Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile, 47911-47914 [2019-19643]
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Federal Register / Vol. 84, No. 176 / Wednesday, September 11, 2019 / Proposed Rules
substantial number of small entities
under the criteria of the Regulatory
Flexibility Act.
Environmental Review
This proposal will be subject to an
environmental analysis in accordance
with FAA Order 1050.1F,
‘‘Environmental Impacts: Policies and
Procedures’’ prior to any FAA final
regulatory action.
List of Subjects in 14 CFR Part 71
Airspace, Incorporation by reference,
Navigation (air).
The Proposed Amendment
Accordingly, pursuant to the
authority delegated to me, the Federal
Aviation Administration proposes to
amend 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
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.
§ 71.1
[Amended]
2. The incorporation by reference in
14 CFR 71.1 of FAA Order 7400.11C,
Airspace Designations and Reporting
Points, dated August 13, 2018, and
effective September 15, 2018, is
amended as follows:
■
Paragraph 5000
Class D Airspace.
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ASO MS D Meridian, MS [Amended]
Joe Williams NOLF, MS (Lat. 32°47′56″ N,
long. 88°50′04″ W)
That airspace extending upward from the
surface to and including 3,000 feet MSL
within a 4.2-mile radius of Joe Williams
NOLF. This Class D airspace area is effective
during the specific dates and times
established by a Notice to Airmen. The
effective date and time will thereafter be
continuously published in the Chart
Supplement.
ASO MS D Meridian, MS [Amended]
Key Field, MS (Lat. 32°19′57″ N, long.
88°45′07″ W)
That airspace extending upward from the
surface to and including 2,800 feet MSL
within a 4.5-mile radius of Key Field. This
Class D airspace area is effective during the
specific dates and times established in
advance by a Notice to Airmen. The effective
date and time will thereafter be continuously
published in the Char Supplement.
ASO MS D Meridian, MS [Amended]
NAS Meridian/McCain Field, MS (Lat.
32°33′13″ N, long. 88°33′19″ W)
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Meridian TACAN (Lat. 32°34′42″ N, long.
88°32′43″ W)
That airspace extending upward from the
surface to and including 2,800 feet MSL
within a
5.3-mile radius of NAS Meridian/McCain
Field, and within 1 mile each side of the 009°
bearing from the airport extending from the
5.3 mile radius to 5.5 miles north of the
airport; and within 1.5 miles each side of the
189° bearing from the airport extending from
the 5.3-mile radius to 6 miles south of the
airport; and within 1.6 miles each side of the
Meridian TACAN 331° radial extending from
the 5.3-mile radius to 5.6 miles northwest the
Meridian TACAN. This Class D airspace area
is effective during the specific dates and
times established in advance by a Notice to
Airmen. The effective date and time will
thereafter be continuously published in the
Chart Supplement.
Paragraph 6004 Class E Airspace Areas
Designated as an Extension to a Class D or
Class E Surface Area.
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ASO MS E4 Meridian, MS [Amended]
Key Field, MS (Lat. 32°19′57″ N, long.
88°45′07″ W)
Meridian VORTAC (Lat. 32°22′42″ N, long.
88°48′15″ W)
That airspace extending upward from the
surface within 1 mile each side of the 009°
bearing from Key Field extending from the
4.5-mile radius of Key Field to 4.9 miles
north of Key Field, and within 1 mile each
side of the 044° bearing from Key Field
extending from the 4.5-mile radius of Key
Field to 4.6 miles northeast of Key Field, and
within 2.9 miles each side of the Meridian
VORTAC 141° radial extending from the 4.5mile radius of Key Field to 11 miles
southeast of the Meridian VORTAC, and
within 1 mile each side of the 189° bearing
from Key Field extending from the 4.5-mile
radius of Key Field to 4.6 miles south of Key
Field, and within 1 mile each side of the 224°
bearing from Key Field extending from the
4.5-mile radius of Key Field to 4.6 miles
southwest of Key Field. This Class E airspace
area is effective during the specific dates and
times established in advance by a Notice to
Airmen. The effective date and time will
thereafter be continuously published in the
Chart Supplement.
Paragraph 6005 Class E Airspace Areas
Extending Upward From 700 Feet or More
Above the Surface of the Earth.
