CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`
`
`
`APPLICATION NUMBER:
`
`
`213051Orig1s000
`
`
`PROPRIETARY NAME REVIEW(S)
`
`
`
`
`
`
`

`

`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:
`Application Type and Number:
`Product Name and Strength:
`Product Type:
`Rx or OTC:
`Applicant/Sponsor Name:
`Panorama #:
`DMEPA Safety Evaluator:
`DMEPA Team Leader:
`DMEPA Associate Director:
`
`May 8, 2019
`IND 114464, NDA 213051, NDA 213182
`Rybelsus (semaglutide) tablet, 3 mg, 7 mg, and 14 mg
`Single Ingredient Product
`Prescription (Rx)
`Novo Nordisk Inc. (Novo)
`2018-27266112, 2019-30202491, 2019-30252981
`Ariane O. Conrad, PharmD, BCACP, CDE
`Hina Mehta, PharmD
`Mishale Mistry, PharmD, MPH
`
`
`
`Reference ID: 4430490Reference ID: 4497378
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`

`

`1
`
`Contents
`INTRODUCTION....................................................................................................................1
`
`1.1
`Product Information ..........................................................................................................1
`
`2 RESULTS.................................................................................................................................1
`
`2.1 Misbranding Assessment ..................................................................................................1
`
`2.2
`Safety Assessment.............................................................................................................2
`
`3 CONCLUSION ........................................................................................................................5
`
`3.1 Comments to the Applicant/Sponsor ................................................................................5
`
`4 REFERENCES.........................................................................................................................6
`
`APPENDICES .................................................................................................................................7
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`Reference ID: 4430490Reference ID: 4497378
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`1
`INTRODUCTION
`
`This review evaluates the proposed proprietary name, Rybelsus, from a safety and misbranding
`perspective. The sources and methods used to evaluate the proposed proprietary name are
`outlined in the reference section and Appendix A respectively. Novo submitted an external
`
`name study, conducted by
` for this proposed proprietary name.
`
`o
`
`1.1 PRODUCT INFORMATION
`The following product information is provided in the proprietary name submissions received on
`November 13, 2018 under IND 114464 and on March 20, 2019 under NDA 213051 and NDA
`213182:
`
`Intended Pronunciation: rye bel’ sus
`
`
` Active Ingredient: semaglutide
`
`Indication of Use:
`
`
`o an adjunct to diet and exercise to improve glycemic control in adults with type 2
`diabetes (NDA 213051)
`to reduce the risk of major adverse cardiovascular events in adults with type 2
`diabetes and established cardiovascular
` disease (NDA
`213182)
` Route of Administration: oral
` Dosage Form: tablet
` Strength: 3 mg, 7 mg, and 14 mg
`
` Dose and Frequency: The usual dosage for this product is 3 mg, 7 mg or 14 mg once
`daily. The maximum daily dose is 14 mg.
` How Supplied: 30-day supply (3x10) of 3 mg, 7 mg, or 14 mg blister pack (Trade Packs);
`also 30-day supply (3x10) of 3 mg in blister pack (Sample Pack)
` Storage: Do not store above 30°C (86°F). Do not freeze.
`
`2 RESULTS
`
`The following sections provide information obtained and considered in the overall evaluation of
`the proposed proprietary name, Rybelsus.
`
`2.1 MISBRANDING ASSESSMENT
`The Office of Prescription Drug Promotion (OPDP) determined that Rybelsus would not
`misbrand the proposed product per their November 27, 2018 email. The Division of Medication
`Error Prevention and Analysis (DMEPA) and the Division of Metabolism and Endocrinology
`
`Products (DMEP) concurred with the findings of OPDP’s assessment for Rybelsus.
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`Reference ID: 4430490Reference ID: 4497378
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`1
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`2.2 SAFETY ASSESSMENT
`The following aspects were considered in the safety evaluation of the proposed proprietary name,
`Rybelsus.
`
`2.2.1 United States Adopted Names (USAN) Search
`There is no USAN stem present in the proposed proprietary name1F .
`a
`
`
`2.2.2 Components of the Proposed Proprietary Name
`Novo indicated in their submission that the proposed proprietary name, Rybelsus, is a “blank
`
`canvas”. This proprietary name is comprised of a root name, Rybelsus, 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 November 27, 2018 email, the Division of Metabolism and
`Endocrinology Products (DMEP) did not forward any comments or concerns relating to
