Proposal To Withdraw Approval of MAKENA; Hearing, 50626-50629 [2022-17715]
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Dated: August 11, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
questions to be posed to the advisory
committee at the hearing.
The hearing will be held
virtually October 17 to 19, 2022,
beginning at 8 a.m. Eastern Time on
each day and concluding at 4 p.m. on
Days 1 and 2 and 12:30 p.m. on Day 3.
Either electronic or written comments
on the hearing must be submitted by
November 3, 2022.
DATES:
[FR Doc. 2022–17643 Filed 8–16–22; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
Proposal To Withdraw Approval of
MAKENA; Hearing
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of hearing.
The Food and Drug
Administration (FDA, Agency, or we)
has granted a hearing on the Center for
Drug Evaluation and Research’s
(CDER’s) proposal to withdraw approval
of MAKENA (hydroxyprogesterone
caproate injection, 250 milligrams (mg)
per milliliter (mL), once weekly), new
drug application (NDA) 021945, held by
Covis Pharma Group/Covis Pharma
GmbH (Covis). This notice provides
information and details regarding the
hearing, including the time, date, and
format of the hearing, as well as the
SUMMARY:
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The docket number for this
matter is FDA–2020–N–2029. The
docket will close on November 3, 2022.
Either electronic or written comments
on this hearing must be submitted by
November 3, 2022. Please note that late,
untimely filed comments will not be
considered. The https://
www.regulations.gov electronic filing
system will accept comments until
11:59 p.m. Eastern Time on November
3, 2022. Comments received by mail/
hand delivery/courier (for written/paper
submissions) will be considered timely
if they are received on or before that
date. Comments received on or before
October 11, 2022, will be provided to
the advisory committee for
consideration.
You may submit comments as
follows:
ADDRESSES:
[Docket No. FDA–2020–N–2029]
JSPEARS on DSK121TN23PROD with NOTICES
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search-fda-guidance-documents.
Persons unable to download an
electronic copy of ‘‘Replacement
Reagent and Instrument Family Policy
for In Vitro Diagnostic Devices’’ may
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electronic copy of the document. Please
use the document number 950 and
PO 00000
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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’’).
E:\FR\FM\17AUN1.SGM
17AUN1
Federal Register / Vol. 87, No. 158 / Wednesday, August 17, 2022 / Notices
JSPEARS on DSK121TN23PROD with NOTICES
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–
2020–N–2029 for ‘‘Proposal to
Withdraw Marketing Approval;
Hearing.’’ 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, 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
our 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-201509-18/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://
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Jkt 256001
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, 240–402–7500.
FOR FURTHER INFORMATION CONTACT:
Rachael Vieder Linowes, Office of
Scientific Integrity, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 1, Rm. 4206, Silver Spring,
MD 20993; 240–402–5931,
rachael.linowes@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
Section 506 of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) (21 U.S.C.
356) provides that a drug sponsor may
request to expedite the review and
approval of a drug intended to treat an
unmet need related to a serious or lifethreatening disease or condition. Under
the accelerated approval pathway, FDA
may grant accelerated approval based on
the drug’s effect on a surrogate or an
intermediate clinical endpoint. FDA’s
regulations, at § 314.510 (21 CFR
314.510), require that accelerated
approval be subject to a sponsor’s
engaging in further study ‘‘to verify and
describe [the drug’s] clinical benefit,
where there is uncertainty as to the
relation of the surrogate endpoint to
clinical benefit, or of the observed
clinical benefit to ultimate outcome.’’
Under section 506(c)(3) of the FD&C
Act, FDA may withdraw approval of a
drug approved under this pathway if,
among other reasons, the required study
fails to verify ‘‘the predicted effect on
irreversibility morbidity or mortality or
other clinical benefit.’’ Under
§ 314.530(a) (21 CFR 314.530(a)), FDA
may withdraw accelerated approval of a
drug when ‘‘[a] postmarketing clinical
study fails to verify clinical benefit’’ or
‘‘[o]ther evidence demonstrates that the
drug product is not shown to be safe or
effective under its conditions of use,’’
among other circumstances.
To initiate the process for
withdrawing accelerated approval of a
drug, the Director of CDER must provide
the applicant with notice of an
opportunity for a hearing on the
proposed grounds for withdrawal under
§ 314.530(b). To obtain a hearing, the
applicant must, pursuant to
§ 314.530(c), request one within 15 days
after receiving CDER’s notice and
submit ‘‘the data and information upon
which [it] intends to rely at the hearing’’
within 30 days thereafter.
