Bayer HealthCare Pharmaceuticals Inc., et al.; Withdrawal of Approval of CIPRO (Ciprofloxacin Hydrochloride) Oral Tablet, Equivalent to 100 Milligrams Base, and Five Generic Ciprofloxacin Hydrochloride, Oral Tablet, Equivalent to 100 Milligrams Base Drug Products, 85636-85638 [2023-27015]
Download as PDF
<![CDATA[
85636
Federal Register / Vol. 88, No. 235 / Friday, December 8, 2023 / Notices
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.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.
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:
khammond on DSKJM1Z7X2PROD with NOTICES
I. Background
The Drug Price Competition and
Patent Term Restoration Act of 1984
(Pub. L. 98–417) and the Generic
Animal Drug and Patent Term
Restoration Act (Pub. L. 100–670)
generally provide that a patent may be
extended for a period of up to 5 years
so long as the patented item (human
drug or biological product, animal drug
product, medical device, food additive,
or color additive) was subject to
regulatory review by FDA before the
item was marketed. Under these acts, a
product’s regulatory review period
forms the basis for determining the
amount of extension an applicant may
receive.
A regulatory review period consists of
two periods of time: a testing phase and
an approval phase. For human drug
products, the testing phase begins when
the exemption to permit the clinical
investigations of the drug becomes
effective and runs until the approval
phase begins. The approval phase starts
with the initial submission of an
application to market the human drug
product and continues until FDA grants
permission to market the drug product.
Although only a portion of a regulatory
review period may count toward the
actual amount of extension that the
Director of USPTO may award (for
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16:50 Dec 07, 2023
Jkt 262001
example, half the testing phase must be
subtracted as well as any time that may
have occurred before the patent was
issued), FDA’s determination of the
length of a regulatory review period for
a human drug product will include all
of the testing phase and approval phase
as specified in 35 U.S.C. 156(g)(1)(B).
FDA has approved for marketing the
human drug product SEYSARA
(sarecycline hydrochloride). SEYSARA
is indicated for the treatment of
inflammatory lesions of non-nodular
moderate to severe acne vulgaris in
patients 9 years of age and older.
Subsequent to this approval, the USPTO
received a patent term restoration
application for SEYSARA (U.S. Patent
No. 8,318,706) from Paratek
Pharmaceuticals, Inc., and the USPTO
requested FDA’s assistance in
determining the patent’s eligibility for
patent term restoration. In a letter dated
December 23, 2019, FDA advised the
USPTO that this human drug product
had undergone a regulatory review
period and that the approval of
SEYSARA represented the first
permitted commercial marketing or use
of the product. Thereafter, the USPTO
requested that FDA determine the
product’s regulatory review period.
II. Determination of Regulatory Review
Period
FDA has determined that the
applicable regulatory review period for
SEYSARA is 2,946 days. Of this time,
2,599 days occurred during the testing
phase of the regulatory review period,
while 347 days occurred during the
approval phase. These periods of time
were derived from the following dates:
1. The date an exemption under
section 505(i) of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) (21 U.S.C.
355(i)) became effective: September 9,
2010. The applicant claims August 10,
2010, as the date the investigational new
drug application (IND) became effective.
However, FDA records indicate that the
IND effective date was September 9,
2010, which was 30 days after FDA
receipt of the IND.
2. The date the application was
initially submitted with respect to the
human drug product under section 505
of the FD&C Act: October 20, 2017. FDA
has verified the applicant’s claim that
the new drug application (NDA) for
SEYSARA (NDA 209521) was initially
submitted on October 20, 2017.
3. The date the application was
approved: October 1, 2018. FDA has
verified the applicant’s claim that NDA
209521 was approved on October 1,
2018.
This determination of the regulatory
review period establishes the maximum
PO 00000
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potential length of a patent extension.
However, the USPTO applies several
statutory limitations in its calculations
of the actual period for patent extension.
In its application for patent extension,
this applicant seeks 1,227 days of patent
term extension.
