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

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 pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Acetaminophen in the PAB container, 500mg/50mL and 1000mg/100mL.

We acknowledge receipt of your amendment dated October 24, 2019, which constituted a complete response to our March 27, 2019, 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.

FACILITY INSPECTIONS (1) During a recent inspection of B. Braun Medical Inc. (FEI 2021236), drug product manufacturer for this application, our field investigator conveyed deficiencies to

the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

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PRESCRIBING INFORMATION

(2) 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(I)(1)(i)] in structured product labeling (SPL) format as described at FDA.gov.?

CARTON AND CONTAINER LABELING

(3) We acknowledge receipt of the revised draft carton and container labeling on October 24, 2019. We reserve our comments on the acceptability of the packaging labels for the next review cycle.

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.

’ http:/Awww.fda.gov/Drugs/GuidanceComplianceRequlatoryInformation/LawsActsandRules/ucm08415 9.htm

2 http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm09330 Zhtm

3 http://www.fda.gov/Forlndustry/DataStandards/StructuredProductLabeling/default.htm

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

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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 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 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.

ADDITIONAL COMMENTS

We refer to the following deficiency communicated to you in our March 27, 2019, complete response (CR) letter and in further detail in our March 25, 2019, information request letter that preceded the CR letter: “Provide updated letters from Mallinckrodt that clearly indicate a specific date upon which your application can be approved.”

Your October 17, 2019, response to the CR letter (i.e., resubmission received October 24, 2019) stated: “Updated letters from Mallinckrodt (titled “update waiver © “update waiver! “update consent approval”), clearly indicating a specific date (October 12, 2018) upon which our application can be approved are provided in Module 1.3.5.2.” We note that legal review of these updated letters is still pending at this time and therefore we have not made a determination as to whether this is still deficient.

U.S. Food and Drug Administration

Silver Spring, MD 20993

www.fda.gov

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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 314.65. 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

If you have any questions, call Jaimin Patel, Regulatory Project Manager, at (301) 796- 0412.

Sincerely, {See appended electronic signature page}

Rigoberto Roca, MD

Acting Director

Division of Anesthesiology, Addiction Medicine and Pain Medicine

Office of Neuroscience

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.

RIGOBERTO A ROCA 04/24/2020 12:37:37 PM

Reference ID: 4597675