CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`213801Orig1s000
`
`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:
`February 5, 2021
`Application Type and Number: NDA 213801
`Product Name and Strength:
`Myrbetriq Granules (mirabegron for Oral Suspension),
`8 mg/mL after reconstitutiona
`Product Type:
`Single Ingredient Product
`Rx or OTC:
`Prescription (Rx)
`Applicant/Sponsor Name:
`Astellas Pharma Global Development, Inc. (Astellas)
`Panorama #:
`2020-43140108
`DMEPA Safety Evaluator:
`Beverly Weitzman, PharmD
`DMEPA Team Leader (Acting): Celeste Karpow, PharmD, MPH
`
`a Each bottle contains 8.3 g of granules equivalent to 830 mg mirabegron prior to reconstitution.
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`1
`
`Contents
`INTRODUCTION....................................................................................................................1
`1.1
`Regulatory History...........................................................................................................1
`1.2
`Product Information.........................................................................................................1
`2 RESULTS.................................................................................................................................3
`2.1
`Misbranding Assessment.................................................................................................3
`2.2
`Safety Assessment ...........................................................................................................3
`3 CONCLUSION ......................................................................................................................10
`3.1
`Comments to Astellas Pharma Global Development, Inc. ............................................10
`4 REFERENCES.......................................................................................................................11
`APPENDICES ...............................................................................................................................12
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`INTRODUCTION
`1
`This review evaluates the proposed proprietary name, Myrbetriq Granules, 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. Astellas did not submit
`an external name study for this proposed proprietary name.
`
`REGULATORY HISTORY
`1.1
`Myrbetriq (mirabegron) Extended-release tablets, 25 mg and 50 mg was approved under NDA
`202611 on June 28, 2012 and is currently approved for the treatment of overactive bladder
`(OAB) in adults.
`The Applicant proposes to expand the Myrbetriq product line to include a new dosage form,
`mirabegron (8 mg/mL) granules for oral suspension for the treatment of neurogenic detrusor
`overactivity (NDO) in pediatric patients aged 3 years and older.
` Granules
`The Applicant previously submitted the proposed proprietary name, Myrbetriq
`under NDA 213801 for review on September 29, 2020. On December 18, 2020 we submitted an
`information request (IR) requesting the Applicant provide additional information or rationale to
`support the use of two modifiers
` and ‘Granules’ as part of the Sponsor’s proposed
`proprietary name.b In response to our information request, the Applicant submitted a Proprietary
`Name Review amendment on December 22, 2020c to amend the proposed proprietary name to
`Myrbetriq Granules (i.e., to include only one modifier) which is the subject of this review.
`In parallel, Astellas has submitted efficacy supplement (017) under NDA 202611 proposing the
`addition of the same pediatric indication (treatment of neurogenic detrusor overactivity (NDO) in
`pediatric patients aged 3 years and older) for the extended-release tablet dosage form.
`
`PRODUCT INFORMATION
`
`1.2
`
`
`Table 1. Relevant Product Informationd for Myrbetriq Granules and Myrbetriq
`Product Name Myrbetriq Granules
`Myrbetriq
`Intended
`meer-BEH-trick
`meer-BEH-trick
`Pronunciation
`Application #
`
`NDA 202611
`
`NDA 213801
`
`b Information request available in DARRTS via:
`https://darrts fda.gov/darrts/faces/ViewDocument?documentId=090140af805bce25& afrRedirect=99561704967256
`4
`c PNR Amendment available in docuBridge via: \\CDSESUB1\evsprod\nda213801\0013\m1\us\1-12-4-proprietary-
`name-request-amendment.pdf
`d Prescribing Information labeling proposed under NDA 213801 and NDA 202611/S-017 available in EDR via:
`\\CDSESUB1\evsprod\nda213801\0001\m1\us\myrbetriq-uspi-redline.doc
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`Initial
`Approval Date
`Active
`Ingredient
`Indicatione
`
`N/A
`
`Mirabegron
`
`June 28, 2012
`
`Mirabegron
`
`For the treatment of neurogenic detrusor
`overactivity (NDO) in pediatric patients
`aged 3 years and older.