`
`Rybelsus at the initial phase of the review.
`
`2.2.4 FDA Name Simulation Studies
`Thirty-eight practitioners participated in DMEPA’s prescription studies for Rybelsus. The
`responses did not overlap with any currently marketed products. However, one voice study
`participant interpreted the name as ‘Rivelsus’, which sounds like the currently marketed product
`Rivelsa. Orthographically, the prefixes of the name pair (‘Ryb’ versus ‘Riv’) look different.
`
`Phonetically, the last syllables (‘sus’ versus ‘sa’) sound different. Rivelsa is an oral
`
`contraceptive, available as a dose pack containing varying strengths of levonorgestrel-ethinyl
`estradiol and ethinyl estradiol (0.15 mg/0.02 mg, 0.15 mg/0.025 mg, 0.15 mg/0.03 mg and 0.01
`mg ethinyl estradiol). Rybelsus will be available as 3 mg, 7 mg, or 14 mg tablets. We note that
`
`the product strength would have to be specified on a prescription or medication order for
`Rybelsus and the product strengths of Rybelsus and Rivelsa do not overlap. See Appendix E for
`our evaluation of this name pair.
`Appendix B contains the results from the verbal and written prescription studies.
`
`2.2.5 Phonetic and Orthographic Computer Analysis (POCA) Search Results
`b identified 39 names with a combined phonetic and orthographic score of
`Our POCA search4F
`≥55% or an individual phonetic or orthographic score ≥70%. These names are included in Table
`
`1 below.
`
`a USAN stem search conducted on January 18, 2019.
`b POCA search conducted on January 18, 2019 in version 4.3.
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`2.2.6 Names Retrieved for Review Organized by Name Pair Similarity
`Table 1 lists the 56 names retrieved from our POCA search and the
` external study. These
`
`name pairs are organized as highly similar, moderately similar or low similarity for further
`evaluation.
`
`Table 1. Names Retrieved for Review Organized by Name Pair Similarity
`Similarity Category
`Number of
`Names
`1
`
`Highly similar name pair:
`combined match percentage score ≥70%
`Moderately similar name pair:
`combined match percentage score ≥55% to ≤ 69%
`Low similarity name pair:
`combined match percentage score ≤54%
`
`37
`
`18
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`2.2.7 Safety Analysis of Names with Potential Orthographic, Spelling, and Phonetic
`
`Similarities
`
`Our analysis of the 56 names contained in Table 1 determined none of the names will pose a risk
`
`for confusion with Rybelsus as described in Appendices C through H.
`
`2.2.8 Discussion of Dual Proprietary Name
`Novo currently markets Ozempic (semaglutide) injection which is indicated as an adjunct to diet
`and exercise to improve glycemic control in adults with type 2 diabetes (NDA 209637). Novo
`proposes to introduce a tablet dosage form of semaglutide under the proprietary name Rybelsus.
`
`Rybelsus will be indicated for the treatment of type 2 diabetes (NDA 213051) and to reduce the
`
`risk of major adverse cardiovascular events in adults with type 2 diabetes and established
` disease (NDA 213182). Table 2 provides relevant product
`cardiovascular
`
`information for Ozempic and Rybelsus.
`
`Table 2. Comparison of Rybelsus and Ozempic
`
`Product Name
` Rybelsus (IND 114464,
`NDA 213051, NDA 213182)
`n/a
`
`Initial Approval Date
`Active Ingredient
`
`Ozempicc (NDA 209637)
`
`December 5, 2017
`semaglutide
`
` c Ozempic [Prescribing Information]. Drugs@FDA. U.S. Food and Drug Administration. 2017 Dec. Available from:
`
`https://www.accessdata.fda.gov/drugsatfda docs/label/2017/209637lbl.pdf.
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`(b) (4)
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`(b) (4)
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`Indication
`
`Route of Administration
`Dosage Form
`Strength
`Dose and Frequency
`
`How Supplied
`
`
`
` adjunct to diet and
`exercise to improve
`glycemic control in adults
`with type 2 diabetes
`
`(NDA 213051)
`to reduce the risk of major
`adverse cardiovascular
`events in adults with type
`2 diabetes and established
`
`cardiovascular
`disease
`
`(NDA 213182)
`Oral
`Tablet
`3 mg, 7 mg, 14 mg
` 3 mg, 7 mg or 14 mg by
`mouth once daily at least
`30 minutes before first
`food, beverage, or other
`medications
` 3 mg once daily for 1
`month, then increase to 7
`
`mg daily. If additional
`benefit is needed after 1
`month on the 7 mg dose,
`then can increase to 14
`mg daily.
` The maximum daily dose
`is 14 mg
`30-day supply (3x10) of 3
`mg, 7 mg, or 14 mg blister
`pack (Trade Packs); also 30­
`day supply (3x10) of 3 mg in
`blister pack (Sample Pack)
`
` adjunct to diet and
`exercise to improve
`glycemic control in adults
`with type 2 diabetes
`
`Subcutaneous
`Injection
`2 mg per 1.5 mL
`Inject subcutaneously in
`
`the abdomen, thigh, or
`upper arm once weekly at
`any time of the day, with
`or without meals
` 0.25 mg once weekly then
`increase to 0.5 mg once
`weekly after 4 weeks; if
`after 4 weeks on the 0.5
