Waco, TX.

The Rule

    This action amends Title 14 Code of Federal Regulations (14 CFR)
part 71 by correcting the end point in the legal description of V-358
from Will Rogers, OK, to Waco, TX. The rule reflects the end point
coinciding with the FAA's aeronautical database.
    Since this is an administrative change, and does not affect the
dimensions, altitude, or operating requirements of that airspace,
notice and public procedure under 5 U.S.C. 553(b) are unnecessary.
    The FAA has determined that this regulation only involves an
established body of technical regulations for which frequent and
routine amendments are necessary to keep them operationally current.
Therefore, this regulation: (1) Is not a ``significant regulatory
action'' under Executive Order 12866; (2) is not a ``significant rule''
under DOT Regulatory Policies and Procedures (44 FR 11034; February 26,
1979); and (3) does not warrant preparation of a Regulatory Evaluation
as the anticipated impact is so minimal. Since this is a routine matter
that will only affect air traffic procedures and air navigation, it is
certified that this rule, when promulgated, will not have a significant
economic impact on a substantial number of small entities under the
criteria of the Regulatory Flexibility Act.
    Domestic VOR Federal airways are published in paragraph 6010(a) of
FAA Order 7400.9U, dated August 18, 2010, and effective September 15,
2010, which is incorporated by reference in 14 CFR 71.1. The domestic
Federal VOR airway listed in this document will be published
subsequently in the Order.

Environmental Review

    There are no changes to the lateral limits. Therefore, the FAA has
determined that this action is not subject to environmental assessments
and procedures in accordance with FAA Order 1050.1E, Policies and
Procedures for Considering Environmental Impacts, and the National
Environmental Policy Act.

List of Subjects in 14 CFR Part 71

    Airspace, Incorporation by reference, Navigation (air).

Adoption of the Amendment

    In consideration of the foregoing, the Federal Aviation
Administration amends 14 CFR part 71 as follows:

PART 71--DESIGNATION OF CLASS A, B, C, D, AND E AIRSPACE AREAS; AIR
TRAFFIC SERVICE ROUTES; AND REPORTING POINTS

0
1. The authority citation for 14 CFR part 71 continues to read as
follows:

    Authority:  49 U.S.C. 106(g), 40103, 40113, 40120; E.O. 10854,
24 FR 9565, 3 CFR, 1959-1963 Comp., p. 389.

Sec.  71.1  [Amended]

0
2. The incorporation by reference in 14 CFR 71.1 of the Federal
Aviation Administration Order 7400.9U, Airspace Designations and
Reporting Points, dated August 18, 2010, and effective September 15,
2010, is amended as follows:

Paragraph 6010(a) Domestic VOR federal airways.

* * * * *

V-358 [Amended]

From San Antonio, TX, via Stonewall, TX; Gooch Springs, TX; INT
Gooch Springs 041[deg] and Waco, TX, 280[deg] radials; to Waco.
* * * * *

    Issued in Washington, DC, on March 2, 2011.
Edith V. Parish,
Manager, Airspace, Regulations and ATC Procedures Group.
[FR Doc. 2011-5057 Filed 3-9-11; 8:45 am]
BILLING CODE 4910-13-P


[Federal Register: July 28, 2008 (Volume 73, Number 145)]
[Notices]
[Page 43819-43820]
[DOCID:fr28jy08-134]

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DEPARTMENT OF TRANSPORTATION

Federal Motor Carrier Safety Administration

[Docket No. FMCSA-99-5748, FMCSA-99-6480, FMCSA-01-11426, FMCSA-02-
11714, FMCSA-05-23099, FMCSA-06-23773]

Qualification of Drivers; Exemption Renewals; Vision

AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT.

ACTION: Notice of final disposition.

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

SUMMARY: FMCSA previously announced its decision to renew the
exemptions from the vision requirement in the Federal Motor Carrier
Safety Regulations for 17 individuals. FMCSA has statutory authority to
exempt individuals from the vision requirement if the exemptions
granted will not compromise safety. The Agency has reviewed the comment
submitted in response to the previous announcement and concluded that
granting these exemptions will provide a level of safety that will be
equivalent to, or greater than, the level of safety maintained without
the exemptions for these commercial motor vehicle (CMV) drivers.

FOR FURTHER INFORMATION CONTACT: Dr. Mary D. Gunnels, Director, Medical
Programs,<PHONE_NUMBER><EMAIL_ADDRESS>FMCSA, Department of
Transportation, 1200 New Jersey Avenue, SE., Room W64-224, Washington,
DC 20590-0001. Office hours are from 8:30 a.m. to 5 p.m. Monday through
Friday, except Federal holidays.

SUPPLEMENTARY INFORMATION:

Electronic Access

    You may see all the comments online through the Federal Document
Management System (FDMS) at http://www.regulations.gov.

Background

    Under 49 U.S.C. 31136(e) and 31315, FMCSA may grant an exemption
for a 2-year period if it finds ``such exemption would likely achieve a
level of safety that is equivalent to, or greater than, the level that
would be achieved absent such exemption.'' The statute also allows the
Agency to renew exemptions at the end of the 2-year period. The notice
was published on May 12, 2008 (FR 73 27017), and the comment period
ended on June 11, 2008.

Discussion of Comments

    FMCSA received one comment in this proceeding. The comment was
considered and discussed below.
    Advocates for Highway and Auto Safety (Advocates) expressed
opposition to FMCSA's policy to grant exemptions from the FMCSR,
including the driver qualification standards. Specifically, Advocates:
(1) Objects to the manner in which FMCSA presents driver information to
the public and makes safety determinations; (2) objects to the Agency's
reliance on conclusions drawn from the vision waiver program; (3)
claims the Agency has misinterpreted statutory language on the granting
of exemptions (49 U.S.C. 31136(e) and 31315); and finally (4) suggests
that a 1999 Supreme Court decision affects the legal validity of vision
exemptions.
    The issues raised by Advocates were addressed at length in 64 FR
51568 (September 23, 1999), 64 FR 66962 (November 30, 1999), 64 FR
69586 (December 13, 1999), 65 FR 159 (January 3, 2000), 65 FR 57230
(September 21, 2000), and 66 FR 13825 (March 7, 2001). We will not
address these points again here, but refer interested parties to those
earlier discussions.

Conclusion

    The Agency has not received any adverse evidence on any of these
drivers that indicates that safety is being compromised. Based upon its
evaluation of the 17 renewal applications, FMCSA renews the Federal
vision exemptions for Guy M. Alloway, Joe W. Brewer, James D. Coates,
Donald D. Dunphy, James W. Ellis, IV., John E. Engstad, David W.
Grooms, Walter D. Hague, Jr., David A. Inman, Alfred G. Jeffus, Teddie
W. King, Aaron C. Lougher, Lawrence C. Moody, Stanley W. Nunn, Roberto
G. Serna, Bobby C. Spencer, and Kevin R. Stoner.