`
`For the treatment of overactive
`bladder (OAB) with symptoms of
`urge urinary incontinence, urgency,
`and urinary frequency.
`In combination with the muscarinic
`antagonist solifenacin succinate, is
`indicated for the treatment of OAB
`with symptoms of urge urinary
`incontinence, urgency, and urinary
`frequency.
` Oral
`
`Extended-release tablet
`25 mg and 50 mg
`
`OAB Indication:
`• Recommended starting dose is 25
`mg once daily, alone or in
`combination with solifenacin
`succinate 5 mg, once daily.
`• Based on individual efficacy and
`tolerability, may increase dose to
`50 mg once daily, alone or in
`combination with solifenacin
`succinate 5 mg, once daily.
`• Patients with Severe Renal
`Impairment or Patients with
`Moderate Hepatic Impairment:
`Maximum dose is 25 mg
`MYRBETRIQ once daily
`• Patients with End Stage Renal
`Disease (ESRD) or Patients with
`
`Route of
`Administration
`Dosage Form
`Strength
`
`Dose and
`Frequencye
`
`Oral
`
`for Oral Suspension
`Each bottle contains 8.3 g of granules
`equivalent to 830 mg mirabegron prior to
`reconstitution.
`8 mg/mL after reconstitution
`OAB Indication: N/A
`
`e NDA 202611/S-017 proposes to expand the indication of Myrbetriq extended-release tablets to include treatment
`of NDO in pediatric patients aged 3 years and older. S-017 is currently under review by the Agency.
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`Severe Hepatic Impairment: Not
`recommended.
`
`NDO Indication:
`Myrbetriq Granules for Oral Suspension Monotherapy for Pediatric Patients < 35
`kg or ≥ 35 kg:
`The recommended starting dose of MYRBETRIQ Granules is determined based
`on patient weight (refer to Table 1). Dosing should be initiated at the
`recommended starting dose. Dosage may be titrated to the lowest effective dose
`but should not exceed the maximum recommended dose.
`
`--: not applicable; NDO: neurogenic detrusor overactivity.
`1. MYRBETRIQ Granules for oral suspension formulation (granules were reconstituted with water to
`prepare a suspension with a concentration of 8 mg/mL suspension).
`2. Patients ≥ 35 kg who cannot swallow tablets may take a suspension dose.
`• The oral suspension and extended-release tablet are not bioequivalent;
`the doses in the table account for the difference in bioavailability between
`the two formulations.
`Supplied as granules in bottles with a
`child-resistant cap packaged in an
`aluminum pouch with desiccant.
`Each bottle is reconstituted by the
`pharmacy with 100 mL
` water.
`Store at 20°C to 25°C (68°F to 77°F) with
`excursions permitted from 15°C to 30°C
`(59°F to 86°F) [see USP Controlled
`Room Temperature].
`Reconstituted oral suspension can be
`stored at room temperature
`
` for up to 28 days
`
`oval, film-coated, extended-release
`tablets available as:
`Bottle of 30 count; bottle of 90
`count,
`.
`Store at 25°C (77°F) with excursions
`permitted from 15°C to 30°C (59°F
`to 86°F) {see USP controlled Room
`Temperature}.
`
`
`
`How Supplied
`
`Storage
`
`2 RESULTS
`
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`(b) (4)
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`(b) (4)
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`The following sections provide information obtained and considered in the overall evaluation of
`the proposed proprietary name, Myrbetriq Granules.
`
`2.1 MISBRANDING ASSESSMENT
`The Office of Prescription Drug Promotion (OPDP) determined that Myrbetriq Granules would
`not misbrand the proposed product. The Division of Medication Error Prevention and Analysis
`(DMEPA) and the Division of Urology, Obstetrics, and Gynecology (DUOG) concurred with the
`findings of OPDP’s assessment for Myrbetriq Granules.
