Federal Register / Vol. 88, No. 196 / Thursday, October 12, 2023 / Notices 70665 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket Nos. FDA–2020–P–1344 and FDA– 

2023–P–2655] 

Determination That CYTOXAN 

(Cyclophosphamide) for Injection 

(Sterile Dry Powder Excipient-Free 

Formulation), 500 Milligrams/Vial, 1 

Gram/Vial, and 2 Grams/Vial, and 

CYTOXAN (Cyclophosphamide) for 

Injection (Sterile Dry Powder With 

Sodium Chloride Formulation), 500 

Milligrams/Vial, 1 Gram/Vial, and 2 

Grams/Vial, Were Not Withdrawn From 

Sale for Reasons of Safety or 

Effectiveness 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or the Agency) has 

determined that the sterile dry powder 

excipient-free formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

milligrams (mg)/vial, 1 gram (g)/vial, 

and 2 g/vial, and the sterile dry powder 

with sodium chloride formulation of 

CYTOXAN (cyclophosphamide) for 

Injection, 500 mg/vial, 1 g/vial, and 2 g/ 

vial, were not withdrawn from sale for 

reasons of safety or effectiveness. This 

determination means that FDA will not 

begin procedures to withdraw approval 

of abbreviated new drug applications 

(ANDAs) that refer to the sterile dry 

powder excipient-free formulation or 

the sterile dry powder with sodium 

chloride formulation of these drug 

products, and it will allow FDA to 

continue to approve ANDAs that refer to 

these formulations of CYTOXAN as long 

as they meet relevant legal and 

regulatory requirements. 

FOR FURTHER INFORMATION CONTACT: 

Tereza Hess, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 6221, Silver Spring, 

MD 20993–0002, 202–768–5659, 

Tereza.Hess@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: Section 

505(j) of the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) (21 U.S.C. 

355(j)) allows the submission of an 

ANDA to market a generic version of a 

previously approved drug product. To 

obtain approval, the ANDA applicant 

must show, among other things, that the 

generic drug product: (1) has the same 

active ingredient(s), dosage form, route 

of administration, strength, conditions 

of use, and (with certain exceptions) 

labeling as the listed drug, which is a 

version of the drug that was previously 

approved, and (2) is bioequivalent to the 

listed drug. ANDA applicants do not 

have to repeat the extensive clinical 

testing otherwise necessary to gain 

approval of a new drug application 

(NDA). 

Section 505(j)(7) of the FD&C Act 

requires FDA to publish a list of all 

approved drugs. FDA publishes this list 

as part of the ‘‘Approved Drug Products 

With Therapeutic Equivalence 

Evaluations,’’ which is known generally 

as the ‘‘Orange Book.’’ Under FDA 

regulations, drugs are removed from the 

list if the Agency withdraws or 

suspends approval of the drug’s NDA or 

ANDA for reasons of safety or 

effectiveness or if FDA determines that 

the listed drug was withdrawn from sale 

for reasons of safety or effectiveness (21 

CFR 314.162). 

A person may petition the Agency to 

determine, or the Agency may 

determine on its own initiative, whether 

a listed drug was withdrawn from sale 

for reasons of safety or effectiveness. 

This determination may be made at any 

time after the drug has been withdrawn 

from sale, but must be made: (1) 

whenever a listed drug is voluntarily 

withdrawn from sale and ANDAs that 

referred to the listed drug have been 

approved and (2) prior to approving an 

ANDA that refers to the listed drug 

(§ 314.161 (21 CFR 314.161)). FDA may 

not approve an ANDA that does not 

refer to a listed drug. 

CYTOXAN (cyclophosphamide) for 

Injection (sterile dry powder with 

sodium chloride formulation), with the 

500 mg/vial, initially approved on May 

4, 1964, the 1 g/vial, initially approved 

on August 30, 1982, and the 2 g/vial, 

initially approved on August 30, 1982, 

are the subjects of NDA 012142, held by 

Baxter Pharmaceuticals. Subsequently, 

CYTOXAN (cyclophosphamide) for 

Injection (lyophilized powder with 

mannitol) was also approved under 

NDA 012142, with the 500 mg/vial 

approved on January 4, 1984; the 1 g/ 

vial approved on September 24, 1985; 

