Almatica Pharma, LLCzolpidem tartrate capsules

NDA 215721 COMPLETE RESPONSE

Almatica Pharma, LLC

Attention: Michelle R. Ryder

Vice President, Regulatory Affairs 44 Whippany Rd, Suite 300 Morristown, NJ 07960

Dear Ms. Ryder:

Please refer to your new drug application (NDA) dated and received March 15, 2022, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for zolpidem tartrate capsules.

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

Considering that provide updated release and stability speci unidentified © ‘provide the anal

©® are likely present in the drug product,

ications to include any identified and lytical methods and respective validations,

and release and stability data on at least three batches of drug product to demonstrate

that the levels of any potential

©® in all drug

product batches have not and will not exceed the allowable daily intakes stated in FDA

Guidance monitoring such © “from release studies for all the commercial batches.

PRESCRIBING INFORMATION

© Commit to continue ‘0 the end of shelf-life during the stability

We reserve comment on the proposed label! adequate. We encourage you to review the Prescription Drug Labeling Resources! and

ing until the application is otherwise labeling review resources on the Pregnancy and Lactation Labeling Final

Rule? websites, including regulations and related guidance documents and the Selected

1 https://www.fda.gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources

2 https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs-

final-rule

Reference ID: 5109885

NDA 215721 Page 2

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

We reserve comment on the proposed labeling until the application is otherwise adequate.

MEDICATION GUIDE

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

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.

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

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

Reference ID: 5109885

NDA 215721 Page 3

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 subject 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.

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.

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

Reference ID: 5109885

NDA 215721 Page 4

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 Pawanprit (Pinky) Singh, Regulatory Project Manager, at pawanprit.singh@fda.hhs.gov.

Sincerely,

{See appended electronic signature page}

Tiffany R. Farchione, MD

Director

Division of Psychiatry

Office of Neuroscience

Center for Drug Evaluation and Research

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

Reference ID: 5109885

‘ 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.

TIFFANY R FARCHIONE 01/13/2023 02:48:44 PM

Reference ID: 5109885