CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`208411Orig1s000
`
`PROPRIETARY NAME REVIEW(S)
`
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`PROPRIETARY NAME REVIEW
`Division of Medication Error Prevention and Analysis (DMEPA)
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`Office of Surveillance and Epidemiology (OSE)
`Center for Drug Evaluation and Research (CDER)
`
`*** This document contains proprietary information that cannot be released to the
`public***
`
`Date of This Review:
`September 25, 2015
`Application Type and Number: NDA 208411
`Product Name and Strength:
`Narcan Nasal Spray (naloxone hydrochloride) nasal spray
`4 mg per 0.1 mL
`Combination product
`Rx
`Adapt Pharma, Inc.
`2015-1000441
`Millie Shah, PharmD, BCPS
`Vicky Borders-Hemphill, PharmD
`
`Product Type:
`Rx or OTC:
`Applicant/Sponsor Name:
`Panorama #:
`DMEPA Primary Reviewer:
`DMEPA Team Leader:
`
`Reference ID: 3825057
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`

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`1
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`2
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`Contents
`INTRODUCTION........................................................................................................1
`1.1
`Regulatory History................................................................................................1
`1.2
`Product Information ..............................................................................................1
`RESULTS.....................................................................................................................1
`2.1 Misbranding Assessment ......................................................................................1
`2.2
`Safety Assessment.................................................................................................2
`CONCLUSIONS..........................................................................................................3
`3.1
`Comments to the Applicant...................................................................................4
`REFERENCES.............................................................................................................5
`4
`APPENDICES .....................................................................................................................6
`
`3
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`
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`Reference ID: 3825057
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`

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`INTRODUCTION
`1
`This review evaluates the proposed proprietary name, Narcan Nasal Spray, from a safety
`and misbranding perspective. The sources and methods used to evaluate the proposed
`name are outlined in the reference section and Appendix A respectively. The Applicant
`submitted an external name study, conducted by
` for this
`product.
` identified ten sound-alike and/or look-alike product names with Narcan
`Nasal Spray; however, the overall results of the
` name safety research support the use
`of Narcan Nasal Spray as a proposed proprietary name for Adapt Pharma’s proposed
`product for the treatment of opioid overdose. We agree with
` assessment that these
`names do not pose a concern.
`
`REGULATORY HISTORY
`1.1
`Narcan (naloxone hydrochloride injection, USP) Injection was approved on April
`13, 1971 (NDA 016636) as a single-dose,
` pre-filled syringe (0.02
`mg/mL, 0.4 mg/mL, and 1 mg/mL) to be administered intravenously,
`intramuscularly, or subcutaneously. The brand product is no longer marketed in
`the U.S., but generic alternatives are available.
`Adapt Pharma, Inc. acquired both the Narcan proprietary name and rights to the Narcan
`injection NDA.
`
`PRODUCT INFORMATION
`1.2
`The Sponsor provided the following product information in the July 20, 2015 proprietary
`name submission.
`Intended Pronunciation: nar' kan nay' sal spray
`
` Active Ingredient: naloxone hydrochloride
`Indication of Use: opioid overdose
`
` Route of Administration: intranasal
` Dosage Form: nasal spray
` Strength: 4 mg per 0.1 mL
` Dose and Frequency: One spray once
` How Supplied: Single nasal spray device packaged in clear blister pack. Carton
`configurations will include
` 2 blister packs per carton
` Storage: Room temperature
` Container and Closure Systems: Blister pack
`
`2 RESULTS
`The following sections provide information obtained and considered in the overall
`evaluation of the proposed proprietary name.
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`Reference ID: 3825057
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`2.1 MISBRANDING ASSESSMENT
`The Office of Prescription Drug Promotion (OPDP) determined that the proposed name
`would not misbrand the proposed product. DMEPA and the Division of Anesthesia,
`Analgesia, and Addiction Products (DAAAP) concurred with the findings of OPDP’s
`assessment of the proposed name.
`
`2.2 SAFETY ASSESSMENT
`The following aspects were considered in the safety evaluation of the name.
`
`2.2.1 United States Adopted Names (USAN) Search
`There is no USAN stem present in the proprietary name1.
