FDA NDA 215487 Naloxone Hydrochloride Nasal Spray User Guide

: June 1, 2024
: FDA

Table of Contents

FDA NDA 215487 Naloxone Hydrochloride Nasal Spray
Product Information
Product Usage Instructions
FAQs
NDA APPROVAL
APPROVAL & LABELING
CONTENT OF LABELING
CARTON AND CONTAINER LABELING
REQUIRED PEDIATRIC ASSESSMENTS
PROMOTIONAL MATERIALS
REPORTING REQUIREMENTS
CONTACT
References
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FDA NDA 215487 Naloxone Hydrochloride Nasal Spray

Product Information

Specifications
- Product Name: Rezenopy (naloxone hydrochloride) nasal spray, 10 mg
- Manufacturer: Summit Biosciences Inc.
- Indication: Emergency treatment of known or suspected opioid overdose
- Age Group: Adults and pediatric patients
- Route of Administration: Nasal spray

Product Usage Instructions

Administration
- Ensure that the nasal spray is readily accessible for immediate administration in emergency settings where opioids may be present.
Dosage
- The recommended dosage for adults and pediatric patients is 10 mg administered intranasally. Follow the instructions provided in the labelling for proper administration.
Expiration Date
- The expiration date of the product is dependent on the shortest expiration date of any component. Check the packaging for the expiration date before use.
Pediatric Assessments
- This product is appropriately labelled for use in pediatric populations. No additional pediatric studies are required at this time.
Postmarketing Requirements
- As per FDA regulations, postmarketing studies and clinical trials may be required. Follow any additional instructions or studies mandated by the FDA for this product.

FAQs

Q: How should I store the product?
- A: Store the product at room temperature, away from direct sunlight and moisture.
Q: Can the nasal spray be used on pets?
- A: This product is intended for use in humans only. Do not administer to pets.

NDA APPROVAL

Summit Biosciences Inc.
1513 Bull Lea Road
Lexington, KY 40511
Attention: Tracie Hill Sr. Manager of Regulatory Affairs
Dear Tracie Hill: Please refer to your new drug application (NDA) dated and received March 24, 2023, and your amendments, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Rezenopy (naloxone hydrochloride) nasal spray, 10 mg. This NDA provides for the use of Rezenopy (naloxone hydrochloride) nasal spray,10 mg, for the indication of the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression in adults and pediatric patients, and is intended for immediate administration as emergency therapy in settings where opioids may be present.

APPROVAL & LABELING

We have completed our review of this application, as amended.
It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labelling.

CONTENT OF LABELING

As soon as possible, but no later than 14 days from the date of this letter, submit the content of labelling [21 CFR 314.50(l)] in structured product labelling (SPL) format using the FDA automated drug registration and listing system (ELISA), as described at FDA.gov.1 Content of labelling must be identical to the enclosed labelling (text for the Prescribing Information, Patient Package Insert, Instructions for Use, and Quick Start Guide) as well as annual reportable changes not included in the enclosed labelling.
Information on submitting SPL files using a list may be found in the guidance for industry SPL Standard for Content of Labeling Technical Qs and As. 2

http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.
We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
- Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
- The SPL will be accessible via publicly available labelling repositories.

CARTON AND CONTAINER LABELING

Submit final printed carton and container labelling that is identical to the enclosed carton and container labelling, except with the minor revisions listed below [e.g., changes consistent with annual reportable changes under 314.70(d)], as soon as they are available, but no more than 30 days after they are printed.
Please submit these labelling electronically according to the guidance for industry SPL Standard for Content of Labeling Technical Qs & As.
For administrative purposes, designate this submission “Final Printed Carton and Container Labeling for approved NDA 215487.
Approval of this submission by the FDA is not required before the labelling is used.
- a. Container label designated as “device back” should show the established name

DATING PERIOD

Based on the stability data submitted to date, the expiry dating period for Rezenopy (naloxone hydrochloride) nasal spray shall be 36 months from the date of manufacture when stored at 2°C to 25°C (36°F to 77°F) with excursions permitted up to 40°C (104°F).
The expiration date for the packaged product, naloxone hydrochloride, plus pre-filled and pre-assembled nasal spray, shall be dependent on the shortest expiration date of any component.

REQUIRED PEDIATRIC ASSESSMENTS

Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients (which includes new salts and new fixed combinations), new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication in pediatric patients unless this requirement is waived, deferred, or inapplicable.
This product is appropriately labelled for use in all relevant pediatric populations.
Therefore, no additional pediatric studies are needed at this time.

