Drugs for Human Use; Drug Efficacy Study Implementation; Certain Prescription Drugs Offered for Various Indications; Final Resolution of Hearing Requests Under Dockets, 1875-1877 [2014-00256]
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Federal Register / Vol. 79, No. 7 / Friday, January 10, 2014 / Notices
FOR FURTHER INFORMATION CONTACT:
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Sumati Nambiar, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6232,
Silver Spring, MD 20993–0002, 301–
796–1300; or Joseph G. Toerner, Center
for Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6244,
Silver Spring, MD 20993–0002, 301–
796–1300.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a draft guidance for industry entitled
‘‘Community-Acquired Bacterial
Pneumonia: Developing Drugs for
Treatment.’’ The purpose of this draft
guidance is to assist clinical trial
sponsors and investigators in the
development of antibacterial drugs for
the treatment of CABP. Issues in CABP
clinical trials were discussed at a 2008
workshop cosponsored by FDA and
professional societies. Recently, there
have been additional discussions about
clinical trial design and endpoints for
CABP at several meetings of the AntiInfective Drugs Advisory Committee. As
a result of these public discussions, the
science of clinical trial design and our
understanding of endpoints and
approaches to clinical development
have advanced.
This revised draft guidance
supersedes the draft guidance published
in March 2009 and informs sponsors of
the changes in our recommendations.
Although we acknowledge the
challenges in conducting clinical trials
of investigational antibacterial drugs in
CABP, this revised draft guidance
incorporates changes intended to attain
a greater degree of balance between the
practicability of conducting CABP
clinical trials and the trial procedures
needed for a scientifically sound and
interpretable trial. We are specifically
requesting input from the public on
these changes for consideration before
finalizing the guidance. Specifically, the
changes from the 2009 draft guidance
include:
• A description of two potential
primary efficacy endpoints for CABP
clinical trials: (1) Improvement in
patient symptoms early in the course of
therapy for CABP (at day 3 to day 5) and
(2) all-cause mortality.
• A justification for a noninferiority
margin based on clinical responses
observed early in the course of therapy,
as well as a justification for all-cause
mortality as a primary efficacy
endpoint.
• Suggestions for efficacy analyses
based on: (1) An overall ITT population
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and (2) a microbiological intent-to-treat
population consisting of those patients
who have a documented bacterial
pathogen known to cause CABP.
• An approach for accommodating
enrollment of patients who have
received prior antibacterial therapy,
provided certain constraints are met.
Issuance of this guidance fulfills a
portion of the requirements of Title VIII,
section 804, of the Food and Drug
Administration Safety and Innovation
Act (Publ. L. 112–144), which requires
FDA to ‘‘review and, as appropriate,
revise not fewer than 3 guidance
documents per year . . . for the conduct
of clinical trials with respect to
antibacterial and antifungal
drugs. . . .’’
This draft guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The draft guidance, when finalized, will
represent the Agency’s current thinking
on this topic. It does not create or confer
any rights for or on any person and does
not operate to bind FDA or the public.
An alternative approach may be used if
such approach satisfies the
requirements of the applicable statutes
and regulations.
II. The Paperwork Reduction Act of
1995
This draft guidance refers to
previously approved collections of
information that are subject to review by
the Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995 (44 U.S.C. 3501–3520). The
collections of information in 21 CFR
part 312 have been approved under
OMB control number 0910–0014 and
the collections of information in 21 CFR
part 314 have been approved under
OMB control number 0910–0001.
III. Comments
Interested persons may submit either
electronic comments regarding this
document to https://www.regulations.gov
or written comments to the Division of
Dockets Management (see ADDRESSES). It
is only necessary to send one set of
comments. Identify comments with the
docket number found in brackets in the
heading of this document. Received
comments may be seen in the Division
of Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday, and
will be posted to the docket at https://
www.regulations.gov.
IV. Electronic Access
Persons with access to the Internet
may obtain the document at either
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
PO 00000
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Guidances/default.htm or https://www.
regulations.gov.
