Sun Pharmaceutical Industries Limitednilotinib capsules

NDA 215644 COMPLETE RESPONSE

Sun Pharmaceutical Industries Limited C/O: Sun Pharmaceutical Industries, Inc. Attention: Juan Grijalva

US Agent, Senior Manager

2 Independence Way

Princeton, NJ 08540

Dear Juan Grijalva:

Please refer to your new drug application (NDA) oe

(b) (4)

for (nilotinib) capsules.

We acknowledge receipt of your amendment dated oe

complete response to our o , action letter.

, which constituted a

We have completed our review of this application, 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.

PRESCRIBING INFORMATION

(1) We reserve comment on the proposed labeling until the application is otherwise adequate. We encourage you to review the labeling review resources on the Prescription Drug Labeling Resources! and Pregnancy and Lactation Labeling Final Rule? websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances.

If you revise labeling, use the SRPI checklist to ensure that the Prescribing Information conforms with format items in regulations and guidances. Your response must include updated content of labeling [21 CFR 314.50(I)(1)] in structured product labeling (SPL) format as described at FDA.gov.?

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NDA 215644 Page 2

CARTON AND CONTAINER LABELING

(2) We reserve comment on the proposed labeling until the application is otherwise adequate.

MEDICATION GUIDE

(3) Add the following bolded statement or appropriate alternative to the carton and container labeling per 21 CFR 208.24(d): "ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide."

PROPRIETARY NAME

(4) Please refer to correspondence dated, ©® which addresses the proposed proprietary name, _—. 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.

FACILITY INSPECTIONS

(5) Following a Current Good Manufacturing Practice (CGMP) inspection and pre-

approval inspection of tad listed in this application, FDA

conveyed deficiencies to the representative of the facility. The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA 483 prior to your complete response to your application. Our determination that the facility's responses are satisfactory will depend on a finding that the facility has come into compliance with CGMP and has addressed any deficiencies specific to your application. You should coordinate with the facility for timely resolution of all inspection deficiencies, as well as to determine if any deficiencies may require updates to your application. Your complete response should include the date(s) of the facility’s response(s) to the FDA Form 483. Please refer to Compliance Program CP 7356.002 for guidance on post- inspection activities specific to CGMP compliance evaluation. FDA may determine that a CGMP reinspection and/or additional pre-approval inspection (PAI) is needed to confirm satisfactory resolution of inspection deficiencies before this application can be approved. If both CGMP and PAI reinspection are needed, the PAI coverage will generally occur following a determination that the facility is in compliance with CGMP.

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

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

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NDA 215644 Page 3

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 application data.

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

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

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NDA 215644 Page 4

ADDITIONAL COMMENTS

We have the following comments/recommendations that are not approvability issues:

(9) may name for Nilotinib oe (b) (4)

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 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 that this application is approved.

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

Reference ID: 5468452

NDA 215644

Page 5 If you have a uestions, contact

Sincerely,

{See appended electronic signature page}

Center for Drug Evaluation and Research

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

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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.

(b) (4)

10/25/2024 09:13:39 AM

Reference ID: 5468452