`
`2.2 SAFETY ASSESSMENT
`The following aspects were considered in the safety evaluation of the proposed proprietary name,
`Myrbetriq Granules.
`
`2.2.1 United States Adopted Names (USAN) Search
`There is no USAN stem present in the proposed proprietary name f.
`
`2.2.2 Components of the Proposed Proprietary Name
`The proposed proprietary name, Myrbetriq Granules, is comprised of two components: (1) the
`root name ‘Myrbetriq’ and (2) the modifier ‘Granules’. The Applicant indicates that the
`modifier “Granules” is intended to mean ‘Granules that need to be reconstituted with water to
`create an oral suspension.’
`The product with the root name Myrbetriq was approved on June 28, 2012 and is currently
`marketed as an Extended-release tablet. The applicant proposes to add a for oral suspension
`formulation to the currently marketed Myrbetriq product line. Therefore, we have evaluated the
`appropriateness of using the same root name and the appropriateness of the proposed modifier
`‘Granules’ in Section 2.2.5 below.
`
`2.2.3 Comments from Other Review Disciplines at Initial Review
`In response to the OSE, October 15, 2020 e-mail, the Division of Urology, Obstetrics, and
`Gynecology (DUOG) forwarded the following comment relating to Myrbetriq Granules at the
`initial phase of the review: The word “Granules” in the tradename could imply use as
`“sprinkles” on soft foods.
`We address this comment in Section 2.2.5 Safety assessment of the modifier “Granules.”
`
`2.2.4 FDA Name Simulation Studies
`Seventy-one practitioners participated in DMEPA’s prescription studies for Myrbetriq Granules.
`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.
`Five participants (Voice n=4 and CPOE n=1) in the FDA name simulation studies omitted the
`modifier “Granules.” We discuss the risk associated with omission of the modifier, granules in
`Section 2.2.5 below.
`
`f USAN stem search conducted on November 23, 2020.
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`Appendix B contains the results from the prescription simulation studies.
`
`2.2.5 Safety Assessment of the Root Name and Modifier, Granules
`The applicant currently markets the active ingredient, mirabegron, under the name, Myrbetriq,
`for the Extended-release tablet formulation. The product is currently approved as 25 mg and 50
`mg oral Extended-release tablets for the treatment of overactive bladder (OAB) with symptoms
`of urge urinary incontinence, urgency, and urinary frequency. For their proposed mirabegron for
`oral suspension, the applicant proposes to use the name, Myrbetriq Granules. The differences
`between the proposed formulation and the currently marketed formulation are listed in Table 1
`under Section 1.2 of our review.
`
`1. Evaluation of use of the same root name, “Myrbetriq”
`Myrbetriq has been marketed as the proprietary name for mirabegron since approval on June
`28, 2012. We note that Myrbetriq and Myrbetriq Granules*** share the same active
`ingredient and route of administration. Our routine postmarketing surveillance has not
`identified any signals attributed to name confusion involving Myrbetriq. Thus, we do not
`object to the use of the root name, Myrbetriq, for this product.
`
`2. Evaluation of the use of the modifier to differentiate the products
`Myrbetriq Granules is the second product proposed by the Applicant for the currently
`marketed Myrbetriq product line. The proposed product represents a new strength (8 mg/mL
`after reconstitutiong vs. 25 mg and 50 mg) and new dosage form (for oral suspension vs.
`Extended-release tablet). Thus, the Applicant proposes to use the modifier “Granules” to
`distinguish the proposed Myrbetriq Granules product from the currently marketed Myrbetriq
`product. We evaluated the use of the modifier to determine if the naming strategy helps to
`distinguish the proposed Myrbetriq Granules product from the currently marketed Myrbetriq
`product.
