CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`212660Orig1s000
`
`PROPRIETARY NAME REVIEW(S)
`
`
`
`
`
`

`

`PROPRIETARY NAME REVIEW
`Division of Medication EITor Prevention and Analysis (DMEPA)
`Office of Medication EITor Prevention and Risk Management (OMEPRM)
`Office of Surveillance and Epidemiology (OSE)
`Center for Dmg Evaluation and Research (CDER)
`
`*** This document contains proprietary information that cannot be released to the
`public***
`
`Date of This Review:
`
`March 23, 2020
`
`Application Type and Number:
`
`NDA 212690
`
`Product Name and Strength:
`
`Xywav (calcium oxybate, potassilllll oxybate,
`magnesilllll oxybate, sodium oxybate) oral solution,
`0.5 g/mLa
`
`Product Type:
`
`Combination Product (Dmg-Device)
`
`Rxor OTC:
`Applicant/Sponsor Name:
`Panorama #:
`
`DMEPA Safety Evaluator:
`DMEPA Team Leader:
`
`Prescription (Rx)
`
`Jazz Phaim aceuticals Ireland Limited (Jazz)
`2020-3 7 463 829
`
`Justine Kalonia, PhannD
`
`Briana Rider, PhaimD, CPPS
`
`•The actual potency is 0.413 g/mL (active moiety· oxybate . The Applicant requested an exception to the salt
`policy. The decision is~
`(bJ <4I
`
`Reference ID 4579414
`
`

`

`
`
`1
`
`Contents
`INTRODUCTION ................................................................................................................... 1
`1.1
`Product Information ........................................................................................................ 1
`2 RESULTS ................................................................................................................................ 1
`2.1 Misbranding Assessment ................................................................................................ 2
`2.2
`Safety Assessment .......................................................................................................... 2
`3 CONCLUSION ....................................................................................................................... 3
`3.1
`Comments to Jazz Pharmaceuticals Ireland Limited ...................................................... 3
`4 REFERENCES ........................................................................................................................ 5
`APPENDICES ................................................................................................................................ 6
`
`
`
`
`
`Reference ID: 4579414
`
`

`

`1
`
`INTRODUCTION
`
`This review evaluates the proposed proprietaiy name, Xywav, from a safety and misbranding
`perspective. The sources an d methods used to evaluate the proposed proprietaiy name are
`outlined in the reference section and Appendix A, respectively. Jazz submitted an external name
`(b)(4f £ h"
`d
`.
`
`
`
`
`d stu y, con ucte d db y
`or t 1s propose propnetary name.
`
`1.1
`
`P RODUCT INFORMATION
`
`The following product info1mation is provided in the proprietaiy name submission received on
`Januaiy 21, 2020.
`
`•
`
`Intended Pronunciation: ZIE-wav
`
`• Active Ingredient: calcium oxybate, potassium oxybate, magnesium oxybate, sodium
`oxybate
`
`•
`
`Indication of Use: treatment of cataplexy or excessive daytime sleepiness (EDS) in
`patients 7 years of age an d older with narcolepsy
`
`• Route of Administration: oral
`
`• Dosage Fon n : oral solution
`
`• Strength: 0.5 g/mL b
`
`• Dosec and Frequency:
`
`o Adults: The recommended staiiing dose is 4.5 g per night, divided into two doses:
`2.25 g at bedtime an d 2.25 g taken 2.5 to 4 hours later. Increase the dosage by up
`to 1.5 g per night at weekly intervals to the effective dose range of 6 g to 9 g.
`
`o Pediatric (7 yeai·s of age and older): Administer orally twice per night. The
`recommended staiiing pediatric dosage, titration regimen, and maximum nightly
`dosage ai·e based on patient weight, as specified in Table 2 of the prescribing
`info1mation section 2.2.
`
`• How Supplied: Clear slightly opalescent oral solution in one 180 mL amber bottle with
`child-resistant caps an d attached press in bottle adaptor, an oral measuring device (plastic
`syringe), an d a Medication Guide.
`
`• Storage: Store between 20°C to 25°C (68°F to 77°F); excursions pe1mitted between 15°C
`to 30°C (59°F to 86°F) (see USP Controlled Room Temperature).
`
`• Reference Listed Drng/Reference Product: N/ A
`
`2 RESULTS
`
`b Actual potency 0.413 g/mL (active moiety).
`
`(b)(4f
`
`c Dose is subject to change pending OPQ USP Salt Policy decision.
`
`Reference ID 4579414
`
`1
`
`

