[Federal Register Volume 87, Number 158 (Wednesday, August 17, 2022)]
[Notices]
[Pages 50629-50630]
[FR Doc No: 2022-17642]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-0986]

Hydrogen Peroxide-Based Contact Lens Care Products: Consumer
Labeling Recommendations--Premarket Notification (510(k)) Submissions;
Draft Guidance for Industry and Food and Drug Administration Staff;
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of the draft guidance entitled ``Hydrogen Peroxide-
Based Contact Lens Care Products: Consumer Labeling Recommendations--
Premarket Notification (510(k)) Submissions.'' FDA is issuing this
draft guidance to provide labeling recommendations for hydrogen
peroxide-based contact lens care products (HPCPs) submitted in
premarket notification (510(k)) submissions. The labeling
recommendations in this draft guidance are intended to promote the safe
and effective use of HPCPs and ensure that consumers receive and
understand information regarding the benefits and risks associated with
the use of the device. This draft guidance is not final nor is it for
implementation at this time.

DATES: Submit either electronic or written comments on the draft
guidance by October 17, 2022 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as
follows:

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-2022-D-0986 for ``Hydrogen Peroxide-Based Contact Lens Care
Products: Consumer Labeling Recommendations--Premarket Notification
(510(k)) Submissions.'' Received comments 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, 240-
402-7500.
     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.govinfo.gov/content/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,<PHONE_NUMBER>.
    You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
    An electronic copy of the guidance document is available for
download from the internet. See the SUPPLEMENTARY INFORMATION section
for information on electronic access to the guidance. Submit written
requests for a single hard copy of the draft guidance document entitled
``Hydrogen Peroxide-Based Contact Lens Care Products: Consumer Labeling
Recommendations--Premarket Notification (510(k)) Submissions'' to the
Office of Policy, Center for Devices and Radiological Health, Food and
Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431,
Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to
assist that office in processing your request.

FOR FURTHER INFORMATION CONTACT: Angelo Green, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 1306, Silver Spring, MD 20993-0002,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    The safety and effectiveness of HPCPs when used as directed has
been well

established in the last few decades; however, FDA has become aware of
an increase in the number of adverse event reports related to the
misuse of these products. These reports led FDA to convene a meeting of
the Ophthalmic Devices Panel of the Medical Devices Advisory Committee
and the Risk Communication Advisory Committee on March 17, 2017, to
discuss additional measures to mitigate the potential risk for misuse
of these devices. The meeting covered a range of important issues,
including appropriate labeling and packaging of these products and the
importance of clearly communicating these concerns to the consumer
public, which were incorporated into this draft guidance. When
finalized, this guidance is intended to provide recommendations
concerning the content and format of labeling for HPCPs. FDA believes
that the labeling recommendations in this guidance may help
manufacturers develop labeling with information about specific risks
and directions for use of the HPCPs in conjunction with a user's
prescribed contact lenses.
    This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the current thinking of FDA on ``Hydrogen
Peroxide-Based Contact Lens Care Products: Consumer Labeling
Recommendations--Premarket Notification (510(k)) Submissions.'' It does
not establish any rights for any person and is not binding on FDA or
the public. You can use an alternative approach if it satisfies the
requirements of the applicable statutes and regulations.

II. Electronic Access

    Persons interested in obtaining a copy of the draft guidance may do
so by downloading an electronic copy from the internet. A search
capability for all Center for Devices and Radiological Health guidance
documents is available at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products. This guidance document is also
available at https://www.regulations.gov or https://www.fda.gov/regulatory-information/search-fda-guidance-documents. Persons unable to
download an electronic copy of ``Hydrogen Peroxide-Based Contact Lens
Care Products: Consumer Labeling Recommendations--Premarket
Notification (510(k)) Submissions'' may send an email request to [email protected] to receive an electronic copy of the document.
Please use the document number 18041 and complete title to identify the
guidance you are requesting.

III. Paperwork Reduction Act of 1995

    While this guidance contains no new collection of information, it
does refer to previously approved FDA collections of information.
Therefore, clearance by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in the following FDA regulations, guidance, and forms
have been approved by OMB as listed in the following table:

------------------------------------------------------------------------
                                                            OMB control
            21 CFR part                     Topic               No.
------------------------------------------------------------------------
807, subpart E....................  Premarket                  0910-0120
                                     notification.
800, 801, and 809.................  Medical Device             0910-0485
                                     Labeling
                                     Regulations.
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    Dated: August 11, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-17642 Filed 8-16-22; 8:45 am]
BILLING CODE 4164-01-P


species stage year impinged. est entrained. est notes notes. 2 QC dummy dummy  999  999  999 dummy dummy dummy largemouth. bass age01 1978 33 na Table V A 6. pg 824 . . smallmouth. bass age01 1978 344 na Table V A 6. pg 824 . . rock. bass age01 1978 116 na Table V A 6. pg 824 . . bullhead. spp age01 1978 484 na Table V A 6. pg 824 . . carp age01 1978 1183 na Table V A 6. pg 824 . . channel. catfish age01 1978 16884 na Table V A 6. pg 824 . . forage. fish age01 1978 213230 na Table V A 6. pg 824 . . crappie. spp age01 1978 883 na Table V A 6. pg 824 . . american. eel age01 1978 25 na Table V A 6. pg 824 . . madtoms age01 1978 751 na Table V A 6. pg 824 . . yellow. perch age01 1978 30 na Table V A 6. pg 824 . . sucker. spp age01 1978 2493 na Table V A 6. pg 824 . . sunfish. spp age01 1978 19656 na Table V A 6. pg 824 . . carp larvae 1978 na 5000000 Table V B 3. pg 866 . . spottail. shiner egg 1978 na 1000000 Table V B 3. pg 866 . . spottail. shiner larvae 1978 na 17000000 Table V B 3. pg 866 . . spotfin. shiner. bluntnose. minnow larvae 1978 na 7000000 Table V B 3. pg 866 . . channel. catfish larvae 1978 na 1000000 Table V B 3. pg 866 . . tessellated. darter larvae 1978 na 6000000 Table V B 3. pg 866 . . other. spp egg 1978 na 2000000 Calculated. . . other. spp juvenile 1978 na 500000 Table V B 3. pg 866 . . other. spp larvae 1978 na 9000000 Calculated from Table V B 3. pg 866. Losses data from Dickerson, MD. A. Gage, 8/ 11/ 2003 species stage year impinged. est entrained. est notes largemouth. bass age01 1978 33 na RM# 35227; Table V A 6. pg 824 smallmouth. bass age01 1978 344 na RM# 35227; Table V A 6. pg 824 rock. bass age01 1978 116 na RM# 35227; Table V A 6. pg 824 bullhead. spp age01 1978 484 na RM# 35227; Table V A 6. pg 824 carp age01 1978 1183 na RM# 35227; Table V A 6. pg 824 channel. catfish age01 1978 16884 na RM# 35227; Table V A 6. pg 824 forage. fish age01 1978 213230 na RM# 35227; Table V A 6. pg 824 crappie. spp age01 1978 883 na RM# 35227; Table V A 6. pg 824 american. eel age01 1978 25 na RM# 35227; Table V A 6. pg 824 madtoms age01 1978 751 na RM# 35227; Table V A 6. pg 824 yellow. perch age01 1978 30 na RM# 35227; Table V A 6. pg 824 sucker. spp age01 1978 2493 na RM# 35227; Table V A 6. pg 824 sunfish. spp age01 1978 19656 na RM# 35227; Table V A 6. pg 824 carp protolarvae 1978 na 5000000 RM# 35227; Table V B 3. pg 866 spottail. shiner eggs 1978 na 1000000 RM# 35227; Table V B 3. pg 866 spottail. shiner protolarvae 1978 na 17000000 RM# 35227; Table V B 3. pg 866 spotfin. shiner. bluntnose. minnow protolarvae 1978 na 7000000 RM# 35227; Table V B 3. pg 866 channel. catfish metalarvae 1978 na 1000000 RM# 35227; Table V B 3. pg 866 tessellated. darter protolarvae 1978 na 6000000 RM# 35227; Table V B 3. pg 866 all. species eggs 1978 na 3000000 RM# 35227; Table V B 3. pg 866 all. species protolarvae 1978 na 39000000 RM# 35227; Table V B 3. pg 866 all. species mesolarvae 1978 na 4000000 RM# 35227; Table V B 3. pg 866 all. species metalarvae 1978 na 2000000 RM# 35227; Table V B 3. pg 866 all. species juvenile 1978 na 500000 RM# 35227; Table V B 3. pg 866 other. spp eggs 1978 na 2000000 Calculated. other. spp protolarvae 1978 na 4000000 Calculated. other. spp mesolarvae 1978 na 4000000 Calculated. other. spp metalarvae 1978 na 1000000 Calculated. other. spp juvenile 1978 na 500000 RM# 35227; Table V B 3. pg 866 other. spp larvae 1978 na 9000000 Calculated. notes. 2 QC Don't include in losses  used for calc only. Don't include in losses  used for calc only. Don't include in losses  used for calc only. Don't include in losses  used for calc only. Don't include in losses  used for calc only.