and the 2 g/vial approved on December 

10, 1985. On November 7, 2003, the 

lyophilized powder with mannitol 

formulation in 500 mg/vial, 1 g/vial, and 

2 g/vial strengths was reformulated and 

approved as a sterile dry powder 

excipient-free formulation under 

Supplement 107 to NDA 012142. On 

March 31, 2012, the CYTOXAN 

(cyclophosphamide) for Injection, sterile 

dry powder with sodium chloride 

formulation in 500 mg/vial, 1 g/vial, and 

2 g/vial strengths was reformulated and 

approved as a lyophilized powder with 

mannitol formulation under 

Supplement 113. CYTOXAN is 

indicated for treatment of malignant 

lymphomas: Hodgkin’s disease, 

lymphocytic lymphoma, mixed-cell 

type lymphoma, histiocytic lymphoma, 

Burkitt’s lymphoma, multiple myeloma, 

leukemias, mycosis fungoides, 

neuroblastoma, adenocarcinoma of the 

ovary, retinoblastoma, breast carcinoma, 

and minimal change nephrotic 

syndrome in pediatric patients. 

FDA previously determined that 

certain CYTOXAN (cyclophosphamide) 

for Injection formulations and strengths 

were not discontinued from sale for 

reasons of safety or effectiveness, but 

these determinations did not address all 

previously approved formulations and 

strengths. In the Federal Register of 

March 1, 2004 (69 FR 9630), FDA issued 

a determination that CYTOXAN 

(cyclophosphamide) for Injection (nonlyophilized formulation), 2 g/vial, was 

not withdrawn from sale for reasons of 

safety or effectiveness. In the Federal 

Register of August 5, 2013 (78 FR 

47321), FDA issued a determination that 

CYTOXAN (cyclophosphamide) for 

Injection (lyophilized formulations), 100 

mg/vial, 200 mg/vial, 500 mg/vial, 1 g/ 

vial, and 2 g/vial, and CYTOXAN 

(cyclophosphamide) for Injection (nonlyophilized formulations), 100 mg/vial 

and 200 mg/vial, were not withdrawn 

from sale for reasons of safety or 

effectiveness. Neither of the previous 

Federal Register notices expressly 

indicate that the determinations were 

made for the sterile dry powder 

excipient-free formulation of CYTOXAN 

(cyclophosphamide) for Injection in the 

500 mg/vial, 1 g/vial, and 2 g/vial 

strengths or the sterile dry powder with 

sodium chloride formulation of 

CYTOXAN (cyclophosphamide) for 

Injection, 500 mg/vial, 1 g/vial, and 2 g/ 

vial. 

The sterile dry powder excipient-free 

formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, and the 

sterile dry powder with sodium chloride 

formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, are 

discontinued. 

Lachman Consultant Services, Inc., 

submitted a citizen petition dated May 

5, 2020 (Docket No. FDA–2020–P– 

1344), under 21 CFR 10.30, requesting 

that the Agency determine whether 

discontinued formulations of all 

strengths of CYTOXAN 

(cyclophosphamide) for Injection 

approved under NDA 012142, including 

the sterile dry powder excipient-free 

formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, were 

withdrawn from sale for reasons of 

safety or effectiveness. Epic Pharma, 


ddrumheller on DSK120RN23PROD with NOTICES1
70666 Federal Register / Vol. 88, No. 196 / Thursday, October 12, 2023 / Notices 

LLC submitted a citizen petition dated 

June 27, 2023 (Docket No. FDA–2023– 

P–2655), also requesting that the Agency 

determine whether the sterile dry 

powder excipient-free formulation of 

CYTOXAN (cyclophosphamide) for 

Injection, 500 mg/vial, 1 g/vial, and 2 g/ 

vial, were withdrawn from sale for 

reasons of safety or effectiveness. 

Although the citizen petitions did not 

specifically address the sterile dry 

powder with sodium chloride 

formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, this 

formulation also has been discontinued. 

We have also determined whether the 

sterile dry powder with sodium chloride 

formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, was 

withdrawn for safety or effectiveness. 

After considering the citizen petitions 

and reviewing Agency records and 

based on the information we have at this 

time, FDA has determined under 

§ 314.161 that CYTOXAN 

(cyclophosphamide) for Injection 

(sterile dry powder excipient-free 

formulation), 500 mg/vial, 1 g/vial, and 

2 g/vial, and CYTOXAN 

(cyclophosphamide) for Injection 

(sterile dry powder with sodium 

chloride formulation), 500 mg/vial, 1 g/ 

vial, and 2 g/vial, were not withdrawn 

for reasons of safety or effectiveness. 