`

`
`
`The following sections provide information obtained and considered in the overall evaluation of
`the proposed proprietary name, Xywav.
`2.1 MISBRANDING ASSESSMENT
`The Office of Prescription Drug Promotion (OPDP) determined that Xywav would not misbrand
`the proposed product. The Division of Medication Error Prevention and Analysis (DMEPA) and
`the Division of Neurology 1 (DN 1) concurred with the findings of OPDP’s assessment for
`Xywav.
`2.2 SAFETY ASSESSMENT
`The following aspects were considered in the safety evaluation of the proposed proprietary name,
`Xywav.
`
`2.2.1 United States Adopted Names (USAN) Search
`There is no USAN stem present in the proposed proprietary name d.
`
`2.2.2 Components of the Proposed Proprietary Name
`Jazz did not provide a derivation or intended meaning for the proposed proprietary name,
`Xywav, in their submission. This proprietary name is comprised of a single word that does not
`contain any components (i.e. a modifier, route of administration, dosage form, etc.) that are
`misleading or can contribute to medication error.
`
`2.2.3 Comments from Other Review Disciplines at Initial Review
`In response to the OSE, February 24, 2020, the Division of Neurology 1 (DN 1) did not forward
`any comments or concerns relating to Xywav at the initial phase of the review.
`
`2.2.4 FDA Name Simulation Studies
`Seventy-six practitioners participated in DMEPA’s prescription studies for Xywav. 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.
`One respondent in the inpatient study provided a supplemental comment. The respondent stated,
`“close to Xyzal”. We evaluated the name pair, Xywav and Xyzal, further and find that there are
`sufficient orthographic and phonetic differences between the name pair. Orthographically, the
`suffixes (-wav vs. -zal) of the names look sufficiently different. Xyzal has the upstroke letter ‘l’
`in the suffix whereas, Xywav does not contain any upstroke letters, which gives the names
`different shapes when scripted. Additionally, the ‘z’ in Xyzal may scripted with a cross-stroke or
`downstroke, which may provide additional differentiation. Phonetically, the second syllables (-
`wāv vs. -zal) sound different when spoken. When all of the aforementioned mitigations are
`considered in totality, we find the risk of name confusion is minimal (see Appendix E).
`Appendix B contains the results from the prescription simulation studies.
`
`
`d USAN stem search conducted on January 30, 2020.
`
`Reference ID: 4579414
`
`
`2
`
`

`

`2.2.5 Phonetic and Orthographic Computer Analysis (POCA) Search Results
`
`Our POCA searche identified five names with a combined phonetic and 01ihographic score of
`2:::55% or an individual phonetic or 01ihographic score 2:::70%. These names are included in Table
`1 below.
`
`2.2. 6 Names Retrieved for Review Organized by Name Pair Similarity
`Table 1 lists the number of names retrieved from our POCA search, and
`. external study. These name pairs are organized as highly similar, moderately similar or low
`similarity for fmiher evaluation.
`
`-~~-~~,~,~~~~-
`
`(bf(4J
`
`Table 1. Names Retrieved for Review Ore:anized bv Name Pair Similaritv
`
`Similarity Cate2ory
`
`Number of Names
`
`Highly similar name pair:
`combined match percentage score ~70%
`
`Moderately similar name pair:
`combined match percentage score ~55% to :S 69%
`
`Low similarity name pair:
`combined match percentage score :S54%
`
`0
`
`5
`
`2
`
`2.2. 7 Safety Analysis of Names with Potential Orthographic, Spelling, and Phonetic
`Similarities
`
`Our analysis of the seven names contained in Table 1 determined none of the names will pose a
`risk for confusion with Xywav as described in Appendices C through H.
`
`2.2.8 Communication of DMEPA 's Analysis at Midpoint of Review
`
`DMEPA communicated our findings to the Division of Neurology 1 (DN1) via e-mail on March
`17, 2020. At that time, we also requested additional info1mation or concerns that could info1m
`our review. Per e-mail conespondence from the Division of Neurology 1 (DN 1) on March 23,
`2020, they stated no additional concerns with the proposed proprieta1y name, Xywav.
`
`3 CONCLUSION
`
`The proposed proprietaiy name, Xywav, is acceptable.
`If you have any questions or need clai·ifications, please conta.ct Casmir Ogbonna, OSE project
`manager, at 301-796-5272.
`
`3.1
`
`COMMENTS TO JAZZ PHARMACEUTICALS IRELAND LIMITED
`
`We have completed our review of the proposed proprietaiy name, Xywav, and have concluded
`that this name is acceptable.
`
`e POCA search conducted on Janmuy 30, 2020 in version 4.3.
`
`Reference ID 4579414
`
`3
`
`

