CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`205580Orig1s000
`
`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:
`
`March 22, 2018
`
`Application Type and Number: NDA 205580
`
`Product Name and Strength:
`
`Belrapzo (bendamustine HCL) Injection
`
`Total Product Strength:
`
`100 mg/4 mL (25 mg/mL)
`
`Product Type:
`
`
`
`Single Ingredient
`
`Rx or OTC:
`
`Rx
`
`Applicant/Sponsor Name:
`
`Eagle Pharmaceuticals, Inc.
`
`Panorama #:
`
`2018- 20949012
`
`DMEPA Safety Evaluator:
`
`Idalia E. Rychlik, PharmD.
`
`DMEPA Team Leader:
`
`Hina Mehta, PharmD.
`
`DMEPA Associate Director:
`
`Mishale Mistry, PharmD, MPH
`
`DMEPA Division Director:
`
`Todd Bridges, RPh
`
`
`
`
`Reference ID: 4238087
`Reference ID: 4266336
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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 ............................................................................................................ 1
`3 CONCLUSION ....................................................................................................................... 5
`3.1 Comments to the Applicant .............................................................................................. 5
`4 REFERENCES ........................................................................................................................ 6
`APPENDICES ................................................................................................................................ 7
`
`
`
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`Reference ID: 4238087
`Reference ID: 4266336
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`1
`
`INTRODUCTION
`
`This review evaluates the proposed proprietary name, Belrapzo, 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 proposed proprietary name.
`
`1.1 PRODUCT INFORMATION
`
`The following product information is provided in the proprietary name submission received on
`February 2, 2018.
`
`Intended Pronunciation: bell-RAP-zoh
` Active Ingredient: bendamustine hydrochloride
`
`
`Indication of Use: treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell
`non-Hodgkin lymphoma (NHL) that has progressed during or within six months of
`treatment with rituximab or a rituximab-containing regimen.
` Route of Administration: intravenous infusion
` Dosage Form: injection
` Strength: 100 mg/4 mL (25 mg/mL)
` Dose and Frequency: The usual dosage and frequency of administration for this product
`is:
`
`o CLL: 100 mg/m2 infused intravenously over 30 minutes on days 1 and 2 of a 28-
`day cycle, up to 6 cycles
`o NHL: 120 mg/m2 infused intravenously over 60 minutes on days 1 and 2 of a 21-
`day cycle, up to 8 cycles
`
`
`
`
` How Supplied: multi-dose vials with an
` stopper
` Storage: refrigerated (2°C to 8°C), protected from light
`2 RESULTS
`
`The following sections provide information obtained and considered in the overall evaluation of
`the proposed proprietary name.
`
`2.1 MISBRANDING ASSESSMENT
`
`The Office of Prescription Drug Promotion (OPDP) determined that the proposed name would
`not misbrand the proposed product. The Division of Medication Error Prevention and Analysis
`(DMEPA) and the Division of Division of Hematology Products (DHP) concurred with the
`findings of OPDP’s assessment of the proposed name.
`
`2.2 SAFETY ASSESSMENT
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`Reference ID: 4238087
`Reference ID: 4266336
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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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`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 namea.
`
`2.2.2 Components of the Proposed Proprietary Name
`
`The Applicant did not provide a derivation or intended meaning for the proposed name, Belrapzo
`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 22, 2018 e-mail, the Division of Hematology Products (DHP)
`did not forward any comments or concerns relating to the proposed proprietary name at the
`initial phase of the review.
`
`2.2.4 FDA Name Simulation Studies
`
`Ninety-two (92) practitioners participated in DMEPA’s prescription studies. One participant
`misinterpreted the name Belrapzo as “Darazol” in the voice prescription simulation, which is a
`close variation to the currently marketed product “Danazol”. We note that the name pair have
`sufficient orthographic and phonetic differences, with a combined POCA score of 40.
`
`Phonetically the first syllables (“Bel-” vs. “Dan”) of this name pair provide some phonetic
`differences. Orthographically, the prefixes (Bel vs. Dan), infixes (rap vs. a), and the presence of
`an upstroke letter “l” in the suffix of Danazol provide sufficient differences. In addition,
`Belrapzo and Danazol differ in dosage form (injection vs. capsule), routes of administration