Pursuant to § 314.530(e)(1), FDA
conducts hearings under § 314.530 in
accordance with part 15 (21 CFR part
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50627
15), with certain modifications. The key
modification under § 314.530(e)(1) is
that an advisory committee is present at
the hearing and provides advice and
recommendations to the Commissioner.
Under § 314.530(e)(2), the presiding
officer, the members of the advisory
committee, and up to three
representatives from both the applicant
and CDER may ask questions of the
presenters at the hearing. The presiding
officer, as a matter of discretion, may
also permit questions of presenters
posed by others participating in the
hearing upon submission of such
questions in writing. After receiving
advice and recommendations from the
advisory committee, the Commissioner
of Food and Drugs makes the final
decision on whether to withdraw
accelerated approval of the drug product
at issue (see § 314.530(f)).
On February 3, 2011, FDA approved
the NDA for MAKENA under the
accelerated approval pathway to reduce
the risk of preterm birth in women with
a singleton pregnancy who have a
history of singleton spontaneous
preterm birth. As described in CDER’s
proposal to withdraw approval, the
MAKENA NDA ‘‘relied on evidence
from the Maternal Fetal Medicine Unit
(MFMU) Network trial (referred to as
‘Trial 002’) for primary support of
efficacy and safety.’’ CDER granted
accelerated approval based on the
results for Trial 002. Consistent with
section 506(c)(2) of the FD&C Act and
§ 314.510, CDER’s approval letter
required, inter alia, that the sponsor
complete a postmarketing confirmatory
study, described as ‘‘a clinical trial of
MAKENA in women with a singleton
pregnancy who had a previous
spontaneous preterm birth (Protocol
#17P–ES–003)’’ (Trial 003).
On October 5, 2020, CDER proposed
withdrawing accelerated approval of
MAKENA and provided Covis with an
opportunity to request a hearing on the
proposal.1 In the proposal, CDER cited
two grounds under section 506(c)(3) of
the FD&C Act and § 314.530(a) for
withdrawing approval: (1) the
confirmatory study failed to verify
clinical benefit of the drug and (2) the
evidence does not establish that the
drug is effective under its conditions of
use. CDER’s proposal to withdraw
approval also provided notice to all
holders of approved abbreviated new
drug applications (ANDAs) referencing
the NDA for MAKENA (NDA 021945)
that, if the Agency withdraws
1 AMAG Pharmaceuticals, Inc. (AMAG), the
sponsor of NDA 021945 at the time, received this
notice. After AMAG requested a hearing, Covis
acquired AMAG, including NDA 021945. For
efficiency, this notice refers to AMAG as ‘‘Covis.’’
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Federal Register / Vol. 87, No. 158 / Wednesday, August 17, 2022 / Notices
accelerated approval of MAKENA,
CDER would proceed to withdraw
approval of the ANDAs under 21 CFR
314.151(b)(3).
On October 14, 2020, Covis timely
requested a hearing and sought an
additional 30 days in which to submit
data and information in support. On
December 4, 2020, after receiving an
extension of time within which to do so,
Covis further responded to CDER’s
proposal to withdraw accelerated
approval of MAKENA. The response
included data and information and
incorporated other data and information
in FDA’s administrative files by
reference.2
By letter to CDER and Covis dated
August 18, 2021, FDA’s Chief Scientist
granted Covis’s hearing request and
appointed Celia M. Witten as presiding
officer.
JSPEARS on DSK121TN23PROD with NOTICES
II. Notice of Hearing Under Part 15 and
§ 314.530
This public hearing will be held in
accordance with part 15 and § 314.530.
The presiding officer will conduct the
hearing, and an advisory committee will
be present at the hearing for purposes of
considering the data and information
presented by CDER and Covis with
respect to CDER’s proposal to withdraw
accelerated approval of MAKENA and
providing advice to the Commissioner
of Food and Drugs on that proposal (see
§ 314.530(e)).