`mg dose, increase to 1 mg
`once weekly
`
`Single use pens containing a
`total of 2 mg/1.5 mL and
`
`delivers
`
` 0.25 mg or 0.5 mg per
`injection OR
` 1 mg per injection
`
`We have evaluated the risks associated with this naming strategy and do not object to the use of a
`dual proprietary name in this case.
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`(b) (4)
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`2.2.9 Communication of DMEPA’s Analysis at Midpoint of Review
`
`DMEPA communicated our findings to the Division of Metabolism and Endocrinology Products
`(DMEP) via email on May 6, 2019. At that time, we also requested additional information or
`concerns that could inform our review. Per email correspondence from the Division of
`Metabolism and Endocrinology Products (DMEP) on May 8, 2019, they stated no additional
`concerns with the proposed proprietary name, Rybelsus.
`
`3 CONCLUSION
`The proposed proprietary name, Rybelsus, is acceptable.
`If you have any questions or need clarifications, please contact Terrolyn Thomas, OSE project
`manager, at 240-402-3981.
`
`COMMENTS TO NOVO NORDISK INC.
`3.1
`
`
`We have completed our review of the proposed proprietary name, Rybelsus, and have concluded
`that this name is acceptable.
`A request for proprietary name review for Rybelsus should be submitted once the NDA is
`submitted.
`
`
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`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.
`
`
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`Reference ID: 4430490Reference ID: 4497378
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`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
`d
`
`d 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
`
`Y/N
`
`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.
`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 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)).
`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.
`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.
`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.
`
`Y/N
`
`Y/N
`
`Y/N
`
`b. Phonetic and Orthographic Computer Analysis (POCA): Following the preliminary
`screening of the proposed proprietary name, DMEPA staff evaluates the proposed name
`against potentially similar names. In order to identify names with potential similarity to
`
`the proposed proprietary name, DMEPA enters the proposed proprietary name in POCA
`and queries the name against the following drug reference databases, Drugs@fda,
`CernerRxNorm, and names in the review pipeline using a 55% threshold in POCA.
`
`DMEPA reviews the combined orthographic and phonetic matches and group the names
`
`into one of the following three categories:
`
`• Highly similar pair: combined match percentage score ≥70%.
`• Moderately similar pair: combined match percentage score ≥55% to ≤ 69%.
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` • Low similarity: combined match percentage score ≤54%.
`
` 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 names e. 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).
`
`F
`
` 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
`
`
`e Shah, M, Merchant, L, Characteristics That May Help in the Identification of Potentially Confusing Proprietary
`Drug Names. Therapeutic Innovation & Regulatory Science, September 2016
`
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`a low similarity name to the moderate similarity category and review according to the
`moderately similar name pair checklist.
`
` c. 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 (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.
`
`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.
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`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.
`
`Table 3. Highly Similar Name Pair Checklist (i.e., combined Orthographic and Phonetic
`
`
`
`score is ≥ 70%).
`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 render the names less likely to confusion, provided that the pair does not share a
`
`common strength or dose.
`
`
`
`Orthographic Checklist
` Y/N 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.
`Y/N 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.
`Y/N 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?
`Y/N Do the infixes of the name appear
`dissimilar when scripted?
`Y/N Do the suffixes of the names appear
`dissimilar when scripted?
`
`Y/N
`
`Phonetic Checklist
`Y/N Do the names have different
`number of syllables?
`
`Y/N Do the names have different
`syllabic stresses?
`
`
` Y/N Do the syllables have different
`
` phonologic processes, such
`vowel reduction, assimilation,
`or deletion?
`
`Y/N Across a range of dialects, are
`the names consistently
`pronounced differently?
`
`
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` 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: 4430490Reference ID: 4497378
`
`12
`
`

