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-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

FOR FURTHER INFORMATION CONTACT: 

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: 

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 

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 

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. 

SUMMARY: The Food and Drug 

Administration (FDA or the Agency) is 


khammond on DSKJM1Z7X2PROD with NOTICES
Federal Register / Vol. 88, No. 235 / Friday, December 8, 2023 / Notices 85637 

1ANDA 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). 

2See 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. 

4Fluoroquinolone 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. 

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 

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 

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 


khammond on DSKJM1Z7X2PROD with NOTICES
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 

(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)). 

Application No. Drug Applicant 

NDA 019537 ....... CIPRO (ciprofloxacin HCl) oral tablet, 

EQ 100 mg base.

Bayer Healthcare Pharmaceuticals Inc., 100 Bayer Blvd., P.O. Box 915, 

Whippany, NJ 07981–0915. 

ANDA 075593 ..... Ciprofloxacin HCl, oral tablet, EQ 100 

mg base.

Dr. Reddy’s Laboratories Ltd., 107 College Rd. East, 2nd Floor Princeton, NJ 

08540. 

ANDA 075817 ..... Ciprofloxacin HCl, oral tablet, EQ 100 

mg base.

Rising Pharma Holdings, Inc., 2 Tower Center Blvd., Suite 1401A, East Brunswick, NJ 08816. 

ANDA 075939 ..... Ciprofloxacin HCl, oral tablet, EQ 100 

mg base.

Amneal Pharmaceuticals, LLC, 50 Horseblock Rd., Brookhaven, NY 11719. 

ANDA 076794 ..... Ciprofloxacin HCl, oral tablet, EQ 100 

mg base.

Watson Laboratories, Inc., 400 Interpace Pkwy., Building A, Parsippany, NJ 

07054. 

ANDA 076912 ..... Ciprofloxacin HCl, oral tablet, EQ 100 

mg base.

Taro Pharmaceutical Industries, Ltd., 1600 Stewart Ave., Suite 604, Westbury, 

NY 11590. 

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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–E–0791] 

Determination of Regulatory Review 

Period for Purposes of Patent 

Extension; VILTEPSO 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: 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. 

DATES: 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. 

ADDRESSES: 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. 

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– 

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 


khammond on DSKJM1Z7X2PROD with NOTICES