`

`
`
`If any of the proposed product characteristics as stated in your submission, received on January
`21, 2020, are altered prior to approval of the marketing application, the name must be
`resubmitted for review.
`
`
`
`
`Reference ID: 4579414
`
`
`4
`
`

`

`
`
`4 REFERENCES
`
`1. USAN Stems (https://www.ama-assn.org/about/united-states-adopted-names-approved-stems)
`USAN Stems List contains all the recognized USAN stems.
`
`2. Phonetic and Orthographic Computer Analysis (POCA)
`POCA is a system that FDA designed. As part of the name similarity assessment, POCA is used to
`evaluate proposed names via a phonetic and orthographic algorithm. The proposed proprietary name is
`converted into its phonemic representation before it runs through the phonetic algorithm. Likewise, an
`orthographic algorithm exists that operates in a similar fashion. POCA is publicly accessible.
`
`Drugs@FDA
`Drugs@FDA is an FDA Web site that contains most of the drug products approved in the United States
`since 1939. The majority of labels, approval letters, reviews, and other information are available for drug
`products approved from 1998 to the present. Drugs@FDA contains official information about FDA-
`approved brand name and generic drugs; therapeutic biological products, prescription and over-the-
`counter human drugs; and discontinued drugs (see Drugs @ FDA Glossary of Terms, available at
`http://www.fda.gov/Drugs/InformationOnDrugs/ucm079436.htm#ther biological).
`
`RxNorm
`RxNorm contains the names of prescription and many OTC drugs available in the United States. RxNorm
`includes generic and branded:
`• Clinical drugs – pharmaceutical products given to (or taken by) a patient with therapeutic or
`diagnostic intent
`• Drug packs – packs that contain multiple drugs, or drugs designed to be administered in a
`specified sequence
`Radiopharmaceuticals, contrast media, food, dietary supplements, and medical devices, such as bandages
`and crutches, are all out of scope for RxNorm
`(http://www.nlm.nih.gov/research/umls/rxnorm/overview.html).
`
`Division of Medication Errors Prevention and Analysis proprietary name consultation requests
`This is a list of proposed and pending names that is generated by the Division of Medication Error
`Prevention and Analysis from the Access database/tracking system.
`
`
`
`
`
`
`Reference ID: 4579414
`
`
`5
`
`

`

`
`
`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. f
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`f National Coordinating Council for Medication Error Reporting and Prevention.
`http://www nccmerp.org/aboutMedErrors html. Last accessed 10/11/2007.
`
`Reference ID: 4579414
`
`
`6
`
`

