Proposal To Refuse To Approve a New Drug Application for Oxycodone Hydrochloride Immediate-Release Oral Capsules, 5 Milligrams, 15 Milligrams, and 30 Milligrams; Opportunity for a Hearing, 6196-6198 [2018-02903]
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Federal Register / Vol. 83, No. 30 / Tuesday, February 13, 2018 / Notices
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[FR Doc. 2018–02871 Filed 2–12–18; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2018–N–0188]
Proposal To Refuse To Approve a New
Drug Application for Oxycodone
Hydrochloride Immediate-Release Oral
Capsules, 5 Milligrams, 15 Milligrams,
and 30 Milligrams; Opportunity for a
Hearing
sradovich on DSK3GMQ082PROD with NOTICES
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Director of the Center for
Drug Evaluation and Research (Center
Director) of the Food and Drug
Administration (FDA or Agency) is
proposing to refuse to approve a new
drug application (NDA) submitted by
SUMMARY:
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Jkt 244001
Pharmaceutical Manufacturing Research
Services, Inc. (PMRS) for oxycodone
hydrochloride (HCl) immediate-release
(IR) oral capsules, 5 milligrams (mg), 15
mg, and 30 mg in its present form. This
notice summarizes the grounds for the
Center Director’s proposal and offers
PMRS an opportunity to request a
hearing on the matter.
DATES: Submit either electronic or
written requests for a hearing by March
15, 2018; submit data, information, and
analyses in support of the hearing and
any other comments by April 16, 2018.
ADDRESSES: You may submit hearing
requests, documents in support of the
hearing, and any other comments as
follows. Please note that late, untimely
filed requests and documents will not
be considered. Electronic requests for a
hearing must be submitted on or before
March 15, 2018; electronic documents
in support of the hearing and any other
comments must be submitted on or
before April 16, 2018. The https://
www.regulations.gov electronic filing
system will accept hearing requests
until midnight Eastern Time at the end
of March 15, 2018, and will accept
documents in support of the hearing
and any other comments until midnight
Eastern Time at the end of April 16,
2018. Documents 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 these dates.
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
PO 00000
Frm 00038
Fmt 4703
Sfmt 4703
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–
2018–N–0188, for ‘‘Proposal to Refuse to
Approve a New Drug Application for
Oxycodone Hydrochloride ImmediateRelease Oral Capsules, 5 Milligrams, 15
Milligrams, and 30 Milligrams;
Opportunity for a 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.
• 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/
E:\FR\FM\13FEN1.SGM
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Federal Register / Vol. 83, No. 30 / Tuesday, February 13, 2018 / Notices
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:
Patrick Raulerson, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6260,
Silver Spring, MD, 20993, 301–796–
3522, Patrick.Raulerson@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
sradovich on DSK3GMQ082PROD with NOTICES
I. Proposal To Refuse To Approve NDA
209155
PMRS submitted NDA 209155 for
oxycodone HCl IR oral capsules in 5 mg,
15 mg, and 30 mg strengths (oxycodone
HCl IR capsules) under section 505(b)(2)
of the Federal Food, Drug, and Cosmetic
Act (FD&C Act) (21 U.S.C. 355(b)(2)),
proposing to rely in part on the
Agency’s previous finding of safety and
effectiveness for ROXICODONE
(oxycodone HCl) IR Tablets (NDA
021011). PMRS proposed that its
oxycodone HCl IR capsules be indicated
for the management of acute pain severe
enough to require an opioid analgesic
and for which alternative treatments are
inadequate. PMRS also attempted to
show that the product had certain
abuse-deterrent properties and sought
FDA approval of labeling describing
those properties.