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of Key Field, and within 1 mile each side of
the 009° bearing from Key Field extending
from the 7-mile radius of Key Field to 12.5
miles north of Key Field; and within 3.4
miles each side of the 009° bearing from the
Key Field: RWY 19–LOC extending from the
7-mile radius of Key Field to 11.1 miles north
of the Key Field: RWY 19–LOC, and within
2 miles each side of the 044° bearing from
Key Field extending from the 7-mile radius
of Key Field to 11.6 miles northeast of Key
Field, and within 3.6 miles each side of the
Meridian VORTAC 141° radial extending
from the 4.5-mile radius of Key Field to 13.9
miles southeast of the Meridian VORTAC,
and within 1 mile each side of the 189°
bearing from Key Field extending from the 7mile radius of Key Field to 12.6 miles south
of Key Field, and within 3.4 miles each side
of the 189° bearing from the Key Field: RWY
01–LOC extending from the 7-mile radius of
Key Field to 11.2 miles south of the Key
Field: RWY 01–LOC, and within 1.5 miles
each side of the Meridian VORTAC 311°
radial extending from the 7-mile radius of
Key Field to 14.3 miles northwest of the
Meridian VORTAC, and within a 6.7-mile
radius of Joe Williams NOLF, and within a
7.8-mile radius of NAS Meridian/McCain
Field, and within 6.7 miles each side of a line
from Joe Williams NOLF to NAS Meridian/
McCain Field.
Issued in Fort Worth, Texas, on September
4, 2019.
Steve Szukala,
Acting Manager, Operations Support Group,
ATO Central Service Center.
[FR Doc. 2019–19543 Filed 9–10–19; 8:45 am]
BILLING CODE 4910–13–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 15
[Docket No. FDA–2019–N–3631]
Use of Fecal Microbiota for
Transplantation to Treat Clostridium
difficile Infection Not Responsive to
Standard Therapies; Public Hearing;
Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
ASO MS E5 Meridian, MS [Amended]
Key Field, MS (Lat. 32°19′57″ N, long.
88°45′07″ W)
Key Field: RWY 19–LOC (Lat. 32°18′54″ N,
long. 88°45′25″ W)
Meridian VORTAC (Lat. 32°22′42″ N, long.
88°48′15″ W)
Key Field: RWY 01–LOC (Lat. 32°20′52″ N,
long. 88°45′02″ W)
Joe Williams NOLF, MS (Lat. 32°47′56″ N,
long. 88°50′04″ W)
NAS Meridian/McCain Field, MS (Lat.
32°33′13″ N, long. 88°33′19″ W)
That airspace extending upward from 700
feet above the surface within a 7-mile radius
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Notification of public hearing;
request for comments.
ACTION:
The Food and Drug
Administration (FDA, the Agency, or
we) is announcing a public hearing to
obtain input on the use of fecal
microbiota for transplantation (FMT) to
treat Clostridium difficile infection not
responsive to standard therapies. FDA
will consider scientific data and other
information from the public hearing as
we continue to consider ways to support
the development of FMT to treat C.
SUMMARY:
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difficile infection not responsive to
standard therapies and the impact of the
enforcement policy on such
development.
DATES: The public hearing will be held
on November 4, 2019, from 9 a.m. to 4
p.m. The hearing may be extended or
may end early, depending on the level
of public participation. Persons seeking
to present or speak at the public hearing
must register by October 8, 2019.
Persons seeking to attend but not
present at the public hearing must
register by October 22, 2019. Section III
of this document provides attendance
and registration information. Electronic
or written comments will be accepted
after the public hearing until January 21,
2020.
ADDRESSES: The public hearing will be
held at the FDA White Oak Campus,
10903 New Hampshire Ave., Bldg. 31
Conference Center, the Great Room
(Rooms 1503B and 1503C), Silver
Spring, MD 20993–0002. Entrance for
public hearing 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/about-fda/white-oakcampus-information/public-meetingsfda-white-oak-campus.
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 January 21, 2020. The
https://www.regulations.gov electronic
filing system will accept comments
until 11:59 p.m. Eastern Time at the end
of January 21, 2020. 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
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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–
2019–N–3631 for ‘‘Use of Fecal
Microbiota for Transplantation to Treat
Clostridium difficile Infection Not
Responsive to Standard Therapies.’’
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
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‘‘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/201523389.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:
Shruti Modi, Center for Biologics
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301,
Silver Spring, MD 20993–0002, 240–
402–7911.
SUPPLEMENTARY INFORMATION:
I. Background and Purpose of the
Public Hearing
Fecal microbiota collected from
healthy individuals are being
investigated for use in the treatment of
C. difficile infection. Published data
suggest that the use of fecal microbiota
to restore intestinal flora may be an
effective therapy in the management of
C. difficile infection not responsive to
standard therapies. However, the
efficacy and safety profiles of this
intervention have not yet been fully
evaluated in adequate and wellcontrolled clinical trials.