`

`*Table 2- Prescreening C hecklist for Proposed Proprietary Name
`
`Answer the questions in the checklist below. Affinnative answers
`to any of these questions indicate a potential area of concern that
`should be carefully evaluated as described in this guidance.
`
`YIN
`
`Is the proposed name obviously similar in spelling and pronunciation to other
`names?
`
`Proprietaiy names should not be similar in spelling or pronunciation to proprietaiy
`names, established names, or inm:edients of other products.
`
`YIN Are there inert or inactive in2redients referenced in the proprietary name?
`
`Proprietaiy names should not inc01porate any reference to an ine1i or inactive
`ingredient in a way that might create an impression that the ingredient's value is
`m:eater than its tm e functional role in the fo1mulation (21 CFR 201.10( c)(4)).
`
`YIN Does the oroorietarv name include combinations of active in!?:redients?
`
`Proprietaiy names of fixed combination diug 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)).
`
`YIN
`
`Is there a United States Adopted Name (USAN) stem in the proprietary name?
`
`Proprietaiy names should not inco1porate a USAN stem in the position that USAN
`designates for the stem.
`
`YIN
`
`Is this proprietary name used for another product that does not share at least
`one common active ine;redient?
`
`Dmg products that do not contain at least one common active ingredient should not
`use the same (root) proprietary name.
`
`YIN
`
`Is this a proprietary name of a discontinued product?
`
`Proprietaiy names should not use the proprietaiy name of a discontinued product if
`that discontinued mug product does not contain the same active inm:edients.
`
`b. Phonetic and 01thographic Computer Analysis (POCA): Following the preliminaiy
`screening of the proposed proprietaiy name, DMEP A staff evaluates the proposed name
`against potentially similar names. In order to identify names with potential similarity to
`the proposed proprietaiy name, DMEP A enters the proposed proprieta1y name in POCA
`and queries the name against the following diug reference databases, Dmgs@f da,
`Cem erRxN01m, and names in the review pipeline using a 55% threshold in POCA.
`DMEP A reviews the combined 01i hographic and phonetic matches and group the names
`into one of the following three categories:
`Highly similai· pair: combined match percentage score ~70%.
`Moderately similai· pair: combined match percentage score ~55% to:::; 69%.
`Low similai·ity: combined match percentage score :::;54%.
`
`Reference ID 4579414
`
`7
`
`

`

`
`
`Using the criteria outlined in the check list (Table 3-5) that corresponds to each of the three
`categories (highly similar pair, moderately similar pair, and low similarity), DMEPA
`evaluates the name pairs to determine the acceptability or non-acceptability of a proposed
`proprietary name. The intent of these checklists is to increase the transparency and
`predictability of the safety determination of whether a proposed name is vulnerable to
`confusion from a look-alike or sound-alike perspective. Each bullet below corresponds to the
`name similarity category cross-references the respective table that addresses criteria that
`DMEPA uses to determine whether a name presents a safety concern from a look-alike or
`sound-alike perspective.
`• For highly similar names, differences in product characteristics often cannot mitigate the
`risk of a medication error, including product differences such as strength and dose. Thus,
`proposed proprietary names that have a combined score of ≥ 70 percent are at risk for a
`look-alike sound-alike confusion which is an area of concern (See Table 3).
`• Moderately similar names are further evaluated to identify the presence of attributes that
`are known to cause name confusion.
` Name attributes: We note that the beginning of the drug name plays a
`significant role in contributing to confusion. Additionally, drug name pairs
`that start with the same first letter and contain a shared letter string of at
`least 3 letters in both names are major contributing factor in the confusion
`of drug namesg. We evaluate all moderately similar names retrieved from
`POCA to identify the above attributes. These names are further evaluated
`to identify overlapping or similar strengths or doses.
` Product attributes: Moderately similar names of products that have
`overlapping or similar strengths or doses represent an area for concern for
`FDA. The dose and strength information is often located in close
`proximity to the drug name itself on prescriptions and medication orders,
`and the information can be an important factor that either increases or
`decreases the potential for confusion between similarly named drug pairs.
`The ability of other product characteristics to mitigate confusion (e.g.,
`route, frequency, dosage form) may be limited when the strength or dose
`overlaps. DMEPA reviews such names further, to determine whether
`sufficient differences exist to prevent confusion. (See Table 4).
`
`
`• Names with low similarity that have no overlap or similarity in strength and dose are
`generally acceptable (See Table 5) unless there are data to suggest that the name might be
`vulnerable to confusion (e.g., prescription simulation study suggests that the name is
`likely to be misinterpreted as a marketed product). In these instances, we would reassign
`a low similarity name to the moderate similarity category and review according to the
`moderately similar name pair checklist.
`
`
`
`
`g Shah, M, Merchant, L, Characteristics That May Help in the Identification of Potentially Confusing Proprietary
`Drug Names. Therapeutic Innovation & Regulatory Science, September 2016
`
`
`Reference ID: 4579414
`
`
`8
`
`