On November 16, 2017, the Division
of Anesthesia, Analgesia, and Addiction
Products of FDA’s Center for Drug
Evaluation and Research (CDER) issued
a complete response letter to PMRS
under § 314.110(a) (21 CFR 314.110(a))
stating that NDA 209155 could not be
approved in its present form, describing
the specific deficiencies, and, where
possible, recommending ways PMRS
might remedy these deficiencies. The
deficiencies include the following:
1. The application in its present form
is not approvable with the proposed
labeling describing abuse-deterrent
properties, for multiple reasons. In
particular, (1) the oxycodone in the
formulation can be readily extracted in
commonly available solvents into a
solution suitable for injection; (2) there
were insufficient data showing the
presence of excipients (including dye)
in the formulation can be expected to
deter abuse by injection; (3) the data
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Jkt 244001
submitted were insufficient to show the
product was meaningfully resistant to
manipulation for misuse or abuse; and
(4) there were not data submitted,
including data from pharmacokinetic
and human abuse liability studies, fully
characterizing the product’s abuse
potential by all relevant routes of abuse.
Also, the data submitted were not
sufficient to rule out the possibility that
the proposed formulation could result
in a greater proportion of abuse by
injection of PMRS’s product compared
to a conventional IR oxycodone
formulation. Abuse by injection carries
greater risk of overdose and
transmission of infectious disease than
abuse by other routes.
2. The safety and purity of the
excipients intended (but not shown) to
confer abuse deterrent properties were
not adequately characterized, either by
the intended oral route of use or by
expected routes of abuse, including
injection.
3. An overall evaluation of elemental
impurities in the final formulation and
a risk assessment for each heavy metal
(taking into consideration the maximum
daily dose) were not provided.
4. The application did not fully
comply with the patent certification
requirements applicable to applications
submitted under section 505(b)(2) of the
FD&C Act.
5. The complete response letter
describes additional deficiencies, which
generally relate to chemistry,
manufacturing, and controls and current
good manufacturing practice
requirements, that CDER determined
preclude approval of the application in
its present form. The complete response
letter also noted that satisfactory
resolution of objectionable inspection
observations was required before the
application could be approved. Due to
applicable limitations on public
disclosure of information contained in
unapproved NDAs, including trade
secret information, these specific
deficiencies are not described in this
notice.
The complete response letter stated
that PMRS is required to resubmit the
application, fully addressing all
deficiencies listed in the letter, or take
other actions available under § 314.110
(i.e., withdraw the application or
request an opportunity for a hearing).
Applicable regulations, including
§ 10.75 (21 CFR 10.75), also provide a
mechanism for applicants to obtain
formal review of one or more decisions
reflected in a complete response letter
(see FDA’s guidance for industry
‘‘Formal Dispute Resolution: Sponsor
Appeals Above the Division Level’’
(November 2017) available at: https://
PO 00000
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Fmt 4703
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6197
www.fda.gov/downloads/drugs/
guidancecomplianceregulatory
information/guidances/ucm343101.pdf).
In response to the complete response
letter, on November 17, 2017, PMRS
submitted a request for an opportunity
for a hearing under § 314.110(b)(3) on
whether there are grounds under section
505(d) of the FD&C Act for denying
approval of NDA 209155.
II. Notice of Opportunity for a Hearing
For the reasons stated previously and
others described in the complete
response letter, notice is given to PMRS
and to all other interested persons that
the Center Director proposes to issue an
order refusing to approve NDA 209155
on the grounds that the application fails
to meet the criteria for approval under
section 505(d) of the FD&C Act,
including that: (1) PMRS has not
provided sufficient data to show that the
product would be safe (505(d)(1)); (2)
PMRS has not shown that the methods
used in, and the facilities and controls
used for the manufacture, processing, or
packing of the product are adequate to
preserve its identity, strength, quality,
and purity (505(d)(3)); and (3) the
labeling PMRS proposed for the product
is false or misleading (505(d)(7)).
PMRS may request a hearing before
the Commissioner of Food and Drugs
(the Commissioner) on the Center
Director’s proposal to refuse to approve
NDA 209155. If PMRS decides to seek
a hearing, it must file: (1) A written
notice of participation and request for a
hearing (see the DATES section), and (2)
the studies, data, information, and
analyses relied upon to justify a hearing
(see the DATES section), as specified in
§ 314.200.