Dated: January 6, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014–00255 Filed 1–9–14; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket Nos. FDA–1975–N–0355 (Formerly
75N–0185), FDA–1976–N–0272 (Formerly
76N–0056), FDA–1976–N–0344 (Formerly
76N–0057), FDA–1978–N–0701 (Formerly
78N–0070), FDA–1979–N–0224 (Formerly
79N–0169), and FDA–1983–N–0297
(Formerly 83N–0030); DESI 1626, 3265,
12283, and 50213]
Drugs for Human Use; Drug Efficacy
Study Implementation; Certain
Prescription Drugs Offered for Various
Indications; Final Resolution of
Hearing Requests Under Dockets
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that all outstanding hearing requests
pertaining to Docket Nos. FDA–1975–
N–0355 (formerly 75N–0185) (DESI
3265); FDA–1976–N–0272 (formerly
76N–0056), FDA–1976–N–0344
(formerly 76N–0057), and FDA–1978–
N–0701 (formerly 78N–0070) (DESI
1626); FDA–1979–N–0224 (formerly
79N–0169) (DESI 12283); and FDA–
1983–N–0297 (formerly 83N–0030)
(DESI 50213) have been withdrawn.
Shipment in interstate commerce of any
of the products identified in these
dockets, or any identical, related, or
similar (IRS) product to the products in
these dockets, that is not the subject of
an approved new drug application
(NDA) or abbreviated new drug
application (ANDA) (other than an overthe-counter (OTC) product that
complies with an applicable OTC
monograph) is unlawful as of the
effective date of this notice.
DATES: Effective Date: This notice is
effective January 10, 2014.
ADDRESSES: All communications in
response to this notice should be
identified with the appropriate docket
number and directed to Sakineh
Walther, Division of Prescription Drugs,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 5242, Silver Spring,
SUMMARY:
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Federal Register / Vol. 79, No. 7 / Friday, January 10, 2014 / Notices
MD 20993–0002, sakineh.walther@
fda.hhs.gov.
FOR FURTHER INFORMATION CONTACT:
Sakineh Walther, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 5242,
Silver Spring, MD 20993–0002, 301–
796–3349, sakineh.walther@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice published in the Federal
Register of July 24, 2012 (77 FR 43337)
(the July 24, 2012, notice), FDA
described the outstanding hearing
requests pertaining to, among others,
Docket Nos. FDA–1975–N–0355
(formerly 75N–0185) (DESI 3265); FDA–
1976–N–0272 (formerly 76N–0056),
FDA–1976–N–0344 (formerly 76N–
0057), and FDA–1978–N–0701 (formerly
78N–0070) (DESI 1626); FDA–1979–N–
0224 (formerly 79N–0169) (DESI 12283);
and FDA–1983–N–0297 (formerly 83N–
0030) (DESI 50213) established under
the Agency’s Drug Efficacy Study
Implementation (DESI) program. In the
July 24, 2012, notice, FDA offered an
opportunity for companies with
outstanding hearing requests under
those dockets to withdraw or affirm
their outstanding hearing requests.
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A. Docket No. FDA–1975–N–0355
(Formerly 75N–0185) (DESI 3265)
In 1971, FDA published DESI efficacy
findings for single-ingredient
anticholinergic drugs for oral or
injectable use containing dicyclomine
hydrochloride (HCl), among other
ingredients (36 FR 11754, June 18,
1971). In a notice published on
November 11, 1975 (40 FR 52644), FDA
determined that the June 18, 1971,
Federal Register notice should not have
included drugs containing certain
specified ingredients, including
dicyclomine HCl, because the drugs
containing those ingredients were not
anticholinergic drugs (40 FR 52644 at
52648). Elsewhere in the Federal
Register of November 11, 1975 (40 FR
52649), FDA published a notice
concluding that dicyclomine HCl
products, among other products covered
by the notice, were less than effective
and offering an opportunity for hearing
regarding these drugs.
On June 22, 1984, in response to the
submission of data, FDA published a
followup notice regarding single entity
dicyclomine HCl products (49 FR
25681). In that notice, FDA concluded
that such products were effective for the
treatment of functional bowel/irritable
bowel syndrome (irritable colon, spastic
colon, and mucous colitis) and
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established conditions for their
marketing and labeling (49 FR 25681 at
25683 and 25684). The Agency also
found, however, that the products were
lacking substantial evidence of
effectiveness for use in the treatment of
acute enterocolitis or infant colic (49 FR
25681 at 25684) and offered an
opportunity for hearing.