Under 21 CFR 15.30(f), the hearing is
informal, and the rules of evidence do
not apply. In accordance with
§ 314.530(e)(2), however, only the
presiding officer, the members of the
advisory committee, and up to three
representatives from CDER and Covis
may pose questions to the advisory
committee at the hearing itself. The
presiding officer may nonetheless
exercise her discretion under
§ 314.530(e)(2) to allow others to
propose questions by submitting them
in writing for her consideration. In the
interest of economy and efficiency,
particularly given the virtual platform,
the presiding officer has determined
that only the holders of ANDAs
referencing the NDA for MAKENA
(ANDA holders) will be permitted to
submit questions; that all proposed
questions must be submitted to the
docket for this proceeding in advance of
the hearing; and that the questions
selected will be posed to CDER and
Covis at the close of their respective
2 The presiding officer has subsequently granted
requests by Covis to submit additional data and
information that were not included in its December
4, 2020, submission and may do so again based on
a showing of good cause.
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presentations (see section IV of this
document).
III. Questions To Be Addressed at the
Public Hearing
The questions to be posed to the
advisory committee at the hearing are as
follows:
1. For discussion and vote:
Do the findings from Trial 003 verify
the clinical benefit of MAKENA on
neonatal morbidity and mortality from
complications of preterm birth?
2. For discussion and vote:
Does the available evidence
demonstrate that MAKENA is effective
for its approved indication of reducing
the risk of preterm birth in women with
a singleton pregnancy who have a
history of singleton spontaneous
preterm birth?
3. For discussion:
Should FDA allow MAKENA to
remain on the market? As part of that
discussion, you may discuss:
• whether the benefit-risk profile
supports retaining the product on the
market;
• what types of studies could provide
confirmatory evidence to verify the
clinical benefit of MAKENA on neonatal
morbidity and mortality from
complications of preterm birth?
For vote:
Considering your responses to the
previous questions both in the
discussions and votes, should FDA
allow MAKENA to remain on the
market while an appropriate
confirmatory study is designed and
conducted?
IV. Participating in the Public Hearing
Persons wishing to view the hearing
may access the webcast at the following
separate links on the respective days of
the hearing:
Day 1: https://youtu.be/EEm7pM_
LgsM.
Day 2: https://youtu.be/Nt2bcDVgpag.
Day 3: https://youtu.be/Dal27hktzcg.
Request for Oral Presentations: We
currently expect public participation to
occur from 2 p.m. to 4 p.m. Eastern
Time on the first day of the hearing and
from 8 a.m. to 10 a.m. on the second
day. Persons interested in participating
in the hearing by making an oral
presentation during the 4 hours
currently reserved for such
presentations must submit requests by
11:59 p.m. Eastern Time on September
6, 2022, as further described below.
If you wish to make a formal
presentation or present oral comments
during the session for public
participation, you must register at the
following link by 5 p.m. Eastern Time
on September 6, 2022: https://
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When registering, please provide
complete contact information, including
name, title, affiliation, address, email,
and telephone number. To complete
your request for an opportunity to make
a presentation at the hearing, you must
also submit a comment to the docket for
this hearing matter (see ADDRESSES) by
11:59 p.m. Eastern Time on September
6, 2022, and clearly indicate in the
heading and/or cover page that your
comment is a ‘‘Request for Oral
Presentation.’’
In the ‘‘Request for Oral Presentation’’
submitted to the public docket, you
must identify yourself and others who
will join you for your presentation, list
the affiliation (if any) of each individual
participating in your presentation
(including your own), and request a
specific amount of time for your
presentation. You must also include a
summary of what you plan to present at
the hearing and a copy of any slide
deck, along with any data or
information on which you intend to rely
at the hearing that is not already
referenced or included in the public
docket for this hearing matter. No
commercial or promotional material
will be permitted to be presented or
distributed at the public hearing.
We urge organizations with common
interests to consolidate or coordinate
their presentations. In accordance with
21 CFR 15.21(c), the presiding officer
may require joint presentations by
persons with common interests.
The presiding officer will determine
the amount of time allotted to each
presenter and the approximate time
each presentation is to begin and will
select and notify participants by
September 30, 2022. If you are notified
that you will be a presenter, we
encourage you to be online well in
advance of the approximate time
provided in the notice. Actual
presentation times may vary based on
how the hearing progresses.
Proposed Questions: To propose a
question to either CDER or Covis, an
ANDA holder must submit a comment
to the docket for this hearing matter (see
ADDRESSES) by 11:59 p.m. Eastern Time
on September 30, 2022; indicate in the
heading and/or cover page that the
comment includes ‘‘Proposed
Question(s)’’; and state in the
submission that the question or
questions are being proposed by a
specific ANDA holder or someone
authorized to do so on that specific
ANDA holder’s behalf. The comment
should also indicate whether each
proposed question is intended for
CDER, Covis, or both.
