Mylan Laboratories LimitedAcetaminophen ®® for Injection, 1 g/vial

NDA 206610

COMPLETE RESPONSE Mylan Laboratories Limited c/o Mylan Pharmaceuticals Inc. 781 Chestnut Ridge Road Morgantown, WV 26505

Attention: Anil Sachdeva Senior Director - Regulatory Affairs

Dear Mr. Sachdeva:

Please refer to your New Drug Application (NDA) dated May 3, 2014, received May 5, 2014, and your amendments, submitted pursuant to Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Acetaminophen ®® for Injection, 1 g/vial.

We acknowledge receipt of your amendment dated September 10, 2015, which constituted a complete response to our February 27, 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.

NONCLINICAL

You have not provided an adequate assessment of the presence of possible extractables from the © in the final drug product formulation.

Based on your extraction study, as much as approximately! (4) meg/day) of

unknown material could be present © This exceeds the threshold of

toxicological concern of fncg/day and, therefore, requires adequate safety justification based

on a toxicological risk assessment for the identified materials.

To address this deficiency, provide the following information:

1. Finalize and submit the study report for the ongoing scientific study designed to analyze the final drug product for the presence of potential leachables from

2. Definitively identify the unknown extractables (4)

) and determine if they are present in the final drug product formulation.

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3. Quantitate and characterize any unidentified foreign material from the © that is

present in the final drug product. The study must be conducted on the final drug product at release.

4. Submit a revised toxicological risk assessment for every leachable that is above the Toxicological Threshold of Concern of) famcg/day. We remind you that GRAS designations are not applicable to intravenous drug products.

5. Include copies of all relevant literature cited as part of your toxicological justification. Any publication that is not in English must be translated.

PRESCRIBING INFORMATION

We reserve comment on the proposed labeling until the application is otherwise adequate. We encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPD — 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(1)(1)(i)] in structured product labeling (SPL) format as described at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm

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 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.

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NDA 206610 Page 3

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 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.

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 FDA Guidance for Industry, “Formal Meetings Between 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 until you have been notified in writing that this application is approved.

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If you have any questions, call Christopher Hilfiger, Regulatory Project Manager, at (301) 796- 4131.

Sincerely, {See appended electronic signature page}

Ellen Fields, MD

Deputy Division Director

Division of Anesthesia, Analgesia, and Addiction Products

Office of Drug Evaluation II

Center for Drug Evaluation and Research

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

ELLEN W FIELDS 03/10/2016

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