    In accordance with 49 U.S.C. 31136(e) and 31315, each renewal
exemption will be valid for 2 years unless revoked earlier by FMCSA.
    The exemption will be revoked if: (1) The person fails to comply
with the terms and conditions of the exemption; (2) the exemption has
resulted in a lower level of safety than was maintained before it was
granted; or (3) continuation of the exemption would not be consistent
with the goals and objectives of 49 U.S.C. 31136 and 31315.

    Issued on: July 21, 2008.
Larry W. Minor,
Associate Administrator for Policy and Program Development.
 [FR Doc. E8-17191 Filed 7-25-08; 8:45 am]

BILLING CODE 4910-EX-P


[Federal Register Volume 81, Number 169 (Wednesday, August 31, 2016)]
[Notices]
[Page 59998]
[FR Doc No: 2016-20971]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Project No. 12796-004]

City of Wadsworth, Ohio; Notice of Teleconference

    a. Project Name and Number: R.C. Byrd Hydroelectric Project No.
12796.
    b. Date and Time of Meeting: Tuesday, September 20, 2016 at 2:00
p.m. (Eastern Daylight Time).
    c. FERC Contact: Andy Bernick<EMAIL_ADDRESS>or (202)
502-8660.
    d. Purpose of Meeting: Commission staff will hold a teleconference
to discuss: (1) Additional information needs regarding listed
freshwater mussel species filed by U.S. Fish and Wildlife Service's
Pennsylvania Field Office (FWS) on June 16, 2016; and (2) the response
to FWS' request, filed by American Municipal Power, Inc. (agent for the
City of Wadsworth, Ohio) on July 15, 2016.
    e. All local, state, and federal agencies, Indian tribes, and other
interested entities are invited to participate by phone. Please call
Andy Bernick at<PHONE_NUMBER> by Tuesday, September 13, 2016, to RSVP
and to receive specific instructions on how to participate.

    Dated: August 24, 2016.
Kimberly D. Bose,
Secretary.
[FR Doc. 2016-20971 Filed 8-30-16; 8:45 am]
 BILLING CODE 6717-01-P


[Federal Register: October 21, 2009 (Volume 74, Number 202)]
[Notices]
[Page 54415-54422]
[DOCID:fr21oc09-128]

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Part VII

Environmental Protection Agency

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Endocrine Disruptor Screening Program (EDSP); Announcing the
Availability of the Tier 1 Screening Battery and Related Test
Guidelines; Notice

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

ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPPT-2008-0521; FRL-8432-6]

Endocrine Disruptor Screening Program (EDSP); Announcing the
Availability of the Tier 1 Screening Battery and Related Test
Guidelines

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

SUMMARY: EPA is announcing the availability of the Endocrine Disruptor
Screening Program (EDSP) Tier 1 battery of assays and availability of
test guidelines (protocols) for conducting the assays included in the
battery. The EDSP was established under section 408(p) of the Federal
Food, Drug, and Cosmetic Act (FFDCA), which directed EPA ``to develop a
screening program. . .to determine whether certain substances may have
an effect in humans that is similar to an effect produced by a
naturally occurring estrogen, or such other endocrine effect as the
Administrator may designate.'' Coordinated by EPA, several in vitro and
in vivo screening assays were developed, standardized, and validated to
identify the potential of a chemical substance to interact with the
estrogen, androgen or thyroid (E, A, or T) hormonal systems. Test
chemicals that were thought to be potentially interactive as well as
non-interactive with the E, A, or T hormonal systems were used to
evaluate feasibility of the protocols, relevance of endpoints and
reliability of results within and among independent contract
laboratories. Subsequent independent peer review of individual assays
helped to clarify the strengths and limitations of each assay and
define their modes of action involving the E, A, or T hormonal systems
within the context of the EDSP Tier 1 battery. EPA submitted a proposed
battery of assays to the Federal Insecticide, Fungicide, and
Rodenticide Act Scientific Advisory Panel (FIFRA SAP) for external peer
review in March 2008. Based on the SAP recommendation, which found the
proposed battery adequate to begin screening chemicals to detect the
potential for interaction with the E, A, or T hormonal systems, EPA is
finalizing the Tier 1 battery as proposed.

FOR FURTHER INFORMATION CONTACT: Don Bergfelt, Office of Science
Coordination and Policy (7203M), Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number:
(202) 564-8472; e-mail address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    This action is directed to the public in general. You may be
potentially affected by this action if you produce, manufacture, use,
consume, work with, or import pesticide chemicals. To determine whether
you or your business may be affected by this action, you should
carefully examine section 408(p) of FFDCA, 21 U.S.C. 346a(p).
    Potentially affected entities may include, but are not limited to:
     Chemical manufacturers, importers and processors (NAICS
code 325), e.g., persons who manufacture, import or process chemical
substances.
     Pesticide, fertilizer and other agricultural chemical
manufacturers (NAICS code 3253), e.g., persons who manufacture, import
or process pesticide, fertilizer and agricultural chemicals.
     Scientific research and development services (NAICS code
5417), e.g., persons who conduct testing of chemical substances for
endocrine effects.
This listing is not intended to be exhaustive, but rather provides a
guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. If you have any questions regarding the applicability of this
action to a particular entity, consult the person listed under FOR
FURTHER INFORMATION CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    1. The Tier 1 battery announcement. EPA has established a docket
for this action under docket identification (ID) number EPA-HQ-OPPT-
2008-0521. All documents in the docket are listed in the docket's index
available at http://www.regulations.gov. Although listed in the index,
some information is not publicly available, e.g., Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. Certain other material, such as copyrighted material, will
be publicly available only in hard copy. Publicly available docket
materials are available electronically at http://www.regulations.gov,
or, if only available in hard copy, at the OPPT Docket. The OPPT Docket
is located in the EPA Docket Center (EPA/DC) at Rm. 3334, EPA West
Bldg., 1301 Constitution Ave., NW., Washington, DC. The EPA/DC Public
Reading Room hours of operation are 8:30 a.m. to 4:30 p.m., Monday
through Friday, excluding Federal holidays. The telephone number of the
EPA/DC Public Reading Room is<PHONE_NUMBER>, and the telephone number
for the OPPT Docket is<PHONE_NUMBER>. Docket visitors are required to
show photographic identification, pass through a metal detector, and
sign the EPA visitor log. All visitor bags are processed through an X-
ray machine and subject to search. Visitors will be provided an EPA/DC
badge that must be visible at all times in the building and returned
upon departure.
    2. The EDSP test guidelines. For additional information about the
test guidelines and to access the guidelines electronically, go to
http://www.epa.gov/oppts and select ``Test Methods & Guidelines'' on
the left side navigation menu. You may also access the EDSP guidelines
in http://www.regulations.gov under docket ID number: EPA-HQ-OPPT-2009-
0576.

II. Endocrine Disruptor Screening Program (EDSP)

    The Food Quality Protection Act (FQPA) of 1996, which amended the
Federal Food, Drug, and Cosmetic Act (FFDCA), directs EPA to:
    develop a screening program, using appropriate validated test
systems and other scientifically relevant information, to determine
whether certain substances may have an effect in humans that is
similar to an effect produced by a naturally occurring estrogen, or
such other endocrine effect as the Administrator may designate. (21
U.S.C. 346a(p)).