At the time of the July 24, 2012,
notice, there was one outstanding
hearing request under this docket filed
by Merrell-National Laboratories, 110
Amity Rd., Cincinnati, OH 45215,
regarding Bentyl Capsules (NDA 7–409),
Bentyl Injection (NDA 8–370), Bentyl
Syrup (NDA 7–961), and Dactil Tablets
(NDA 8–907). FDA believes SanofiAventis U.S. to be the successor-ininterest to Merrell-National
Laboratories, but received no response
to its attempt to contact Sanofi-Aventis
U.S. regarding this hearing request in
September 2011. In the July 24, 2012,
notice, FDA provided the company an
opportunity to affirm or withdraw its
hearing request. Requests that were not
affirmed within 30 days of that notice
were to be deemed by FDA to be
withdrawn.
B. Docket Nos. FDA–1976–N–0272
(Formerly 76N–0056), FDA–1976–N–
0344 (Formerly 76N–0057), and FDA–
1978–N–0701 (Formerly 78N–0070)
(DESI 1626)
In 1972, FDA classified certain
combination drug products containing a
xanthine derivative as lacking
substantial evidence of effectiveness for
some labeled indications and possibly
effective for other labeled indications
(37 FR 14895, July 26, 1972). As
described in a Federal Register notice of
February 29, 1984 (49 FR 7454), FDA
subsequently handled these products in
three groups:
Group 1: Combinations containing 2
grains or less of a xanthine derivative,
ephedrine, and 8 milligrams (mg) or less
of phenobarbital (Docket No. FDA–
1976–N–0344 (formerly 76N–0057));
Group 2: Combinations containing
more than 2 grains of xanthine
derivative, more than 8 mg of
phenobarbital, and/or an ingredient not
considered as part of the OTC drug
review (Docket No. FDA–1976–N–0272
(formerly 76N–0056)); and
Group 3: Combinations containing
theophylline, ephedrine, and
hydroxyzine HCl (Docket No. FDA–
1978–N–0701 (formerly 78N–0070)).
With respect to the products in Group
2, a notice of opportunity for hearing
was published on April 9, 1976 (41 FR
15051). No hearing was requested, and
approval of applications for products
covered by Docket No. FDA–1976–N–
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0272 (formerly 76N–0056) (DESI 1626)
were withdrawn by notice in the
Federal Register published October 7,
1977 (42 FR 54620).
With respect to the products in Group
3, FDA granted a hearing in response to
requests (49 FR 36443, September 17,
1984). The hearing requests were
subsequently withdrawn, and approval
of applications for products covered by
Docket No. FDA–1078–N–0701
(formerly 78N–0070) (DESI 1626) were
withdrawn by notice in the Federal
Register published July 8, 1998 (63 FR
36923).
With respect to the products in Group
1, in 1976, FDA granted temporary
permission for the products to remain
on the market because similar products
had been marketed OTC in the past and
were then undergoing review in the
Over-the-Counter Drug Study (41 FR
15053, April 9, 1976). In 1984, FDA
amended the April 1976 notice to
include its analysis of new information
regarding combination products
containing a xanthine derivative (49 FR
7454, February 29, 1984). Based on its
analysis of the new information, FDA
concluded that there is a lack of
substantial evidence: (1) That each
ingredient contributes to the claimed
effect of such combination drug
products and (2) that the dosage of each
component is such that the
combinations are safe and effective for
a significant patient population (49 FR
7454). Therefore, FDA proposed in the
1984 notice to withdraw approval of the
applications for combination products
containing a xanthine derivative and
offered an opportunity for hearing
regarding its proposal.
At the time of the July 24, 2012,
notice, there was one outstanding
hearing request under Docket No. FDA–
1976–N–0344 (formerly 76N–0057) filed
by William P. Poythress & Co, Inc., 16
N. 22nd St., P.O. Box 26946, Richmond,
VA 23261, regarding an unidentified
product containing a xanthine
derivative, ephedrine, and 8 mg or less
of phenobarbital. FDA was unable to
find current contact information for
William P. Poythress & Co, Inc. In the
July 24, 2012, notice FDA provided this
company an opportunity to withdraw or
affirm its hearing request. Requests that
were not affirmed within 30 days of that
notice were to be deemed by FDA to be
withdrawn.