III. Petitions
Anyone with knowledge that any of
the dates as published are incorrect may
submit either electronic or written
comments and, under 21 CFR 60.24, ask
for a redetermination (see DATES).
Furthermore, as specified in § 60.30 (21
CFR 60.30), any interested person may
petition FDA for a determination
regarding whether the applicant for
extension acted with due diligence
during the regulatory review period. To
meet its burden, the petition must
comply with all the requirements of
§ 60.30, including but not limited to:
must be timely (see DATES), must be
filed in accordance with § 10.20, must
contain sufficient facts to merit an FDA
investigation, and must certify that a
true and complete copy of the petition
has been served upon the patent
applicant. (See H. Rept. 857, part 1, 98th
Cong., 2d sess., pp. 41–42, 1984.)
Petitions should be in the format
specified in 21 CFR 10.30.
Submit petitions electronically to
https://www.regulations.gov at Docket
No. FDA–2013–S–0610. Submit written
petitions (two copies are required) to the
Dockets Management Staff (HFA–305),
Food and Drug Administration, 5630
Fishers Lane, Rm. 1061, Rockville, MD
20852.
Dated: December 5, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023–27003 Filed 12–7–23; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2023–N–4973]
Bayer HealthCare Pharmaceuticals
Inc., et al.; Withdrawal of Approval of
CIPRO (Ciprofloxacin Hydrochloride)
Oral Tablet, Equivalent to 100
Milligrams Base, and Five Generic
Ciprofloxacin Hydrochloride, Oral
Tablet, Equivalent to 100 Milligrams
Base Drug Products
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or the Agency) is
SUMMARY:
E:\FR\FM\08DEN1.SGM
08DEN1
khammond on DSKJM1Z7X2PROD with NOTICES
Federal Register / Vol. 88, No. 235 / Friday, December 8, 2023 / Notices
withdrawing the approval of CIPRO
(ciprofloxacin hydrochloride (HCl)) oral
tablet, equivalent to (EQ) 100 milligrams
(mg) base under new drug application
(NDA) 019537 and five generic
ciprofloxacin HCl, oral tablet, EQ 100
mg base products which referenced it as
their basis of submission. The holders of
the applications requested withdrawal
of the 100 mg strength products and
waived their opportunity for a hearing.
DATES: Approval is withdrawn as of
December 8, 2023.
FOR FURTHER INFORMATION CONTACT:
Ayako Sato, Center for Drug Evaluation
and Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 6206, Silver Spring,
MD 20993–0002, 240–402–4191.
SUPPLEMENTARY INFORMATION: On
October 22, 1987, FDA approved NDA
019537 for CIPRO (ciprofloxacin HCl)
oral tablet, EQ 250 mg, 500 mg, and 750
mg base. On April 8, 1996, FDA
approved a supplement to NDA 019537
to add the oral tablet, EQ 100 mg base
to treat acute uncomplicated cystitis in
adult females to be supplied as a cystitis
pack containing six 100 mg oral tablets
with a dosing regimen of 100 mg twice
daily for 3 days. FDA approved the
following generic ciprofloxacin HCl,
oral tablet, EQ 100 mg base products
under section 505(j) of the Federal Food,
Drug, and Cosmetic Act (FD&C Act)
which identified as their reference listed
drug (RLD) the 100 mg strength tablet
approved in NDA 019537: 1
• ANDA 075593 approved on June 9,
2004;
• ANDA 075817 approved on June
25, 2007;
• ANDA 075939 approved on March
3, 2005;
• ANDA 076794 approved on
February 10, 2005; and
• ANDA 076912 approved on
February 18, 2005.
On May 18, 2005, FDA approved
labeling revisions for NDA 019537,
including updates to reflect that the 100
mg oral tablet product was no longer
being marketed. Subsequently, the
Agency made a safety and effectiveness
determination that CIPRO (ciprofloxacin
HCl) oral tablet, EQ 100 mg base was not
discontinued for reasons of safety or
effectiveness, which was later published
in the Federal Register on October 1,
2019 (84 FR 52113). Since the Agency’s
initial safety and effectiveness
1 ANDA 076426 for ciprofloxacin HCl, oral tablet,
EQ 100 mg was approved on June 15, 2005. In the
Federal Register of October 4, 2016, FDA
announced it was withdrawing the approval of
ANDA 076426 upon request by the applicant under
21 CFR 314.150(c) (see 81 FR 68427, October 4,
2016).