    In 1998, after considering public comments, external consultations
and peer review, EPA established the EDSP as a two-tiered approach to
implement the statutory testing requirements of FFDCA section 408(p)
(21 U.S.C. 346a). For additional information about the history of EDSP
go to http://www.epa.gov/endo.
    Under Tier 1 of the EDSP, the screening battery will be used to
identify substances that have the potential to interact with the
estrogen (E), androgen (A), or thyroid (T) hormonal systems (Tier 1
``screening''). The determination will be made on a weight-of-evidence
basis taking into account data from the Tier 1 assays and other
scientifically relevant information available. The fact that a
substance may interact with a hormone system, however, does not mean
that when the substance is used, it will cause adverse effects in
humans or ecological systems.
    Chemicals that go through Tier 1 screening and are found to have
the potential to interact with E, A, or T hormonal systems will proceed
to the next stage of the EDSP where EPA will

determine which, if any, of the Tier 2 tests are necessary based on the
available data. Tier 2 testing is designed to identify any adverse
endocrine-related effects caused by the substance, and establish a
quantitative relationship between the dose and the E, A, or T effect.
    EPA intends to use the data collected under the EDSP, along with
other information, to determine if a pesticide chemical, or other
substances, may pose a risk to human health or the environment due to
disruption of the endocrine system.

III. Assay Validation Process

    The use of validated assays is required by section 408(p) of the
FFDCA. The process of assay validation used by the EDSP is based, in
part, on principles developed by the Interagency Coordinating Committee
for the Validation of Alternative Methods (ICCVAM). In addition to the
ICCVAM approach to assay validation in the United States, EPA
considered the European approach by the European Center for the
Validation of Alternative Methods (ECVAM), as well as the international
approach by the Organization for Economic Co-operation and Development
(OECD) since some screening assays (Amphibian Metamorphosis, Estrogen
Receptor Transcriptional Activation, Fish Short-term Reproduction,
Hershberger, and Uterotrophic assays) involved a collaborative
validation effort with OECD. Validation is still an ongoing process for
EDSP Tier 2 tests, which are expected to be completed in 2011.
    The purpose of assay validation is to establish relevance and
reliability. In the context of the EDSP Tier 1 screening battery,
relevance is the ability of an assay or endpoints within an assay to
detect chemicals with the potential to interact with one or more of the
E, A, or T hormonal systems, whereas reliability is the reproducibility
of those results within and between or among laboratories. Throughout
the validation process of individual assays between 2001 and 2007 and
in accord with the FACA, the EDSP sought guidance on protocol
development, selection of test chemicals, and interpretation of results
from federal advisory committees such as the Endocrine Disruptor
Methods Validation Sub-committee (EDMVS), Endocrine Disruptor Methods
Validation Advisory Committee (EDMVAC) and the FIFRA SAP. Each
committee meeting provided an opportunity for public comment. Materials
from these meetings are available on the Agency's website.
    In the Federal Register of July 13, 2007 (72 FR 13672) (FRL 8238-
4), EPA announced the approach it intends to take for conducting peer
reviews of the Tier 1 screening assays and Tier 2 testing assays that
are being validated, as well as EPA's approach for conducting the peer
review of the Tier 1 battery. For the Tier 1 screening assays, EPA
followed a five-stage assay validation process as summarized:
    1. Test development. A Detailed Review Paper (DRP) or an analogous
document (e.g., Background Review Document) was first prepared as a
comprehensive document to discuss the purpose of a proposed assay, the
context in which it would be used, and the scientific basis on which an
initial protocol design would be developed.
    2. Pre-validation. With selected test chemicals, the initial
protocols were refined, optimized, standardized and assessed for
feasibility, transferability and performance in a number of independent
laboratories based, in part, on the degree of intra-laboratory
variability associated with relevant endpoints.
    3. Inter-laboratory validation. With standardized protocols, each
assay was assessed primarily for reliability (i.e., inter-laboratory
variability) by running the same test chemicals in multiple,
independent laboratories. Assay performance criteria and processes for
data interpretation were also optimized during this stage.
    4. Peer review. An independent scientific review of individual
screening assays initially proposed for the EDSP Tier 1 battery was
conducted by qualified experts using two processes. EPA conducted the
peer review for six assays (i.e., the Androgen Receptor Binding,
Aromatase, Estrogen Receptor Binding, Pubertal female, Pubertal male,
and Steroidogenesis assays) in accord with EPA's Peer Review Handbook.
The EDSP peer review process was published in a Federal Register notice
of July 13, 2007 (72 FR 38577). In general, EPA prepared an Integrated
Summary Report (ISR) for each of these six screening assays. Each ISR
served as the main document during peer review, providing an overview
of development, pre-validation and inter-laboratory testing of
individual assays. Coordinated by an EPA contractor, each peer reviewer
responded independently to a list of charges prepared by EPA. The peer
reviewers' comments were compiled in a peer review record for each
assay and submitted to the Agency. The five assays that were validated
in collaboration with OECD (i.e., the Amphibian Metamorphosis, Estrogen
Receptor Transcriptional Activation, Fish Short-term Reproduction,
Hershberger, and Uterotrophic assays) were peer reviewed by qualified
experts using the OECD process, which includes the preparation of a
peer review summary report for each of these five screening assays. EPA
did not conduct a separate individual assay peer review of these
assays. Assessment of the EDSP peer review records and OECD peer review
summary reports for each screening assay provided an opportunity for
EPA to clarify the strengths and limitations of each assay as well as
the complementary nature among assays. This information was then used
for selecting assays to include in the Tier 1 screening battery for SAP
review.
    5. Regulatory acceptance. Acknowledgment by EPA that the Agency
accepts a test method for regulatory use. EPA adopted the EDSP Tier 1
screening battery (Table 1) in accord with recommendations made by the
SAP who found the proposed suite of assays adequate to begin screening
for E, A, or T effects as detailed in a final report to the Agency
which can be found at the SAP website http://www.epa.gov/scipoly/ sap/
meetings/2008/ march/minutes2008-03-25.pdf. The SAP report is
summarized in Unit III.E.