`(intravenous vs. oral), and frequency (once every 21 or 28-day cycle, for a total 6 to 8 cycles vs.
`2 to 3 times daily). We evaluate this name pair in Appendix E.
`
`Appendix B contains the results from the verbal and written prescription studies.
`
`2.2.5 Phonetic and Orthographic Computer Analysis (POCA) Search Results
`
`Our POCA searchb identified 34 names with a combined phonetic and orthographic score of
`≥55% or an individual phonetic or orthographic score ≥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, FDA Name Simulation
`Studies and the
` external study. These name pairs are organized as highly
`similar, moderately similar or low similarity for further evaluation.
`
`
`
`a USAN stem search conducted on (2/13/18).
`
`b POCA search conducted on (2/13/18) in version 4.2.
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`(b) (4)
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`combined match u;ercentae score 255% to S 69%
`
`Moderately similarname pair: -
`Low similarityname pair:
`_
`
`Highly similar name pair.
`combined match percentage score >70%
`
`combined match -_ercentae score 554%
`
`2.2. 7 Safety Analysis ofNames with Potential Orthographic, Spelling, and Phonetic
`Similarities
`
`Our analysis of the 36 names contained in Table 1 determined that 35 of the names will not pose
`a risk for confusion as described in Appendices C through H. However, the proposed name could
`be confirsed with another proposed proprietary name,- *** for the reasons described
`below (see section titled “Belrapzo vs. Perhazo”). Thus, the ultimate acceptability of the
`proposed proprietary name, Belrapzo is dependent upon which underlying application is
`approved first. We evaluated the status of the underlying application of the conflicting name,
`_*** and determined that the application remains in [ND status. Therefore, if the
`proposed proprietary name, Belrapzo, is granted approval under NDA 205580 on or before the
`March 30, 2018 PDUFA goal date for the application, this application approval will precede
`approval of the application with the conflicting name,_***. Based on our assessment, we
`do not object to the proposed proprietary name, Belrapzo, at this time.
`
`Belrapzo vs.-2
`
`
`
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`Reference ID: 4238087
`Reference ID: 4266336
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`(b) (4)
`
`We acknowledge that our conclusion differs from that of the external study conducted by
`(m4) However, the external study did not identify the pending proprietary name as
`it is not an approved product.
`
`2.2.8 Discussion ofDual Proprietary Name
`
`Eagle Pharmaceuticals has proposed two different marketing applications for their bendamustine
`hydrochloride injection. NDA 208194 was approved on December 7, 2015 under the proprietary
`name Bendeka. The Applicant now proposes NDA 205580 under the proposed proprietary name
`Belrapzo. Both products are indicated for treatment of chronic lymphocytic leukemia (CLL) and
`indolent B-cell non—Hodgkin lymphoma (NHL) that has progressed during or within six months
`of treatment with rituximab or a rituximab-containing regimen. The products are available in 100
`mg/4 mL injection dosage form. However, the preparation instructions for the products differ.
`
`Table 2 provides a side-by—side comparison of the two proposed products.
`
`Table 2. Com n arison of Belra n 10 and Bendeka
`
`Attribute
`
`Belra . zo
`
`A » ulication Number NDA 205580
`
`Bendeka
`
`NDA 208194
`
`
`
`Stren_ h
`
`100m 4mL 25mo mL
`
`100mo 4mL 25m mL
`
`How Su n lied
`
`4 ml. multi-dose vial
`
`4 mL multi-dose vial
`
`Dosing and
`Administration
`
`The usual dosage and frequency of The usual dosage and frequency of
`administration for this product is:
`administration for this product is:
`o CLL: 100 mg/m2 infused
`CLL: 100 mg/m2 infused
`intravenously over 30 minutes
`intravenously over 10 minutes
`on days 1 and 2 of a 28-day
`on days 1 and 2 of a 28-day
`c cle, u to 6 c cles
`cycle, up to 6 cycles
`
`‘ Institute for Safe Medication Practices. Safety briefs: Vitamin D-angerous? ISMP Med Saf Alert
`Community/Ambulatory Care. 2012: 1 1(11): 1-4.
`
`‘ Institute for Safe Medication Practices. Safety Briefs: On the watch. ISMP Med Saf Alert Acute Care. 2006:
`1 1(2): 1 .
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` NHL: 120 mg/m2 infused
`intravenously over 60 minutes
`on days 1 and 2 of a 21-day
`cycle, up to 8 cycles
`
` NHL: 120 mg/m2 infused
`intravenously over 10 minutes
`on days 1 and 2 of a 21-day
`cycle, up to 8 cycles
`
`Diluted in a 500 mL infusion bag
`of 0.9% Sodium Chloride
`Injection, USP, or 2.5%
`Dextrose/0.45% Sodium Chloride
`Injection, USP
`
`Diluted in a 50 mL infusion bag of