`
`2.2.2 Components of the Proposed Proprietary Name
`The Applicant indicated in their submission that the proposed name, Narcan Nasal Spray,
`is derived from, “Narcan is an FDA approved name.” This proposed proprietary name is
`comprised of multiple words that contain the modifier, “Nasal Spray.” The Sponsor’s
`intended meaning of the modifier is the nasal spray dosage form. The use of the
`modifier, “Nasal Spray” does not pose a safety concern because nasal spray is the dosage
`form.
`
`2.2.3 FDA Name Simulation Studies
`Seventy-seven practitioners participated in DMEPA’s prescription studies. Of the 77
`participants, 73 correctly interpreted the name Narcan Nasal Spray. The responses did
`not overlap with any currently marketed products nor did the responses sound or look
`similar to any currently marketed products or any products in the pipeline.
`Appendix B contains the results from the verbal and written prescription studies.
`
`2.2.4 Comments from Other Review Disciplines at Initial Review
`In response to the OSE e-mail dated August 7, 2015, the Division of Anesthesia,
`Analgesia, and Addiction Products (DAAAP) did not forward any comments or concerns
`relating to the proposed proprietary name at the initial phase of the review.
`
`2.2.5 Medication Error Data Selection of Cases
`We searched the FDA Adverse Event Reporting System (FAERS) database using the
`strategy listed in Table 2 (see Appendix A1 for a description of FAERS database) for
`name confusion errors involving Narcan that would be relevant for this review.
`
`1USAN stem search conducted on August 19, 2015.
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`Table 2. FAERS Search Strategy
`Search Date
`July 21, 2015
`Narcan [product name]
`Drug Name
`Event (MedDRA Terms) DMEPA Official Proprietary Name Review
`Search Terms Event List:
`Product name confusion (PT)
`Medication error (PT)
`Intercepted medication error (PT)
`Drug dispensing error (PT)
`Intercepted drug dispensing error (PT)
`Circumstance or information capable of
`leading to a medication error (PT)
`Date Limits
`All reports through July 1, 2015
`Each report was reviewed for relevancy and duplication. Duplicates were merged into a
`single case. The NCC MERP Taxonomy of Medication Errors was used to code the case
`outcome and error root causes when provided by the reporter.
`Our search resulted in 30 reports. After individual review, 28 reports were not included
`in the final analysis because the cases did not describe possible name confusion between
`Narcan and another product.
`Following exclusions, the search yielded 2 relevant cases. Both cases describe wrong
`drug errors between Narcan and Norcuron. The outcomes reported in the cases include
`respiratory depression (n=1) and no harm (n=1). The cases do not provide enough
`information to determine a root cause. Therefore, it is unclear that the medication error
`cases can be attributed to look-alike and/or sound-alike name confusion. Furthermore,
`the proprietary name Norcuron is withdrawn from the market (FR effective July 8, 2011),
`although generic equivalents of vecuronium bromide are available. The cases of error
`between Narcan and Norcuron were reported between 1993 and 2003, which is before
`Norcuron was withdrawn. Based on this information, we do not anticipate look-alike
`and/or sound-alike name confusion medication errors between Narcan and Norcuron.
`
`2.2.6 Communication of DMEPA’s Analysis at Midpoint of Review
`DMEPA communicated our findings to the Division of Anesthesia, Analgesia, and
`Addiction Products (DAAAP) via e-mail on September 8, 2015. At that time, we also
`requested additional information or concerns that could inform our review. Per e-mail
`correspondence from the DAAAP on September 21, 2015, they stated no additional
`concerns with the proposed proprietary name, Narcan Nasal Spray.
`
`3 CONCLUSIONS
`The proposed proprietary name is acceptable.
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`Reference ID: 3825057
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`If you have any questions or need clarifications, please contact Lisa Skarupa, OSE
`project manager, at 301-796-2219.
`
`COMMENTS TO THE APPLICANT
`3.1
`We have completed our review of the proposed proprietary name, Narcan Nasal Spray,
`and have concluded that this name is acceptable.
`If any of the proposed product characteristics as stated in your July 20, 2015 submission
`are altered prior to approval of the marketing application, the name must be resubmitted
`for review.