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16:50 Dec 07, 2023
Jkt 262001
determination, new information related
to the safe and effective use of
ciprofloxacin HCl, oral tablet, EQ 100
mg base for its indication has become
available.
The resistance of Escherichia coli (E.
coli), the main causative pathogen for
acute uncomplicated cystitis, to
ciprofloxacin has been increasing since
CIPRO (ciprofloxacin HCl) oral tablet,
EQ 100 mg base for the treatment of
acute uncomplicated cystitis was
removed from the product labeling in
2005. The effectiveness of CIPRO
(ciprofloxacin HCl) oral tablet, EQ 100
mg base and ciprofloxacin HCl, oral
tablet, EQ 100 mg base for the treatment
of acute uncomplicated cystitis is not
supported by the current ciprofloxacin
Susceptibility Test Interpretive Criteria
(STIC) (a.k.a., breakpoints),2 established
by the Clinical and Laboratory
Standards Institute and recognized by
FDA on June 10, 2019.3 Recent
pharmacokinetic/pharmacodynamic
analyses conducted by FDA indicated
that the dosage regimen of ciprofloxacin
HCl oral tablet, 100 mg twice daily for
3 days may not be effective for the
treatment of acute uncomplicated
cystitis. A review of published literature
also showed that more contemporary
studies of the treatment of acute
uncomplicated cystitis with
ciprofloxacin were conducted with the
dosage of 250 mg twice daily or 500 mg
extended-release tablet daily. A
literature search produced no studies
comparing the efficacy of ciprofloxacin
100 mg twice daily versus ciprofloxacin
250 mg twice daily or 500 mg extendedrelease tablet daily in treatment of acute
uncomplicated cystitis. Finally,
significant adverse reactions associated
with the use of fluoroquinolones,
including ciprofloxacin HCl, have been
identified.4 Given that the safe and
effective use of ciprofloxacin
hydrochloride tablets, 100 mg twice
daily for 3 days for the treatment of
acute uncomplicated cystitis is not
supported by its current STIC, and
considering the risks of serious adverse
reactions along with the increased
2 See Ciprofloxacin Oral, Injection products,
available at https://www.fda.gov/drugs/
development-resources/ciprofloxacin-oral-injectionproducts. Note E. coli is within the family of
Enterobacteriaceae.
3 21st Century Cures Act: Annual Compilation of
Notices of Updates from the Susceptibility Test
Interpretive Criteria web page; Request for
Comments, 85 FR 67353 at 67354–55, recognizing
on June 10, 2019, updated standard susceptibility
test interpretive criteria for ciprofloxacin.
4 Fluoroquinolone Antimicrobial Drugs
Information, available at https://www.fda.gov/
drugs/information-drug-class/fluoroquinoloneantimicrobial-drugs-information#:∼:text=
Fluoroquinolones%20are%20drugs%20approved
%20for,such%20as%20colds%20or%20flu.
PO 00000
Frm 00060
Fmt 4703
Sfmt 4703
85637
resistance of E. coli to ciprofloxacin,
FDA believes that the potential
problems associated with ciprofloxacin
hydrochloride tablets, 100 mg are
sufficiently serious that the product
should be removed from the market
under § 314.150(d) (21 CFR 314.150(d)).
On June 16, 2023, the Agency notified
Bayer HealthCare Pharmaceuticals Inc.
that it believes the potential problems
associated with the drug are sufficiently
serious that the 100 mg strength product
should be removed from the market
pursuant to § 314.150(d). Bayer
requested in a letter dated July 7, 2023,
that FDA withdraw approval of the 100
mg strength product in NDA 019537
under § 314.150(d) and waived its
opportunity for a hearing.