FMT administered to treat C. difficile
infection meets the definition of a
biological product, as defined in section
351(i) of the Public Health Service
(PHS) Act (42 U.S.C. 262(i)), and the
definition of a drug within the meaning
of section 201(g) of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C.
321(g)). As a biological product, FMT
administered to treat C. difficile
infection is subject to the licensing
requirements set forth in section 351 of
the PHS Act. FDA has received public
comments from some stakeholders
suggesting that FMT might be regulated
as a human cell, tissue, and cellular and
tissue-based product (HCT/P; see 21
CFR part 1271). FMT is a live
biotherapeutic product composed of
microorganisms. Microorganisms are
not human cells or tissues and do not
meet the definition of HCT/P (see 21
CFR 1271.3(d)). The hearing will not
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include discussions about these
comments.
In the Federal Register of July 18,
2013 (78 FR 42965), following a public
workshop, held on May 2 and 3, 2013,
entitled ‘‘Fecal Microbiota for
Transplantation,’’ FDA announced the
availability of a guidance for industry
entitled ‘‘Enforcement Policy Regarding
Investigational New Drug Requirements
for Use of Fecal Microbiota for
Transplantation to Treat Clostridium
difficile Infection Not Responsive to
Standard Therapies’’ (July 2013
Guidance) (available at: https://
www.fda.gov/media/86440/download).
The July 2013 Guidance, which is still
in effect, informed members of the
medical and scientific communities and
other interested persons that we intend
to exercise enforcement discretion
regarding the investigational new drug
(IND) requirements for the use of FMT
to treat C. difficile infection not
responding to standard therapies,
provided that the treating physician
obtains adequate consent from the
patient or his or her legally authorized
representative for the use of FMT
products. The guidance states that
consent should include, at a minimum,
a statement that the use of FMT
products to treat C. difficile is
investigational and a discussion of its
potential risks.
In the Federal Register of February
26, 2014 (79 FR 10814), we announced
the availability of a draft guidance for
industry entitled ‘‘Enforcement Policy
Regarding Investigational New Drug
Requirements for Use of Fecal
Microbiota for Transplantation to Treat
Clostridium difficile Infection Not
Responsive to Standard Therapies’’
(March 2014 Draft Guidance). The
March 2014 Draft Guidance informed
members of the medical and scientific
communities and other interested
persons that we intended to exercise
enforcement discretion regarding the
IND requirements for the use of FMT to
treat C. difficile infection not
responding to standard therapies,
provided: (1) The licensed healthcare
provider treating the patient obtains
adequate consent from the patient or his
or her legally authorized representative
for use of the FMT product; (2) the FMT
product is obtained from a donor known
to either the patient or the licensed
healthcare provider treating the patient;
and (3) the stool donor and stool are
qualified by screening and testing
performed under the direction of the
licensed healthcare provider for the
purpose of providing the FMT product
to treat his or her patient. FDA received
many public comments in favor of
patient access to FMT to treat C.
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difficile, including access to FMT
products from stool banks, but objecting
to the provision that the donor be
known to the patient or the treating
licensed healthcare provider.
After considering the comments on
the March 2014 Draft Guidance, in the
Federal Register of March 1, 2016 (81
FR 10632), FDA announced the
availability of a revised draft guidance
for industry entitled ‘‘Enforcement
Policy Regarding Investigational New
Drug Requirements for Use of Fecal
Microbiota for Transplantation to Treat
Clostridium difficile Infection Not
Responsive to Standard Therapies’’
(March 2016 Draft Guidance) (available
at: https://www.fda.gov/media/96562/
download). The March 2016 Draft
Guidance replaced the March 2014 Draft
Guidance and proposed to revise our
policy with regard to patient access to
FMT product. We noted that centralized
manufacturing in stool banks presents
safety concerns related to the use of
FMT from a limited number of donors
administered to multiple patients.
Therefore, we stated that FDA does not
intend to extend enforcement discretion
with respect to the IND requirements
applicable to stool banks distributing
FMT products. We stated that the
sponsor’s compliance with the IND
requirements would help to ensure that
the stool donor and stool are
appropriately qualified by screening and
testing and that centralized processing
of FMT adheres to appropriate current
good manufacturing conditions. FDA
received many public comments on this
draft guidance, and we are continuing to
evaluate our enforcement policy.