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Transcripts: Please be advised that as
soon as a transcript of the public
hearing is available, it will be accessible
at https://www.regulations.gov. It may
also be viewed at the address where
Dockets Management Staff is located
(see ADDRESSES). A link to the transcript
will also be available on the Agency’s
website.
Dated: August 12, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022–17715 Filed 8–16–22; 8:45 am]
BILLING CODE 4164–01–P
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.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of the draft
guidance entitled ‘‘Hydrogen PeroxideBased 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:
JSPEARS on DSK121TN23PROD with NOTICES
SUMMARY:
Electronic Submissions
Submit electronic comments in the
following way:
VerDate Sep<11>2014
17:22 Aug 16, 2022
Jkt 256001
• 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 PeroxideBased 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
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50629
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-201509-18/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, 240–402–7500.
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 PeroxideBased 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, 301–796–6860.
SUPPLEMENTARY INFORMATION:
I. Background
The safety and effectiveness of HPCPs
when used as directed has been well
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]]>Agencies
[Federal Register Volume 87, Number 158 (Wednesday, August 17, 2022)]
[Notices]
[Pages 50626-50629]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-17715]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-N-2029]
Proposal To Withdraw Approval of MAKENA; Hearing
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of hearing.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) has
granted a hearing on the Center for Drug Evaluation and Research's
(CDER's) proposal to withdraw approval of MAKENA (hydroxyprogesterone
caproate injection, 250 milligrams (mg) per milliliter (mL), once
weekly), new drug application (NDA) 021945, held by Covis Pharma Group/
Covis Pharma GmbH (Covis). This notice provides information and details
regarding the hearing, including the time, date, and format of the
hearing, as well as the questions to be posed to the advisory committee
at the hearing.
DATES: The hearing will be held virtually October 17 to 19, 2022,
beginning at 8 a.m. Eastern Time on each day and concluding at 4 p.m.
on Days 1 and 2 and 12:30 p.m. on Day 3. Either electronic or written
comments on the hearing must be submitted by November 3, 2022.
ADDRESSES: The docket number for this matter is FDA-2020-N-2029. The
docket will close on November 3, 2022. Either electronic or written
comments on this hearing must be submitted by November 3, 2022. Please
note that late, untimely filed comments will not be considered. The
https://www.regulations.gov electronic filing system will accept
comments until 11:59 p.m. Eastern Time on November 3, 2022. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.
Comments received on or before October 11, 2022, will be provided to
the advisory committee for consideration.
You may submit comments 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'').
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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-2020-N-2029 for ``Proposal to Withdraw Marketing Approval;
Hearing.'' 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, 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
our 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, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Rachael Vieder Linowes, Office of
Scientific Integrity, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 1, Rm. 4206, Silver Spring, MD 20993; 240-402-5931,
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
Section 506 of the Federal Food, Drug, and Cosmetic Act (FD&C Act)
(21 U.S.C. 356) provides that a drug sponsor may request to expedite
the review and approval of a drug intended to treat an unmet need
related to a serious or life-threatening disease or condition. Under
the accelerated approval pathway, FDA may grant accelerated approval
based on the drug's effect on a surrogate or an intermediate clinical
endpoint. FDA's regulations, at Sec. 314.510 (21 CFR 314.510), require
that accelerated approval be subject to a sponsor's engaging in further
study ``to verify and describe [the drug's] clinical benefit, where
there is uncertainty as to the relation of the surrogate endpoint to
clinical benefit, or of the observed clinical benefit to ultimate
outcome.''
Under section 506(c)(3) of the FD&C Act, FDA may withdraw approval
of a drug approved under this pathway if, among other reasons, the
required study fails to verify ``the predicted effect on
irreversibility morbidity or mortality or other clinical benefit.''
Under Sec. 314.530(a) (21 CFR 314.530(a)), FDA may withdraw
accelerated approval of a drug when ``[a] postmarketing clinical study
fails to verify clinical benefit'' or ``[o]ther evidence demonstrates
that the drug product is not shown to be safe or effective under its
conditions of use,'' among other circumstances.
To initiate the process for withdrawing accelerated approval of a
drug, the Director of CDER must provide the applicant with notice of an
opportunity for a hearing on the proposed grounds for withdrawal under
Sec. 314.530(b). To obtain a hearing, the applicant must, pursuant to
Sec. 314.530(c), request one within 15 days after receiving CDER's
notice and submit ``the data and information upon which [it] intends to
rely at the hearing'' within 30 days thereafter.