[Federal Register Volume 85, Number 133 (Friday, July 10, 2020)]
[Notices]
[Page 41581]
[FR Doc No: 2020-14907]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. ER20-2318-000]

Milford Solar I, LLC; Supplemental Notice That Initial Market-
Based Rate Filing Includes Request for Blanket Section 204
Authorization

    This is a supplemental notice in the above-referenced proceeding of
Milford Solar I, LLC's application for market-based rate authority,
with an accompanying rate tariff, noting that such application includes
a request for blanket authorization, under 18 CFR part 34, of future
issuances of securities and assumptions of liability.
    Any person desiring to intervene or to protest should file with the
Federal Energy Regulatory Commission, 888 First Street NE, Washington,
DC 20426, in accordance with Rules 211 and 214 of the Commission's
Rules of Practice and Procedure (18 CFR 385.211 and 385.214). Anyone
filing a motion to intervene or protest must serve a copy of that
document on the Applicant.
    Notice is hereby given that the deadline for filing protests with
regard to the applicant's request for blanket authorization, under 18
CFR part 34, of future issuances of securities and assumptions of
liability, is July 27, 2020.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper, using the FERC Online links at http://www.ferc.gov. To facilitate electronic service, persons with internet
access who will eFile a document and/or be listed as a contact for an
intervenor must create and validate an eRegistration account using the
eRegistration link. Select the eFiling link to log on and submit the
intervention or protests.
    Persons unable to file electronically may mail similar pleadings to
the Federal Energy Regulatory Commission, 888 First Street NE,
Washington, DC 20426. Hand delivered submissions in docketed
proceedings should be delivered to Health and Human Services, 12225
Wilkins Avenue, Rockville, Maryland 20852.
    In addition to publishing the full text of this document in the
Federal Register, the Commission provides all interested persons an
opportunity to view and/or print the contents of this document via the
internet through the Commission's Home Page (http://ferc.gov) using the
``eLibrary'' link. Enter the docket number excluding the last three
digits in the docket number field to access the document. At this time,
the Commission has suspended access to the Commission's Public
Reference Room, due to the proclamation declaring a National Emergency
concerning the Novel Coronavirus Disease (COVID-19), issued by the
President on March 13, 2020. For assistance, contact the Federal Energy
Regulatory Commission at<EMAIL_ADDRESS>or call toll-free,
(886) 208-3676 or TYY,<PHONE_NUMBER>.

    Dated: July 6, 2020.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2020-14907 Filed 7-9-20; 8:45 am]
BILLING CODE 6717-01-P


63
regulation, requirements for the approval, suspension, and revocation of biologics licenses.”
Approval of a biologics license application (BLA) must be based on a demonstration that the
biological product is “safe, pure, and potent” (section 351(a)(2)(C)(i)(I) of the PHS Act).
Limiting the use of prohibited cattle materials in biological products is designed to ensure the
safety, purity, and potency of such licensed biological products.  Based on the scientific data and
information available to FDA regarding the possibility of disease transmission to humans from
exposure to prohibited cattle materials, under the proposed rule FDA would not approve a BLA
or supplement for a biological product containing prohibited cattle materials unless an exception
or alternative has been granted based upon the Center Director's determination that the safety
standard in section 351(a)(2)(C) of the PHS Act would still be met. In addition, under the
proposed rule, a biological product containing prohibited cattle materials that is already licensed
would no longer be demonstrated to be safe based on the presence of prohibited cattle materials,
and would be in violation of section 351(a)(1) of the PHS Act and section 505 of the act, unless
an exception or alternative for use of the prohibited cattle materials has been granted.
Accordingly, FDA is proposing to amend its biological product regulations to prohibit the use of
certain cattle materials in biological products as provided by proposed § 600.16.
With respect to devices, FDA is proposing to issue these regulations under the
adulteration provision in section 501(g) of the act, under the misbranding provision in section
502
(t)
of the act, and under sections 516, 519(a), 701(a) and (b), and 801 of the act.
Under section 516 of the act, FDA may issue a regulation making a device a banned
device if the agency determines, on the basis of all available data and information, that a device
presents an unreasonable and substantial risk of illness or injury that can not be corrected or
eliminated by labeling.  A banned device is deemed adulterated under section 501(g) of the act.