The purpose of this public hearing is
to obtain public input on the state of the
science regarding FMT to treat C.
difficile infection not responsive to
standard therapies, including the
available clinical evidence for safety
and effectiveness of FMT for this use
and to understand better the impact of
FDA’s enforcement policy on product
development.
II. Issues for Consideration and Request
for Data and Information
FDA would like input from
stakeholders, including patients,
clinicians, research scientists, industry,
healthcare providers, and stool banks.
We encourage public comments and
presentations at the public hearing. If
submitting comments, data, and
information to the docket, please
identify available references for the data
and information, as well as the general
category area and specific question
listed below.
As noted above, fecal microbiota
collected from healthy individuals are
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47913
being investigated for use in the
treatment of C. difficile infection.
Published data suggest that the use of
fecal microbiota to restore intestinal
flora may be an effective therapy in the
management of refractory C. difficile
infection. However, the efficacy and
safety profiles of this intervention have
not yet been fully evaluated in
controlled clinical trials. To inform
FDA’s understanding of the current
scientific status of FMT, especially as it
relates to the use of FMT to treat C.
difficile infection not responsive to
standard therapies, we are interested in
obtaining information, including data
and studies, from all stakeholders,
including patients, clinicians, research
scientists, industry, healthcare
providers and stool banks on the
following topics:
1. Clinical Evidence of Effectiveness
• What is the strength of the evidence
for the use of FMT to treat C. difficile
infection not responsive to standard
therapies?
• Please identify any published data
from rigorously conducted randomized
controlled (placebo or non-FMT
standard of care comparator) trials that
support the use of FMT for:
Æ Prevention of recurrent C. difficile
infection.
Æ Treatment of refractory C. difficile
infection.
2. Safety Evaluation
• What is the strength of evidence for
the safety of FMT in patients with C.
difficile infection not responsive to
standard therapies?
• Has meaningful safety information
been collected under FDA’s
enforcement policy? How can any
deficiencies in safety data collection be
remedied?
• Are there particular safety issues
FDA should consider regarding these
products (e.g., donor screening/mixing
donations)?
3. Impact of FDA’s current Enforcement
Policy on FMT Product Development
• What impact has FDA’s
enforcement policy had on recruitment
and ability to conduct clinical trials to
assess safety and effectiveness of FMT
for C. difficile infection not responsive
to standard therapies?
Æ Can specific examples be cited?
Æ How can any negative impacts be
remedied?
• How does the existing availability
of FMT affect the incentives for, and the
feasibility of, FMT drug-development
programs?
• The use of FMT is addressed in
some treatment guidelines (Infectious
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Diseases Society of America and
American Gastroenterological
Association). What impact has this had
on patient recruitment and conduct of
clinical trials?
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4. Future and Path Forward
• What additional scientific
information is needed to determine the
safety and effectiveness of FMT for C.
difficile infection not responsive to
standard therapies?
• How generalizable are the existing
safety and effectiveness data on use of
a specific FMT product for C. difficile
infection not responsive to standard
therapies to other FMT products for
which safety and effectiveness data are
not available?
• Please comment on how FDA can
facilitate patient access, protect patient
safety, and include enough flexibility to
support innovation for the development
and licensure of safe and effective FMT
products for C. difficile infection not
responsive to standard therapies.
III. Participating in the Public Hearing
Registration and Requests to Speak
and for Formal Oral Presentations: The
FDA Conference Center at the White
Oak location is a Federal facility with
security procedures and limited seating.
Attendance will be free. An agenda for
the hearing and any other background
materials will be made available on
October 25, 2019, at https://
www.fda.gov/vaccines-blood-biologics/
news-events-biologics/workshopsmeetings-conferences-biologics. If you
need special accommodations because
of a disability, please contact Sherri
Revell or Loni Warren Henderson at
240–402–8010 at least 7 days before the
hearing.
For those interested in speaking at the
hearing or presenting at the hearing
with a formal oral presentation, please
register at https://www.eventbrite.com/
e/use-of-fecal-microbiota-fortransplantation-to-treat-clostridiumdifficile-infection-not-responsive-tickets63906239282 as ‘‘In-person presenter.’’
Speaker and presenter registrations are
due October 8, 2019.
FDA will try to accommodate all
persons who wish to make a formal oral
presentation. Formal oral presenters
may use an accompanying slide deck.
Individuals wishing to present should
identify their name, which stakeholder
group they represent (e.g., patient,
clinician, research scientist, industry,
stool bank), and the number of the
specific question, or questions, they
wish to address. FDA will consider this
information when organizing the
agenda. Individuals and organizations
with common interests should consider
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consolidating or coordinating their
presentations and request time for a
joint presentation. Individual
organizations are limited to a single
presentation slot. FDA will notify
registered presenters of their scheduled
presentation times on October 21, 2019.