C. Docket No. FDA–1979–N–0224
(Formerly 79N–0169) (DESI 12283)
In 1979, FDA announced its DESI
conclusions regarding the effectiveness
of chlorthalidone for the treatment of
hypertension and certain types of edema
(44 FR 54124, September 18, 1979).
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Specifically, FDA determined that there
was substantial evidence to support the
effectiveness of the 25- and 50-mg
strengths for use in hypertension and
edema, but that there was no longer
justification for the 100-mg dosage form
of chlorthalidone because of safety
concerns at that dosage level (44 FR
54124 at 54126). In the 1979 notice,
FDA proposed to withdraw approval of
the 100-mg strength and offered an
opportunity for hearing regarding its
proposal.
At the time of the July 24, 2012,
notice, there was one outstanding
hearing request under this docket filed
by Generics International Division of
Apotex, Inc., 2400 North Commerce
Pkwy., Suite 400, Weston, FL 33326,
regarding chlorthalidone. In the July 24,
2012, notice, FDA provided this
company an opportunity to withdraw or
affirm its hearing request. Requests that
were not affirmed within 30 days of that
notice were to be deemed by FDA to be
withdrawn.
D. Docket No. FDA–1983–N–0297
(Formerly 83N–0030) (DESI 50213)
Under Docket No. FDA–1983–N–0297
(formerly 83N–0030), FDA evaluated the
evidence of effectiveness for certain
fixed-combination drugs containing
antibiotics and sulfonamides and
determined that these products lacked
substantial evidence of effectiveness (34
FR 6008, April 2, 1969). In the April
1969 Federal Register notice, FDA
proposed to revoke provisions for
certification of these products, and
offered interested persons 30 days to
submit data concerning the proposal.
Data submitted in response to the April
1969 notice did not provide substantial
evidence of effectiveness, so FDA
amended the antibiotic regulations on
June 30, 1970, by revoking provisions
for the certification of these drugs (35
FR 10587, June 30, 1970). The order was
to become effective in 40 days and
allowed 30 days for interested persons
to file objections and request a hearing.
The time for responding to the June
1970 order was subsequently extended
until August 17, 1970 (35 FR 12653,
August 8, 1970).
In response to the June 1970 order,
Pfizer Inc. submitted data regarding its
affected product, Urobiotic 250
Capsules, and requested a hearing.
Despite the filing of timely objections,
the amendments were inadvertently not
stayed, and succeeding codifications of
the antibiotic regulations did not
explicitly provide for certification of
Urobiotic 250 Capsules. However, FDA
permitted Pfizer to continue distribution
of its product pending resolution of the
firm’s hearing request. In July 2010,
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Pfizer voluntarily withdrew its
application for Urobiotic (see 75 FR
42455, July 21, 2010).
At the time of the July 24, 2012,
notice, there was one outstanding
hearing request under this docket filed
by Pfizer, Inc., 235 East 42nd St., New
York, NY 10017, regarding Urobiotic. As
noted in the previous paragraph, the
product itself was withdrawn, but FDA
attempted to contact the company to
verify that it no longer wished to pursue
its hearing request. The company did
not respond, and in the July 24, 2012,
notice, FDA provided this company an
opportunity to withdraw or affirm its
hearing request. Requests that were not
affirmed within 30 days of that notice
were to be deemed by FDA to be
withdrawn.
II. Resolution of Hearing Requests
Pertaining to Dockets Subject to This
Notice
The time period for responding to the
July 24, 2012, notice has elapsed, and
no companies with outstanding hearing
requests pertaining to the dockets listed
in this document responded to the
notice. Because no outstanding hearing
requests relating to these dockets were
affirmed in response to the July 24,
2012, notice (or in response to FDA’s
previous attempts to contact companies
with outstanding hearing requests), all
of the outstanding hearing requests
pertaining to Docket Nos. FDA–1975–
N–0355 (formerly 75N–0185) (DESI
3265); FDA–1976–N–0272 (formerly
76N–0056), FDA–1976–N–0344
(formerly 76N–0057), and FDA–1978–
N–0701 (formerly 78N–0070) (DESI
1626); FDA–1979–N–0224 (formerly
79N–0169) (DESI 12283); and FDA–
1983–N–0297 (formerly 83N–0030)
(DESI 50213) are deemed to be
withdrawn.