Pursuant to Sec. 314.530(e)(1), FDA conducts hearings under Sec.
314.530 in accordance with part 15 (21 CFR part 15), with certain
modifications. The key modification under Sec. 314.530(e)(1) is that
an advisory committee is present at the hearing and provides advice and
recommendations to the Commissioner. Under Sec. 314.530(e)(2), the
presiding officer, the members of the advisory committee, and up to
three representatives from both the applicant and CDER may ask
questions of the presenters at the hearing. The presiding officer, as a
matter of discretion, may also permit questions of presenters posed by
others participating in the hearing upon submission of such questions
in writing. After receiving advice and recommendations from the
advisory committee, the Commissioner of Food and Drugs makes the final
decision on whether to withdraw accelerated approval of the drug
product at issue (see Sec. 314.530(f)).
On February 3, 2011, FDA approved the NDA for MAKENA under the
accelerated approval pathway to reduce the risk of preterm birth in
women with a singleton pregnancy who have a history of singleton
spontaneous preterm birth. As described in CDER's proposal to withdraw
approval, the MAKENA NDA ``relied on evidence from the Maternal Fetal
Medicine Unit (MFMU) Network trial (referred to as `Trial 002') for
primary support of efficacy and safety.'' CDER granted accelerated
approval based on the results for Trial 002. Consistent with section
506(c)(2) of the FD&C Act and Sec. 314.510, CDER's approval letter
required, inter alia, that the sponsor complete a postmarketing
confirmatory study, described as ``a clinical trial of MAKENA in women
with a singleton pregnancy who had a previous spontaneous preterm birth
(Protocol #17P-ES-003)'' (Trial 003).
On October 5, 2020, CDER proposed withdrawing accelerated approval
of MAKENA and provided Covis with an opportunity to request a hearing
on the proposal.\1\ In the proposal, CDER cited two grounds under
section 506(c)(3) of the FD&C Act and Sec. 314.530(a) for withdrawing
approval: (1) the confirmatory study failed to verify clinical benefit
of the drug and (2) the evidence does not establish that the drug is
effective under its conditions of use. CDER's proposal to withdraw
approval also provided notice to all holders of approved abbreviated
new drug applications (ANDAs) referencing the NDA for MAKENA (NDA
021945) that, if the Agency withdraws
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accelerated approval of MAKENA, CDER would proceed to withdraw approval
of the ANDAs under 21 CFR 314.151(b)(3).
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\1\ AMAG Pharmaceuticals, Inc. (AMAG), the sponsor of NDA 021945
at the time, received this notice. After AMAG requested a hearing,
Covis acquired AMAG, including NDA 021945. For efficiency, this
notice refers to AMAG as ``Covis.''
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On October 14, 2020, Covis timely requested a hearing and sought an
additional 30 days in which to submit data and information in support.
On December 4, 2020, after receiving an extension of time within which
to do so, Covis further responded to CDER's proposal to withdraw
accelerated approval of MAKENA. The response included data and
information and incorporated other data and information in FDA's
administrative files by reference.\2\
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\2\ The presiding officer has subsequently granted requests by
Covis to submit additional data and information that were not
included in its December 4, 2020, submission and may do so again
based on a showing of good cause.
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By letter to CDER and Covis dated August 18, 2021, FDA's Chief
Scientist granted Covis's hearing request and appointed Celia M. Witten
as presiding officer.
II. Notice of Hearing Under Part 15 and Sec. 314.530
This public hearing will be held in accordance with part 15 and
Sec. 314.530. The presiding officer will conduct the hearing, and an
advisory committee will be present at the hearing for purposes of
considering the data and information presented by CDER and Covis with
respect to CDER's proposal to withdraw accelerated approval of MAKENA
and providing advice to the Commissioner of Food and Drugs on that
proposal (see Sec. 314.530(e)).
Under 21 CFR 15.30(f), the hearing is informal, and the rules of
evidence do not apply. In accordance with Sec. 314.530(e)(2), however,
only the presiding officer, the members of the advisory committee, and
up to three representatives from CDER and Covis may pose questions to
the advisory committee at the hearing itself. The presiding officer may
nonetheless exercise her discretion under Sec. 314.530(e)(2) to allow
others to propose questions by submitting them in writing for her
consideration. In the interest of economy and efficiency, particularly
given the virtual platform, the presiding officer has determined that
only the holders of ANDAs referencing the NDA for MAKENA (ANDA holders)
will be permitted to submit questions; that all proposed questions must
be submitted to the docket for this proceeding in advance of the
hearing; and that the questions selected will be posed to CDER and
Covis at the close of their respective presentations (see section IV of
this document).
