AFT Pharmaceuticals, Inc.Combogesic (acetaminophen and ibuprofen) tablets

NDA 209471 COMPLETE RESPONSE

AFT Pharmaceuticals, Inc.

c/o Chesapeake Regulatory Group, Inc. 6574 River Clyde Drive

Highland, MD 20777

Attention: David Zuchero, MS, JD US Agent for AFT Pharmaceuticals, Inc.

Dear Mr. Zuchero:

Please refer to your new drug application (NDA) dated and received March 1, 2017, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Combogesic (acetaminophen and ibuprofen) tablets.

We acknowledge receipt of your amendment dated May 7, 2020, which constituted a complete response to our December 22, 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 reason for this action below.

FACILITY INSPECTIONS 1. An inspection of the aa

facility is required before this application can be approved as the FDA must assess the ability of that facility to conduct the listed manufacturing operations in compliance with CGMP. Due to U.S. Government and/or Agency-wide restrictions on travel to we were unable to conduct an inspection of the “ facility during the current review cycle for your application. Currently, the need for a facility inspection, and an assessment of the findings, is the only deficiency with your application. If approval of your application will continue to rely upon

facility, we request that you do not respond to this Complete Response letter until after the travel restrictions are lifted so that the Agency can work with you to plan and conduct the required inspection.

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

Reference ID: 4698565

NDA 209471 Page 2

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

Submit draft carton and container labeling revised as follows:

A. Container ( Label and Carton Labeling

1. It is unclear if the placeholders, “barcode space” on the container label or the “Space for BARCODE” on the carton labeling, are intended to be linear barcodes. The drug linear barcode is often used as an additional verification; therefore, it is an important safety feature that should be part of the label whenever possible. Revise the container label and carton labeling to include the graphical representation of the linear barcode. Furthermore, ensure that the linear barcode is surrounded by sufficient white space to allow scanners to correctly read the linear barcode in accordance with 21 CFR 201.25(c)(i).

2. As currently presented, the format for the expiration date is not defined. To minimize confusion and reduce the risk for deteriorated drug medication errors, identify the format you intend to use. We recommend that the human- readable expiration date on the drug package label include a year, month, and non-zero day. We also recommend that the expiration date appear in YYYY-MM-DD format if only numerical characters are used or in YYYY- MM\N-DD if alphabetical characters are used to represent the month. If there are space limitations on the drug package, the human-readable text may include only a year and month, to be expressed as: YYYY-MM if only numerical characters are used or YYYY-MMM if alphabetical characters are used to represent the month. We recommend that a hyphen or a space be used to separate the portions of the expiration date.

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

2 http://www. fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm09330 7.htm

3 http://www.fda.gow/ForIndustry/DataStandards/StructuredProductLabeling/default.htm

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

Reference ID: 4698565

NDA 209471 Page 3

3. Add the following bolded statement or appropriate alternative to the carton and container labels per 21 CFR 208.24(d): "ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.”

OO)

C. Carton Labeling

4) This

statement is not consistent with the Prescribing Information. To ensure

consistency with the Prescribing Information, revise the statement)

1. The carton labeling includes the following statement

to read “Recommended Dosage: See prescribing information for full dosage information.”

2. The carton labeling does not include product identifiers. In September 2018,

FDA released draft guidance on product identifiers required under the Drug Supply Chain Security Act.a The Act requires manufacturers and repackagers, respectively, to affix or imprint a product identifier to each package and homogenous case of a product intended to be introduced in a transaction in(to) commerce beginning November 27, 2017, and November 27, 2018, respectively. We recommend that you review the draft guidance to determine if the product identifier requirements apply to your product's labeling.

PROPRIETARY NAME

Please refer to correspondence dated, August 5, 2020, which addresses the proposed proprietary name, Combogesic. This name was found acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to the application deficiencies.

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

Reference ID: 4698565

NDA 209471 Page 4

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.

(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.

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

Reference ID: 4698565

NDA 209471 Page 5

(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 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 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 that this application is approved.

If you have any questions, call Sandy Truong, PharmD, Regulatory Project Manager, at 301-796-5719.

Sincerely, {See appended electronic signature page}

Rigoberto Roca, MD

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

Reference ID: 4698565

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 11/06/2020 02:46:46 PM

Reference ID: 4698565