IV. Peer Review of the Proposed EDSP Tier 1 Screening Battery

    EPA announced the independent scientific peer review of the
proposed EDSP Tier 1 screening battery by the FIFRA SAP in the Federal
Register notice of January 24, 2008 (73 FR 4216) (FRL-8348-6), which
was held March 25-26, 2008. The SAP serves as the primary peer review
mechanism of EPA's Office of Prevention, Pesticides and Toxic
Substances (OPPTS) and it provides comments, evaluations and
recommendations to improve the effectiveness and quality of analyses
made by Agency scientists. EPA provided the SAP with a technical review
document that served as a basic guide and source of information about
the proposed Tier 1 battery. Respective ISRs or summary reports and
reviewer responses from individual review of each assay were also
provided to the SAP as additional material for reviewing the proposed
battery. The SAP was charged with commenting on whether the collection
of assays comprising the proposed battery fulfills its intended purpose
to identify the potential of a chemical to interact with the E, A, or T
hormonal systems. For consideration during the peer review, the SAP
received oral and written comments from EPA, the general public and

various stakeholders. The final SAP report to the Agency is summarized
in this Unit and a copy can be found at the SAP website http://
www.epa.gov/scipoly/sap/ meetings/2008/ march/minutes2008-03-25.pdf.
EPA provided the SAP with two main charges:
    1. Please comment on the ability of the proposed Tier 1 screening
battery (Table 1 in Unit V.A.) to provide sufficient information to
determine whether or not a substance potentially interacts with the E,
A, or T hormonal systems based on the modes of action covered within
the battery (Table 2 in Unit V.B.).
    2. EPA proposed a Tier 1 screening battery that includes assays
that are complementary in nature (i.e., the strengths of one assay
offset the limitations of another) in their coverage of the E, A, or T
hormonal systems, albeit by different taxa, life-stages, endpoints,
exposure and use of in vitro and in vivo methods executed at different
levels of biological organization (i.e., cellular and whole organism).
    a. Please comment on how well the proposed battery minimizes the
potential for ``false negatives'' and ``false positives.''
    b. Are there any unnecessary redundancies for Mode of Action (MOA)
across the battery?
    c. Please comment on whether a different combination of validated
assays would be more effective in achieving the purpose of the battery
than that proposed by EPA.
In response to the charges, the panel discussed assays individually and
as a complete set of assays regarding the ability to detect
interactions with the E, A, or T hormonal systems with few false
positives and false negatives as possible. The conclusions drawn upon
completion of this review as quoted from the SAP report were:
     Chemicals testing positive in the battery of Tier 1 assays
would be identified as potential estrogenic, androgenic and thyroid
hormone active substances.
     The ability to identify endocrine active substances is
enhanced in the Tier 1 battery because the tests provide adequate
replication and redundancy.
     It was clear that the inclusion of apical assays of
amphibian metamorphosis and fish short-term reproduction were important
to detect endocrine active substances that may operate by mechanisms of
action yet to be discovered.
     The 15-day adult male rat assay proposed during some
public comments would not be an appropriate substitute for the male and
female pubertal assays because the pubertal assays provide for
differences between the sexes and provide the only approach to testing
for organizational effects during development.
Overall, the SAP agreed that the battery of Tier 1 assays in Table 1 in
Unit V.A. is appropriate to begin screening for chemical substances
that may interact with the E, A, or T hormonal systems. In addition,
the SAP recommended that EPA continue to develop, refine and review the
Tier 1 screening battery as the state of the science advances and to
consider other hormonal systems that may be affected by exposure to
environmental chemicals. After EPA considered the SAP final report and
public comments, the Agency adopted the EDSP Tier 1 screening battery
presented in Table 1 in Unit V.A.

V. The Final EDSP Tier 1 Screening Battery

A. Assays Included in the Tier 1 Screening Battery

    The EDSP Tier 1 battery with its suite of in vitro and in vivo
screening assays is indicated in Table 1 of this unit. The following
discussion provides an overview of the nature and complementary aspects
within and among assays that were selected to include in the battery.

          Table 1.--Screening Assays in the EDSP Tier 1 Battery
------------------------------------------------------------------------
                 In vitro                              In vivo
------------------------------------------------------------------------
 Estrogen receptor (ER) binding - rat       Uterotrophic (rat)
 uterine cytosol                             Hershberger (rat)
Estrogen receptor [alpha] (hER[alpha])      Pubertal female (rat)
 transcriptional activation - Human cell     Pubertal male (rat)
 line (HeLa-9903).                          Amphibian metamorphosis
Androgen receptor (AR) binding - rat         (frog)
 prostate cytosol.                          Fish short-term reproduction
Steroidogenesis - Human cell line (H295R).
Aromatase - Human recombinant microsomes..
------------------------------------------------------------------------

B. Basis for Assay Selection for the Tier 1 Screening Battery

    The EDSP Tier 1 battery was designed to work as a whole with all of
the screening assays. The basis for selecting an assay to include in
the battery involved two principal aspects: (1) The capacity of an
assay to detect estrogen- and androgen-mediated effects by various
modes of action including receptor binding (agonist and antagonist) and
transcriptional activation, steroidogenesis, and hypothalamic-
pituitary-gonadal (HPG) feedback, and (2) the degree that in vitro and
in vivo assays complemented one another in the battery as summarized in
Table 2 of this unit. In addition, rodent and amphibian in vivo assays
were selected for the proposed battery based on their capacity to
detect direct and indirect effects on thyroid function (hypothalamic-
pituitary-thyroidal, HPT, feedback). Thus, the robustness of the
proposed battery is based on the strengths of each individual assay and
their complementary nature within the battery to detect effects on the
E, A, or T hormonal systems.

                                Table 2.--Complementary Modes of Action among Screening Assays in the EDSP Tier 1 Battery
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Modes of Action
                                                 -------------------------------------------------------------------------------------------------------
                Screening Assays                                   Receptor Binding                        Steroidogensis
                                                 ------------------------------------------------------------------------------ HPG\3\ Axis  HPT\3\ Axis
                                                      E\2\        Anti-E        A\2\        Anti-A        E\2\         A\2\
--------------------------------------------------------------------------------------------------------------------------------------------------------
In vitro
--------------------------------------------------------------------------------------------------------------------------------------------------------
ER Binding\1\                                          \4\
--------------------------------------------------------------------------------------------------------------------------------------------------------
ER[alpha] Transcriptional Activation
--------------------------------------------------------------------------------------------------------------------------------------------------------
AR Binding\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------

Steroidogenesis H295R
--------------------------------------------------------------------------------------------------------------------------------------------------------
Aromatase Recombinant
--------------------------------------------------------------------------------------------------------------------------------------------------------
In vivo
--------------------------------------------------------------------------------------------------------------------------------------------------------
Uterotrophic
--------------------------------------------------------------------------------------------------------------------------------------------------------
Hershberger
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pubertal Male
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pubertal Female                                        \4\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Amphibian Metamorphosis
--------------------------------------------------------------------------------------------------------------------------------------------------------
Fish Short-term Reproduction (male & female)           \4\
--------------------------------------------------------------------------------------------------------------------------------------------------------
 \1\Estrogen and Androgen Receptor binding
\2\Estrogen and Androgen, respectively
\3\Hypothalamic-pituitary-gonadal or -thyroidal axis
\4\Estrogen receptor antagonists were not tested during the validation process, but the assay is expected to detect anti-estrogens.

