Dr. Reddy’s Laboratories, Limited-bortezomib for injection

NDA 206927/Original 1 (o)(4)

Food and Drug Administration Silver Spring MD 20993

COMPLETE RESPONSE

Dr. Reddy’s Laboratories, Limited-

c/o Dr. Reddy’s Laboratories, Inc.

Attention: Srinivasa Rao, PharmD

Senior Director and Head Regulatory Affairs 07 College Road East, 2"! Floor

Princeton, NJ 08540

Dear Dr. Rao:

Please refer to your New Drug Application (NDA) dated March 3, 2014, received March 4, 2014, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for bortezomib for injection 3.5 mg/vial.

We acknowledge receipt of your amendment(s) dated June 6; August 14 (2), 18, and 27; and October 14, 2014.

NDA 206927 provides for the use of bortezomib for injection 3.5 mg/vial for the following indications wo)

e NDA 206927/Original 1 — Route of administration - Intravenous = Treatment of patients with multiple myeloma = Treatment of patients with mantle cell lymphoma who have received at least 1

rior therapy. oI Dy (b) (4)

The subject of this action letter is NDA 206927/Original 1 om

All future submissions to NDA 206927/Original 1 oS

the NDA number and the Original number to which each submission pertains.

should specify

We have completed our review of NDA 206927/Original 1 eM and have determined that we cannot approve these application(s) in their present form. We have described our reasons for this action below and, where possible, our recommendations to address these issues.

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NDA 206927/Original 1) Page 2

PRODUCT QUALITY

Deficiencies - Original 1 (intravenous route of administration):

1. Your application referenced the Drug Master File (DMF) 23996. This DMF was found inadequate to support your submission and a deficiency letter was sent to the DMF holder on December 4, 2014. These deficiencies must be adequately addressed before this application can be approved. As part of your response to this letter, include the date the DMF holder amended their DMF to address the deficiencies.

2. The waiver request for the CFR requirement to provide data from an in vivo bioequivalence study for the intravenous route of administration cannot be granted at this time due to outstanding issues with the identity of the drug substance (refer to DMF) and the identity of the structures in the drug product and reconstituted solution. You may resubmit the biowaiver request or alternatively you may conduct a bioequivalence study between the proposed drug product and the listed drug product for the intravenous route of administration.

LABELING 5. We reserve comment on the proposed labeling until NDA 206927/Original 1! In are otherwise adequate. If you revise labeling, your response must include updated content of labeling [21 CFR 314.50(1)(1)(i)] in structured product

labeling (SPL) format as described at

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NDA 206927/Original 1) ©)

Page 3

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.

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

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 the original NDA 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.

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.

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.

Describe any information that suggests a substantial change in the incidence of common, ut less serious, adverse events between the new data and the original NDA data.

Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).

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

Provide English translations of current approved foreign labeling not previously submitted.

OTHER

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 NDA 206927/Original 1 Coy may be approved. If you wish to have such a meeting, submit your meeting request as described

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Reference ID: 4504436

NDA 206927/Original 1) Page 4

in the FDA’s “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.

The drug product may not be legally marketed for these indication(s) until you have been notified in writing that NDA 206927/Original 1 © are approved.

If you have any questions, call Alycia Anderson, Regulatory Project Manager, at (240) 402-4270.

Sincerely, {See appended electronic signature page}

Ann T. Farrell, MD

Director

Division of Hematology Products

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

Reference ID: 3674417 Reference ID: 4504436

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

ANN T FARRELL 12/17/2014

Reference ID: 3674417 Reference ID: 4504436