64
There are several routes through which devices intended for use in or on the body have the
potential to introduce the BSE agent into humans if the devices contain prohibited cattle
materials.  It is well documented that central nervous system tissue, including the optic nerve,
carries infectivity in animals with TSEs and humans with vCJD.  Infectivity has also been
transmitted to animals via mucosal tissue.  Finally, although transmission through intact skin is
not likely, the BSE agent has the potential to be introduced into the body through cut or abraded
skin.  FDA has concluded, therefore, that devices intended for use in or on the body that contain
prohibited cattle materials have the potential to expose recipients of those devices if the
originating cattle had BSE.   Although the over all risk of exposure is low given the low rate of
BSE in U.S. cattle, this risk is deemed unacceptable given the fatal nature of vCJD.  The agency
is not aware of any device that can be manufactured only with prohibited cattle materials; thus,
there should be no benefit to the public health from the continued marketing of devices
containing these materials. FDA has determined, therefore, that devices intended for use in or on
the body that contain prohibited cattle materials present an unreasonable risk to health in relation
to the benefit to the public health from their continued marketing.  Moreover, because there is no
safe way to use these devices, the risk of disease cannot be corrected or eliminated by labeling.
It is clear, based on all available data and information, that the risk of BSE exposure may
be significantly reduced by banning devices intended for use in or on the body that contain
prohibited cattle materials. The agency is proposing to ban such devices, therefore, in
accordance with section 516 of the act.  Devices already in commercial distribution or already
sold to the ultimate user are not subject to this ban because FDA is not aware of any currently
marketed device that contains prohibited cattle materials. Manufacturers currently are not
required to maintain records that contain information about bovine materials that would be

65
needed to identify devices that might contain such materials. In accordance with section 516 of
the act and 21 CFR part 895, interested persons may request an informal hearing on the
provisions of the proposed regulation with respect to medical devices within 30 days.  If a
request for an informal hearing is granted, the hearing will be conducted as a regulatory hearing
under 21 CFR part 16.
The proposed recordkeeping requirements for devices in this proposed rule are authorized
under section 519(a) of the act.  Under section 519(a), the agency may, by regulation, require
that manufacturers and importers establish and maintain records, make reports, and provide
information that the agency determines is necessary to ensure that devices are not adulterated or
misbranded and to otherwise ensure their safety and effectiveness.  FDA has determined that the
recordkeeping requirements in this proposed rule are necessary to ensure that devices intended
for use in or on the body do not contain prohibited cattle materials and, thus, are not adulterated
under section 501(g) of the act.  A device for which there is a failure or refusal to furnish any
material or information required under this proposed regulation would be deemed misbranded
under section 502(t) of the act.
The proposed recordkeeping requirements are also authorized under sections 701(a) and
(b) and 801(a) of the act. Because at this time there is no way to screen reliably for the presence
of the BSE agent or the presence of the cattle materials prohibited under this proposed rule,
applicants and manufacturers of medical devices would have to depend on records from their
suppliers of cattle materials to ensure that their source material does not contain any prohibited
cattle materials. The proposed requirements also would allow the agency to monitor compliance
with the proposed ban and, therefore, are necessary for the efficient enforcement of the act, in
accordance with section 701(a) of the act.  Section 801(a) of the act contains requirements with

66
regard to imported devices and provides for refusal of admission into the United States of
devices that appear to be adulterated or misbranded. Section 701(b) of the act authorizes the
Secretaries of the Treasury and Health and Human Services to jointly prescribe regulations for
the efficient enforcement of section 801 of the act.
With respect to new animal drugs, FDA is proposing to issue these regulations under the
adulteration provision in section 501(a)(2)(B) of the act and sections 512, 701(a) and (b) and
801
(a) of the act.  The adulteration provision in section 501(a)(2)(B) of the act provides FDA the
same authority for new animal drugs as described for drugs for humans previously in this
document.
FDA is proposing to amend its CGMP regulations to prohibit the use of certain cattle
materials in drug products and components intended for use in ruminant animals (proposed §
211
.116
)
.
Proposed § 500.200 would require that no drug product or component intended for use
in ruminants "be manufactured from or otherwise contain prohibited cattle materials."  Proposed
§ 211.116 would apply to drugs that are directly subject to the CGMP regulations.  For drugs for
ruminants that are not directly subject to the CGMP regulations, section 501(a)(2)(B) of the act
supports the proposed requirements in proposed § 500.200.
As provided in proposed § 500.200(d), a drug that fails to comply with the requirements
of § 500.200(b) would be adulterated under section 501(a)(2)(B) of the act.  Because of the
possibility of disease transmission to ruminants from exposure to prohibited cattle materials and
to humans from consuming food from animals exposed to prohibited cattle material, prohibiting
such cattle materials in drugs for ruminants would help ensure that new animal drugs for
ruminants meet the requirements of the act with respect to safety, and have the identity, and meet
the quality and purity characteristics they are purported or represented to possess.

67
Section 201(v) of the act defines a new animal drug to include "[a]ny drug intended for
use for animals other than man *** the composition of which is such that such drug is not
generally recognized, among experts qualified by scientific training and experience to evaluate
the safety and effectiveness of animal drugs, as safe and effective for use under the conditions
prescribed, recommended, or suggested in the labeling thereof ***." Based on the scientific data
and information available to FDA regarding the possibility of disease transmission to ruminants
from exposure to prohibited cattle materials, under this proposed rule any drug for ruminants
manufactured from or otherwise containing prohibited cattle materials is not GRAS/GRAE, and
therefore is a new animal drug under section 201(v) of the act.
Section 512 of the act provides that a new animal drug is unsafe for purposes of the
adulteration provisions in section 501(a)(5) and section 402(a)(2)(C)(ii) of the act (21 U.S.C.
342
(a)(2)(c)(ii)) unless there is an approval of that new animal drug application in effect.  For a
new animal drug application to be approved, the drug must be safe and effective for its intended
use(s).  Based on the scientific data and information available to FDA regarding the possibility of
disease transmission to humans from exposure to prohibited cattle materials, under the proposed
rule FDA would not approve an application or supplement for a drug for ruminants containing
prohibited cattle materials unless an exception or alternative has been granted based upon the
Center Director’s determination that the safety standard in section 512 of the act would still be
met.  In addition, under the proposed rule, a drug for ruminants containing prohibited cattle
materials that is already subject to an approval would no longer be shown to be safe based on the
presence of prohibited cattle materials, and would be in violation of section 512 of the act unless
an exception or alternative for use of the prohibited cattle materials has been granted.

