Mylan Laboratories LimitedAcetaminophen for Injection, 1 g/vial

NDA 206610 COMPLETE RESPONSE Mylan Laboratories Limited c/o Mylan Pharmaceuticals Inc. 81 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. it to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for ‘Acetaminophen J gym for Injection, 1 g/vial.

We acknowledge receipt of your submission dated June 7, 2017, which constituted a complete response to our February 1, 2017, 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 fe assessment of the ence of leachable compounds from the

drug product formulation. An adequate safety justification was not leachable/extractable compounds that includes

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© Include a dosing regimen that mimics the clinical dosing regimen. The study design must define a NOAEL for the levels of each of these compounds. Calculate the safety margin for human exposure for these NOAELs based on body surface area (mg/m?). The study report must also include quantitative analysis of the above compounds with an identification of the i compound in the solutions administered to the animals to ensure that the safety of the compounds leached from the | have been adequately qualified for safety in the study.

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 (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(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 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.

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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, ut 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.

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. 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/ucem 43743 L.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 12/06/2017

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