`

`
`
`
`
`c. FDA Prescription Simulation Studies: DMEPA staff also conducts a prescription
`simulation studies using FDA health care professionals.
`Four 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, verbal pronunciation of the drug name or
`during computerized provider order entry. The studies employ healthcare professionals
`(pharmacists, physicians, and nurses), and attempts to simulate the prescription ordering
`process. The primary Safety Evaluator uses the results to identify vulnerability of the
`proposed name to be misinterpreted by healthcare practitioners during written, verbal, or
`electronic prescribing.
`In order to evaluate the potential for misinterpretation of the proposed proprietary name
`during written, verbal, or electronic prescribing of the name, written inpatient medication
`orders, written outpatient prescriptions, verbal orders, and electronic orders are simulated,
`each consisting of a combination of marketed and unapproved drug products, including
`the proposed name.
`
`d. 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.
`
`
`
`
`
`
`Reference ID: 4579414
`
`
`9
`
`

`

`Table 3. Highly Similar Name Pair Checklist (i.e., combined Orthographic and Phonetic
`score is 2::. 70% .
`
`Answer the questions in the checklist below. Affinnative answers to some of these
`questions suggest that the pattern of 01thographic or phonetic differences in the names
`may render the names less likely to confusion, provided that the pair does not share a
`common strength or dose.
`
`Orthographic Checklist
`
`Phonetic Checklist
`
`YIN Do the names begin with different
`first letters?
`
`YIN
`
`Do the names have different
`number of syllables?
`
`Note that even when names begin with
`different first letters, certain letters may be
`confiJsed with each other when scrip ted.
`
`YIN Are the lengths of the names
`dissimilar* when scripted?
`
`YIN
`
`Do the names have different
`syllabic stresses?
`
`YIN
`
`*FDA considers the length of names
`different if the names differ by two or more
`letters.
`
`Considering variations in scripting of
`some letters (such as z and}), is there
`a different number or placement of
`upstroke/downstroke letters present
`in the names?
`
`YIN
`
`Do the syllables have different
`phonologic processes, such
`vowel reduction, assimilation,
`or deletion?
`
`YIN
`
`Is there different number or
`placement of cross-stroke or dotted
`letters present in the names?
`
`YIN
`
`Across a range of dialects, are
`the names consistently
`pronounced differently?
`
`YIN Do the infixes of the name appear
`dissimilar when scri ted?
`
`YIN Do the suffixes of the names appear
`dissimilar when scripted?
`
`Reference ID 4579414
`
`10
`
`

`

`
`
`Table 4: Moderately Similar Name Pair Checklist (i.e., combined score is ≥55% to ≤69%).
`Step 1 Review the DOSAGE AND ADMINISTRATION and HOW
`SUPPLIED/STORAGE AND HANDLING sections of the prescribing
`information (or for OTC drugs refer to the Drug Facts label) to determine if
`strengths and doses of the name pair overlap or are very similar. Different
`strengths and doses for products whose names are moderately similar may
`decrease the risk of confusion between the moderately similar name pairs. Name
`pairs that have overlapping or similar strengths or doses have a higher potential
`for confusion and should be evaluated further (see Step 2). Because the strength
`or dose could be used to express an order or prescription for a particular drug
`product, overlap in one or both of these components would be reason for further
`evaluation.
`For single strength products, also consider circumstances where the strength may
`not be expressed.
`For any i.e. drug products comprised of more than one active ingredient,
`consider whether the strength or dose may be expressed using only one of the
`components.
`To determine whether the strengths or doses are similar to your proposed
`product, consider the following list of factors that may increase confusion:
`• Alternative expressions of dose: 5 mL may be listed in the prescribing
`information, but the dose may be expressed in metric weight (e.g., 500
`mg) or in non-metric units (e.g., 1 tsp, 1 tablet/capsule). Similarly, a
`strength or dose of 1000 mg may be expressed, in practice, as 1 g, or vice
`versa.
`
`• Trailing or deleting zeros: 10 mg is similar in appearance to 100 mg
`which may potentiate confusion between a name pair with moderate
`similarity.
`
`• Similar sounding doses: 15 mg is similar in sound to 50 mg
`
`Step 2
`
`
`
`Answer the questions in the checklist below. Affirmative answers to some of
`these questions suggest that the pattern of orthographic or phonetic differences in
`the names may reduce the likelihood of confusion for moderately similar names
`with overlapping or similar strengths or doses.
`
`Reference ID: 4579414
`
`
`11
`
`