68
Under section 512(a)(4) and section (a)(5) of the act, extralabel use of an approved
animal drug or human drug in animals is authorized if done under certain conditions set out in
FDA regulations. However, section 512(a)(4)(A) of the act also allows FDA to prohibit
particular extralabel uses of an approved new animal drug.  Thus, for example, a drug approved
for use in treating an animal of a nonruminant species could legally be used extralabelly to treat a
ruminant animal, if it meets required conditions, unless specifically prohibited.  Such drugs for
nonruminant animals are allowed to contain cattle materials prohibited from use in drugs for
ruminants.  Absent a special prohibition, these drugs also could be used in ruminants, through
extralabel use, thereby providing an avenue through which ruminants could be exposed to
prohibited cattle material.  Any human drug for which an exception or alternative is granted
could also be used extralabelly in ruminants, which could also provide another avenue through
which ruminants could be exposed to prohibited cattle materials.  Therefore, under section
512
(a)(4)(A) of the act (for drugs for animals) and section 512(a)(5) of the act (for drugs for
humans), FDA is proposing to prohibit such extralabel use in ruminants of drugs for
nonruminants or for humans containing the prohibited material.
FDA is issuing the proposed labeling requirement under sections 502(a) and 201(n) of the
act (21 U.S.C. 352(a) and 321(n)).  Section 502(a) provides that a drug is deemed misbranded if
its labeling is false or misleading in any particular.  Section 201(n) provides that “*** in
determining whether the labeling *** is misleading, there shall be taken into account (among
other things) not only representations made or suggested by statement, word, design, device, or
any combination thereof, but also the extent to which the labeling *** fails to reveal facts
material in the light of such representations or material with respect to consequences which may
result from the use of the article to which the labeling *** relates under the conditions of use ***

69
as are customary or usual."  The proposed rule would require drugs for non-ruminants that
contain prohibited materials that are prohibited from extralabel use in ruminants to be labeled
"Federal law prohibits the extralabel use of this product in ruminants."  We believe this statement
is material with respect to the consequences that may result from the extralabel use of
nonruminant drugs with prohibited materials in ruminants.  As discussed in other sections of this
preamble, the use of materials prohibited in drugs for ruminants presents a risk of BSE.
Therefore, under this proposed rule, the failure to include the labeling statement on drugs for
nonruminants which contain prohibited materials would render the drugs misbranded under
section 502(a) of the act. Under section 701(a) of the act, FDA is authorized to issue regulations
for the act's efficient enforcement.  Regulations that propose measures to ensure that drugs for
animals are being manufactured, processed, packed, or held in conformity with CGMP, and to
ensure that they comply with section 512 of the act, allow for efficient enforcement of the act.
These proposed regulations would require applicants and manufacturers of drugs for ruminants
that are manufactured from or otherwise contain material from cattle to establish and maintain
records that document the absence of prohibited cattle materials in such products and make such
records readily available to FDA for inspection and copying. These proposed recordkeeping
requirements are also authorized under sections 501(a)(2)(B) and 512(l) of the act.
Once material is removed from cattle, we may not be able to obtain the information
necessary to determine whether it is prohibited cattle material.  As noted previously, we would
not know from examination of a spinal cord whether the source animal was over 30 months of
age at the time of slaughter or whether it was inspected and passed.  Because at this time there is
no way to test reliably for the presence of the BSE agent or the presence of the cattle materials
prohibited in proposed § 500.200, applicants and manufacturers of drugs for ruminants must

70
depend on records from their suppliers of cattle materials to ensure that their source material
does not contain any cattle materials prohibited under proposed § 500.200.  Therefore, the
proposed recordkeeping requirements are necessary for the efficient enforcement of the proposed
rule.  Under proposed § 500.200(e), the failure of an applicant or manufacturer to comply with
the requirements of § 500.200(c) would render a drug for ruminants adulterated.
We are also proposing provisions relating to records regarding imported drugs for
ruminants under sections 801(a) and 701(b) of the act.  Importers of record of a drug for
ruminants that was manufactured from or otherwise contains cattle material would be required to
affirm that the drug product for import was manufactured from or contains cattle material, and
affirm that it was manufactured in compliance with the proposed rule.  If a drug was
manufactured from or otherwise contains cattle material, then importers of record would also be
required, if requested, to provide records to FDA within 5 days sufficient to demonstrate
compliance.  Under proposed § 500.200(f), failure of an importer of record to comply with these
requirements causes a drug to appear to be adulterated. Section 801(a) of the act provides
requirements with regard to imported drugs and provides for refusal of admission into the United
States of drugs for ruminants that appear to be adulterated. Section 701(b) of the act authorizes
the Secretaries of Treasury
3
and Health and Human Services to jointly prescribe regulations for
the efficient enforcement of section 801 of the act.
FDA has invoked section 361 of the PHS Act (42 U.S.C. 264) to prevent the transmission
of numerous communicable diseases, including diseases spread through certain shellfish, turtles,
birds, and human tissue intended for transplantation (see 21 CFR 1240.60 (molluscan shellfish),
3
Under the Homeland Security Act of 2002 (Public Law 107-296), the Secretary of the Treasury has
delegated all relevant Customs revenue authorities to the Secretary of Homeland Security, who has, in
turn, delegated them to the Commissioner of Customs and Border Protection (CBP or Customs).  If
finalized, we will issue this rule jointly with the Department of Homeland Security.

71
124
0.62
(turtles), 1240.65 (parrots and other psittacine birds), and parts 1270 and 1271 (human
tissue)).  Recently, FDA also issued under section 361 of the PHS Act regulations designed to
prevent the spread of monkeypox from African rodents to humans (21 CFR 1240.63).
Section 361 of the PHS Act provides legal authority for FDA to limit the use of
prohibited cattle materials in drugs, biological products, devices, new animal drugs for
ruminants, and HCT/Ps and to inspect and copy pertinent manufacturing records to ensure
compliance.  Section 361(a) of the PHS Act authorizes issuance and enforcement of regulations
necessary to prevent the introduction, transmission, or spread of communicable diseases from
foreign countries or between states.   Section 361(a) of the PHS Act also provides for such
inspection and destruction of articles found to be so infected or contaminated as to be "sources of
dangerous infection to human beings," as well as other measures that may be necessary to
prevent the introduction, transmission, or spread of communicable diseases from a foreign
country into a State, or from one State to another State.
Because the use of prohibited cattle materials in medical products for humans and drugs
for ruminants increases the risk that the agent that causes BSE could be transmitted to humans,
limiting the use of prohibited cattle materials in medical products for humans and drugs for
ruminants is a needed component of our efforts to prevent the transmission and spread of TSEs
including vCJD, in humans.  Scientists have concluded that exposure to the BSE agent is the
most plausible explanation for the occurrence of vCJD (Refs. 24 through 27).  For medical
products for humans, by prohibiting use of certain cattle materials, the proposed rule would
reduce the risk that the BSE agent would be transmitted directly into any person through
exposure to an infectious medical product.  For drugs for ruminants, by prohibiting use of certain
cattle materials, the proposed rule would reduce the risk that the BSE agent would be transmitted

72
directly into any ruminant.  By protecting ruminants from exposure to the BSE agent through
animal drugs, the proposed rule would also prevent transmission of the BSE agent to humans
who may be exposed to products containing any ruminant materials.  Consistent with the
authority granted by section 361 of the PHS Act to issue and enforce such regulations as are
necessary to prevent communicable disease transmission from foreign countries into the United
States and from one State or possession into another, this proposed rule would provide for FDA
to be able to inspect and copy pertinent manufacturing records.  Because at this time there is no
way to screen reliably for the presence of the BSE agent or the presence of the cattle materials
prohibited under this proposed rule, the requirements with respect to the maintenance,
inspection, and copying of manufacturing records are directly necessary to permit FDA to
enforce the other measures designed to prevent transmission of BSE.
The proposed rule contains a procedure under which FDA could permit a manufacturer
an exception or alternative to the restrictions on the use of prohibited cattle materials under
limited circumstances.  Specifically, a manufacturer would submit a written request for an
exception or alternative to the requirements by describing: (1) Why an exception or alternative is
needed; (2) the implicated product, including the type of prohibited cattle material, its
manufacturing and purification processes, and its route of administration; (3) the source of the
prohibited cattle material including information on the location where the cattle was born, raised,
and slaughtered; and (4) any other information relevant to the likelihood of the cattle having
ingested material prohibited under § 589.2000.  For medical products for humans, the written
request also would include:  (1) How the limitations are not necessary based on the risks of the
prohibited cattle materials in the product and the benefits of the product or (2) how such
restrictions are not necessary to ensure the safety of the product. For drugs for ruminants, the