Effective as of the date of this notice,
it is unlawful to introduce into
interstate commerce any of the products
identified in any of the dockets
included in this notice, or any IRS
product to any product identified in
these dockets, that is not the subject of
an approved NDA or ANDA. Any
person who wishes to determine
whether a specific product is covered by
this notice should write to the Center for
Drug Evaluation and Research (see
ADDRESSES).
III. Discontinued Products
Some firms may have previously
discontinued manufacturing or
distributing products covered by this
notice without removing them from the
listing of their products under section
510(j) of the Federal Food, Drug, and
Cosmetic Act (the FD&C Act) (21 U.S.C.
PO 00000
Frm 00059
Fmt 4703
Sfmt 4703
1877
360(j)). Other firms may discontinue
manufacturing or distributing listed
products in response to this notice.
Firms that wish to notify the Agency of
product discontinuation should send a
letter identifying the discontinued
product(s), including the National Drug
Code number(s), and stating that the
manufacturing and/or distribution of the
product(s) has (have) been
discontinued. The letter should be sent
electronically to Sakineh Walther (see
ADDRESSES).
Firms should also electronically
update the listing of their products
under section 510(j) of the FD&C Act to
reflect discontinuation of products
covered by this notice. Firms should be
aware that, after the effective date of this
notice, FDA intends to take enforcement
action without further notice against
any firm that manufactures or ships in
interstate commerce any unapproved
product covered by this notice.
Dated: January 6, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014–00256 Filed 1–9–14; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–N–1658]
Characterizing and Communicating
Uncertainty in the Assessment of
Benefits and Risks in Drug Regulatory
Decision-Making; Public Workshop;
Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
Notice of Public Workshop;
request for public comments.
ACTION:
The Food and Drug
Administration (FDA or the Agency) is
announcing the following workshop
convened by the Institute of Medicine
(IOM): ‘‘Characterizing and
Communicating Uncertainty in the
Assessment of Benefits and Risks in
Drug Regulatory Decision-Making.’’ The
purpose of the workshop is twofold: To
explore potential approaches to
addressing and communicating
uncertainty and to identify key
considerations on developing,
evaluating, and incorporating potential
approaches for addressing uncertainty
into the assessment of benefits and risks
in the human drug review process. The
format of the meeting consists of a series
of presentations on topics related to
uncertainty in the assessment of benefits
SUMMARY:
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]]>Agencies
[Federal Register Volume 79, Number 7 (Friday, January 10, 2014)]
[Notices]
[Pages 1875-1877]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-00256]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket Nos. FDA-1975-N-0355 (Formerly 75N-0185), FDA-1976-N-0272
(Formerly 76N-0056), FDA-1976-N-0344 (Formerly 76N-0057), FDA-1978-N-
0701 (Formerly 78N-0070), FDA-1979-N-0224 (Formerly 79N-0169), and FDA-
1983-N-0297 (Formerly 83N-0030); DESI 1626, 3265, 12283, and 50213]
Drugs for Human Use; Drug Efficacy Study Implementation; Certain
Prescription Drugs Offered for Various Indications; Final Resolution of
Hearing Requests Under Dockets
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that all
outstanding hearing requests pertaining to Docket Nos. FDA-1975-N-0355
(formerly 75N-0185) (DESI 3265); FDA-1976-N-0272 (formerly 76N-0056),
FDA-1976-N-0344 (formerly 76N-0057), and FDA-1978-N-0701 (formerly 78N-
0070) (DESI 1626); FDA-1979-N-0224 (formerly 79N-0169) (DESI 12283);
and FDA-1983-N-0297 (formerly 83N-0030) (DESI 50213) have been
withdrawn. Shipment in interstate commerce of any of the products
identified in these dockets, or any identical, related, or similar
(IRS) product to the products in these dockets, that is not the subject
of an approved new drug application (NDA) or abbreviated new drug
application (ANDA) (other than an over-the-counter (OTC) product that
complies with an applicable OTC monograph) is unlawful as of the
effective date of this notice.
