Sun Pharma Advanced Research Company LimitedXelpros (latanoprost ophthalmic emulsion)

NDA 206185

Food and Drug Administration Silver Spring MD 20993

COMPLETE RESPONSE

Sun Pharma Advanced Research Company Limited c/o Ora, Inc. Attention: Mr. Aron Shapiro Vice President 300 Brickstone Square Andover, MA 01810

Dear Mr. Shapiro: Please refer to your New Drug Application (NDA) dated and received January 31, 2014, pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Xelpros

(latanoprost ophthalmic emulsion), 0.005%.

We acknowledge receipt of your amendment dated July 28, 2016, which constituted a complete response to our July 30, 2015, action letter.

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/FACILITIES INSPECTION

During a recent inspection of the Sun Pharmaceutical Industries, Ltd., FEI# 3002809586 manufacturing facility for this application, our field investigators conveyed deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

LABELS AND LABELING We acknowledge the submission of proposed carton and container labels as well as proposed

labeling (prescribing information) on July 28, 2016. We reserve comment on the proposed labeling until the application is otherwise adequate.

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PROPRIETARY NAME

Please refer to correspondence dated October 3, 2016, which addresses the proposed proprietary name, Xelpros. This name was found acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to the application deficiencies.

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:

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 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.

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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 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 cover letter of the submission. The cover letter should clearly state that you consider this 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 take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the draft FDA Guidance for Industry, “Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products,” March 2015 at http://www. fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm 43743 L.pdf.

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

If you have any questions, call Judit Milstein, Chief, Project Management Staff at 301-796-0763. Sincerely, {See appended electronic signature page} Renata Albrecht, MD Director Division of Transplant and Ophthalmology Products Office of Antimicrobial Products

Office of New Drugs Center for Drug Evaluation and Research

Reference ID: 4030396

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

RENATA ALBRECHT 12/19/2016

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