III. Questions To Be Addressed at the Public Hearing
The questions to be posed to the advisory committee at the hearing
are as follows:
1. For discussion and vote:
Do the findings from Trial 003 verify the clinical benefit of
MAKENA on neonatal morbidity and mortality from complications of
preterm birth?
2. For discussion and vote:
Does the available evidence demonstrate that MAKENA is effective
for its approved indication of reducing the risk of preterm birth in
women with a singleton pregnancy who have a history of singleton
spontaneous preterm birth?
3. For discussion:
Should FDA allow MAKENA to remain on the market? As part of that
discussion, you may discuss:
whether the benefit-risk profile supports retaining the
product on the market;
what types of studies could provide confirmatory evidence
to verify the clinical benefit of MAKENA on neonatal morbidity and
mortality from complications of preterm birth?
For vote:
Considering your responses to the previous questions both in the
discussions and votes, should FDA allow MAKENA to remain on the market
while an appropriate confirmatory study is designed and conducted?
IV. Participating in the Public Hearing
Persons wishing to view the hearing may access the webcast at the
following separate links on the respective days of the hearing:
Day 1: https://youtu.be/EEm7pM_LgsM.
Day 2: https://youtu.be/Nt2bcDVgpag.
Day 3: https://youtu.be/Dal27hktzcg.
Request for Oral Presentations: We currently expect public
participation to occur from 2 p.m. to 4 p.m. Eastern Time on the first
day of the hearing and from 8 a.m. to 10 a.m. on the second day.
Persons interested in participating in the hearing by making an oral
presentation during the 4 hours currently reserved for such
presentations must submit requests by 11:59 p.m. Eastern Time on
September 6, 2022, as further described below.
If you wish to make a formal presentation or present oral comments
during the session for public participation, you must register at the
following link by 5 p.m. Eastern Time on September 6, 2022: https://www.surveymonkey.com/r/B72THCF. When registering, please provide
complete contact information, including name, title, affiliation,
address, email, and telephone number. To complete your request for an
opportunity to make a presentation at the hearing, you must also submit
a comment to the docket for this hearing matter (see ADDRESSES) by
11:59 p.m. Eastern Time on September 6, 2022, and clearly indicate in
the heading and/or cover page that your comment is a ``Request for Oral
Presentation.''
In the ``Request for Oral Presentation'' submitted to the public
docket, you must identify yourself and others who will join you for
your presentation, list the affiliation (if any) of each individual
participating in your presentation (including your own), and request a
specific amount of time for your presentation. You must also include a
summary of what you plan to present at the hearing and a copy of any
slide deck, along with any data or information on which you intend to
rely at the hearing that is not already referenced or included in the
public docket for this hearing matter. No commercial or promotional
material will be permitted to be presented or distributed at the public
hearing.
We urge organizations with common interests to consolidate or
coordinate their presentations. In accordance with 21 CFR 15.21(c), the
presiding officer may require joint presentations by persons with
common interests.
The presiding officer will determine the amount of time allotted to
each presenter and the approximate time each presentation is to begin
and will select and notify participants by September 30, 2022. If you
are notified that you will be a presenter, we encourage you to be
online well in advance of the approximate time provided in the notice.
Actual presentation times may vary based on how the hearing progresses.
Proposed Questions: To propose a question to either CDER or Covis,
an ANDA holder must submit a comment to the docket for this hearing
matter (see ADDRESSES) by 11:59 p.m. Eastern Time on September 30,
2022; indicate in the heading and/or cover page that the comment
includes ``Proposed Question(s)''; and state in the submission that the
question or questions are being proposed by a specific ANDA holder or
someone authorized to do so on that specific ANDA holder's behalf. The
comment should also indicate whether each proposed question is intended
for CDER, Covis, or both.
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Transcripts: Please be advised that as soon as a transcript of the
public hearing is available, it will be accessible at https://www.regulations.gov. It may also be viewed at the address where Dockets
Management Staff is located (see ADDRESSES). A link to the transcript
will also be available on the Agency's website.
Dated: August 12, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-17715 Filed 8-16-22; 8:45 am]
BILLING CODE 4164-01-P