    1. Assays for detection of compounds that affect the estrogen
signaling pathway. The earliest concern for endocrine disruptors was
related to environmental chemicals that could bind to the estrogen
receptor and thereby interfere with the estrogen signaling pathway.
Estrogen is important for reproductive function in males and females,
including sexual differentiation of the brain and development of
secondary female sex characteristics. In addition, estrogen is involved
in the structural and functional development of other bodily systems
across genders and for maintaining homeostasis.
    Five screening assays within the EDSP Tier 1 battery are capable of
detecting whether or not a chemical interacts with the estrogen
hormonal system and include: (1) Estrogen receptor (ER) binding; (2) ER
transcriptional activation (ERTA); (3) uterotrophic; (4) pubertal
female; and (5) fish short-term reproduction. Of the five assays, the
two in vitro assays (ER binding and ERTA) identify the ability of the
test chemical to interact with the estrogen receptor, thus providing
mechanistic as well as some functional information. The three in vivo
assays provide evidence for the effects of the chemical following
exposure via subcutaneous injection (uterotrophic), oral gavage
(pubertal female), and aquatic medium (fish short-term reproduction).
The different routes of exposure can provide information relevant to
the effects of Absorption, Distribution, Metabolism and Excretion
(ADME). Interpreting the results of the suite of estrogen-detecting
assays within the battery is accomplished by examining the results of
all the assays together using a weight-of-evidence approach. A brief
description as well as value of each of the five assays for detection
of compounds that can potentially interact with the estrogen signaling
pathway is provided.
    a. ER binding assay. The ER receptor binding assay utilizing rat
uterine cytosol (RUC) is a rapid in vitro assay that measures the
binding affinity of a chemical to the estrogen receptor. Although the
ER RUC assay cannot distinguish between chemicals with agonistic,
antagonistic and mixed activity or provide functional, transcriptional
information, the technical simplicity of this assay is important for
screening large numbers of chemicals. Thus, the assay is a valuable
asset for identifying chemicals that can compete with endogenous
estrogen for ER binding. The practical use of this assay and its
relevance to in vivo effects is well documented in the scientific
literature.
    b. ER transcriptional activation assay. The ERTA assay is a method
to detect the interaction and functional effect of a chemical on the
estrogen receptor. The ERTA assay is based on the expression of a
reporter gene induced by a chemical following ligand-receptor binding
and subsequent transcriptional activation. As part of the Endocrine
Disruption Testing and Assessment Task Force activity under the OECD
Test Guidelines Program, Chemical Evaluation and Research Institute
(CERI) of Japan developed and validated a stably transfected
transcriptional activation assay using the hER-HeLa-9903 (HeLa) cell
line with the ER[alpha]. Although the ERTA assay is still being
evaluated to detect ER antagonists, it complements the ER binding assay
within the EDSP Tier 1 battery (Table 2 of this unit) and provides a
functional component for identifying ER[alpha] agonists.
    c. Uterotrophic assay. The uterotrophic assay is an in vivo assay
that was designed to detect estrogenic activity of a chemical through
uterine hypertrophy/hyperplasia. For the EDSP, it is preferred that the
assay be conducted using ovariectomized female rats exposed via
subcutaneous administration because of increased specificity and
information gained on specific estrogen-related responses in the
absence of first-pass liver metabolism. The sole endpoint is a change
in uterine weight (i.e., increase) in response to estrogen-induced
water imbibition and hypertrophy. Thus, data from the uterotrophic
assay can complement the in vitro ER and ERTA

assays (Table 2 of this unit) where metabolic activity is either non-
detectable (ER binding) or minimal (ERTA assay) and provide
differential information in relation to first-pass effects through the
liver since the uterotrophic assay uses subcutaneous exposure compared
to the pubertal female assay that uses oral exposure.
    d. Pubertal female assay. The pubertal female assay is an in vivo
assay with an intact HPG axis that is sensitive to estrogens such that
chemicals with estrogenic activity hasten the age of vaginal opening
(VO). For example, when a selective estrogen receptor modulator (SERM)
with mixed agonistic/antagonistic activity was examined in the pubertal
female assay during the validation process, VO occurred earlier in the
treated group than in controls. Although estrogens also accelerate the
age at first estrus, the interval may or may not correspond to the time
of VO. Nonetheless, the estrogen agonistic effect of the SERM test
chemical was substantiated within the assay by increased uterine
weight. Notably, the change in time to VO is not necessarily a specific
ER binding effect; however, evaluation of results from the pubertal
female and uterotrophic assays and in vitro ER and ERTA assays may
allow distinction between an ER mechanism of action or other
steroidogenic and HPG mechanisms. Since oral gavage is the route of
exposure for the pubertal female assay and subcutaneous exposure is
indicated for the uterotrophic assay, these screening assays can
contribute differential information on specific estrogen-related
responses taking into account ADME, which is crucial to the
identification of compounds that need to be metabolized in order to
interact with the estrogen pathway.
    e. Fish short-term reproduction assay. The fish short-term
reproduction assay with fathead minnows is designed to detect changes
in spawning, reproductive morphology, and specific biochemical
endpoints that reflect disturbances along the HPG axis in response to
estrogen agonists and antagonists. Collectively, the endpoints allow
for inferences with regard to possible endocrine disturbances involving
the estrogen hormonal pathway. Vitellogenin is an egg yolk protein in
which synthesis and secretion is primarily controlled through estrogen-
receptor interaction. There are commercially available immunoassay kits
specific to the fathead minnow that have made vitellogenin production
readily measurable; hence, it is a well-established endpoint. Induction
of vitellogenin in male fish is an extremely sensitive and specific
indication of ER agonists since males have very low circulating
concentrations of endogenous estrogen. Reproductively active females
have moderate circulating concentrations of vitellogenin, which can be
decreased by ER antagonists. Estrogens and anti-estrogens can also
affect egg production in the fish assay. Changes in fecundity combined
with alterations in gonadal histopathology provide a good indication of
reproductive health and have been demonstrated to be sensitive to
estrogenic and anti-estrogenic exposures.
    2. Assays for detection of compounds that affect the androgen
signaling pathway. Androgens are critical for sexual differentiation
and development of secondary sex characteristics in the male, as well
as for a wide variety of reproductive and non-reproductive functions in
both males and females. Four screening assays within the EDSP Tier 1
battery are capable of detecting whether or not a chemical interacts
with the androgen hormonal pathway. Together these assays are expected
to detect chemicals with androgenic and anti-androgenic activity and
include: (1) AR binding; (2) Hershberger; (3) pubertal male; and (4)
fish short-term reproduction assays.
    Of the four assays, the one in vitro assay (AR binding) provides
mechanistic information at the receptor level, while the three in vivo
assays provide evidence for the effects of a chemical on the
reproductive system at the whole organism level. Again, interpreting
the results of the suite of androgen-detecting assays within the
battery is accomplished by examining the results of all the assays
together using a weight-of-evidence approach. A brief description as
well as the value of each of the assays for detection of compounds that
can potentially interact with the androgen signaling pathway is
provided.
    a. AR binding assay. The androgen receptor binding assay (AR
binding), utilizing rat prostate cytosol, is a rapid in vitro assay
that measures the affinity of a test chemical for the androgen
receptor. As with the ER binding assay, the AR binding assay does not
assess functional, transcriptional activity. Nevertheless, the assay's
technical simplicity along with its rapid turn-around time is conducive
for screening large numbers of chemicals. Thus, the assay is a valuable
asset for identifying chemicals that have androgenic or anti-androgenic
activity that can compete with endogenous androgens for receptor
recognition. In addition to detecting androgen agonists and
antagonists, the AR binding assay is complementary in supporting an
agonistic or antagonistic result in the Hershberger assay (Table 2 of
this unit).
    b. Hershberger assay. The Hershberger assay is a short-term in vivo
screen that uses castrated peripubertal male rats exposed via oral
gavage to assess biological activities consistent with either androgen
agonists or antagonists (or 5[alpha]-reductase inhibitors) by measuring
changes in the weights of five androgen-dependent tissues: (i) Ventral
prostate; (ii) seminal vesicle; (iii) levator ani-bulbocavernosus
(LABC) muscle complex; (iv) Cowper's glands; and (v) glans penis. An
increase in tissue weights is diagnostic of androgenic activity. In
contrast, an anti-androgenic chemical will block any increase in tissue
weights when co-administered with a potent androgen such as
testosterone propionate. The Hershberger assay contributes to the
battery by providing information on androgen-related responses that is
complimentary with the intact pubertal male and fish short-term
reproduction assays as well as AR binding and steroidogenesis assays
(Table 2 of this unit).
    c. Pubertal male assay. The male pubertal assay is an in vivo test
system with an intact HPG axis that is sensitive for detecting
chemicals that act as androgens or anti-androgens or interfere with
androgen synthesis. Importantly, as an in vivo assay, it can detect
chemicals which require metabolism in order to interact with the
androgen hormonal system because of its oral route of exposure. The
pubertal male assay is reproducible and sensitive for chemicals that
alter androgenic hormone action which is necessary for preputial
separation (PPS), associated with the onset of puberty, and growth and
development of androgen dependent tissues (e.g., testes, prostate,
seminal vesicles). The pubertal male assay is complementary with the
Hershberger and AR binding assays (Table 2 of this unit).
    d. Fish short-term reproduction. Secondary sex characteristics of
fathead minnows are affected by androgenic and anti-androgenic
substances. Specifically, females will develop external male secondary
sex characteristics (nuptial tubercles) when exposed to an AR agonist.
Not only is this endpoint specific for this mode of action, it is
highly sensitive since female fathead minnows typically do not express
these characteristics. In contrast, AR antagonists decrease the
expression of male secondary sex characteristics in male fathead
minnows. Changes in secondary sex