`It is not uncommon to use modifiers to denote a specific product formulation as part of a
`product line extension. We note the for oral suspension and Extended-release tablet dosage
`forms are not bioequivalent on a mg per mg basis. The addition of a modifier may signal to
`healthcare practitioners that this product differs from the currently marketed Myrbetriq
`Extended-release tablets, which may help differentiate the products and reduce the potential
`for wrong dosage form medication errors.
`We also considered the risk of name confusion if the modifier is dropped. We note that
`omission and oversight of a modifier is cited in literature as a common cause of medication
`errors.h Postmarketing experience shows that the introduction of product line extensions may
`result in medication errors if the modifier is omitted and the product characteristics are
`similar or overlap. In this case, there is no direct overlap in strength (8 mg/mL after
`
`g Each bottle contains 8.3 g of granules equivalent to 830 mg mirabegron prior to reconstitution.
`h Lesar TS. Prescribing Errors Involving Medication Dosage Forms. J Gen Intern Med. 2002; 17(8): 579-587.
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`reconstitutioni vs. 25 mg and 50 mg) or dose (24 mg [3 mL], 32 mg [4 mL], 48 mg [6 mL],
`64 mg [8 mL], 80 mg [10 mL] vs. 25 mg or 50 mg) between Myrbetriq Granules and
`Myrbetriq. As such, other components of the prescription or medication order (e.g., strength,
`dose, dosage form) would help mitigate the risk of wrong dosage form medication errors if
`the modifier is omitted on a prescription or medication order.
`Although modifiers may be omitted, they can assist in differentiating products and may help
`to prevent potential selection errors when used. Thus, based on the totality of this
`information, we do not object to the use of a modifier for this product as it may provide an
`added measure of safety. Furthermore, label and labeling mitigations can help minimize the
`residual risk of product selection errors.
`
`3. Evaluation of the proposed modifier, “Granules”
`The Applicant indicates that the modifier “Granules” is intended to mean ‘Granules that need
`to be reconstituted with water to create an oral suspension.’ We note that the modifier
`“Granules” is consistent with the product formulation (pre-reconstitution). We find that the
`proposed modifier, Granules, is not a medical abbreviationj, is not a USAN Stemk, is not on
`ISMP’s List of Error-Prone Abbreviations, Symbols, and Dose Designationsl, and does not
`appear to present any overt safety concerns from a look-alike or sound-alike perspective.
`At the initial phase of the review, the Division of Urology, Obstetrics, and Gynecology
`(DUOG) expressed concern that the word “Granules” in the tradename could imply use as
`“sprinkles” on soft foods (see section 2.2.3 above). As proposed, the use of the modifier
`“Granules” is inconsistent with USP Nomenclature Guidelinesm that reserve “Granules” for
`instances where the drug product is administered as granules (e.g., Singular (montelukast
`sodium) oral granules that are sprinkled directly in the mouth or in food or liquid). We
`assessed the risk of Myrbetriq Granules being administered without reconstitution. The
`proposed product is intended to be dispensed as an oral suspension (i.e., granules
`reconstituted by the pharmacy before being dispensed to patient/caregiver) and not in its
`native form (i.e., granules), which would eliminate the risk of wrong technique
`administration errors (i.e., administering the granules). Additionally, optimized labels and
`labeling can help mitigate the risk of dispensing and administration errors to an acceptable
`level.
`
`i Each bottle contains 8.3 g of granules equivalent to 830 mg mirabegron prior to reconstitution.
`j Davis, N. Medical Abbreviations 30,000 Conveniences at the Expense of Communication and Safety. 14th ed.
`Warminster, PA; 2009.
`k USAN stem search conducted on November 23, 2020.
`l ISMP’s List of Error-Prone Abbreviations, Symbols, and Dose Designations [Internet]. Horsham (PA): Institute for
`Safe Medication Practices. 2017 [cited 2020 NOV 18]. Available from:
`https://www.ismp.org/recommendations/error-prone-abbreviations-list
`m Available from USP website (http://www.usp.org/health-quality-safety/compendial-nomenclature); USP
`Nomenclature Guidelines, referenced in USP General Chapter <1121> Nomenclature, Revised March 24, 2016, p.