DATES: Effective Date: This notice is effective January 10, 2014.
ADDRESSES: All communications in response to this notice should be
identified with the appropriate docket number and directed to Sakineh
Walther, Division of Prescription Drugs, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 5242, Silver Spring,
[[Page 1876]]
MD 20993-0002, sakineh.walther@fda.hhs.gov.
FOR FURTHER INFORMATION CONTACT: Sakineh Walther, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 5242, Silver Spring, MD 20993-0002, 301-
796-3349, sakineh.walther@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice published in the Federal Register of July 24, 2012 (77
FR 43337) (the July 24, 2012, notice), FDA described the outstanding
hearing requests pertaining to, among others, Docket Nos. FDA-1975-N-
0355 (formerly 75N-0185) (DESI 3265); FDA-1976-N-0272 (formerly 76N-
0056), FDA-1976-N-0344 (formerly 76N-0057), and FDA-1978-N-0701
(formerly 78N-0070) (DESI 1626); FDA-1979-N-0224 (formerly 79N-0169)
(DESI 12283); and FDA-1983-N-0297 (formerly 83N-0030) (DESI 50213)
established under the Agency's Drug Efficacy Study Implementation
(DESI) program. In the July 24, 2012, notice, FDA offered an
opportunity for companies with outstanding hearing requests under those
dockets to withdraw or affirm their outstanding hearing requests.
A. Docket No. FDA-1975-N-0355 (Formerly 75N-0185) (DESI 3265)
In 1971, FDA published DESI efficacy findings for single-ingredient
anticholinergic drugs for oral or injectable use containing dicyclomine
hydrochloride (HCl), among other ingredients (36 FR 11754, June 18,
1971). In a notice published on November 11, 1975 (40 FR 52644), FDA
determined that the June 18, 1971, Federal Register notice should not
have included drugs containing certain specified ingredients, including
dicyclomine HCl, because the drugs containing those ingredients were
not anticholinergic drugs (40 FR 52644 at 52648). Elsewhere in the
Federal Register of November 11, 1975 (40 FR 52649), FDA published a
notice concluding that dicyclomine HCl products, among other products
covered by the notice, were less than effective and offering an
opportunity for hearing regarding these drugs.
On June 22, 1984, in response to the submission of data, FDA
published a followup notice regarding single entity dicyclomine HCl
products (49 FR 25681). In that notice, FDA concluded that such
products were effective for the treatment of functional bowel/irritable
bowel syndrome (irritable colon, spastic colon, and mucous colitis) and
established conditions for their marketing and labeling (49 FR 25681 at
25683 and 25684). The Agency also found, however, that the products
were lacking substantial evidence of effectiveness for use in the
treatment of acute enterocolitis or infant colic (49 FR 25681 at 25684)
and offered an opportunity for hearing.
At the time of the July 24, 2012, notice, there was one outstanding
hearing request under this docket filed by Merrell-National
Laboratories, 110 Amity Rd., Cincinnati, OH 45215, regarding Bentyl
Capsules (NDA 7-409), Bentyl Injection (NDA 8-370), Bentyl Syrup (NDA
7-961), and Dactil Tablets (NDA 8-907). FDA believes Sanofi-Aventis
U.S. to be the successor-in-interest to Merrell-National Laboratories,
but received no response to its attempt to contact Sanofi-Aventis U.S.
regarding this hearing request in September 2011. In the July 24, 2012,
notice, FDA provided the company an opportunity to affirm or withdraw
its hearing request. Requests that were not affirmed within 30 days of
that notice were to be deemed by FDA to be withdrawn.