POSTMARKETING REQUIREMENTS UNDER 505(o)

Section 505(o)(3) of the FDCA authorizes the FDA to require holders of approved drug and biological product applications to conduct postmarketing studies and clinical trials for certain purposes if the FDA makes certain findings required by the statute.
We have determined that an analysis of spontaneous postmarketing adverse events reported under subsection 505(k)(1) of the FDCA will not be sufficient to identify an unexpected serious risk of toxicity in local tissues.
Furthermore, the active postmarket risk identification and analysis system as available under section 505(k)(3) of the FDCA will not be sufficient to assess this serious risk.

Therefore, based on appropriate scientific data, FDA has determined that you are required to conduct the following study:

4440-1
- Conduct a GLP repeat-dose intranasal toxicology study of at least 14 days duration in a single species to adequately characterize the toxicological potential of the naloxone degradant, , to local tissues.
The following adjusted timetable is the schedule by which you will conduct this study: 3
- Draft Protocol Submission: 09/2024
- Final Protocol Submission: 12/2024
- Study Completion: 06/2025
- Final Report Submission: 12/2025

FDA considers the term final to mean that the applicant has submitted a protocol, the FDA review team has sent comments to the applicant, and the protocol has been revised as needed to meet the goal of the study or clinical trial.4 Submit nonclinical and chemistry, manufacturing, and controls protocols and all final report(s) to your NDA. Prominently identify the submission with the following wording in bold capital letters at the top of the first page of the submission, as appropriate: Required Postmarketing Protocol Under 505(o), Required Postmarketing Final Report Under 505(o), Required Postmarketing Correspondence Under 505(o). Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of any study or clinical trial required under this section. This section also requires you to periodically report to the FDA on the status of any study or clinical trial otherwise undertaken to investigate a safety issue. Section 506B(a)(1) of the FDCA, as well as 21 CFR 314.81(b)(2)(vii) you to report annually on the status of any postmarketing commitments or required studies or clinical trials.

The dates from the timetable you submitted on January 10, 2024, were adjusted due to the timing of this action.
See the guidance for Industry Postmarketing Studies and Clinical Trials—Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act (October 2019). https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.

FDA will consider the submission of your annual report under section 506B(a)(1) and 21 CFR 314.81(b)(2)(vii) to satisfy the periodic reporting requirement under section 505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and 21 CFR 314.81(b)(2)(vii). We remind you that to comply with 505(o), your annual report must also include a report on the status of any study or clinical trial otherwise undertaken to investigate a safety issue. Failure to submit an annual report for studies or clinical trials required under 505(o) on the date required will be considered a violation of FDCA section 505(o)(3)(E)(ii) and could result in enforcement action.

PROMOTIONAL MATERIALS

You may request advisory comments on proposed introductory advertising and promotional labelling.
For information about submitting promotional materials, see the final guidance for the industry Providing Regulatory Submissions in Electronic and NonElectronic Format—Promotional Labeling and Advertising Materials for Human Prescription Drugs.5
As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the Prescribing Information, at the time of initial dissemination or publication, accompanied by a Form FDA 2253.
Form FDA 2253 is available at FDA.gov.6 Information and Instructions for completing the form can be found at FDA.gov.7

REPORTING REQUIREMENTS

We remind you that you must comply with reporting requirements for an approved NDA (21 CFR 314.80 and 314.81).
Your product is a Part 3 combination product (21 CFR 3.2(e)); therefore, you must also comply with postmarketing safety reporting requirements for an approved combination product (21 CFR 4, Subpart B).
Additional information on combination product postmarketing safety reporting is available at FDA.gov.8

COMPENDIAL STANDARDS

A drug with a name recognized in the official United States Pharmacopeia or official National Formulary (USP-NF) generally must comply with the compendial standards for strength, quality, and purity, unless the difference in strength, quality, or purity is plainly stated on its label (see FD&C Act § 501(b), 21 USC 351(b)). FDA typically cannot share application-specific information contained in submitted regulatory filings with third

For the most recent version of the guidance, check the FDA guidance web page at
https://www.fda.gov/media/128163/download.
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf.
https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products. parties, which includes USP-NF. To help ensure that a drug continues to comply with compendial standards, application holders may work directly with USP-NF to revise official USP monographs. More information on the USP-NF is available on USP’s website9.
If you have any questions, email Rachel Jang, PharmD, Regulatory Project Manager, at rachel.jang@fda.hhs.gov.

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

ENCLOSURES:

Content of Labeling
- Prescribing Information
- Patient Package Insert
- Instructions for Use
- Quick Start Guide
Carton and Container Labeling

This is a representation of an electronic record that was signed electronically. Following this are manifestations of any electronic signatures for this electronic record.