Dr. Reddy’s Laboratories LimitedCyclophosphamide Injection, 500 mg/mL, 1 g/2mL and 2 g/4mL

NDA 210852 COMPLETE RESPONSE

Dr. Reddy’s Laboratories Limited

c/o Dr. Reddy’s Laboratories, Inc. Attention: Srinivasa Rao, PharmD

Vice President and Head Regulatory Affairs 107 College Road East

Princeton, NJ 08540

Dear Dr. Rao:

Please refer to your new drug application (NDA) dated September 28, 2017, received September 28, 2017, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Cyclophosphamide Injection, 500 mg/mL, 1 g/2mL and

2 g/4mL.

We acknowledge receipt of your amendments dated November 5, 2018 and May 21, 2019, which constituted a complete response to our July 24, 2018 and May 3, 2019, action letters, respectively.

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 O° (FEI oe and Dr. Reddy’s Laboratories Limited (FEI 3006549835) manufacturing facilities for this application, our field investigator conveyed deficiencies to the representative of the facilities. Satisfactory resolution of these deficiencies is required before this application may be approved.

PRESCRIBING INFORMATION Your proposed Prescribing Information (Pl) 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

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NDA 210852 Page 2

Requirements for Prescribing Information’ and Pregnancy and Lactation Labeling Final Rule? websites, which include:

e The Final Rule (Physician Labeling Rule) on the content and format of the Pl 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.

SAFETY UPDATE

When you respond to the above deficiencies, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level.

1 https://www.fda.gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources 2 https://www.fda.gov/drugs/labeling/pregnancy-and-lactation-labeling-drugs-final-rule 3 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm

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

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NDA 210852 Page 3

(1) Describe in detail any significant changes or findings in the safety profile.

(2) When assembling the sections describing discontinuations due to adverse

events, serious adverse e safety data as follows:

vents, and common adverse events, incorporate new

e Present new safety data from the studies/clinical trials for the proposed indication using the same format as in the original submission.

e Present tabulations of application data.

the new safety data combined with the original

e Include tables that compare frequencies of adverse events in the original

application with the re

abulated frequencies described in the bullet above.

e For indications other than the proposed indication, provide separate tables for

the frequencies of adv

erse events occurring in clinical trials.

(3) Present a retabulation of the reasons for premature trial discontinuation by

incorporating the drop-ou

‘s from the newly completed trials. Describe any new

trends or patterns identified.

(4) Provide case report forms and narrative summaries for each patient who died during a clinical trial or who did not complete a trial because of an adverse event.

In addition, provide narra’

(5) Describe any information

ive summaries for serious adverse events.

that suggests a substantial change in the incidence of

common, but less serious, adverse events between the new data and the original

application data.

(6) Provide updated exposure information for the clinical studies/trials (e.g., number

of subjects, person time).

(7) Provide a summary of worldwide experience on the safety of this drug. Include an updated estimate of use for drug marketed in other countries.

(8) Provide English translations of current approved foreign labeling not previously

submitted.

OTHER

Within one year after the date of this letter, you are required to resubmit or take other

actions available under 21 CFR may consider your lack of respo!

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

Reference ID: 4522753

314.110. If you do not take one of these actions, we nse a request to withdraw the application under

NDA 210852 Page 4

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 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 1

Office of Oncologic Diseases

Center for Drug Evaluation and Research

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

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

www.fda.gov 95 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS)

immediately following this page Reference ID: 4522753

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 11/20/2019 02:20:06 PM

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