`0.9% Sodium Chloride Injection,
`USP, or 2.5% Dextrose/0.45%
`Sodium Chloride Injection, USP,
`or 5% Dextrose Injection, USP
`
`Resulting in a final concentration
`between 0.2 mg/mL – 0.7 mg/mL
`
`Dose modifications are toxicity
`Grade specific.
`
`Resulting in a final concentration
`between 1.85 mg/mL – 5.6
`mg/mL
`
`Dose modifications are toxicity
`Grade specific.
`
`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.
`
`2.2.9 Communication of DMEPA’s Analysis at Midpoint of Review
`
`DMEPA communicated our findings to the Division of Hematology Products (DHP) via e-mail
`on March 19, 2018. At that time we also requested additional information or concerns that could
`inform our review. Per e-mail correspondence from the DHP on March 21, 2018, they stated no
`additional concerns with the proposed proprietary name, Belrapzo.
`
`3 CONCLUSION
`
`The proposed proprietary name is acceptable.
`
`If you have any questions or need clarifications, please contact Neil Vora, OSE project manager,
`at 240-402-4845.
`
`3.1
`
`COMMENTS TO THE APPLICANT
`
`We have completed our review of the proposed proprietary name, Belrapzo, and have concluded
`that this name is acceptable.
`
`If any of the proposed product characteristics as stated in your submission, received on February
`2, 2018, are altered prior to approval of the marketing application, the name must be resubmitted
`for review.
`
`Reference ID: 4238087
`Reference ID: 4266336
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`
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`4 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. 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.
`
`3. 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.
`
`
`
`
`
`
`Reference ID: 4238087
`Reference ID: 4266336
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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. e
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`
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`
`
`
`e 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.
`
`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 in edients of other roducts.
`
`Are there inert or inactive in_redients referenced in the ro s rieta
`
`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 flmctional role in the formulation (21 CFR 201 . 10(c)(4)).
`
`Does the nro n rieta
`
`name include combinations of active in_redients?
`
`suggest the name of one or more, but not all, of its active ingredients (see 21 CFR
`
`Y/N Proprietary names of fixed combination drug products should not include or
`
`YIN
`
`YIN
`
`Is there a United States Ado n ted Name
`
`S .
`
`stem in the ro n rieta
`
`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 in_redient?
`
`Drug products that do not contain at least one common active ingredient should not
`use the same root
`01‘0 u.riet
`name.
`
`Is this a ro n rieta
`
`name of a discontinued roduct?
`
`Proprietary names should not use the proprietary name of a discontinued product if
`that discontinued dru roduct does not contain the same active in edients.
`
`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,
`CemerRxNonn, 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:
`
`0 Highly similar pair: combined match percentage score 270%.
`
`° Moderately similar pair: combined match percentage score 255% to S 69%.
`
`0 Low similarity: combined match percentage score 554%.
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`
`
`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 namesf. 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.
`
`
`f 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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`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.
`
`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.
`
`
`
`
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`Reference ID: 4238087
`Reference ID: 4266336
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`Table 3. Highly Similar Name Pair Checklist (i.e., combined Orthographic and Phonetic
`score is Z 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
`
`Phonetic Checklist
`
`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?
`
`Do the names begin with different
`first letters?
`
`Note that even when names begin with
`dzflerentfiist letters, certain letters may be
`
`confilsed with each other when scripted.
`
`Are the lengths of the names
`dissimilar* when scripted?
`
`*FDA considers the length ofnames
`difl'erent ifthe names difi’er by two or more
`letters.
`
`Considering variations in scripting of
`some letters (such as : andj), 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?
`
`Do the suffixes of the names appear
`dissimilar when scripted?
`
`Reference ID: 4238087
`Reference ID: 4266336
`
`11
`
`