FDA also notified abbreviated new
drug applications (ANDAs) 075593,
075817, 075939 and 076794 on June 16,
2023, and ANDA 076912 on June 21,
2023. FDA asked the ANDA holders to
request withdrawal of approval under
§ 314.150(d) of the generic versions of
ciprofloxacin HCl oral tablet, EQ 100 mg
base, and to waive their opportunity for
a hearing. In a letter dated June 26,
2023, Rising Pharma Holdings, Inc.,
requested that FDA withdraw approval
of the 100 mg strength product in ANDA
075817 under § 314.150(d) and waived
its opportunity for a hearing. In a letter
dated June 30, 2023, Amneal
Pharmaceuticals, LLC requested that
FDA withdraw approval of the 100 mg
strength product in ANDA 075939
under § 314.150(d) and waived its
opportunity for a hearing. In separate
letters dated July 7, 2023, Dr. Reddy’s
Laboratories and Watson Laboratories,
Inc. requested that FDA withdraw
approval of their 100 mg strength
products in ANDA 075593 and in
ANDA 076794, respectively, under
§ 314.150(d) and waived their
opportunity for a hearing. In a letter
dated July 12, 2023, Taro
Pharmaceutical Industries, Ltd.,
requested that FDA withdraw approval
of the 100 mg strength product in ANDA
076912 under § 314.150(d) and waived
its opportunity for a hearing.
For the reasons discussed above,
which Bayer and the ANDA holders do
not dispute in their withdrawal request
letters, and pursuant to the applicants’
requests, FDA is withdrawing approval
of the 100 mg strength product from one
NDA and from the five ANDAs listed in
the table below under § 314.150(d). This
notice is limited to CIPRO
(ciprofloxacin HCl) oral tablet, EQ 100
mg base and ciprofloxacin HCl, oral
tablet, EQ 100 mg base for the treatment
of acute uncomplicated cystitis. Other
products approved in NDA 019537 for
CIPRO (ciprofloxacin HCl) oral tablet or
E:\FR\FM\08DEN1.SGM
08DEN1
85638
Federal Register / Vol. 88, No. 235 / Friday, December 8, 2023 / Notices
related ANDAs for ciprofloxacin HCl,
oral tablet (e.g., the 250 mg base, 500 mg
base, or 750 mg base strength products)
remain approved. Distribution of CIPRO
Application No.
NDA 019537 .......
ANDA 075593 .....
ANDA 075817 .....
ANDA 075939 .....
ANDA 076794 .....
ANDA 076912 .....
(ciprofloxacin HCl) oral tablet, EQ 100
mg base and ciprofloxacin HCl, oral
tablet, EQ 100 mg base in interstate
commerce without an approved
Drug
Applicant
CIPRO (ciprofloxacin HCl) oral tablet,
EQ 100 mg base.
Ciprofloxacin HCl, oral tablet, EQ 100
mg base.
Ciprofloxacin HCl, oral tablet, EQ 100
mg base.
Ciprofloxacin HCl, oral tablet, EQ 100
mg base.
Ciprofloxacin HCl, oral tablet, EQ 100
mg base.
Ciprofloxacin HCl, oral tablet, EQ 100
mg base.
Dated: December 5, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
Bayer Healthcare Pharmaceuticals Inc., 100 Bayer Blvd., P.O. Box 915,
Whippany, NJ 07981–0915.
Dr. Reddy’s Laboratories Ltd., 107 College Rd. East, 2nd Floor Princeton, NJ
08540.
Rising Pharma Holdings, Inc., 2 Tower Center Blvd., Suite 1401A, East Brunswick, NJ 08816.
Amneal Pharmaceuticals, LLC, 50 Horseblock Rd., Brookhaven, NY 11719.
Watson Laboratories, Inc., 400 Interpace Pkwy., Building A, Parsippany, NJ
07054.
Taro Pharmaceutical Industries, Ltd., 1600 Stewart Ave., Suite 604, Westbury,
NY 11590.
You may submit comments
as follows. 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 at the end of
February 6, 2024. Comments received
by mail/hand delivery/courier (for
written/paper submissions) will be
considered timely if they are received
on or before that date.