characteristics in fathead minnows are biologically relevant, unique,
robust and reproducible. Androgens and anti-androgens also effectively
inhibit egg production in the fish assay, with corresponding
alterations in gonad histopathology. The fish short-term reproduction
assay is complimentary with in vitro assays and other in vivo assays
(Table 2 of this unit).
    3. Assays for detection of compounds that affect steroid synthesis.
Numerous environmental compounds have been shown to interfere with the
steroidogenic pathways for estrogens (e.g., estradiol) and androgens
(e.g., testosterone) in various in vitro and in vivo test systems. In
this regard, a number of in vitro assays for steroidogenesis were
considered for the battery with the decision to include the H295R cell
line as it offers the potential to identify chemicals that induce or
inhibit estradiol and testosterone synthesis. In addition, since many
environmental compounds are known to inhibit the conversion of androgen
substrates to estrogen, a decision was made to include a human
recombinant aromatase assay. A combination of in vitro and in vivo
assays is expected to provide complementary information to be used in a
weight of evidence approach for making decisions as to whether or not a
compound interferes with the estrogen or androgen hormonal signaling
pathways and includes: (1) Steroidogenesis; (2) aromatase; (3) pubertal
female; (4) pubertal male; and (5) fish short-term reproduction assays.
A brief description as well as the value of each of the five assays for
detection of compounds that can potentially affect steroidogenesis is
provided.
    a. H295R for steroidogenesis. H295R is a human adrenocortical
carcinoma cell line that possesses all of the key enzymes involved in
the steroidogenic pathways. The assay provides a straightforward,
inexpensive and specific way to detect chemicals that affect steroid
hormone synthesis through enzyme induction or inhibition. The
measurement of estradiol and testosterone in culture media are the
essential hormonal endpoints in this assay. Chemical exposure may
inhibit enzymes in the pathway, leading to decreased production of one
or both of the hormonal endpoints or stimulate enzymes, leading to
increased production of one or both of the endpoints.
    b. Human recombinant aromatase. The recombinant aromatase assay
using human recombinant microsomes is an inexpensive and rapid in vitro
method to detect chemicals that inhibit aromatase activity, thus
blocking the conversion of androgens to estrogens. The aromatase and
H295R steroidogenesis assays are complementary within the Tier 1
battery (Table 2 of this unit) and are the only in vitro assays that
have been shown to detect the activity of chemicals that weakly inhibit
aromatase and estrogen synthesis.
    c. The pubertal female and pubertal male assays. A chemical that
interferes with endogenous steroid hormone production by the ovaries or
testes will produce changes in the numerous hormone-dependent endpoints
measured by the female and male pubertal assays, respectively.
Together, the pubertal female and male assays and H295R steroidogenesis
and aromatase assays are complementary within the Tier 1 battery (Table
2 of this unit) and provide diagnostic information to discern impaired
estrogen and androgen production.
    d. Fish short-term reproduction. Interference in the steroid
synthetic pathways is detected by several endpoints in the fish assay.
Proliferation of testicular interstitial cells (males), decreased
circulating concentrations of reproductive steroids (males and females)
and vitellogenin (females), and impaired egg production (females) would
all signal potential alteration in steroid synthesis.
    4. Assays for detection of chemicals that affect the HPG axis.
Environmental compounds have been found to interfere with endocrine
function of the ovaries and testes by altering the hypothalamic
regulation of pituitary hormone synthesis and secretion. By this mode
of action, it has been shown that many of these same chemicals can
interfere with reproductive development and fertility. The EDSTAC
recommended and EPA agreed that the effect of environmental chemicals
on the hypothalamic-pituitary-gonadal axis (HPG) be evaluated. To
address this issue, the Tier 1 battery includes: (1) Pubertal male; (2)
pubertal female; and (3) fish short-term reproduction assays.
    The EDSP Tier 1 battery is designed to use the combined results of
the in vitro and in vivo assays included in the battery to
differentiate between hormone-receptor binding and non-receptor binding
at the cellular and whole organism levels that may involve the HPG
axis.
    Hypothetically, if a test chemical is found to delay PPS and VO in
the in vivo pubertal male and female assays, respectively, but none of
the in vitro assays were altered, it would likely be concluded that the
delay in male and female puberty is due to impaired hypothalamic-
pituitary function. This scenario has been demonstrated in the pubertal
male and female assays with compounds that act on the central nervous
system and alter gonadotropin-releasing hormone (GnRH) and luteinizing
hormone (LH).
    The fish short-term reproduction assay with fathead minnows is
designed to detect changes in spawning, morphology and specific
biochemical endpoints that reflect alterations in the HPG axis. Again,
the combined results of the in vitro and in vivo assays included in the
battery are to determine and differentiate if an alteration involves
the HPG axis, which may be information for Tier 2 testing.
    5. Assays for detection of chemicals that affect the HPT axis. In
addition to identifying environmental compounds that have the potential
to alter the hormonal regulation of reproductive function involving the
estrogen and androgen hormonal pathways, certain assays included in the
EDSP Tier 1 screening battery (Tables 1 and 2 of this unit) will also
provide relevant information about the potential of a chemical to
interfere with thyroid function. Thyroid hormones (thyroxine, T4 and
triiodothyronine, T3) are essential for normal development and
maintenance of physiological functions in vertebrates. Delivery of
thyroid hormones to tissues and cells is highly regulated throughout
life and is governed by complex physiological processes involving the
HPT axis, including peripheral organs/tissues. Environmental factors,
such as the presence of specific toxicants, can perturb this system at
various points of regulation, inducing a variety of responses that can
be detected with thyroid-related endpoints in the in vivo assays. Three
screening assays have been designed for this purpose within the EDSP
Tier 1 battery and include: (1) Pubertal female; (2) pubertal male; and
(3) amphibian metamorphosis assays. A brief description as well as the
value of each of the three assays for detection of compounds that can
potentially interfere with thyroid development and function is
provided.
    a. Pubertal male and female assays. The pubertal male and female
assays include multiple endpoints that can detect an interaction of a
chemical with the thyroid hormonal system, including circulating
concentrations of thyroid stimulating hormone (TSH) and T4, thyroid
organ weight and histology, and liver weight. Both the male and the
female assays have been shown to detect chemicals that act through
various thyroid-related mechanisms. The male and female pubertal assays
include the same thyroid endpoints; thus,