73
written request would also include:  (1) How the requirement is not necessary:  (i) Based on the
risks of the prohibited cattle materials in the product to the target animal and the benefits of the
product to the target animal and (ii) to ensure a reasonable certainty of no harm to humans from
any food derived from the target animal to which the product is administered, or (2) how the
requirement is not necessary to ensure the safety of the product with respect to both the target
animal and any food derived from the target animal to which the product is administered. The
relevant Center Director could also grant written permission for an exception or alternative to the
proposed requirements on his own initiative, based on these same criteria.
As discussed previously, under this proposal, FDA expects that applicants or
manufacturers may submit a request for an exception or alternative when filing a new application
or premarket notification for a product containing prohibited cattle materials, or if an existing
product contains prohibited cattle materials.  Although FDA believes it is unlikely that applicants
or manufacturers who currently are not using prohibited cattle materials in their products will
reformulate their products to include prohibited cattle materials, proposing to do so would
require not only a request for an exception or alternative but also a supplement to the approved
application or a new premarket notification, consistent with existing regulations.
In considering whether an exception or alternative to requirements of this proposed rule
would meet the criteria described previously and therefore be appropriate, FDA would be
required to ensure that the statutory safety standards would still be met if the exception or
alternative were permitted.  For drugs for humans, FDA intends to apply the safety standards set
forth in sections 501(a)(2)(B) and 505 of the act.  Specifically, FDA would only approve a
request for an exception or alternative to the proposed limitations on prohibited cattle material if,
notwithstanding the exception or alternative: (1) The drug and the methods used in, or the

74
facilities or controls used for, its manufacturing, processing, packing, or holding conform to or
are operated or administered in conformity with CGMP to ensure that such drug meets the
requirements of the act as to safety and (2) the drug is safe for its intended use(s).
For biological products, FDA intends to apply the safety standard provided in section 351
of the PHS Act.  Specifically, FDA would only approve a request for an exception or alternative
to the proposed limitations on prohibited cattle material if, notwithstanding the exception or
alternative:  (1) The biological product that is the subject of the application is safe and (2) the
facility in which the biological product is manufactured, processed, packed, or held meets
standards designed to ensure that the biological product continues to be safe.
For human cells, tissues, and cellular and tissue-based products and other products
regulated under the authority of section 361 of the PHS Act, FDA would only approve a request
for an exception or alternative to the proposed limitations on prohibited cattle material if such
limitations are not necessary to prevent the introduction, transmission, or spread of TSE.
For devices, FDA intends to apply the standard in section 516 of the act.  Specifically,
FDA would approve a request for an exception or alternative to the proposed ban on prohibited
cattle materials only if, notwithstanding the exception or alternative, the device does not present
an unreasonable and substantial risk of illness or injury.
For new animal drugs, FDA intends to apply the safety standards set forth in section 512
and 501(a)(2)(B) of the act.  Specifically, FDA would approve a request for an exception or
alternative to the proposed limitations on prohibited cattle material only if, notwithstanding the
exception or alternative: (1) The drug and the methods used in, or the facilities or controls used
for, its manufacturing, processing, packing, or holding conform to or are operated or

75
administered in conformity with CGMP to ensure that such drug meets the requirements of the
act as to safety and (2) the drug is safe for its intended use(s).
VII. Effective Date and Opportunity for Public Comment
We are proposing that any final rule based on this proposal be effective 30 days after its
issuance in the Federal Register.
Requests for an informal hearing on the proposed ban related to medical devices must be
submitted by [insert date 30 days after date of publication in the FEDERAL REGISTER].
FDA invites public comment on this proposed rule, including the proposed effective date
for any final rule issued as a result of this proposal.  The comment period on this proposed rule
will be 60 days.  The agency will consider modifications to this proposed rule based on
comments made during the comment period.  Interested persons may submit to the Division of
Dockets Management (see ADDRESSES) written or electronic comments regarding this
proposed rule.  Submit a single copy of electronic comments or two paper copies of any mailed
comments, except that individuals may submit one paper copy.  Comments are to be identified
with the docket number found in brackets in the heading of this document.  Received comments
may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
VIII.  Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive Order 12866, the
Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995
(Public Law 104-4).  Executive Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to select regulatory
approaches that maximize net benefits (including potential economic, environmental, public

76
health and safety, and other advantages; distributive impacts; and equity). The agency believes
that this proposed rule is not an economically significant regulatory action as defined by the
Executive Order.
The Regulatory Flexibility Act requires agencies to analyze regulatory options that would
minimize any significant impact of a rule on small entities.  Because FDA has taken regulatory
action to reduce the risk of exposure to BSE in the United States and kept affected entities
informed on best practices, FDA believes the proposed rule would codify current practices of
most affected entities and ensure regulatory consistency across FDA-regulated products.  Few
entities will need to reformulate with alternative ingredients, submit a request for exception or
alternative to the limitation on the use of prohibited cattle material, or cease marketing.  The
FDA believes most market adjustments have taken place and this rule will not have a significant
economic impact on a substantial number of small entities.  A few manufacturers of certain drugs
prohibited from extralabel use in ruminants would incur one-time costs to add a warning
statement to the product labeling.  In addition, all manufacturers that use cattle material would
incur minor annual incremental recordkeeping costs.  Over 10 years, the annualized costs of the
proposed rule range from about $235,000 to $922,000 (at a 3 percent discount rate) and from
about $235,000 to $923,000 (at a 7 percent discount rate).
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires that agencies
prepare a written statement, which includes an assessment of anticipated costs and benefits,
before proposing “any rule that includes any Federal mandate that may result in the expenditure
by State, local, and tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation) in any one year.” The current threshold
after adjustment for inflation is $118 million, using the most current (2004) Implicit Price

