Apiject Systems Corp.glycopyrrolate solution

NDA 219107 COMPLETE RESPONSE

Apiject Systems Corp.

Attention: Ashley Dynan

Senior Director of Regulatory Affairs 2 High Ridge Park

Stamford, CT 06905

Dear Ashley Dynan:

Please refer to your new drug application (NDA) received September 25, 2025, and = amendments, submitted pursuant to

, for glycopyrrolate solution.

We also acknowledge receipt of your amendments dated June 8, 12, and 25, 2026, which were not reviewed for this action. You may incorporate applicable sections of the amendment by specific reference as part of your response to the deficiencies cited in this 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.

DRUG-DEVICE COMBINATION PRODUCT QUALITY

Drug Constituent of the Drug-Device Combination Product

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Information needed to resolve the deficiency:

Information needed to resolve the deficiency:

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

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Device Constituent of the Drug-Device Combination Product: Performance and Safety

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

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Information needed to resolve the deficiency:

HUMAN FACTORS

Packaging of the Drug-Device Combination Product

(6) There are foreseeable use-related error concerns stemming from your proposal

These foreseeable issues were identified in the results of your Human Factors (HF) validation study. One use difficulty and one use error were observed with the critical task of selecting the needle. Specificall

Additionally, the HF validation study environment only tested the scenario in which needles were stored in their carton and therefore was not reflective of other potential use environments. For example, subjective feedback from the study participants

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

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sequently, there is a foreseeable risk that users my ave difficulty selecting the correct needle Oy

Information needed to resolve the deficiency:

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 Prescription Drug Labeling Resources! 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

Please refer to our correspondence dated, December 12, 2025, which addresses the proposed proprietary name, This name was found conditionally acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to all of the application deficiencies that have been identified in this letter.

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:

' https: + httos/hwww fda.covidruas/iaws. fda. covidruas/laws-acts-and-tules/prescription-drua-labelina-resources

final-rule

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

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e Present new safety data from the studies/clinical trials for the proposed indication using the same format as in the original submission.

« 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 dropouts 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.

ADDITIONAL COMMENTS

We have the following comments and recommendations that are not approvability issues.

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

3 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance Documents Database -

U.S. Food and Drug Administration

Silver Spring, MD 20993

www.fda.gov

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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 (September 2023).4

The product may not be legally marketed until you have been notified in writing that this application is approved.

If you have any questions, contact

Sincerely,

{See appended electronic signature page}

Center for Drug Evaluation and Research

4 When final, this guidance will represent the FDA's current thinking on this topic. For the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/regulatory- information/search-fda-guidance-documents.

U.S. Food and Drug Administration

Silver Spring, MD 20993

www.fda.gov

Reference ID: 5838071

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.

(b) (4)

07/21/2026 01:14:36 PM

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