B. Docket Nos. FDA-1976-N-0272 (Formerly 76N-0056), FDA-1976-N-0344
(Formerly 76N-0057), and FDA-1978-N-0701 (Formerly 78N-0070) (DESI
1626)
In 1972, FDA classified certain combination drug products
containing a xanthine derivative as lacking substantial evidence of
effectiveness for some labeled indications and possibly effective for
other labeled indications (37 FR 14895, July 26, 1972). As described in
a Federal Register notice of February 29, 1984 (49 FR 7454), FDA
subsequently handled these products in three groups:
Group 1: Combinations containing 2 grains or less of a xanthine
derivative, ephedrine, and 8 milligrams (mg) or less of phenobarbital
(Docket No. FDA-1976-N-0344 (formerly 76N-0057));
Group 2: Combinations containing more than 2 grains of xanthine
derivative, more than 8 mg of phenobarbital, and/or an ingredient not
considered as part of the OTC drug review (Docket No. FDA-1976-N-0272
(formerly 76N-0056)); and
Group 3: Combinations containing theophylline, ephedrine, and
hydroxyzine HCl (Docket No. FDA-1978-N-0701 (formerly 78N-0070)).
With respect to the products in Group 2, a notice of opportunity
for hearing was published on April 9, 1976 (41 FR 15051). No hearing
was requested, and approval of applications for products covered by
Docket No. FDA-1976-N-0272 (formerly 76N-0056) (DESI 1626) were
withdrawn by notice in the Federal Register published October 7, 1977
(42 FR 54620).
With respect to the products in Group 3, FDA granted a hearing in
response to requests (49 FR 36443, September 17, 1984). The hearing
requests were subsequently withdrawn, and approval of applications for
products covered by Docket No. FDA-1078-N-0701 (formerly 78N-0070)
(DESI 1626) were withdrawn by notice in the Federal Register published
July 8, 1998 (63 FR 36923).
With respect to the products in Group 1, in 1976, FDA granted
temporary permission for the products to remain on the market because
similar products had been marketed OTC in the past and were then
undergoing review in the Over-the-Counter Drug Study (41 FR 15053,
April 9, 1976). In 1984, FDA amended the April 1976 notice to include
its analysis of new information regarding combination products
containing a xanthine derivative (49 FR 7454, February 29, 1984). Based
on its analysis of the new information, FDA concluded that there is a
lack of substantial evidence: (1) That each ingredient contributes to
the claimed effect of such combination drug products and (2) that the
dosage of each component is such that the combinations are safe and
effective for a significant patient population (49 FR 7454). Therefore,
FDA proposed in the 1984 notice to withdraw approval of the
applications for combination products containing a xanthine derivative
and offered an opportunity for hearing regarding its proposal.
At the time of the July 24, 2012, notice, there was one outstanding
hearing request under Docket No. FDA-1976-N-0344 (formerly 76N-0057)
filed by William P. Poythress & Co, Inc., 16 N. 22nd St., P.O. Box
26946, Richmond, VA 23261, regarding an unidentified product containing
a xanthine derivative, ephedrine, and 8 mg or less of phenobarbital.
FDA was unable to find current contact information for William P.
Poythress & Co, Inc. In the July 24, 2012, notice FDA provided this
company an opportunity to withdraw or affirm its hearing request.
Requests that were not affirmed within 30 days of that notice were to
be deemed by FDA to be withdrawn.
C. Docket No. FDA-1979-N-0224 (Formerly 79N-0169) (DESI 12283)
In 1979, FDA announced its DESI conclusions regarding the
effectiveness of chlorthalidone for the treatment of hypertension and
certain types of edema (44 FR 54124, September 18, 1979).
[[Page 1877]]
Specifically, FDA determined that there was substantial evidence to
support the effectiveness of the 25- and 50-mg strengths for use in
hypertension and edema, but that there was no longer justification for
the 100-mg dosage form of chlorthalidone because of safety concerns at
that dosage level (44 FR 54124 at 54126). In the 1979 notice, FDA
proposed to withdraw approval of the 100-mg strength and offered an
opportunity for hearing regarding its proposal.
At the time of the July 24, 2012, notice, there was one outstanding
hearing request under this docket filed by Generics International
Division of Apotex, Inc., 2400 North Commerce Pkwy., Suite 400, Weston,
FL 33326, regarding chlorthalidone. In the July 24, 2012, notice, FDA
provided this company an opportunity to withdraw or affirm its hearing
request. Requests that were not affirmed within 30 days of that notice
were to be deemed by FDA to be withdrawn.