examining the thyroid axis in both sexes provides the opportunity to
detect potential gender differences in response to treatment at a
relatively early life stage.
    b. Amphibian metamorphosis assay. The amphibian metamorphosis assay
(AMA) is an in vivo screening assay intended to identify substances
which interfere with the normal function of the HPT axis. The AMA
represents a generalized vertebrate model based on the conserved
structure and function of thyroid systems among species. The AMA is
based on the principle that the dramatic morphological changes that
occur during post-embryonic development are dependent upon the normal
functioning of the HPT axis, and that interference with these processes
leads to measurable effects. During tadpole metamorphosis, thyroid
hormone (TH) influences virtually every tissue in the body initiating
diverse morphological, physiological and biochemical changes that
include cell proliferation, differentiation and death. The result is de
novo organ formation, organ loss, and extensive tissue remodeling.
Given the dependence of metamorphosis on TH and the strict biochemical
control under which these processes occur, the transformations that
occur can serve as endpoints representative of thyroid axis function.
The primary endpoints in the AMA are the hindlimb length during the
developmental stage and the thyroid histology. Each endpoint can be
affected by chemicals that interact with the HPT axis. For example,
antagonists of thyroid production, iodination and action have been
shown to delay development and induce diagnostic lesions in the thyroid
gland. Thyroid agonists (e.g., native thyroid hormone) will accelerate
development. Additionally, unlike the mammalian assays that have been
developed to detect interactions along the HPT axis, the AMA has the
ability to detect chemicals that act on peripheral tissues. For
example, inhibition of monodeiodinases that transform T4 to T3 can
cause asynchronous development, detected by an inability to assign a
developmental stage to a tadpole. Knowledge of this mechanism is
important because development can be affected without concomitant
effects on thyroid histology or circulating thyroid hormone
concentrations. Although post-embryonic development is different
between mammals and most amphibians (i.e., metamorphosis), there is a
high level of evolutionary conservation of the thyroid system and
underlying molecular and cellular pathways among vertebrates. Hence,
the AMA, particularly with the use of Anurans, is a general model for
evaluating the interaction of chemicals with the HPT axis in the EDSP
Tier 1 screening battery. In addition, the results can be used to
complement or corroborate results in the pubertal male and female
assays (Table 2 of this unit).

VI. Test Guidelines for EDSP Tier 1 Screening Battery

    EPA is also announcing the availability of the test guidelines for
conducting the assays included in the EDSP Tier 1 Screening Battery
(Table 1 in Unit V.A.).
    The Androgen Receptor Binding, Aromatase, Estrogen Receptor Binding
(Rat Uterine Cytosol), Female Pubertal, Male Pubertal, and
Steroidogenesis assays were developed and validated by the Agency.
    The Amphibian Metamorphosis, Estrogen Receptor Transcriptional
Activation, Fish Short-term Reproduction, Hershberger and Uterotrophic
assays were developed and validated using a collaborative process
involving EPA's Office of Science Coordination and Policy (OSCP),
Office of Research and Development (ORD), and Office of Pesticide
Programs (OPP) as well as OECD as previously outlined in a Federal
Register notice of July 13, 2007 (72 FR 38577) (FRL-8138-4). The
process took into account the harmonized testing strategy for the
screening and testing of potential endocrine disrupting chemicals and
consequences of such a strategy on the development and validation of
test guidelines involving regulatory systems for new and existing
substances according to OECD's Endocrine Disrupter Testing and
Assessment (EDTA) Task Force in 1998.
    In both cases, the draft protocols (and all related materials) were
made available as part of the independent peer review. The draft
protocols were revised to reflect comments received during the peer
review process, and have been incorporated into the OPPTS compendium of
harmonized test guidelines, under Series 890-Endocrine Disruptor
Screening Program Test Guidelines as follows:
     890.1100-Amphibian Metamorphosis (Frog)
     890.1150-Androgen Receptor Binding (Rat Prostate Cytosol)
     890.1200-Aromatase (Human Recombinant)
     890.1250-Estrogen Receptor Binding (Rat Uterine Cytosol)
     890.1300-Estrogen Receptor Transcriptional Activation
(Human Cell Line -- HeLa-9903)
     890.1350-Fish Short-term Reproduction
     890.1400-Hershberger (Rat)
     890.1450-Female Pubertal (Rat)
     890.1500-Male Pubertal (Rat)
     890.1550-Steroidogenesis (Human Cell Line -- H295R)
     890.1600-Uterotrophic (Rat)
    For information on accessing these guidelines see Unit I.B.2.

List of Subjects

    Environmental protection, Chemicals, Chemical testing, Endocrine
disruptors, Pesticides, Test guideline.

    Dated: October 14, 2009.
Stephen A. Owens,
Assistant Administrator, Office of Prevention, Pesticides and Toxic
Substances.

[FR Doc. E9-25348 Filed 10-20-09; 8:45 am]

BILLING CODE 6560-50-S


[Federal Register Volume 84, Number 24 (Tuesday, February 5, 2019)]
[Notices]
[Pages 1743-1745]
[FR Doc No: 2019-01067]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-6644]

Fiscal Year 2019 Generic Drug Regulatory Science Initiatives;
Public Workshop; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop; request for comments.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
announcing the following public workshop entitled ``FY 2019 Generic
Drug Regulatory Science Initiatives.'' The purpose of the public
workshop is to provide an overview of the status of regulatory science
initiatives for generic drugs and an opportunity for public input on
these initiatives. FDA is seeking this input from a variety of
stakeholders--industry, academia, patient advocates, professional
societies, and other interested parties--as it fulfills its commitment
under the Generic Drug User Fee Amendments of 2017 (GDUFA II) to
develop an annual list of regulatory science initiatives specific to
generic drugs. FDA will take the information it obtains from the public
workshop into account in developing its fiscal year (FY) 2020
regulatory science initiatives.