`

`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: 4430490Reference ID: 4497378
`
`13
`
`

`

`Appendix B: Prescription Simulation Samples and Results
`
`
`Figure 1. Rybelsus Study (Conducted on December 7, 2018)
`
`
`Handwritten Medication Order/Prescription
`
`Medication Order:
`
`Outpatient Prescription:
`
`Verbal
`Prescription
`Rybelsus 3 mg
`
` Take 1 tablet by
`mouth daily
`Dispense 90
`
`FDA Prescription Simulation Responses (Aggregate Report)
`
`
`
`Reference ID: 4430490Reference ID: 4497378
`
`14
`
`
`

`

`Appendix C: Highly Similar Names (e.g., combined POCA score is ≥70%)
`No.
`Proposed name: Rybelsus
`POCA
`Orthographic and/or phonetic
`Established name: semaglutide
`Score (%)
`differences in the names sufficient to
`Dosage form: tablet
`prevent confusion
`Strength(s): 3 mg, 7 mg, and
`14 mg
`Usual Dose: 1 tablet by mouth
`once daily
`Rybelsus***
`
`Other prevention of failure mode
`expected to minimize the risk of
`confusion between these two names.
`This name is subject of the review.
`
`100
`
`1.
`
`
`
` Appendix D: Moderately Similar Names (e.g., combined POCA score is ≥55% to ≤69%) with
`no overlap or numerical similarity in Strength and/or Dose
`No.
`Name
`POCA
`Score (%)
`62
`60
`59
`58
`57
`56
`56
`56
`56
`56
`55
`55
`
`2.
`3.
`4.
`5.
`6.
`7.
`8.
`9.
`10.
`11.
`12.
`13.
`
` Regulax Ss
`
`Ryaltris***
`Remular-S
`Xtrelus
`Rebetol
`
`***
`Readyflush
`
` Revive Plus
`***
`Replesta
`Reclast
`Restasis
`
`Appendix E: Moderately Similar Names (e.g., combined POCA score is ≥55% to ≤69%) with
`
`overlap or numerical similarity in Strength and/or Dose
`No.
`Proposed name: Rybelsus
`POCA
`Established name: semaglutide
`Score (%)
`Dosage form: tablet
`Strength(s): 3 mg, 7 mg, and
`14 mg
`Usual Dose: 1 tablet by mouth
`once daily
`Rivelsa***
`
`14.
`
`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
`
`62
`
`Orthographically, the prefixes of the
`name pair (‘Ryb’ versus ‘Riv’) look
`different. Phonetically, the last
`syllables (‘sus’ versus ‘sa’) sound
`different.
`
`
`Rivelsa is an oral contraceptive,
`available as a dose pack containing
`
`
`
`Reference ID: 4430490Reference ID: 4497378
`
`15
`
`(b) (4)
`
`(b) (4)
`
`

`

`No.
`
`Proposed name: Rybelsus
`Established name: semaglutide
`Dosage form: tablet
`Strength(s): 3 mg, 7 mg, and
`14 mg
`Usual Dose: 1 tablet by mouth
`once daily
`
`POCA
`Score (%)
`
`15.
`
`***
`
`60
`
`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
`
`varying strengths of levonorgestrel­
`ethinyl estradiol and ethinyl estradiol
`(0.15 mg/0.02 mg, 0.15 mg/0.025 mg,
`0.15 mg/0.03 mg and 0.01 mg ethinyl
`estradiol). Rybelsus will be available
`as 3 mg, 7 mg, or 14 mg tablets. We
`note that the product strength would
`
`have to be specified on a prescription
`or medication order for Rybelsus; the
`product strengths of Rybelsus and
`
`
`Rivelsa do not overlap.
`
`16.
`
`Envarsus
`
`55
`
` This name pair has sufficient
`
`orthographic and phonet