ADDRESSES:
[FR Doc. 2023–27015 Filed 12–7–23; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2021–E–0791]
Electronic Submissions
Determination of Regulatory Review
Period for Purposes of Patent
Extension; VILTEPSO
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or the Agency) has
determined the regulatory review period
for VILTEPSO and is publishing this
notice of that determination as required
by law. FDA has made the
determination because of the
submission of an application 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 (see
SUPPLEMENTARY INFORMATION) are
incorrect must submit either electronic
or written comments and ask for a
redetermination by February 6, 2024.
Furthermore, any interested person may
petition FDA for a determination
regarding whether the applicant for
extension acted with due diligence
during the regulatory review period by
June 5, 2024. See ‘‘Petitions’’ in the
SUPPLEMENTARY INFORMATION section for
more information.
khammond on DSKJM1Z7X2PROD with NOTICES
DATES:
VerDate Sep<11>2014
16:50 Dec 07, 2023
Jkt 262001
application is illegal and subject to
regulatory action (see sections 505(a)
and 301(d) of the FD&C Act (21 U.S.C.
355(a) and 331(d)).
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:
PO 00000
Frm 00061
Fmt 4703
Sfmt 4703
• 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–
2021–E–0791 for ‘‘Determination of
Regulatory Review Period for Purposes
of Patent Extension; VILTEPSO.’’
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
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
E:\FR\FM\08DEN1.SGM
08DEN1
]]>Agencies
[Federal Register Volume 88, Number 235 (Friday, December 8, 2023)]
[Notices]
[Pages 85636-85638]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-27015]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-N-4973]
Bayer HealthCare Pharmaceuticals Inc., et al.; Withdrawal of
Approval of CIPRO (Ciprofloxacin Hydrochloride) Oral Tablet, Equivalent
to 100 Milligrams Base, and Five Generic Ciprofloxacin Hydrochloride,
Oral Tablet, Equivalent to 100 Milligrams Base Drug Products
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or the Agency) is
[[Page 85637]]
withdrawing the approval of CIPRO (ciprofloxacin hydrochloride (HCl))
oral tablet, equivalent to (EQ) 100 milligrams (mg) base under new drug
application (NDA) 019537 and five generic ciprofloxacin HCl, oral
tablet, EQ 100 mg base products which referenced it as their basis of
submission. The holders of the applications requested withdrawal of the
100 mg strength products and waived their opportunity for a hearing.
DATES: Approval is withdrawn as of December 8, 2023.
FOR FURTHER INFORMATION CONTACT: Ayako Sato, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 51, Rm. 6206, Silver Spring, MD 20993-0002, 240-402-4191.
SUPPLEMENTARY INFORMATION: On October 22, 1987, FDA approved NDA 019537
for CIPRO (ciprofloxacin HCl) oral tablet, EQ 250 mg, 500 mg, and 750
mg base. On April 8, 1996, FDA approved a supplement to NDA 019537 to
add the oral tablet, EQ 100 mg base to treat acute uncomplicated
cystitis in adult females to be supplied as a cystitis pack containing
six 100 mg oral tablets with a dosing regimen of 100 mg twice daily for
3 days. FDA approved the following generic ciprofloxacin HCl, oral
tablet, EQ 100 mg base products under section 505(j) of the Federal
Food, Drug, and Cosmetic Act (FD&C Act) which identified as their
reference listed drug (RLD) the 100 mg strength tablet approved in NDA
019537: \1\
---------------------------------------------------------------------------
\1\ ANDA 076426 for ciprofloxacin HCl, oral tablet, EQ 100 mg
was approved on June 15, 2005. In the Federal Register of October 4,
2016, FDA announced it was withdrawing the approval of ANDA 076426
upon request by the applicant under 21 CFR 314.150(c) (see 81 FR
68427, October 4, 2016).
---------------------------------------------------------------------------
ANDA 075593 approved on June 9, 2004;
ANDA 075817 approved on June 25, 2007;
ANDA 075939 approved on March 3, 2005;
ANDA 076794 approved on February 10, 2005; and
ANDA 076912 approved on February 18, 2005.