`

`
`
`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: 4238087
`Reference ID: 4266336
`
`
`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: 4238087
`Reference ID: 4266336
`
`
`13
`
`

`

`Appendix B: Prescription Simulation Samples and Results
`
`Figure 1. Belrapzo Stud! (Conducted on 2/21/2018!
`
`Handwritten Medication Order/Prescription
`
`Medication Order:
`
`Outpatient Prescription:
`
`P Verlral
`
`rescrl n tlon
`
`Belrapzo
`
`Bring to clinic
`
`#1 vial
`
`FDA Prescription Simulation Responses (Aggregate l Rx Studies Report!
`
`Study Name: Belrapzo
`
`Total
`
`30
`
`30
`
`32
`
`INTERPRETATION
`
`OUTPATIENT
`
`VOICE
`
`INPATIENT
`
`TOTAL
`
`306 People Received Study
`
`92 People Responded
`
`BEBRAPZS
`
`BELARAPSO
`
`BELARAPZO
`
`BELIAPZO
`
`BELRAPOZO
`
`BELRAPRO
`
`BELRAPSO
`
`BELRAPYS
`
`BELRAPZA BELRAPZO
`
`BELRAPYS CIDI
`
`Reference ID: 4238087
`Reference ID: 4266336
`
`14
`
`

`

`
`
`BELRAPZO 0R BELRAPSO
`
`BELRAPZS
`
`BELRAPZYS
`
`BELREMZO
`
`BELROPZO
`
`BELROYZO
`
`BELSAPZO
`
`BELWRAPSO
`
`BLERAPSO
`
`DALRAPSO
`
`DARAZOL
`
`ELRAPSO
`
`L-RAPSO
`
`OLRAPZO
`
`VALRAPSO
`
`VELRAPSO
`
`0
`
`0
`
`0
`
`0
`
`1
`
`1
`
`1
`
`0
`
`0
`
`0
`
`0
`
`0
`
`O
`
`O
`
`O
`
`0
`
`1
`
`0
`
`0
`
`1
`
`0
`
`0
`
`0
`
`1
`
`1
`
`1
`
`1
`
`2
`
`1
`
`1
`
`3
`
`1
`
`0
`
`1 5
`
`1
`
`0
`
`0
`
`O
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`O
`
`0
`
`0
`
`1
`
`1 5
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`2
`
`1
`
`1
`
`3
`
`1
`
`
`
`0 1 0VELRAPZO 1
`
`
`
`
`
`
`
`Reference ID: 4238087
`Reference ID: 4266336
`
`15
`
`

`

`Appendix C: Highly Similar Names (e. g., combined POCA score is 270%)
`
`POCA
`Score (%)
`
`Orthographic 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.
`
`Proposed name: Belrapzo
`Established name:
`Bendamustine HCl
`Dosage form: Injection
`Strength(s): 25 mglmL
`Usual Dose:
`o CLL: 100 mg/m2 infused
`intravenously over 30 minutes
`on days 1 and 2 ofa 28-day
`cycle, up to 6 cycles
`NHL: 120 mg/m2 infused
`intrav