As stated in § 314.200(g), a request for
a hearing may not rest upon mere
allegations or denials, but must present
specific facts showing that there is a
genuine and substantial issue of fact
that requires a hearing to resolve. We
note in this regard that because CDER
proposes to refuse to approve NDA
209155 for multiple reasons, any
hearing request from PMRS must
address all of those reasons, including
reasons described in the complete
response letter but not described in this
notice due to applicable limitations on
public disclosure of information
contained in unapproved NDAs,
including trade secret information.
Failure to request a hearing within the
time provided and in the manner
required by § 314.200 constitutes a
waiver of the opportunity to request a
hearing. If a hearing request is not
properly submitted, FDA will issue a
notice refusing to approve NDA 209155.
E:\FR\FM\13FEN1.SGM
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Federal Register / Vol. 83, No. 30 / Tuesday, February 13, 2018 / Notices
The Commissioner will grant a
hearing if there exists a genuine and
substantial issue of fact or if the
Commissioner concludes that a hearing
would otherwise be of public interest
(§ 314.200(g)(6)). If a hearing is granted,
it will be conducted according to the
procedures provided in 21 CFR parts 10
through 16 (21 CFR 314.201).
Paper submissions under this notice
of opportunity for a hearing must be
filed in two copies. Except for data and
information prohibited from public
disclosure under 21 U.S.C. 331(j) or 18
U.S.C. 1905, submissions may be seen
in the Dockets Management Staff
between 9 a.m. and 4 p.m., Monday
through Friday, and on the internet at
https://www.regulations.gov. This notice
is issued under section 505(c)(1)(B) of
the FD&C Act, §§ 314.110(b)(3) and
314.200.
Dated: February 8, 2018.
Janet Woodcock,
Director, Center for Drug Evaluation and
Research.
[FR Doc. 2018–02903 Filed 2–12–18; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket Nos. FDA–2015–E–2666; FDA–
2015–E–2758; and FDA–2015–E–2664]
Determination of Regulatory Review
Period for Purposes of Patent
Extension; FARYDAK
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or the Agency) has
determined the regulatory review period
for FARYDAK and is publishing this
notice of that determination as required
by law. FDA has made the
determination because of the
submission of applications to the
Director of the U.S. Patent and
Trademark Office (USPTO), Department
of Commerce, for the extension of a
patent which claims that human drug
product.
SUMMARY:
Anyone with knowledge that any
of the dates as published (in the
SUPPLEMENTARY INFORMATION section) are
incorrect may submit either electronic
or written comments and ask for a
redetermination by April 16, 2018.
Furthermore, any interested person may
petition FDA for a determination
regarding whether the applicant for
extension acted with due diligence
sradovich on DSK3GMQ082PROD with NOTICES
DATES:
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Jkt 244001
during the regulatory review period by
August 13, 2018. See ‘‘Petitions’’ in the
SUPPLEMENTARY INFORMATION section for
more information.
ADDRESSES: 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 April 16,
2018. The https://www.regulations.gov
electronic filing system will accept
comments until midnight Eastern Time
at the end of April 16, 2018. 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 Nos. FDA–
PO 00000
Frm 00040
Fmt 4703
Sfmt 4703
2015–E–2666; FDA–2015–E–2758; and
FDA–2015–E–2664 for ‘‘Determination
of Regulatory Review Period for
Purposes of Patent Extension;
FARYDAK.’’ Received comments, those
filed in a timely manner (see
ADDRESSES), will be placed in the
dockets 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 § 10.20 (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:
Beverly Friedman, Office of Regulatory
Policy, Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 51,
Rm. 6250, Silver Spring, MD 20993,
301–796–3600.
SUPPLEMENTARY INFORMATION:
E:\FR\FM\13FEN1.SGM
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]]>Agencies
[Federal Register Volume 83, Number 30 (Tuesday, February 13, 2018)]
[Notices]
[Pages 6196-6198]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-02903]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-N-0188]
Proposal To Refuse To Approve a New Drug Application for
Oxycodone Hydrochloride Immediate-Release Oral Capsules, 5 Milligrams,
15 Milligrams, and 30 Milligrams; Opportunity for a Hearing
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Director of the Center for Drug Evaluation and Research
(Center Director) of the Food and Drug Administration (FDA or Agency)
is proposing to refuse to approve a new drug application (NDA)
submitted by Pharmaceutical Manufacturing Research Services, Inc.