On May 18, 2005, FDA approved labeling revisions for NDA 019537,
including updates to reflect that the 100 mg oral tablet product was no
longer being marketed. Subsequently, the Agency made a safety and
effectiveness determination that CIPRO (ciprofloxacin HCl) oral tablet,
EQ 100 mg base was not discontinued for reasons of safety or
effectiveness, which was later published in the Federal Register on
October 1, 2019 (84 FR 52113). Since the Agency's initial safety and
effectiveness determination, new information related to the safe and
effective use of ciprofloxacin HCl, oral tablet, EQ 100 mg base for its
indication has become available.
The resistance of Escherichia coli (E. coli), the main causative
pathogen for acute uncomplicated cystitis, to ciprofloxacin has been
increasing since CIPRO (ciprofloxacin HCl) oral tablet, EQ 100 mg base
for the treatment of acute uncomplicated cystitis was removed from the
product labeling in 2005. The effectiveness of CIPRO (ciprofloxacin
HCl) oral tablet, EQ 100 mg base and ciprofloxacin HCl, oral tablet, EQ
100 mg base for the treatment of acute uncomplicated cystitis is not
supported by the current ciprofloxacin Susceptibility Test Interpretive
Criteria (STIC) (a.k.a., breakpoints),\2\ established by the Clinical
and Laboratory Standards Institute and recognized by FDA on June 10,
2019.\3\ Recent pharmacokinetic/pharmacodynamic analyses conducted by
FDA indicated that the dosage regimen of ciprofloxacin HCl oral tablet,
100 mg twice daily for 3 days may not be effective for the treatment of
acute uncomplicated cystitis. A review of published literature also
showed that more contemporary studies of the treatment of acute
uncomplicated cystitis with ciprofloxacin were conducted with the
dosage of 250 mg twice daily or 500 mg extended-release tablet daily. A
literature search produced no studies comparing the efficacy of
ciprofloxacin 100 mg twice daily versus ciprofloxacin 250 mg twice
daily or 500 mg extended-release tablet daily in treatment of acute
uncomplicated cystitis. Finally, significant adverse reactions
associated with the use of fluoroquinolones, including ciprofloxacin
HCl, have been identified.\4\ Given that the safe and effective use of
ciprofloxacin hydrochloride tablets, 100 mg twice daily for 3 days for
the treatment of acute uncomplicated cystitis is not supported by its
current STIC, and considering the risks of serious adverse reactions
along with the increased resistance of E. coli to ciprofloxacin, FDA
believes that the potential problems associated with ciprofloxacin
hydrochloride tablets, 100 mg are sufficiently serious that the product
should be removed from the market under Sec. 314.150(d) (21 CFR
314.150(d)).
---------------------------------------------------------------------------
\2\ See Ciprofloxacin Oral, Injection products, available at
https://www.fda.gov/drugs/development-resources/ciprofloxacin-oral-injection-products. Note E. coli is within the family of
Enterobacteriaceae.
\3\ 21st Century Cures Act: Annual Compilation of Notices of
Updates from the Susceptibility Test Interpretive Criteria web page;
Request for Comments, 85 FR 67353 at 67354-55, recognizing on June
10, 2019, updated standard susceptibility test interpretive criteria
for ciprofloxacin.
\4\ Fluoroquinolone Antimicrobial Drugs Information, available
at https://www.fda.gov/drugs/information-drug-class/fluoroquinolone-
antimicrobial-drugs-
information#:~:text=Fluoroquinolones%20are%20drugs%20approved%20for,s
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On June 16, 2023, the Agency notified Bayer HealthCare
Pharmaceuticals Inc. that it believes the potential problems associated
with the drug are sufficiently serious that the 100 mg strength product
should be removed from the market pursuant to Sec. 314.150(d). Bayer
requested in a letter dated July 7, 2023, that FDA withdraw approval of
the 100 mg strength product in NDA 019537 under Sec. 314.150(d) and
waived its opportunity for a hearing.