The time allotted for each presentation
will depend on the number of
individuals who wish to speak. If
registered presenters are using an
accompanying slide deck, those
presenters must submit an electronic
copy of their presentation (PowerPoint
or PDF) to CBERPublicEvents@
fda.hhs.gov on or before October 28,
2019. Persons registered to present are
encouraged to arrive at the hearing room
early and check in at the onsite
registration table to confirm their
designated presentation time. Actual
presentation times, however, may vary
based on how the hearing progresses in
real time.
In-person attendance: For those who
would like to attend in-person, but who
are not making a formal presentation,
please register at https://
www.eventbrite.com/e/use-of-fecalmicrobiota-for-transplantation-to-treatclostridium-difficile-infection-notresponsive-tickets-63906239282 as ‘‘Inperson attendee—no participation.’’
Seating is limited, and early registration
is recommended to allow for broad
participation.
Streaming Webcast of the Public
Hearing: For those unable to attend in
person, FDA will provide a live webcast
of the hearing. Please register at https://
www.eventbrite.com/e/use-of-fecalmicrobiota-for-transplantation-to-treatclostridium-difficile-infection-notresponsive-tickets-63906239282 as
‘‘online (webcast only)’’.
Media: Please register at https://
www.eventbrite.com/e/use-of-fecalmicrobiota-for-transplantation-to-treatclostridium-difficile-infection-notresponsive-tickets-63906239282 as
‘‘Media’’ by October 28, 2019.
Transcripts: Please be advised that as
soon as a transcript is available, it will
be accessible at https://www.fda.gov/
vaccines-blood-biologics/news-eventsbiologics/workshops-meetingsconferences-biologics and https://
www.regulations.gov. It may be viewed
at the Dockets Management Staff (see
ADDRESSES).
IV. Notification of Hearing Under 21
CFR Part 15
The Commissioner of Food and Drugs
is announcing that the public hearing
will be held in accordance with part 15
(21 CFR part 15). The hearing will be
conducted by a presiding officer, who
will be accompanied by FDA senior
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management officials. Under § 15.30(f)
(21 CFR 15.30(f)), the hearing is
informal and the rules of evidence do
not apply. No participant may interrupt
the presentation of another participant.
Only the presiding officer and panel
members may question any person
during or at the conclusion of each
presentation. Public hearings under part
15 are subject to FDA’s policy and
procedures for electronic media
coverage of FDA’s public administrative
proceedings (21 CFR part 10, subpart C).
Under 21 CFR 10.205, representatives
of the electronic media may be
permitted, subject to certain limitations,
to videotape, film, or otherwise record
FDA’s public administrative
proceedings, including presentations by
participants. Persons attending FDA’s
public hearings are advised that the
Agency is not responsible for providing
access to electrical outlets.
The hearing will be transcribed as
stipulated in § 15.30(b) (see section III of
this document). To the extent that the
conditions for the hearing, as described
in this notification, conflict with any
provisions set out in part 15, this
notification acts as a waiver of those
provisions as specified in § 15.30(h).
Dated: September 5, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019–19643 Filed 9–10–19; 8:45 am]
BILLING CODE 4164–01–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 52
[EPA–R03–OAR–2019–0207; FRL–9999–64–
Region 3]
Approval and Promulgation of Air
Quality Implementation Plans; District
of Columbia; Reasonably Available
Control Technology State
Implementation Plan for Nitrogen
Oxides Under the 2008 Ozone National
Ambient Air Quality Standard
Environmental Protection
Agency (EPA).
ACTION: Proposed rule.
AGENCY:
The Environmental Protection
Agency (EPA) is proposing to approve a
state implementation plan (SIP) revision
submitted by the District of Columbia.
This revision pertains to reasonably
available control technology (RACT)
requirements for nitrogen oxides (NOX)
under the 2008 8-hour ozone national
ambient air quality standard (2008
ozone NAAQS). The District of
Columbia’s submittal for the NOX RACT
SUMMARY:
E:\FR\FM\11SEP1.SGM
11SEP1
]]>Agencies
[Federal Register Volume 84, Number 176 (Wednesday, September 11, 2019)]
[Proposed Rules]
[Pages 47911-47914]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-19643]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 15
[Docket No. FDA-2019-N-3631]
Use of Fecal Microbiota for Transplantation to Treat Clostridium
difficile Infection Not Responsive to Standard Therapies; Public
Hearing; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notification of public hearing; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
announcing a public hearing to obtain input on the use of fecal
microbiota for transplantation (FMT) to treat Clostridium difficile
infection not responsive to standard therapies. FDA will consider
scientific data and other information from the public hearing as we
continue to consider ways to support the development of FMT to treat C.