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`Reference ID: 3825057
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`4
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`REFERENCES
`
`1. USAN Stems (http://www.ama-assn.org/ama/pub/physician-resources/medical-
`science/united-states-adopted-names-council/naming-guidelines/approved-stems.page)
`USAN Stems List contains all the recognized USAN stems.
`
`2. Electronic Drug Registration and Listing System (eDRLS) database
`
`The electronic Drug Registration and Listing System (eDRLS) was established to supports
`the FDA’s Center for Drug Evaluation and Research (CDER) goal to establish a common
`Structured Product Labeling (SPL) repository for all facilities that manufacture regulated
`drugs. The system is a reliable, up-to-date inventory of FDA-regulated, drugs and
`establishments that produce drugs and their associated information.
`
`APPENDICES
`Appendix A
`FDA’s Proprietary Name Risk Assessment evaluates proposed proprietary names for
`misbranding and safety concerns.
`1. Misbranding Assessment: For prescription drug products, OPDP assesses the
`name for misbranding concerns. . For over-the-counter (OTC) drug products, the
`misbranding assessment of the proposed name is conducted by DNDP. OPDP or
`DNDP evaluates proposed proprietary names to determine if the name is false or
`misleading, such as by making misrepresentations with respect to safety or
`efficacy. For example, a fanciful proprietary name may misbrand a product by
`suggesting that it has some unique effectiveness or composition when it does not
`(21 CFR 201.10(c)(3)). OPDP or DNDP provides their opinion to DMEPA for
`consideration in the overall acceptability of the proposed proprietary name.
`2. Safety Assessment: The safety assessment is conducted by DMEPA, and
`includes the following:
`a. Preliminary Assessment: We consider inclusion of USAN stems or other
`characteristics that when incorporated into a proprietary name may cause or
`contribute to medication errors (i.e., dosing interval, dosage form/route of
`administration, medical or product name abbreviations, names that include or
`suggest the composition of the drug product, etc.) See prescreening checklist
`below in Table 2*. DMEPA defines a medication error as any preventable event
`that may cause or lead to inappropriate medication use or patient harm while the
`medication is in the control of the health care professional, patient, or consumer. 2
`
`2 National Coordinating Council for Medication Error Reporting and Prevention.
`http://www nccmerp.org/aboutMedErrors.html. Last accessed 10/11/2007.
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`*Table 2- Prescreening Checklist for Proposed Proprietary Name
`
`Answer the questions in the checklist below. Affirmative answers
`to any of these questions indicate a potential area of concern that
`should be carefully evaluated as described in this guidance.
`Y/N Is the proposed name obviously similar in spelling and pronunciation to other
`names?
`Proprietary names should not be similar in spelling or pronunciation to proprietary
`names, established names, or ingredients of other products.
`Y/N Are there medical and/or coined abbreviations in the proprietary name?
`Proprietary names should not incorporate medical abbreviations (e.g., QD, BID, or
`others commonly used for prescription communication) or coined abbreviations
`that have no established meaning.
`Y/N Are there inert or inactive ingredients referenced in the proprietary name?
`Proprietary names should not incorporate any reference to an inert or inactive
`ingredient in a way that might create an impression that the ingredient’s value is
`greater than its true functional role in the formulation (21 CFR 201.10(c)(4)).
`Y/N Does the proprietary name include combinations of active ingredients?
`Proprietary names of fixed combination drug products should not include or
`suggest the name of one or more, but not all, of its active ingredients (see 21 CFR
`201.6(b)).
`Y/N Is there a United States Adopted Name (USAN) stem in the proprietary name?
`Proprietary names should not incorporate a USAN stem in the position that USAN
`designates for the stem.
`Y/N Is this proprietary name used for another product that does not share at least
`one common active ingredient?
`Drug products that do not contain at least one common active ingredient should not
`use the same (root) proprietary name.
`Y/N Is this a proprietary name of a discontinued product?
`Proprietary names should not use the proprietary name of a discontinued product if
`that discontinued drug product does not contain the same active ingredients.
`
`b. FDA Prescription Simulation Studies: DMEPA staff also conducts a prescription
`simulation studies using FDA health care professionals.