(PMRS) for oxycodone hydrochloride (HCl) immediate-release (IR) oral
capsules, 5 milligrams (mg), 15 mg, and 30 mg in its present form. This
notice summarizes the grounds for the Center Director's proposal and
offers PMRS an opportunity to request a hearing on the matter.
DATES: Submit either electronic or written requests for a hearing by
March 15, 2018; submit data, information, and analyses in support of
the hearing and any other comments by April 16, 2018.
ADDRESSES: You may submit hearing requests, documents in support of the
hearing, and any other comments as follows. Please note that late,
untimely filed requests and documents will not be considered.
Electronic requests for a hearing must be submitted on or before March
15, 2018; electronic documents in support of the hearing and any other
comments must be submitted on or before April 16, 2018. The https://www.regulations.gov electronic filing system will accept hearing
requests until midnight Eastern Time at the end of March 15, 2018, and
will accept documents in support of the hearing and any other comments
until midnight Eastern Time at the end of April 16, 2018. Documents
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 these dates.
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-2018-N-0188, for ``Proposal to Refuse to Approve a New Drug
Application for Oxycodone Hydrochloride Immediate-Release Oral
Capsules, 5 Milligrams, 15 Milligrams, and 30 Milligrams; Opportunity
for a 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.
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/
[[Page 6197]]
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: Patrick Raulerson, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6260, Silver Spring, MD, 20993, 301-796-
3522, [email protected].
SUPPLEMENTARY INFORMATION:
I. Proposal To Refuse To Approve NDA 209155
PMRS submitted NDA 209155 for oxycodone HCl IR oral capsules in 5
mg, 15 mg, and 30 mg strengths (oxycodone HCl IR capsules) under
section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C
Act) (21 U.S.C. 355(b)(2)), proposing to rely in part on the Agency's
previous finding of safety and effectiveness for ROXICODONE (oxycodone
HCl) IR Tablets (NDA 021011). PMRS proposed that its oxycodone HCl IR
capsules be indicated for the management of acute pain severe enough to
require an opioid analgesic and for which alternative treatments are
inadequate. PMRS also attempted to show that the product had certain
abuse-deterrent properties and sought FDA approval of labeling
describing those properties.
On November 16, 2017, the Division of Anesthesia, Analgesia, and
Addiction Products of FDA's Center for Drug Evaluation and Research
(CDER) issued a complete response letter to PMRS under Sec. 314.110(a)
(21 CFR 314.110(a)) stating that NDA 209155 could not be approved in
its present form, describing the specific deficiencies, and, where
possible, recommending ways PMRS might remedy these deficiencies. The
deficiencies include the following:
1. The application in its present form is not approvable with the
proposed labeling describing abuse-deterrent properties, for multiple
reasons. In particular, (1) the oxycodone in the formulation can be
readily extracted in commonly available solvents into a solution
suitable for injection; (2) there were insufficient data showing the
presence of excipients (including dye) in the formulation can be
expected to deter abuse by injection; (3) the data submitted were
insufficient to show the product was meaningfully resistant to
manipulation for misuse or abuse; and (4) there were not data
submitted, including data from pharmacokinetic and human abuse
liability studies, fully characterizing the product's abuse potential
by all relevant routes of abuse. Also, the data submitted were not
sufficient to rule out the possibility that the proposed formulation
could result in a greater proportion of abuse by injection of PMRS's
product compared to a conventional IR oxycodone formulation. Abuse by
injection carries greater risk of overdose and transmission of
infectious disease than abuse by other routes.
2. The safety and purity of the excipients intended (but not shown)
to confer abuse deterrent properties were not adequately characterized,
either by the intended oral route of use or by expected routes of
abuse, including injection.
3. An overall evaluation of elemental impurities in the final
formulation and a risk assessment for each heavy metal (taking into
consideration the maximum daily dose) were not provided.
