Roxane Laboratories, Inc.Cyclophosphamide Capsules, 25 mg and 50 mg

NDA 203856

Food and Drug Administration Silver Spring MD 20993

COMPLETE RESPONSE

Roxane Laboratories, Inc.

Attention: Randall Wilson

Vice President, Scientific, Medical and Regulatory Affairs 1809 Wilson Road

Columbus, OH 43228

Dear Mr. Wilson:

Please refer to your New Drug Application (NDA) dated July 3, 2012, received July 3, 2012, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Cyclophosphamide Capsules, 25 mg and 50 mg.

We acknowledge receipt of your amendments dated July 17, August 16, November 8, and 30, December 12, and 20, 2012; January 4, and 16, February 22, March 13, 14, 18, and 25, and April 26, 2013.

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.

PRODUCT QUALITY

One of the three NDA registration batches did not pass the proposed NDA specifications for the dissolution and impurity.

Recommendation to address this issue:

At the time of your resubmission of this NDA, submit data from three registration batches (for each dosage strength) that conforms to the NDA-proposed specifications for dissolution and impurity levels.

LABELING

We reserve comment on the proposed labeling until the application is otherwise adequate. If you revise labeling, your response must include updated content of labeling

[21 CFR 314.50(1)(1)(@)] in structured product labeling (SPL) format as described at http://www.fda.gov/ForIndustry/DataS tandards/StructuredProductLabeling/default.htm.

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NDA 203856 Page 2

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. 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 events, and common adverse events, incorporate new safety data as follows:

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

¢ Present tabulations of the new safety data combined with the original NDA data.

e Include tables that compare frequencies of adverse events in the original NDA with the retabulated frequencies described in the bullet above.

e For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.

3. Present a retabulation of the reasons for premature trial discontinuation by incorporating the drop-outs 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 narrative summaries for serious adverse events.

5. Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original NDA 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 314.110. If you do not take one of these actions, we may consider your

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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. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle.

Under 21 CFR 314.102(d), you may request a meeting or telephone conference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the FDA Guidance for Industry, “Formal Meetings Between the FDA and Sponsors or Applicants,” May 2009 at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U

CM153222.pdf.

If you have any questions, call Lisa Skarupa, Regulatory Project Manager, at (301) 796-2219. Sincerely, {See appended electronic signature page} Amna Ibrahim, M.D. Deputy Director Division of Oncology Products 1

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

Reference ID: 3303465

This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature.

AMNA IBRAHIM 05/03/2013

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