[[Page 47912]]
difficile infection not responsive to standard therapies and the impact
of the enforcement policy on such development.
DATES: The public hearing will be held on November 4, 2019, from 9 a.m.
to 4 p.m. The hearing may be extended or may end early, depending on
the level of public participation. Persons seeking to present or speak
at the public hearing must register by October 8, 2019. Persons seeking
to attend but not present at the public hearing must register by
October 22, 2019. Section III of this document provides attendance and
registration information. Electronic or written comments will be
accepted after the public hearing until January 21, 2020.
ADDRESSES: The public hearing will be held at the FDA White Oak Campus,
10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great Room
(Rooms 1503B and 1503C), Silver Spring, MD 20993-0002. Entrance for
public hearing 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/about-fda/white-oak-campus-information/public-meetings-fda-white-oak-campus.
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 January 21, 2020. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of January 21, 2020. 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-2019-N-3631 for ``Use of Fecal Microbiota for Transplantation to
Treat Clostridium difficile Infection Not Responsive to Standard
Therapies.'' 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: Shruti Modi, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.
SUPPLEMENTARY INFORMATION:
I. Background and Purpose of the Public Hearing
Fecal microbiota collected from healthy individuals are being
investigated for use in the treatment of C. difficile infection.
Published data suggest that the use of fecal microbiota to restore
intestinal flora may be an effective therapy in the management of C.
difficile infection not responsive to standard therapies. However, the
efficacy and safety profiles of this intervention have not yet been
fully evaluated in adequate and well-controlled clinical trials.
FMT administered to treat C. difficile infection meets the
definition of a biological product, as defined in section 351(i) of the
Public Health Service (PHS) Act (42 U.S.C. 262(i)), and the definition
of a drug within the meaning of section 201(g) of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 321(g)). As a biological product, FMT
administered to treat C. difficile infection is subject to the
licensing requirements set forth in section 351 of the PHS Act. FDA has
received public comments from some stakeholders suggesting that FMT
might be regulated as a human cell, tissue, and cellular and tissue-
based product (HCT/P; see 21 CFR part 1271). FMT is a live
biotherapeutic product composed of microorganisms. Microorganisms are
not human cells or tissues and do not meet the definition of HCT/P (see
21 CFR 1271.3(d)). The hearing will not
[[Page 47913]]
include discussions about these comments.
In the Federal Register of July 18, 2013 (78 FR 42965), following a
public workshop, held on May 2 and 3, 2013, entitled ``Fecal Microbiota
for Transplantation,'' FDA announced the availability of a guidance for
industry entitled ``Enforcement Policy Regarding Investigational New
Drug Requirements for Use of Fecal Microbiota for Transplantation to
Treat Clostridium difficile Infection Not Responsive to Standard
Therapies'' (July 2013 Guidance) (available at: https://www.fda.gov/media/86440/download). The July 2013 Guidance, which is still in
effect, informed members of the medical and scientific communities and
other interested persons that we intend to exercise enforcement
discretion regarding the investigational new drug (IND) requirements
for the use of FMT to treat C. difficile infection not responding to
standard therapies, provided that the treating physician obtains
adequate consent from the patient or his or her legally authorized
representative for the use of FMT products. The guidance states that
consent should include, at a minimum, a statement that the use of FMT
products to treat C. difficile is investigational and a discussion of
its potential risks.
In the Federal Register of February 26, 2014 (79 FR 10814), we
announced the availability of a draft guidance for industry entitled
``Enforcement Policy Regarding Investigational New Drug Requirements
for Use of Fecal Microbiota for Transplantation to Treat Clostridium
difficile Infection Not Responsive to Standard Therapies'' (March 2014
Draft Guidance). The March 2014 Draft Guidance informed members of the
medical and scientific communities and other interested persons that we
intended to exercise enforcement discretion regarding the IND
requirements for the use of FMT to treat C. difficile infection not
responding to standard therapies, provided: (1) The licensed healthcare
provider treating the patient obtains adequate consent from the patient
or his or her legally authorized representative for use of the FMT
product; (2) the FMT product is obtained from a donor known to either
the patient or the licensed healthcare provider treating the patient;
and (3) the stool donor and stool are qualified by screening and
testing performed under the direction of the licensed healthcare
provider for the purpose of providing the FMT product to treat his or
her patient. FDA received many public comments in favor of patient
access to FMT to treat C. difficile, including access to FMT products
from stool banks, but objecting to the provision that the donor be
known to the patient or the treating licensed healthcare provider.
