CMP Development LLCTADLIQ (Tadalafil) Oral Suspension, 4 mg/ml

NDA 214522

COMPLETE RESPONSE

CMP Development LLC Attention: Ellen Barkley Regulatory Affairs Manager P.O. Box 147

8026 US Highway 264A Farmville, NC 27828

Dear Ms. Barkley:

Please refer to your new drug application (NDA) dated April 23, 2020, received April 23, 2020, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for TADLIQ (Tadalafil) Oral Suspension, 4 mg/ml.

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.

PRODUCT QUALITY

(1) Facility deficiencies

Reference ID: 4751240

a. During a review of records requested under section 704(a)(4) of the

Federal Food, Drug, and Cosmetic Act, and provided by

manufacturing facility, the FDA noted objectionable conditions. These objectionable conditions will be conveyed to the representative of the facility within 10 business days of this Complete Response Letter. Satisfactory resolution of these objectionable conditions is required (e.g., preapproval inspection and/or adequate facility responses addressing these conditions) before this application may be approved.

If it is determined that an inspection is needed to approve your application, please note that FDA continues to monitor the public health situation as well as travel restrictions. We are actively working to define an approach for scheduling outstanding inspections, once safe travel may resume and based on public health need and other factors.

For more information, please see FDA guidances related to COVID 19. These guidances can be found at: https://www.fda.gov/emergency-

NDA 214522 Page 2

preparedness-and-response/coronavirus-disease-2019- _covid-19/covid- 19-related-quidance-documents-industry-fda-staff-and-other-stakeholders

b. During a recent inspection of the | , Manufacturing facility 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.

PRESCRIBING INFORMATION

(2) We reserve further comment on the proposed labeling until the application is otherwise adequate. When you resubmit your application, please reference the draft labeling you submitted on February 10, 2021. 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.

PROPRIETARY NAME

(3) Please refer to correspondence dated, August 13, 2020 which addresses the proposed proprietary name, TADLIQ. 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.

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:

1 http:/Awww.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/LawsActsandRules/ucm08415 9.htm 2 http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm09330 7.htm

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

Reference ID: 4751240

NDA 214522 Page 3

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.

(8) Provide English translations of current approved foreign labeling not previously submitted.

ADDITIONAL COMMENTS We have the following comments/recommendations that are not approvability issues: Drug Product

(1) In light of the Ce proposed, please include the following additional in-

process controls for validation and during commercial manufacturing; submit

revised Modules 3.2.P.3.3 and 3.2.P.3.4.: () (4)

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

Reference ID: 4751240

NDA 214522 Page 4

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

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

Reference ID: 4751240

NDA 214522 Page 5

his 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 ‘ake 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 hat this application is approved.

If you have any questions, contact Christine (Tina) Sadr, Regulatory Health Project Manager, at 240-402-6554.

Sincerely, {See appended electronic signature page}

Norman Stockbridge, MD, PhD

Director

Division of Cardiology and Nephrology

Office of Cardiology, Hematology, Endocrinology, and Nephrology

Center for Drug Evaluation and Research

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

Reference ID: 4751240

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.

NORMAN L STOCKBRIDGE 02/23/2021 12:20:36 PM

Reference ID: 4751240