The petitioners have identified no data 

or other information suggesting that the 

sterile dry powder excipient-free 

formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, or the 

sterile dry powder with sodium chloride 

formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, were 

withdrawn for reasons of safety or 

effectiveness. We have carefully 

reviewed our files for records 

concerning the withdrawal of the sterile 

dry powder excipient-free formulation 

of CYTOXAN (cyclophosphamide) for 

Injection, 500 mg/vial, 1 g/vial, and 2 g/ 

vial, and the sterile dry powder with 

sodium chloride formulation of 

CYTOXAN (cyclophosphamide) for 

Injection, 500 mg/vial, 1 g/vial, and 2 g/ 

vial, from sale. We have also 

independently evaluated relevant 

literature and data for possible 

postmarketing adverse events. We have 

found no information that would 

indicate that these drug products were 

withdrawn from sale for reasons of 

safety or effectiveness. 

Accordingly, the Agency has 

determined that the sterile dry powder 

excipient-free formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, and the 

sterile dry powder with sodium chloride 

formulation of CYTOXAN 

(cyclophosphamide) for Injection, 500 

mg/vial, 1 g/vial, and 2 g/vial, drug 

products have been discontinued from 

marketing for reasons other than safety 

or effectiveness. FDA will not begin 

procedures to withdraw approval of 

approved ANDAs that have the sterile 

dry powder excipient-free formulation 

or the sterile dry powder with sodium 

chloride formulation. ANDAs that refer 

to CYTOXAN (cyclophosphamide) for 

Injection, 500 mg/vial, 1 g/vial, and 2 g/ 

vial may be approved by the Agency as 

long as they meet all other legal and 

regulatory requirements for the approval 

of ANDAs. If FDA determines that 

labeling for these drug products should 

be revised to meet current standards, the 

Agency will advise ANDA applicants to 

submit such labeling. 

Dated: October 5, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–22494 Filed 10–11–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–N–2030] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Allegations of 

Regulatory Misconduct Voluntarily 

Submitted to the Center for Devices 

and Radiological Health 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or we) is 

announcing that a proposed collection 

of information has been submitted to the 

Office of Management and Budget 

(OMB) for review and clearance under 

the Paperwork Reduction Act of 1995. 

DATES: Submit written comments 

(including recommendations) on the 

collection of information by November 

13, 2023. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be submitted to https://

www.reginfo.gov/public/do/PRAMain. 

Find this particular information 

collection by selecting ‘‘Currently under 

Review—Open for Public Comments’’ or 

by using the search function. The OMB 

control number for this information 

collection is 0910–0769. Also include 

the FDA docket number found in 

brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

Domini Bean, Office of Operations, 

Food and Drug Administration, Three 

White Flint North, 10A–12M, 11601 

Landsdown St., North Bethesda, MD 

20852, 301–796–5733, PRAStaff@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. 

Allegations of Regulatory Misconduct 

Voluntarily Submitted to the Center for 

Devices and Radiological Health 

OMB Control Number 0910–0769— 

Extension 

This information collection supports 

the voluntary submission of allegations 

of regulatory misconduct to FDA’s 

Center for Devices and Radiological 

Health (CDRH). An allegation of 

regulatory misconduct is a claim that a 

medical device manufacturer or 

individuals marketing medical devices 

or electronic products regulated by 

CDRH may be doing so in a manner that 

violates the law. Reporting these 

allegations can help make FDA aware of 

regulatory concerns it may not learn of 

otherwise. This information can help 

FDA identify the potential risks to 

patients and determine whether further 

investigation is warranted, as well as 

any steps needed to address or correct 

a potential violation. Anyone may file a 

complaint reporting an allegation of 

regulatory misconduct. FDA encourages 

people submitting allegations to include 

supporting information and contact 

information in case additional 

information is needed for FDA to 

understand the allegation and act on the 

report; however, you can choose to 

submit a report anonymously. FDA will 

not share your identity or contact 

information with anyone outside FDA 

unless required to do so by law, 

regulation, or court order. 

Allegations of regulatory misconduct 

may include failure to register and list 

a medical device, marketing uncleared 

or unapproved products, failure to 

follow quality system requirements, or 

misleading promotion. 

You can submit an allegation through 

the Allegations of Regulatory 

Misconduct Form (https://www.fda.gov/ 

medical-devices/reporting-allegationsregulatory-misconduct/allegationsregulatory-misconduct-form), by email, 

or by regular mail. 


ddrumheller on DSK120RN23PROD with NOTICES1