DATES: The public workshop will be held on May 1, 2019, from 8:30 a.m.
to 4:30 p.m. Submit either electronic or written comments on this
public workshop by June 1, 2019. See the SUPPLEMENTARY INFORMATION
section for registration date and information.

ADDRESSES: The public workshop will be held at the FDA White Oak
Campus, 10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great
Room (Rm. 1503, sections B and C), Silver Spring, MD 20993-0002.
Entrance for the public workshop participants (non-FDA employees) is
through Building 1, where routine security check procedures will be
performed. For parking and security information, please refer to
https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    You may submit comments as follows. Please note that late, untimely

filed comments will not be considered. Electronic comments must be
submitted on or before June 1, 2019. The https://www.regulations.gov
electronic filing system will accept comments until 11:59 p.m. Eastern
Time at the end of June 1, 2019. Comments received by mail/hand
delivery/courier (for written/paper submissions) will be considered
timely if they are postmarked or the delivery service acceptance
receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, 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-2017-N-6644 for ``FY 2019 Generic Drug Regulatory Science
Initiatives; Public Workshop; Request for Comments.'' Received
comments, those filed in a timely manner (see ADDRESSES), will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff 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 https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. 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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Stephanie Choi, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 3742, Silver Spring, MD 20993, 240-402-
7960<EMAIL_ADDRESS>or Robert Lionberger, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 4722, Silver Spring, MD 20993, 240-402-
7957<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. Background

    In July 2012, Congress passed the Generic Drug User Fee Amendments
of 2012 (GDUFA I) (Pub. L. 112-144). GDUFA I was designed to enhance
public access to safe, high-quality generic drugs and to modernize the
generic drug program. To support this goal, FDA agreed in the GDUFA I
commitment letter to work with industry and interested stakeholders on
identifying regulatory science initiatives specific to generic drugs
for each fiscal year covered by GDUFA I.
    In August 2017, GDUFA I was reauthorized until September 2022
through GDUFA II (Pub. L. 115-52). In the GDUFA II commitment
letter,\1\ FDA agreed to conduct annual public workshops ``to solicit
input from industry and stakeholders for inclusion in an annual list of
GDUFA II [r]egulatory [s]cience initiatives.'' The public workshop
scheduled for May 1, 2019, seeks to fulfill this agreement.
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    \1\ The GDUFA II commitment letter is available at https://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM525234.pdf.
---------------------------------------------------------------------------

II. Topics for Discussion at the Public Workshop

    The purpose of the public workshop is to obtain input from industry
and other interested stakeholders on the identification of generic drug
regulatory science initiatives for FY 2020.
    FDA is particularly interested in receiving input on the following
three topics:
    1. FY 2019 regulatory science initiatives,\2\ including specific
products or actions that FDA should consider as it implements those
initiatives, including, for example:
---------------------------------------------------------------------------

    \2\ The FY 2019 regulatory science initiatives are available at
https://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/GenericDrugs/UCM626329.pdf.
---------------------------------------------------------------------------

    a. The value to the generic drug product industry in expanding the
Biopharmaceutics Classification System Class III waivers to include
non-Q1/Q2 formulations,
    b. Scientific gaps that impact the prediction of the results of fed
bioequivalence studies (when the drug product is administered shortly
after a meal, as opposed to administration under fasting conditions),
and
    c. Challenges for industry in implementing new analytical or
computational methods that arise from regulatory science initiatives.
    2. Recently approved new drug applications that may pose scientific
challenges to the future development of generic drug products
referencing those applications.

    3. Regulatory science initiatives that FDA should begin to consider
in FY 2019, including, for example:
    a. Scientific challenges in the evaluation of sensitization for
transdermal systems and
    b. The development of alternative approaches to in vivo
bioequivalence studies to evaluate product equivalence.
    FDA will consider all comments made at this workshop or received
through the docket (see ADDRESSES) as it develops its FY 2020
regulatory science initiatives. Information concerning the regulatory
science initiatives for generic drugs can be found at https://www.fda.gov/gdufaregscience.

III. Participating in the Public Workshop

    Registration: To register for the public workshop, please email
complete contact information for each attendee--including the
attendee's name, title, affiliation, address, email, and telephone
number--to<EMAIL_ADDRESS>Please also indicate in
the email whether attendance will be by webcast or in person.
    Registration is free and based on space availability, with priority
given to early registrants. Persons interested in attending this public
workshop must register online by April 1, 2019, 11:59 p.m. Eastern
Time. Early registration is recommended because seating is limited;
therefore, FDA may limit the number of participants from each
organization. Registrants will receive confirmation when they have been
accepted.
    If you need special accommodations due to a disability, please
contact Stephanie Choi (see FOR FURTHER INFORMATION CONTACT) no later
than April 1, 2019.
    Requests for Oral Presentations: During online registration you may
indicate if you wish to present during a public comment session or
participate in a specific session, and which topic(s) you wish to
address. We will do our best to accommodate requests to make public
comments (and requests to participate in the focused sessions).
Individuals and organizations with common interests are urged to
consolidate or coordinate their presentations, and request time for a
joint presentation, or submit requests for designated representatives
to participate in the focused sessions. Following the close of
registration, we will determine the amount of time allotted to each
presenter and the approximate time each oral presentation is to begin,
and will select and notify participants by April 8, 2019. All requests
to make oral presentations must be received by the close of
registration on April 1, 2019, 11:59 p.m. Eastern Time. If selected for
presentation, any presentation materials must be emailed to
<EMAIL_ADDRESS>no later than April 22, 2019, 11:59
p.m. Eastern Time. No commercial or promotional material will be
permitted to be presented or distributed at the public workshop.
    Streaming Webcast of the Public Workshop: This public workshop will
also be webcast. Please register online by April 1, 2019, 11:59 p.m.
Eastern Time to attend the workshop remotely. Please note that remote
attendees will not be able to speak or make presentations during the
public comment period or during any other session of the workshop. To
join the workshop via the webcast, please go to https://collaboration.fda.gov/gdufa2019/.
    If you have never attended a Connect Pro event before, test your
connection at https://collaboration.fda.gov/common/help/en/support/meeting_test.htm. To get a quick overview of the Connect Pro program,
visit https://www.adobe.com/go/connectpro_overview. FDA has verified
the website addresses in this document, as of the date this document
publishes in the Federal Register, but websites are subject to change
over time.
    Transcripts: Please be advised that as soon as a transcript of the
public workshop is available, it will be accessible at https://www.regulations.gov or at https://www.fda.gov/gdufaregscience. It may
be viewed at the Dockets Management Staff (see ADDRESSES). A link to
the transcript will also be available on the internet at https://www.fda.gov/gdufaregscience.

    Dated: January 16, 2019.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2019-01067 Filed 2-4-19; 8:45 am]
 BILLING CODE 4164-01-P