`

`
`
`
`
`
`
`Phonetic Checklist (Y/N to each
`question)
`• Do the names have
`different number of
`syllables?
`• Do the names have
`different syllabic stresses?
`• Do the syllables have
`different phonologic
`processes, such vowel
`reduction, assimilation, or
`deletion?
`• Across a range of dialects,
`are the names consistently
`pronounced differently?
`
`
`
`Orthographic Checklist (Y/N to each
`question)
`• Do the names begin with different
`first letters?
`Note that even when names begin with
`different first letters, certain letters may be
`confused with each other when scripted.
`• Are the lengths of the names
`dissimilar* when scripted?
`*FDA considers the length of names
`different if the names differ by two or
`more letters.
`• Considering variations in scripting
`of some letters (such as z and f), is
`there a different number or
`placement of upstroke/downstroke
`letters present in the names?
`Is there different number or
`placement of cross-stroke or dotted
`letters present in the names?
`• Do the infixes of the name appear
`dissimilar when scripted?
`• Do the suffixes of the names appear
`dissimilar when scripted?
`
`•
`
`
`Table 5: Low Similarity Name Pair Checklist (i.e., combined score is ≤54%).
`Names with low similarity are generally acceptable unless there are data to suggest that
`the name might be vulnerable to confusion (e.g., prescription simulation study suggests
`that the name is likely to be misinterpreted as a marketed product). In these instances,
`we would reassign a low similarity name to the moderate similarity category and
`review according to the moderately similar name pair checklist.
`
`
`
`
`
`
`Reference ID: 4579414
`
`
`12
`
`

`

`Appendix B: Prescription Simulation Samples and Results
`
`Ffoure 1. Xvwav Studv (Conducted on Februarv 7 2020)
`
`Handwritten Medication Order/Prescription
`
`Verbal
`Prescription
`
`Xywav
`Medication Order:
`' ~WM oi~~ f7P hs1 ~ ~ .f ~ Take 4.5 g po at
`bedtime then
`PAJ?r
`repeat same dose
`2.5 hom s later
`
`Outpatient Prescription:
`
`Dispense:
`# 180 mL
`
`Y ~ wi:.1._V
`-l kJtu_ ~ . S c r I.) ce- b-e-&~ >~ tk ,N..f-d
`7
`s u-~ c\ci~ d_, c;
`f!J~ ic.Jv.
`~ \ ::ie- *' l W N1L
`
`CPOE Study Sample (displayed as sans-serif, 12-point, bold font)
`
`Xywav
`
`FDA Prescription Simulation Responses (Aggregate Repor t)
`Study Name: Xywav
`As of Date 2/21/2020
`
`212 People Received Study
`
`7 6 People Responded
`
`Study Name: Xywav
`
`Total
`
`27
`
`14
`
`15
`
`20
`
`INTERPRETATION OPTPATIENT CPOE
`
`VOICE !~PATIENT TOTAL
`
`DIWAYS
`
`XYUCEV
`
`XYUSV
`
`0
`
`1
`
`1
`
`0
`
`0
`
`0
`
`1
`
`0
`
`0
`
`0
`
`0
`
`0
`
`1
`
`1
`
`1
`
`Reference ID 4579414
`
`13
`
`

`

`XYVAV
`
`XYWAN
`
`XYWAU
`
`XYWAV
`
`XYWA V (CLOSE TO
`XYZAL)
`
`XYWCEV
`
`XYWEEV
`
`XYWERV
`
`XYWUV
`
`ZIWAVE
`
`ZYWAVE
`
`ZYWAY
`
`ZYWAYS
`
`ZYWAZE
`
`1
`
`0
`
`0
`
`20
`
`0
`
`1
`
`1
`
`1
`
`1
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`14
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`2
`
`8
`
`1
`
`2
`
`1
`
`0
`
`1
`
`1
`
`17
`
`1
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`1
`
`1
`
`1
`
`51
`
`1
`
`1
`
`1
`
`1
`
`1
`
`2
`
`8
`
`1
`
`2
`
`1
`
`Reference ID 4579414
`
`14
`
`