77
Deflator for the Gross Domestic Product.  FDA does not expect this rule to result in any 1-year
expenditure that would meet or exceed this amount.
A. Need for the Proposed Rule
The need for this rule stems from inadequate information.  Consumers, physicians,
farmers, and veterinarians lack the information necessary to determine whether medical products
for humans or drugs for ruminants have the potential to contain materials contaminated with the
agent that causes BSE.
Currently, no validated method exists for testing medical products for humans and drugs
for ruminants for the agent that causes BSE; therefore, we do not have a means of distinguishing
products that contain infectious material from products that do not.  For example, rendered
material including brain and spinal cord may become an ingredient in medical products for
humans or drugs for ruminants even though its presence may not be indicated as such on the
label.  Furthermore, end users have no way to determine whether cattle material in these products
was sourced from nonambulatory disabled cattle or from cattle that were not inspected and
passed for human consumption.
Based on what is known about the transmission of BSE, there is some risk of occurrence
of vCJD in humans or of BSE in ruminants from the use of certain cattle-derived materials in
medical products for humans and drugs for ruminants, respectively.  While the results from
USDA's ongoing testing are reassuring, one cannot rule out the possible future discovery of
4
other positive animals in the United States or in a country allowed to export cattle material to the
United States, or of a future introduction of BSE.
To provide consistent protection across the
range of FDA-regulated products, it is necessary to put in place measures to reduce further the
4
USDA began a BSE testing program for cattle on June 1, 2004, after discovery of a case of BSE in a
cow in Washington State on December 23, 2003.
Deleted:
no surveillance program can
give absolute assurance of the absence of
BSE. In addition,

78
risk of spread of BSE in cattle and the risk of vCJD in humans. This risk may be reduced by
restricting the use of high-risk cattle materials in the manufacture of drugs for ruminants and
medical products for humans, similar to existing restrictions for food and cosmetics.
As discussed in section IV of this document, for over a decade the FDA has taken various
actions to reduce the risk of exposure to BSE in agency-regulated medical products for humans
and drugs for ruminants, including: (1) Providing information (through letters to manufacturers),
import alerts, and guidances to industry related to bovine materials, (2) convening TSE advisory
committee meetings to provide guidance on the sourcing of certain bovine products, including
gelatin, (3) encouraging companies to be aware of and to document sourcing of bovine material
through letters to manufacturers of drugs, biologics, and medical devices, and through the
product approval processes, and (4) recommending that manufacturers develop plans to ensure,
with a high degree of certainty, that bovine and ovine materials used in their products were not
from countries where BSE exists (“BSE countries” specified by USDA’s APHIS in 9 CFR
94.
18) or from sheep flocks (foreign or domestic) infected with scrapie.  Moreover,
manufacturers who also operate in Europe have taken steps to comply with European Union TSE
regulations and guidances.  The agency has also taken regulatory action to decrease the
likelihood of human and ruminant exposure to BSE (e.g., FDA 1997 ruminant feed rule,
FDA/USDA Animal Feed ANPRM, FDA 2005 Animal Feed proposed rule, Foods IFR, and
Foods Recordkeeping/Access proposed rule).
The agency is proposing additional regulatory action with this rule for medical products
for humans and drugs for ruminants that contain certain cattle material.  Existing regulations do
not explicitly bar the use of prohibited cattle material for these products.  By requiring that no
medical product for humans or drug for ruminants be manufactured from or otherwise contain

79


[Federal Register Volume 83, Number 192 (Wednesday, October 3, 2018)]
[Notices]
[Pages 49933-49934]
[FR Doc No: 2018-21531]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-3438]

Selection of the Appropriate Package Type Terms and
Recommendations for Labeling Injectable Medical Products Packaged in
Multiple-Dose, Single-Dose, and Single-Patient-Use Containers for Human
Use; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled ``Selection
of the Appropriate Package Type Terms and Recommendations for Labeling
Injectable Medical Products Packaged in Multiple-Dose, Single-Dose, and
Single-Patient-Use Containers for Human Use.'' This guidance finalizes
the draft guidance issued October 22, 2015, which provides
recommendations on the selection of appropriate package type terms and
selection of appropriate discard statements for injectable medical
products for human use, packaged in multiple-dose, single-dose, and
single-patient-use containers.

DATES: The announcement of the guidance is published in the Federal
Register on October 3, 2018.

ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:

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-2015-D-3438 for ``Selection of the Appropriate Package Type Terms
and Recommendations for Labeling Injectable Medical Products Packaged
in Multiple-Dose, Single-Dose, and Single-Patient-Use Containers for
Human Use.'' Received comments 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.
    You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
    Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002, or Office of
Communication, Outreach, and Development, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Yana Mille, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 51, Rm. 4166, Silver Spring, MD 20993,<PHONE_NUMBER>; or Stephen
Ripley, Center for Biologics Evaluation and Research, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry
entitled ``Selection of the Appropriate Package Type Terms and
Recommendations for Labeling Injectable Medical Products Packaged in
Multiple-Dose, Single-Dose, and Single-Patient-Use Containers for Human
Use.'' Unsafe injection practices, including the use of needles or
syringes for more than one patient or the improper use of medication
vials for more than one patient, threaten patient safety and have
resulted in multiple blood borne bacterial and viral infection
outbreaks. Bacterial and viral infections have been transmitted to
patients when single-dose containers were used improperly, the contents
became contaminated, and these contents were then administered to
multiple patients. Failure to follow standard precautions and aseptic
techniques has also been associated with several outbreaks of
infections involving multiple-dose vials.
    As part of its review of medical products, FDA clears or approves
package type terms and discard statements as part of the labeling of
injectable medical products. FDA believes that consistent use of
correct package type terms and discard statements for injectable
medical products for human use will promote their proper use and
provide a foundation for educational efforts to reduce the transmission
of blood borne pathogens. All the stakeholder comments on the draft
guidance were carefully reviewed and, where appropriate, clarifying
edits were made in the final guidance. The major change made in
response to stakeholder comments on the draft guidance was the addition
of a subsection titled ``Addition of a discard statement or changes to
an existing discard statement'' to the ``Labeling Requirements and
Recommendations'' section of the final guidance.
    Specifically, this guidance provides FDA's revised definitions for
single-dose and multiple-dose containers as well as the definition for
the new package type term single-patient-use container. These
containers may be part of a drug, a biological product, or a
combination product assigned to FDA's Center for Drug Evaluation and
Research, Center for Biologics Evaluation and Research, or certain
combination products assigned to FDA's Center for Devices and
Radiological Health. Marketing applications for such products include
new drug applications (NDAs), abbreviated new drug applications
(ANDAs), biologics license applications (BLAs), premarket approval
applications (PMAs), premarket notifications under the Federal Food,
Drug, and Cosmetic Act (FD&C Act), and requests for classification
submitted under the FD&C Act De Novo request.
    This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on the selection of the appropriate package
type terms and recommendations for labeling injectable medical products
packaged in multiple-dose, single-dose, and single-patient-use
containers for human use. It does not establish any rights for any
person and is not binding on FDA or the public. You can use an
alternative approach if it satisfies the requirements of the applicable
statutes and regulations. This guidance is not subject to Executive
Order 12866.