After considering the comments on the March 2014 Draft Guidance, in
the Federal Register of March 1, 2016 (81 FR 10632), FDA announced the
availability of a revised draft guidance for industry entitled
``Enforcement Policy Regarding Investigational New Drug Requirements
for Use of Fecal Microbiota for Transplantation to Treat Clostridium
difficile Infection Not Responsive to Standard Therapies'' (March 2016
Draft Guidance) (available at: https://www.fda.gov/media/96562/download). The March 2016 Draft Guidance replaced the March 2014 Draft
Guidance and proposed to revise our policy with regard to patient
access to FMT product. We noted that centralized manufacturing in stool
banks presents safety concerns related to the use of FMT from a limited
number of donors administered to multiple patients. Therefore, we
stated that FDA does not intend to extend enforcement discretion with
respect to the IND requirements applicable to stool banks distributing
FMT products. We stated that the sponsor's compliance with the IND
requirements would help to ensure that the stool donor and stool are
appropriately qualified by screening and testing and that centralized
processing of FMT adheres to appropriate current good manufacturing
conditions. FDA received many public comments on this draft guidance,
and we are continuing to evaluate our enforcement policy.
The purpose of this public hearing is to obtain public input on the
state of the science regarding FMT to treat C. difficile infection not
responsive to standard therapies, including the available clinical
evidence for safety and effectiveness of FMT for this use and to
understand better the impact of FDA's enforcement policy on product
development.
II. Issues for Consideration and Request for Data and Information
FDA would like input from stakeholders, including patients,
clinicians, research scientists, industry, healthcare providers, and
stool banks. We encourage public comments and presentations at the
public hearing. If submitting comments, data, and information to the
docket, please identify available references for the data and
information, as well as the general category area and specific question
listed below.
As noted above, fecal microbiota collected from healthy individuals
are being investigated for use in the treatment of C. difficile
infection. Published data suggest that the use of fecal microbiota to
restore intestinal flora may be an effective therapy in the management
of refractory C. difficile infection. However, the efficacy and safety
profiles of this intervention have not yet been fully evaluated in
controlled clinical trials. To inform FDA's understanding of the
current scientific status of FMT, especially as it relates to the use
of FMT to treat C. difficile infection not responsive to standard
therapies, we are interested in obtaining information, including data
and studies, from all stakeholders, including patients, clinicians,
research scientists, industry, healthcare providers and stool banks on
the following topics:
1. Clinical Evidence of Effectiveness
What is the strength of the evidence for the use of FMT to
treat C. difficile infection not responsive to standard therapies?
Please identify any published data from rigorously
conducted randomized controlled (placebo or non-FMT standard of care
comparator) trials that support the use of FMT for:
[cir] Prevention of recurrent C. difficile infection.
[cir] Treatment of refractory C. difficile infection.
2. Safety Evaluation
What is the strength of evidence for the safety of FMT in
patients with C. difficile infection not responsive to standard
therapies?
Has meaningful safety information been collected under
FDA's enforcement policy? How can any deficiencies in safety data
collection be remedied?
Are there particular safety issues FDA should consider
regarding these products (e.g., donor screening/mixing donations)?
3. Impact of FDA's current Enforcement Policy on FMT Product
Development
What impact has FDA's enforcement policy had on
recruitment and ability to conduct clinical trials to assess safety and
effectiveness of FMT for C. difficile infection not responsive to
standard therapies?
[cir] Can specific examples be cited?
[cir] How can any negative impacts be remedied?
How does the existing availability of FMT affect the
incentives for, and the feasibility of, FMT drug-development programs?
The use of FMT is addressed in some treatment guidelines
(Infectious
[[Page 47914]]
Diseases Society of America and American Gastroenterological
Association). What impact has this had on patient recruitment and
conduct of clinical trials?
4. Future and Path Forward
What additional scientific information is needed to
determine the safety and effectiveness of FMT for C. difficile
infection not responsive to standard therapies?
How generalizable are the existing safety and
effectiveness data on use of a specific FMT product for C. difficile
infection not responsive to standard therapies to other FMT products
for which safety and effectiveness data are not available?
Please comment on how FDA can facilitate patient access,
protect patient safety, and include enough flexibility to support
innovation for the development and licensure of safe and effective FMT
products for C. difficile infection not responsive to standard
therapies.