`Three separate studies are conducted within the Centers of the FDA for the
`proposed proprietary name to determine the degree of confusion of the proposed
`proprietary name with marketed U.S. drug names (proprietary and established)
`due to similarity in visual appearance with handwritten prescriptions or verbal
`pronunciation of the drug name. The studies employ healthcare professionals
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`(pharmacists, physicians, and nurses), and attempts to simulate the prescription
`ordering process. The primary Safety Evaluator uses the results to identify
`orthographic or phonetic vulnerability of the proposed name to be misinterpreted
`by healthcare practitioners.
`In order to evaluate the potential for misinterpretation of the proposed proprietary
`name in handwriting and verbal communication of the name, inpatient medication
`orders and/or outpatient prescriptions are written, each consisting of a
`combination of marketed and unapproved drug products, including the proposed
`name. These orders are optically scanned and one prescription is delivered to a
`random sample of participating health professionals via e-mail. In addition, a
`verbal prescription is recorded on voice mail. The voice mail messages are then
`sent to a random sample of the participating health professionals for their
`interpretations and review. After receiving either the written or verbal
`prescription orders, the participants record their interpretations of the orders,
`which are recorded electronically.
`c. Comments from Other Review Disciplines: DMEPA requests the Office of New
`Drugs (OND) and/or Office of Generic Drugs (OGD), ONDQA or OBP for their
`comments or concerns with the proposed proprietary name, ask for any clinical
`issues that may impact the DMEPA review during the initial phase of the name
`review. Additionally, when applicable, at the same time DMEPA requests
`concurrence/non-concurrence with OPDP’s decision on the name. The primary
`Safety Evaluator addresses any comments or concerns in the safety evaluator’s
`assessment.
`The OND/OGD Regulatory Division is contacted a second time following our
`analysis of the proposed proprietary name. At this point, DMEPA conveys their
`decision to accept or reject the name. The OND or OGD Regulatory Division is
`requested to provide any further information that might inform DMEPA’s final
`decision on the proposed name.
`Additionally, other review disciplines opinions such as ONDQA or OBP may be
`considered depending on the proposed proprietary name.
`When provided, DMEPA considers external proprietary name studies conducted
`by or for the Applicant/Sponsor and incorporates the findings of these studies into
`the overall risk assessment.
`The DMEPA primary reviewer assigned to evaluate the proposed proprietary name is
`responsible for considering the collective findings, and provides an overall risk
`assessment of the proposed proprietary name.
`
`Appendix A1: Description of FAERS
`The FDA Adverse Event Reporting System (FAERS) is a database that contains
`information on adverse event and medication error reports submitted to FDA. The
`database is designed to support the FDA's postmarket safety surveillance program for
`drug and therapeutic biologic products. The informatic structure of the FAERS database
`adheres to the international safety reporting guidance issued by the International
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`Reference ID: 3825057
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`Conference on Harmonisation. FDA’s Office of Surveillance and Epidemiology codes
`adverse events and medication errors to terms in the Medical Dictionary for Regulatory
`Activities (MedDRA) terminology. Product names are coded using the FAERS Product
`Dictionary. More information about FAERS can be found at:
`http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/Adv
`erseDrugEffects/default.htm.
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`Reference ID: 3825057
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`Appendix B: Prescription Simulation Samples and Results
`Figure 1. Narcan Nasal Spray Study (Conducted on August 5, 2015)
`
`Handwritten Requisition Medication Order
`Medication Order:
`
`Verbal Prescription
`Narcan Nasal Spray
`Use as directed
`Dispense number one
`
`Outpatient Prescription:
`
`FDA Prescription Simulation Responses (Aggregate 1 Rx Studies Report)
`
`244 People Received Study
`77 People Responded
`
`Total
`INTERPRETATION
`??
`NARAN NASAL SPRAY
`NARCAN NASAL SPRAY
`NARCANE NASAL SPRAY
`NON CAN NASAL SPRAY
`
`25
`OUTPATIENT
`0
`0
`25
`0
`0
`
`25
`VOICE
`1
`0
`22
`1
`1
`
`27
`INPATIENT
`0
`1
`26
`0
`0
`
`
`TOTAL
`1
`1
`73
`1
`1
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`Reference ID: 3825057
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MILLIE C BRAHMBHATT
`09/25/2015
`
`BRENDA V BORDERS-HEMPHILL
`09/25/2015
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`Reference ID: 3825057
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