II. The Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of
information that are subject to review by the Office of Management and
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information discussed in this guidance have
been approved under the following OMB control numbers: OMB control
number 0910-0001 for NDAs, ANDAs, supplements to NDAs and ANDAs, and
annual reports; OMB control number 0910-0572 for prescription drug
product labeling; OMB control number 0910-0338 for BLA, BLA
supplements, and annual reports; OMB control number 0910-0120 for
premarket notifications (510(k)s); OMB control number 0910-0231 for
PMAs; OMB control number 0910-0485 for medical device labeling; and OMB
control number 0910-0577 for prominent and conspicuous mark of
manufactures on single-use devices.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm, or https://www.regulations.gov.

    Dated: September 27, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-21531 Filed 10-2-18; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register: July 24, 2008 (Volume 73, Number 143)]
[Proposed Rules]
[Page 43178-43180]
[DOCID:fr24jy08-20]

=======================================================================
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DEPARTMENT OF HOMELAND SECURITY

Coast Guard

33 CFR Part 117

[Docket No. USCG-2008-0648]
RIN 1625-AA09

Drawbridge Operation Regulation; Islais Creek, San Francisco, CA

AGENCY: Coast Guard, DHS.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Coast Guard proposes to change the operating regulation
for the Illinois Street drawbridge, mile 0.3, and the 3rd Street
drawbridge, mile 0.4, over Islais Creek to open on signal if at least
72 hours notice is given. This action is proposed due to the minimal
amount of vessels requiring drawbridge openings on the waterway.

DATES: Comments and related material must reach the Coast Guard on or
before September 22, 2008.

ADDRESSES: You may submit comments identified by Coast Guard docket
number USCG-2008-0648 to the Docket Management Facility at the U.S.
Department of Transportation. To avoid duplication, please use only one
of the following methods:
    (1) Online: http://www.regulations.gov.
    (2) Mail: Docket Management Facility (M-30), U.S. Department of
Transportation, West Building Ground Floor, Room W12-140, 1200 New
Jersey Avenue, SE., Washington, DC 20590-0001.
    (3) Hand delivery: Room W12-140 on the Ground Floor of the West
Building, 1200 New Jersey Avenue SE., Washington, DC 20590, between 9
a.m. and 5 p.m., Monday through Friday, except Federal holidays. The
telephone number is<PHONE_NUMBER>.
    (4) Fax:<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: If you have questions on this proposed
rule, call David H. Sulouff, Chief, Bridge Section, Eleventh Coast
Guard District, telephone<PHONE_NUMBER>. If you have questions on
viewing or submitting material to the docket, call Renee V. Wright,
Program Manager, Docket Operations, telephone<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Public Participation and Request for Comments

    We encourage you to participate in this rulemaking by submitting
comments and related materials. All comments received will be posted,
without change, to http://www.regulations.gov and will include any
personal information you have provided. We have an agreement with the
Department of Transportation (DOT) to use the Docket Management
Facility. Please see DOT's ``Privacy Act'' paragraph below.

Submitting Comments

    If you submit a comment, please include the docket number for this
rulemaking (USCG-2008-0648), indicate the specific section of this
document to which each comment applies, and give the reason for each
comment. We recommend that you include your name and a mailing address,
an e-mail address, or a phone number in the body of your document so we
can contact you if we have questions regarding your submission. You may
submit your comments and material by electronic means, mail, fax, or
delivery to the Docket Management Facility at the address under
ADDRESSES; but please submit your comments and material by only one
means. If you submit them by mail or delivery, submit them in an
unbound format, no larger than 8\1/2\ by 11 inches, suitable for
copying and electronic filing. If you submit them by mail and would
like to know they reached the Facility, please enclose a stamped, self-
addressed postcard or envelope. We will consider all comments and
material received during the comment period. We may change this
proposed rule in view of them.

Viewing Comments and Documents

    To view comments, as well as documents mentioned in this preamble
as being available in the docket, go to http://www.regulations.gov at
any time. Enter the docket number for this rulemaking (USCG-2008-0648)
in the Search box, and click ``Go>>.'' You may also visit either the
Docket Management Facility in Room W12-140 on the ground floor of the
DOT West Building, 1200 New Jersey Avenue, SE., Washington, DC 20590,
between 9 a.m. and 5 p.m., Monday through Friday, except Federal
holidays or Commander (dpw), Eleventh Coast Guard District, Building
50-2, Coast Guard Island, Alameda, CA 94501-5100, between 8 a.m. and 4
p.m., Monday through Friday, except Federal holidays.

Privacy Act

    Anyone can search the electronic form of all comments received into
any of our dockets by the name of the individual submitting the comment
(or signing the comment, if submitted on behalf of an association,
business, labor union, etc.). You may review the Department of
Transportation's Privacy Act Statement in the Federal Register
published on April 11, 2000 (65 FR 19477), or you may visit http://
DocketsInfo.dot.gov.

Public Meeting

    We do not now plan to hold a public meeting. But you may submit a
request for one to the Docket Management Facility at the address under
ADDRESSES explaining why one would be beneficial. If we determine that
one would aid this rulemaking, we will hold one at a time and place
announced by a later notice in the Federal Register.

Background and Purpose

    The Port of San Francisco (POSF) Illinois Street drawbridge, mile
0.3, over Islais Creek, in the City and County of San Francisco, CA, is
required to open on signal per 33 CFR 117.5. The drawbridge provides 5
feet of vertical clearance for vessels above Mean High Water (MHW) in
the closed-to-navigation position and unlimited vertical clearance when
open.
    The San Francisco Department of Public Works (SFDPW) 3rd Street

drawbridge, mile 0.4, over Islais Creek is required to open for vessels
if at least one hour notice is given, per 33 CFR 117.163. The
drawbridge provides 4 feet of vertical clearance above MHW.
    Islais Creek is one mile in length from its mouth to its navigable
terminus, an outfall culvert. It is located in an industrial section of
southeast San Francisco with no marinas on the waterway. There have
been no requests for openings of the 3rd Street drawbridge and no
complaints from waterway users since construction of the Illinois
Street drawbridge in 2003.
    Due to infrequent calls for drawbridge openings, the POSF requested
at least 72 hour notification. A 72 hour notification will allow the
POSF to use personnel more efficiently and meet the reasonable needs of
present navigation on the waterway.

Discussion of Proposed Rule

    The proposed regulation would amend the Illinois Street drawbridge,
mile 0.3, operation regulation from opening ``on signal'' to opening
``on signal, if at least 72 hours notice is given.'' The proposed
regulation would amend the 3rd Street drawbridge, mile 0.4, operation
regulation from opening ``on signal, if at least one hour notice is
given'' to open ``on signal, if at least 72 hours notice is given.''
    This amendment would maintain uniformity on the waterway and allow
the bridge owners to manage their personnel more efficiently while
meeting the reasonable needs of navigation.

Regulatory Analyses

    We developed this proposed rule after considering numerous statutes
and executive orders related to rulemaking. Below we summarize our
analyses based on 13 of these statutes or executive orders.

