Ricon Pharma, LLCCyclophosphamide Injection, 500 mg/2

NDA 212501 COMPLETE RESPONSE

Ricon Pharma, LLC

Agent for Ingenus Pharmaceuticals, LLC

Attention: Mukteeshwar Gande, Chief Scientific Officer 100 Ford Road, Suite #9

Denville, NJ 07834

Dear Mr. Gande:

Please refer to your new drug application (NDA) dated September 27, 2018, received September 27, 2018, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Cyclophosphamide Injection, 500 mg/2.5 mL and 1 g/5 mL.

We have completed our review of this application, as amended, and have determined that we cannot approve this application in its present form. We have described our reasons for this action below and, where possible, our recommendations to address these issues.

FACILITY INSPECTIONS During a recent inspection of the | manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

PRESCRIBING INFORMATION

Your proposed Prescribing Information (PI) must conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57. As you develop your proposed PI, we encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information’ and Pregnancy and Lactation Labeling Final Rule? websites, which include:

1 http:/Awww.fda.gov/Drugs/GuidanceComplianceReqgulatoryInformation/LawsActsandRules/ucm08415 9.htm 2 http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm09330 7.htm

Reference ID: 4464139

NDA 212501 Page 2

e The Final Rule (Physician Labeling Rule) on the content and format of the PI for human drug and biological products

e The Final Rule (Pregnancy and Lactation Labeling Rule) on the content and format of information in the PI on pregnancy, lactation, and females and males of reproductive potential

e Regulations and related guidance documents e Asample tool illustrating the format for Highlights and Contents, and

e The Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances.

e FDA's established pharmacologic class (EPC) text phrases for inclusion in the Highlights Indications and Usage heading.

Submit draft labeling that addresses our proposed revisions in the attached labeling.

Prior to resubmitting the labeling, use the SRPI checklist to correct any formatting errors to ensure conformance with the format items in regulations and guidances. In addition, submit updated content of labeling [21 CFR 314.50(I)(1)(i) in structured product labeling (SPL) format as described at FDA.gov.°

To facilitate review of your submission, provide a highlighted or marked-up copy that shows all changes, as well as a clean Word version. The marked-up copy should include annotations that support any proposed changes.

CARTON AND CONTAINER LABELING

Submit draft carton and container labeling revised, as attached, based on our proposed revisions.

OTHER

Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 314.110. If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under

21 CFR 314.65. You may also request an extension of time in which to resubmit the application.

A resubmission must fully address all the deficiencies listed in this letter and should be clearly marked with "RESUBMISSION" in large font, bolded type at the beginning of the

3 http://www.fda.gov/Forlndustry/DataStandards/StructuredProductLabeling/default.htm

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

Reference ID: 4464139

NDA 212501 Page 3

cover letter of the submission. The cover letter should clearly state that you consider

his resubmission a complete response to the deficiencies outlined in this letter. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle.

You may request a meeting or teleconference with us to discuss what steps you need to ‘ake before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products.

The drug product may not be legally marketed until you have been notified in writing hat this application is approved.

If you have any questions, contact Fatima Rizvi, PharmD, Regulatory Project Manager, at (240) 402-7426 or at Fatima.Rizvi@fda.hhs.gov.

Sincerely, {See appended electronic signature page}

Amna Ibrahim, MD

Deputy Director

Division of Oncology Products 1

Office of Hematology and Oncology Products Center for Drug Evaluation and Research

ENCLOSURE(S): e Labeling e Carton/Container Labeling

21 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

Reference ID: 4464139

Signature Page 1 of 1

This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.

AMNA IBRAHIM 07/18/2019 12:36:44 PM

Reference ID: 4464139