`

`Appendix C : Highly Similar Nam es (e.g., combined POCA score is ~70%)
`
`Proposed name: Xywav
`Established name: calcium
`oxybate, potassium oxybate,
`magnesium oxybate, sodium
`oxybate
`Dosage form: oral solution
`Strength(s): 0 gbnL
`(bl\41 4.5 g
`Usual Dose:
`twice nightly (2.5 to 4 hours
`apart)
`
`No.
`
`NIA
`
`POCA
`Score (%)
`
`Ortho~raphic and/or phonetic
`differences in the names sufficient to
`prevent confusion
`
`Other prevention of failure mode
`expected to minimize the risk of
`confusion between these two names.
`
`Appendix D: Moderately Similar Names (e.g., combined POCA score is ~55% to :S.69%) with
`no overlap or numerical similarity in Strength and/or Dose
`
`Name
`
`POCA Score (%)
`
`Appendix E: Moderately Similar Names (e.g., combined POCA score is ~55% to :S.69%) with
`overlap or numerical similarity in Strength and/or Dose
`
`No.
`
`1.
`
`Proposed name: Xywav
`Established name: calcium
`oxybate, potassium oxybate,
`magnesium oxybate, sodium
`oxybate
`Dosage form: oral solution
`Strength(s): 0.5 g/mLh
`(b)(4)
`Usual Dose:
`4.5 g
`twice nightly (2.5 to 4 hours
`apart)
`X-Wax
`
`POCA
`Score (%)
`
`Prevention of Failure Mode
`
`In the conditions outlined below, the
`following combination of factors, are
`expected to minimize the risk of
`confusion between these two names
`
`64
`
`This name pair has sufficient
`01i hographic and phonetic differences.
`
`01ihographically, Xywav contains the
`downstroke letter 'y' whereas, X-Wax
`does not contain any downstroke
`
`b The actual otency is 0.413 g[mL (active moietyJ .
`
`(6)(4)
`
`Reference ID 4579414
`
`15
`
`

`

`
`
`2. Xyzal
`
`62
`
`3. Xerava
`
`4. Xyrem
`
`5.
`
`Zyvox
`
`Reference ID: 4579414
`
`
`58
`
`56
`
`50
`
`16
`
`letters, which gives the names different
`shapes when scripted.
`This name pair has sufficient
`orthographic and phonetic differences.
`
`Orthographically, the suffixes (-wav
`vs. -zal) of the names look sufficiently
`different. Xyzal has the upstroke letter
`‘l’ in the suffix whereas, Xywav does
`not contain any upstroke letters, which
`gives the names different shapes when
`scripted. Additionally, the ‘z’ in Xyzal
`may scripted with a cross-stroke or
`downstroke, which may provide
`additional differentiation.
`
`Phonetically, the second syllables (-
`wāv vs. -zal) sound different when
`spoken.
`This name pair has sufficient
`orthographic and phonetic differences.
`
`Additionally, there is no direct overlap
`in dosage form (solution vs.
`lyophilized powder for injection), or
`route of administration (oral vs.
`intravenous infusion), which may
`provide additional differentiation, if
`included.
`This name pair has sufficient
`orthographic and phonetic differences.
`
`Orthographically, the suffixes (-wav
`vs. -rem) of the names look different.
`
`Phonetically, the second syllables (-
`wāv vs. -rem) sound different when
`spoken.
`This name pair has sufficient
`orthographic and phonetic differences.
`
`Orthographically, the first letters (X vs.
`Z) of the names look sufficiently
`different.
`
`
`

`

`6.
`
`Zoloft
`
`18
`
`Phonetically, the second syllables (-
`wav vs. -vox) sound different when
`spoken.
`This name pair has sufficient
`01i hoizraphic and phonetic differences.
`
`Appendix F: Low Similarity Names (e.g., combined POCA score is ~54%)
`
`Name
`
`POCA Score (%)
`
`Appendix G : Names not likely to be confused or not used in usual practice settings for th e
`reasons described.
`
`No.
`
`Name
`
`7.
`
`I
`
`(b)(4) ***
`l
`
`POCA
`Score
`(% )
`58
`
`Failure preventions
`
`Proposed proprietaiy name withdrawn by the
`Applicant. Product approved under the proprietaiy
`name, Xerava (NDA 2 11109), which is evaluated
`above in Appendix E.
`
`Appendix H: Names not likely to be confused due to absence of attributes that ai·e known to
`cause name confusioni.
`
`Name
`
`POCA Score (%)
`
`'Shah, M, Merchant, L, Chan, I, and Taylor, K. Characteristics That May Help in the Identification of Potentially
`Confusing Proprietary Drug Names. Therapeutic Innovation & Regulatory Science, September 2016
`
`Reference ID 4579414