B. Braun Medical, Inc.Acetaminophen Injection in the PAB Container, 500 mg/50 mL and 1000 mg/100 mL

NDA 204957 COMPLETE RESPONSE

B. Braun Medical, Inc. 901 Marcon Blvd. Allentown, PA 18109

Attention: Cindy Katsempris Director, Regulatory Affairs

Dear Ms. Katsempris:

Please refer to your New Drug Application (NDA) dated and received December 13, 2016, and your amendments, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Acetaminophen Injection in the PAB Container, 500 mg/50 mL and 1000 mg/100 mL.

We acknowledge receipt of your amendment dated September 27, 2018, which constituted a complete response to our September 28, 2017, action letter.

FACILITY INSPECTIONS

1. During a recent inspection of the B. Braun Medical, Inc. manufacturing facility (FEI 2021236), our field investigator observed objectionable conditions at the facility and conveyed that information to the representative of the facility at the close of the inspection.

Information needed to resolve deficiency: Satisfactory resolution of the observations is required before this application may be approved.

REGULATORY

We refer to the following outstanding deficiencies communicated to you in further detail in our March 25, 2019, information request:

2. Provide updated letters from Mallinckrodt that clearly indicate a specific date upon which your application can be approved.

3. Submit documentation that notice of paragraph IV certification to the and “® patents,

which includes © and © Use codes, was sent to the patent owner/NDA holder.

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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 (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)()] in structured product labeling (SPL) format as described at http://www. fda. gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm

CARTON AND CONTAINER LABELING Submit draft carton and container labeling revised as follows:

1. Replace the terminology © with “single dose” on your proposed carton and container labels and in Section 16 of the proposed PI labeling text.

2. The container label of one unit and the carton labeling of 4 units should have different NDC package codes (last 2 digits of the NDC) to minimize the risk for confusion. Thus, revise the NDC numbers so that the carton labeling and vial labels use a different NDC package code (last 2 digits of the NDC).

3. It is unclear why there is space for © jncluded on the carton because ©® Thus, remove Oe or provide your rationale for including.

SAFETY UPDATE

When you respond to the above deficiencies, include a safety update as described at

21 CFR 314.50(d)(5)(vi)(). 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.

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¢ 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.

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, but less serious, adverse events between the new data and the original application 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.

ADDITIONAL COMMENTS

We have the following comments/recommendations that are not approvability issues, however, they should be addressed in your complete response to this action:

1.

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Your reporting of leachables compounds at and above ™ mcg/mL (i.e., { meg/day

taking into consideration the maximum daily dose of acetaminophen) is not acceptable as this exceeds the recommended qualification threshold of 5 mcg/day. Identify all leachable compounds above 5 mcg/day and submit a toxicological risk assessment for any newly identified compound that exceeds the 5 mcg/day threshold of concern.

You have not provided adequate safety justification for the unknown compound at RRT © Ydentify this unknown compound and submit an accompanying toxicological risk assessment.

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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,” December 2017 at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM59054 ZL.

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, contact Ogochukwu Ogoegbunam, PharmD, BCGP, Regulatory Project Manager, at (240) 402-8807.

Sincerely, {See appended electronic signature page}

Sharon Hertz, MD Director Division of Anesthesia, Analgesia, and Addiction Products Office of Drug Evaluation I Center for Drug Evaluation and Research

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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.

SHARON H HERTZ 03/27/2019 01:34:14 PM

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