D. Docket No. FDA-1983-N-0297 (Formerly 83N-0030) (DESI 50213)
Under Docket No. FDA-1983-N-0297 (formerly 83N-0030), FDA evaluated
the evidence of effectiveness for certain fixed-combination drugs
containing antibiotics and sulfonamides and determined that these
products lacked substantial evidence of effectiveness (34 FR 6008,
April 2, 1969). In the April 1969 Federal Register notice, FDA proposed
to revoke provisions for certification of these products, and offered
interested persons 30 days to submit data concerning the proposal. Data
submitted in response to the April 1969 notice did not provide
substantial evidence of effectiveness, so FDA amended the antibiotic
regulations on June 30, 1970, by revoking provisions for the
certification of these drugs (35 FR 10587, June 30, 1970). The order
was to become effective in 40 days and allowed 30 days for interested
persons to file objections and request a hearing. The time for
responding to the June 1970 order was subsequently extended until
August 17, 1970 (35 FR 12653, August 8, 1970).
In response to the June 1970 order, Pfizer Inc. submitted data
regarding its affected product, Urobiotic 250 Capsules, and requested a
hearing. Despite the filing of timely objections, the amendments were
inadvertently not stayed, and succeeding codifications of the
antibiotic regulations did not explicitly provide for certification of
Urobiotic 250 Capsules. However, FDA permitted Pfizer to continue
distribution of its product pending resolution of the firm's hearing
request. In July 2010, Pfizer voluntarily withdrew its application for
Urobiotic (see 75 FR 42455, July 21, 2010).
At the time of the July 24, 2012, notice, there was one outstanding
hearing request under this docket filed by Pfizer, Inc., 235 East 42nd
St., New York, NY 10017, regarding Urobiotic. As noted in the previous
paragraph, the product itself was withdrawn, but FDA attempted to
contact the company to verify that it no longer wished to pursue its
hearing request. The company did not respond, and in the July 24, 2012,
notice, FDA provided this company an opportunity to withdraw or affirm
its hearing request. Requests that were not affirmed within 30 days of
that notice were to be deemed by FDA to be withdrawn.
II. Resolution of Hearing Requests Pertaining to Dockets Subject to
This Notice
The time period for responding to the July 24, 2012, notice has
elapsed, and no companies with outstanding hearing requests pertaining
to the dockets listed in this document responded to the notice. Because
no outstanding hearing requests relating to these dockets were affirmed
in response to the July 24, 2012, notice (or in response to FDA's
previous attempts to contact companies with outstanding hearing
requests), all of the outstanding hearing requests pertaining to Docket
Nos. FDA-1975-N-0355 (formerly 75N-0185) (DESI 3265); FDA-1976-N-0272
(formerly 76N-0056), FDA-1976-N-0344 (formerly 76N-0057), and FDA-1978-
N-0701 (formerly 78N-0070) (DESI 1626); FDA-1979-N-0224 (formerly 79N-
0169) (DESI 12283); and FDA-1983-N-0297 (formerly 83N-0030) (DESI
50213) are deemed to be withdrawn.
Effective as of the date of this notice, it is unlawful to
introduce into interstate commerce any of the products identified in
any of the dockets included in this notice, or any IRS product to any
product identified in these dockets, that is not the subject of an
approved NDA or ANDA. Any person who wishes to determine whether a
specific product is covered by this notice should write to the Center
for Drug Evaluation and Research (see ADDRESSES).
III. Discontinued Products
Some firms may have previously discontinued manufacturing or
distributing products covered by this notice without removing them from
the listing of their products under section 510(j) of the Federal Food,
Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360(j)). Other firms
may discontinue manufacturing or distributing listed products in
response to this notice. Firms that wish to notify the Agency of
product discontinuation should send a letter identifying the
discontinued product(s), including the National Drug Code number(s),
and stating that the manufacturing and/or distribution of the
product(s) has (have) been discontinued. The letter should be sent
electronically to Sakineh Walther (see ADDRESSES).
Firms should also electronically update the listing of their
products under section 510(j) of the FD&C Act to reflect
discontinuation of products covered by this notice. Firms should be
aware that, after the effective date of this notice, FDA intends to
take enforcement action without further notice against any firm that
manufactures or ships in interstate commerce any unapproved product
covered by this notice.
Dated: January 6, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-00256 Filed 1-9-14; 8:45 am]
BILLING CODE 4160-01-P