FDA also notified abbreviated new drug applications (ANDAs) 075593,
075817, 075939 and 076794 on June 16, 2023, and ANDA 076912 on June 21,
2023. FDA asked the ANDA holders to request withdrawal of approval
under Sec. 314.150(d) of the generic versions of ciprofloxacin HCl
oral tablet, EQ 100 mg base, and to waive their opportunity for a
hearing. In a letter dated June 26, 2023, Rising Pharma Holdings, Inc.,
requested that FDA withdraw approval of the 100 mg strength product in
ANDA 075817 under Sec. 314.150(d) and waived its opportunity for a
hearing. In a letter dated June 30, 2023, Amneal Pharmaceuticals, LLC
requested that FDA withdraw approval of the 100 mg strength product in
ANDA 075939 under Sec. 314.150(d) and waived its opportunity for a
hearing. In separate letters dated July 7, 2023, Dr. Reddy's
Laboratories and Watson Laboratories, Inc. requested that FDA withdraw
approval of their 100 mg strength products in ANDA 075593 and in ANDA
076794, respectively, under Sec. 314.150(d) and waived their
opportunity for a hearing. In a letter dated July 12, 2023, Taro
Pharmaceutical Industries, Ltd., requested that FDA withdraw approval
of the 100 mg strength product in ANDA 076912 under Sec. 314.150(d)
and waived its opportunity for a hearing.
For the reasons discussed above, which Bayer and the ANDA holders
do not dispute in their withdrawal request letters, and pursuant to the
applicants' requests, FDA is withdrawing approval of the 100 mg
strength product from one NDA and from the five ANDAs listed in the
table below under Sec. 314.150(d). This notice is limited to CIPRO
(ciprofloxacin HCl) oral tablet, EQ 100 mg base and ciprofloxacin HCl,
oral tablet, EQ 100 mg base for the treatment of acute uncomplicated
cystitis. Other products approved in NDA 019537 for CIPRO
(ciprofloxacin HCl) oral tablet or
[[Page 85638]]
related ANDAs for ciprofloxacin HCl, oral tablet (e.g., the 250 mg
base, 500 mg base, or 750 mg base strength products) remain approved.
Distribution of CIPRO (ciprofloxacin HCl) oral tablet, EQ 100 mg base
and ciprofloxacin HCl, oral tablet, EQ 100 mg base in interstate
commerce without an approved application is illegal and subject to
regulatory action (see sections 505(a) and 301(d) of the FD&C Act (21
U.S.C. 355(a) and 331(d)).
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Application No. Drug Applicant
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NDA 019537............... CIPRO Bayer Healthcare
(ciprofloxacin Pharmaceuticals Inc.,
HCl) oral tablet, 100 Bayer Blvd., P.O.
EQ 100 mg base. Box 915, Whippany, NJ
07981-0915.
ANDA 075593.............. Ciprofloxacin HCl, Dr. Reddy's Laboratories
oral tablet, EQ Ltd., 107 College Rd.
100 mg base. East, 2nd Floor
Princeton, NJ 08540.
ANDA 075817.............. Ciprofloxacin HCl, Rising Pharma Holdings,
oral tablet, EQ Inc., 2 Tower Center
100 mg base. Blvd., Suite 1401A,
East Brunswick, NJ
08816.
ANDA 075939.............. Ciprofloxacin HCl, Amneal Pharmaceuticals,
oral tablet, EQ LLC, 50 Horseblock Rd.,
100 mg base. Brookhaven, NY 11719.
ANDA 076794.............. Ciprofloxacin HCl, Watson Laboratories,
oral tablet, EQ Inc., 400 Interpace
100 mg base. Pkwy., Building A,
Parsippany, NJ 07054.
ANDA 076912.............. Ciprofloxacin HCl, Taro Pharmaceutical
oral tablet, EQ Industries, Ltd., 1600
100 mg base. Stewart Ave., Suite
604, Westbury, NY
11590.
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Dated: December 5, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-27015 Filed 12-7-23; 8:45 am]
BILLING CODE 4164-01-P