III. Participating in the Public Hearing
Registration and Requests to Speak and for Formal Oral
Presentations: The FDA Conference Center at the White Oak location is a
Federal facility with security procedures and limited seating.
Attendance will be free. An agenda for the hearing and any other
background materials will be made available on October 25, 2019, at
https://www.fda.gov/vaccines-blood-biologics/news-events-biologics/workshops-meetings-conferences-biologics. If you need special
accommodations because of a disability, please contact Sherri Revell or
Loni Warren Henderson at 240-402-8010 at least 7 days before the
hearing.
For those interested in speaking at the hearing or presenting at
the hearing with a formal oral presentation, please register at https://www.eventbrite.com/e/use-of-fecal-microbiota-for-transplantation-to-treat-clostridium-difficile-infection-not-responsive-tickets-63906239282 as ``In-person presenter.'' Speaker and presenter
registrations are due October 8, 2019.
FDA will try to accommodate all persons who wish to make a formal
oral presentation. Formal oral presenters may use an accompanying slide
deck. Individuals wishing to present should identify their name, which
stakeholder group they represent (e.g., patient, clinician, research
scientist, industry, stool bank), and the number of the specific
question, or questions, they wish to address. FDA will consider this
information when organizing the agenda. Individuals and organizations
with common interests should consider consolidating or coordinating
their presentations and request time for a joint presentation.
Individual organizations are limited to a single presentation slot. FDA
will notify registered presenters of their scheduled presentation times
on October 21, 2019. The time allotted for each presentation will
depend on the number of individuals who wish to speak. If registered
presenters are using an accompanying slide deck, those presenters must
submit an electronic copy of their presentation (PowerPoint or PDF) to
[email protected] on or before October 28, 2019. Persons
registered to present are encouraged to arrive at the hearing room
early and check in at the onsite registration table to confirm their
designated presentation time. Actual presentation times, however, may
vary based on how the hearing progresses in real time.
In-person attendance: For those who would like to attend in-person,
but who are not making a formal presentation, please register at
https://www.eventbrite.com/e/use-of-fecal-microbiota-for-transplantation-to-treat-clostridium-difficile-infection-not-responsive-tickets-63906239282 as ``In-person attendee--no
participation.'' Seating is limited, and early registration is
recommended to allow for broad participation.
Streaming Webcast of the Public Hearing: For those unable to attend
in person, FDA will provide a live webcast of the hearing. Please
register at https://www.eventbrite.com/e/use-of-fecal-microbiota-for-transplantation-to-treat-clostridium-difficile-infection-not-responsive-tickets-63906239282 as ``online (webcast only)''.
Media: Please register at https://www.eventbrite.com/e/use-of-fecal-microbiota-for-transplantation-to-treat-clostridium-difficile-infection-not-responsive-tickets-63906239282 as ``Media'' by October
28, 2019.
Transcripts: Please be advised that as soon as a transcript is
available, it will be accessible at https://www.fda.gov/vaccines-blood-biologics/news-events-biologics/workshops-meetings-conferences-biologics and https://www.regulations.gov. It may be viewed at the
Dockets Management Staff (see ADDRESSES).
IV. Notification of Hearing Under 21 CFR Part 15
The Commissioner of Food and Drugs is announcing that the public
hearing will be held in accordance with part 15 (21 CFR part 15). The
hearing will be conducted by a presiding officer, who will be
accompanied by FDA senior management officials. Under Sec. 15.30(f)
(21 CFR 15.30(f)), the hearing is informal and the rules of evidence do
not apply. No participant may interrupt the presentation of another
participant. Only the presiding officer and panel members may question
any person during or at the conclusion of each presentation. Public
hearings under part 15 are subject to FDA's policy and procedures for
electronic media coverage of FDA's public administrative proceedings
(21 CFR part 10, subpart C).
Under 21 CFR 10.205, representatives of the electronic media may be
permitted, subject to certain limitations, to videotape, film, or
otherwise record FDA's public administrative proceedings, including
presentations by participants. Persons attending FDA's public hearings
are advised that the Agency is not responsible for providing access to
electrical outlets.
The hearing will be transcribed as stipulated in Sec. 15.30(b)
(see section III of this document). To the extent that the conditions
for the hearing, as described in this notification, conflict with any
provisions set out in part 15, this notification acts as a waiver of
those provisions as specified in Sec. 15.30(h).
Dated: September 5, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-19643 Filed 9-10-19; 8:45 am]
BILLING CODE 4164-01-P