Regulatory Planning and Review

    This proposed rule is not a ``significant regulatory action'' under
section 3(f) of Executive Order 12866, Regulatory Planning and Review,
and does not require an assessment of potential costs and benefits
under section 6(a)(3) of that Order. The Office of Management and
Budget has not reviewed it under that Order.
    We expect the economic impact of this proposed rule to be so
minimal that a full Regulatory Evaluation is unnecessary.
    From 1990-2000, the existing 3rd Street drawbridge, mile 0.4,
annually averaged 8 openings for State, Federal, and local vessels, 2.3
openings for recreational vessels, and 1.3 openings for tugs and
barges. There has been an average of 15.8 lifts, including testing of
the drawspan, per year from 1990 to 2000. There are no marinas on the
waterway and none are currently planned. The last commercial vessel to
request a drawspan opening did so to remove an abandoned vessel from
Islais Creek. Economic impact to commercial vessels is expected to be
minimal. Impacts to recreational vessels are also expected to be
minimal.

Small Entities

    Under the Regulatory Flexibility Act (5 U.S.C. 601-612), we have
considered whether this proposed rule would have a significant economic
impact on a substantial number of small entities. The term ``small
entities'' comprises small businesses, not-for-profit organizations
that are independently owned and operated and are not dominant in their
fields, and governmental jurisdictions with populations of less than
50,000.
    The Coast Guard certifies under 5 U.S.C. 605(b) that this proposed
rule would not have a significant economic impact on a substantial
number of small entities.
    This action will not have a significant economic impact on a
substantial number of small entities for the following reasons. Vessel
traffic on this waterway has been minimal since 1990. Recreational
vessels that transit close to the shoreline, i.e. kayaks, canoes, and
other personal water craft, can safely transit under these drawbridges
at any time.
    If you think that your business, organization, or governmental
jurisdiction qualifies as a small entity and that this rule would have
a significant economic impact on it, please submit a comment (see
ADDRESSES) explaining why you think it qualifies and how and to what
degree this rule would economically affect it.

Assistance for Small Entities

    Under section 213(a) of the Small Business Regulatory Enforcement
Fairness Act of 1996 (Pub. L. 104-121), we want to assist small
entities in understanding this proposed rule so they can better
evaluate its effects on them and participate in the rulemaking. If the
rule would affect your small business, organization, or governmental
jurisdiction and you have questions concerning its provisions or
options for compliance, please contact David H. Sulouff, Chief, Bridge
Section, Eleventh Coast Guard District, telephone<PHONE_NUMBER>. The
Coast Guard will not retaliate against small entities that question or
complain about this rule or any policy or action of the Coast Guard.

Collection of Information

    This proposed rule would call for no new collection of information
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

Federalism

    A rule has implications for federalism under Executive Order 13132,
Federalism, if it has a substantial direct effect on State or local
governments and would either preempt State law or impose a substantial
direct cost of compliance on them. We have analyzed this proposed rule
under that Order and have determined that it does not have implications
for federalism.

Unfunded Mandates Reform Act

    The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538)
requires Federal agencies to assess the effects of their discretionary
regulatory actions. In particular, the Act addresses actions that may
result in the expenditure by a State, local, or tribal government, in
the aggregate, or by the private sector of $100,000,000 or more in any
one year. Though this proposed rule will not result in such an
expenditure, we do discuss the effects of this rule elsewhere in this
preamble.

Taking of Private Property

    This proposed rule would not affect a taking of private property or
otherwise have taking implications under Executive Order 12630,
Governmental Actions and Interference with Constitutionally Protected
Property Rights.

Civil Justice Reform

    This proposed rule meets applicable standards in sections 3(a) and
3(b)(2) of Executive Order 12988, Civil Justice Reform, to minimize
litigation, eliminate ambiguity, and reduce burden.

Protection of Children

    We have analyzed this proposed rule under Executive Order 13045,
Protection of Children from Environmental Health Risks and Safety
Risks. This rule is not an economically significant rule and would not
create an environmental risk to health or risk to safety that might
disproportionately affect children.

Indian Tribal Governments

    This proposed rule does not have tribal implications under
Executive Order 13175, Consultation and Coordination with Indian Tribal

Governments, because it would not have a substantial direct effect on
one or more Indian tribes, on the relationship between the Federal
Government and Indian tribes, or on the distribution of power and
responsibilities between the Federal Government and Indian tribes.

Energy Effects

    We have analyzed this proposed rule under Executive Order 13211,
Actions Concerning Regulations That Significantly Affect Energy Supply,
Distribution, or Use. We have determined that it is not a ``significant
energy action'' under that order because it is not a ``significant
regulatory action'' under Executive Order 12866 and is not likely to
have a significant adverse effect on the supply, distribution, or use
of energy. The Administrator of the Office of Information and
Regulatory Affairs has not designated it as a significant energy
action. Therefore, it does not require a Statement of Energy Effects
under Executive Order 13211.

Technical Standards

    The National Technology Transfer and Advancement Act (NTTAA) (15
U.S.C. 272 note) directs agencies to use voluntary consensus standards
in their regulatory activities unless the agency provides Congress,
through the Office of Management and Budget, with an explanation of why
using these standards would be inconsistent with applicable law or
otherwise impractical. Voluntary consensus standards are technical
standards (e.g., specifications of materials, performance, design, or
operation; test methods; sampling procedures; and related management
systems practices) that are developed or adopted by voluntary consensus
standards bodies.
    This proposed rule does not use technical standards. Therefore, we
did not consider the use of voluntary consensus standards.

Environment

    We have analyzed this proposed rule under Commandant Instruction
M16475.lD and Department of Homeland Security Management Directive
5100.1, which guides the Coast Guard in complying with the National
Environmental Policy Act of 1969 (NEPA) (42 U.S.C. 4321-4370f), and
have made a preliminary determination that this action is not likely to
have a significant effect on the human environment because it simply
promulgates the operating regulations or procedures for drawbridges. We
seek any comments or information that may lead to the discovery of a
significant environmental impact from this proposed rule.

List of Subjects in 33 CFR Part 117

    Bridges.
    For the reasons discussed in the preamble, the Coast Guard proposes
to amend 33 CFR part 117 as follows:

PART 117--DRAWBRIDGE OPERATION REGULATIONS

    1. The authority citation for part 117 continues to read as
follows:

    Authority: 33 U.S.C. 499; 33 CFR 1.05-1; Department of Homeland
Security Delegation No. 0170.1.

    2. Revise Sec.  117.163 to read as follows:

Sec.  117.163  Islais Creek (Channel).

    (a) The draw of the Illinois Street Bridge, mile 0.3 at San
Francisco, shall open on signal if at least 72 hours notice is given to
the Port of San Francisco.
    (b) The draw of the 3rd Street Bridge, mile 0.4 at San Francisco,
shall open on signal if at least 72 hours notice is given to the San
Francisco Department of Public Works.

    Dated: July 10, 2008.
J. E. Long,
Captain, U.S. Coast Guard, Acting Commander, Eleventh Coast Guard
District.
[FR Doc. E8-16896 Filed 7-23-08; 8:45 am]

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