CMP Development LLCNORLIQVA (amlodipine) Oral Solution 1 mg/mL

NDA 214439 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 and received June 22, 2020, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for NORLIQVA (amlodipine) Oral Solution 1 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.

FACILITY INSPECTIONS

During a recent inspection of the oO (FEI: om) 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.

During a review of records requested under section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act, and provided by oO FEI: ;

© ‘manufacturing facility, the FDA noted objectionable conditions. Satisfactory resolution of these objectionable conditions is required (e.g., preapproval inspection and adequate facility responses addressing these conditions) before this application may be approved. The FDA will communicate the outstanding issues to the facility no later than 10 business days from issuing this complete response letter. Please contact , FEI: © manufacturing facility for additional information.

(b) (4)

An inspection of the O FEI a we

, facility is required before the application can be approved. FDA must assess the ability of that facility to conduct the listed manufacturing operations in

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NDA 214439 Page 2

compliance with CGMP. Because of restrictions on travel we have been unable to conduct an inspection of the © (FEI: ©) facility.

We will continue 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 the FDA guidances related to COVID-19.!

ADDITIONAL PRODUCT QUALITY COMMENT We acknowledge you added © testing as part of the | commercial production. You stated in Section 3.2.P.3.4 that the acceptance criteria { ®® will be established based on results from first three commercial batches. We remind you that process validation is to confirm the process design and demonstrate that the commercial manufacturing process performs as expected (Guidance for Industry Process Validation: General Principles and Practices (2011)), rather than to develop and finalize the commercial manufacturing process. Therefore, propose acceptance criteria ®® based on data collected from development and registration batches. Proposed ranges should take into account scalability issues for any scale-dependent parameters.

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(I)(1)(i)] in structured product labeling (SPL) format as described at FDA.gov.4

1 https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid- 19-related-gquidance-documents-industry-fda-staff-and-other-stakeholders

2 http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/LawsActsandRules/ucm08415 9.htm

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

4 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm

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

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NDA 214439 Page 3

PROPRIETARY NAME

Please refer to correspondence dated, January 8, 2021, which addresses the proposed proprietary name, NORLIQVA. 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 product 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). U.S. Food and Drug Administration

Silver Spring, MD 20993 www.fda.gov

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NDA 214439 Page 4

(7) Provide a summary of worldwide experience on the safety of this product. Include an updated estimate of use for product 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 314.65. 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

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, please contact Sabry Soukehal, Regulatory Health Project Manager, at (240) 402 6187.

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

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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.

NORMAN L STOCKBRIDGE 04/22/2021 12:00:39 PM

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