4. The application did not fully comply with the patent
certification requirements applicable to applications submitted under
section 505(b)(2) of the FD&C Act.
5. The complete response letter describes additional deficiencies,
which generally relate to chemistry, manufacturing, and controls and
current good manufacturing practice requirements, that CDER determined
preclude approval of the application in its present form. The complete
response letter also noted that satisfactory resolution of
objectionable inspection observations was required before the
application could be approved. Due to applicable limitations on public
disclosure of information contained in unapproved NDAs, including trade
secret information, these specific deficiencies are not described in
this notice.
The complete response letter stated that PMRS is required to
resubmit the application, fully addressing all deficiencies listed in
the letter, or take other actions available under Sec. 314.110 (i.e.,
withdraw the application or request an opportunity for a hearing).
Applicable regulations, including Sec. 10.75 (21 CFR 10.75), also
provide a mechanism for applicants to obtain formal review of one or
more decisions reflected in a complete response letter (see FDA's
guidance for industry ``Formal Dispute Resolution: Sponsor Appeals
Above the Division Level'' (November 2017) available at: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm343101.pdf).
In response to the complete response letter, on November 17, 2017,
PMRS submitted a request for an opportunity for a hearing under Sec.
314.110(b)(3) on whether there are grounds under section 505(d) of the
FD&C Act for denying approval of NDA 209155.
II. Notice of Opportunity for a Hearing
For the reasons stated previously and others described in the
complete response letter, notice is given to PMRS and to all other
interested persons that the Center Director proposes to issue an order
refusing to approve NDA 209155 on the grounds that the application
fails to meet the criteria for approval under section 505(d) of the
FD&C Act, including that: (1) PMRS has not provided sufficient data to
show that the product would be safe (505(d)(1)); (2) PMRS has not shown
that the methods used in, and the facilities and controls used for the
manufacture, processing, or packing of the product are adequate to
preserve its identity, strength, quality, and purity (505(d)(3)); and
(3) the labeling PMRS proposed for the product is false or misleading
(505(d)(7)).
PMRS may request a hearing before the Commissioner of Food and
Drugs (the Commissioner) on the Center Director's proposal to refuse to
approve NDA 209155. If PMRS decides to seek a hearing, it must file:
(1) A written notice of participation and request for a hearing (see
the DATES section), and (2) the studies, data, information, and
analyses relied upon to justify a hearing (see the DATES section), as
specified in Sec. [thinsp]314.200.
As stated in Sec. 314.200(g), a request for a hearing may not rest
upon mere allegations or denials, but must present specific facts
showing that there is a genuine and substantial issue of fact that
requires a hearing to resolve. We note in this regard that because CDER
proposes to refuse to approve NDA 209155 for multiple reasons, any
hearing request from PMRS must address all of those reasons, including
reasons described in the complete response letter but not described in
this notice due to applicable limitations on public disclosure of
information contained in unapproved NDAs, including trade secret
information. Failure to request a hearing within the time provided and
in the manner required by Sec. 314.200 constitutes a waiver of the
opportunity to request a hearing. If a hearing request is not properly
submitted, FDA will issue a notice refusing to approve NDA 209155.
[[Page 6198]]
The Commissioner will grant a hearing if there exists a genuine and
substantial issue of fact or if the Commissioner concludes that a
hearing would otherwise be of public interest (Sec. 314.200(g)(6)). If
a hearing is granted, it will be conducted according to the procedures
provided in 21 CFR parts 10 through 16 (21 CFR 314.201).
Paper submissions under this notice of opportunity for a hearing
must be filed in two copies. Except for data and information prohibited
from public disclosure under 21 U.S.C. 331(j) or 18 U.S.C. 1905,
submissions may be seen in the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday, and on the internet at https://www.regulations.gov. This notice is issued under section 505(c)(1)(B)
of the FD&C Act, Sec. Sec. 314.110(b)(3) and 314.200.
Dated: February 8, 2018.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 2018-02903 Filed 2-12-18; 8:45 am]
BILLING CODE 4164-01-P