`36.
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`As part of our evaluation of the appropriateness of the modifier ‘Granules’, we reviewed
`other products which use ‘Granules’ as part of their proprietary name. The modifier
`‘Granules’ is not new and is currently utilized in the marketplace. We identified one
`marketed product “Prograf Granules” with the modifier “Granules.” Prograf Granules is
`tacrolimus for oral suspension, 0.2 mg and 1 mg and was approved under NDA 210115 on
`May 24, 2018 for the prevention of rejection in pediatric heart, kidney, or liver transplant
`recipients. The proposed dosage form nomenclature (mirabegron for oral suspension) is the
`same as that used for the marketed Prograf Granules (tacrolimus for oral suspension) product.
`We note that Prograf Granules also require reconstitution prior to administration and the
`product labeling contains the instructions “Do not sprinkle Prograf Granules on food”.
`Therefore, there is precedent in the market place for use of the proposed modifier “Granules”
`consistent with the sponsor’s intended meaning for the proposed product. Furthermore, based
`on our postmarketing surveillance activities, we are not aware of any medication error
`concerns stemming from the use of the modifier Granules.
`Therefore, we do not object to the use of modifier ‘Granules’ for the proposed product and
`find Granules is acceptable for conveying this characteristic of the product formulation.
`In summary, we find the use of the root name, Myrbetriq, acceptable for the proposed product.
`Additionally, we find that the addition of the modifier “Granules” to the root name may provide
`a layer of safety to help differentiate the proposed oral suspension from the currently marketed
`Extended-release tablet. Furthermore, optimized labels and labeling may be developed to convey
`the appropriate preparation instructions for the product. Therefore, based on the totality of
`information considered above, we do not object to the proposed name, Myrbetriq Granules, for
`the proposed product.
`
`2.2.6 Communication of DMEPA’s Analysis at Midpoint of Review
`DMEPA communicated our findings to the Division of Urology, Obstetrics, and Gynecology
`(DUOG) via e-mail on February 2, 2021. At that time, we also requested additional information
`or concerns that could inform our review. Per e-mail correspondence from the Division of
`Urology, Obstetrics, and Gynecology (DUOG) on February 5, 2021, they stated no additional
`concerns with the proposed proprietary name, Myrbetriq Granules.
`
`3 CONCLUSION
`The proposed proprietary name, Myrbetriq Granules, is acceptable.
`If you have any questions or need clarifications, please contact Oyinlola Fashina, OSE project
`manager, at 301-796-4446.
`
`COMMENTS TO ASTELLAS PHARMA GLOBAL DEVELOPMENT, INC.
`3.1
`We have completed our review of the proposed proprietary name, Myrbetriq Granules, and have
`concluded that this name is acceptable.
`If any of the proposed product characteristics as stated in your submission, received on
`December 22, 2020, are altered prior to approval of the marketing application, the name must be
`resubmitted for review.
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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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`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. n
`
`n National Coordinating Council for Medication Error Reporting and Prevention.
`http://www nccmerp.org/aboutMedErrors html. Last accessed 10/11/2007.
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`*Table 2- Prescreening Checklist for Proposed Proprietary Name
`
`Answer the questions in the checklist below. Affirmative answers
`to any of these questions indicate a potential area of concern that
`should be carefully evaluated as described in this guidance.
`Y/N Is the proposed name obviously similar in spelling and pronunciation to other
`names?
`Proprietary names should not be similar in spelling or pronunciation to proprietary
`names, established names, or ingredients of other products.
`Y/N Are there inert or inactive ingredients referenced in the proprietary name?
`Proprietary names should not incorporate any reference to an inert or inactive
`ingredient in a way that might create an impression that the ingredient’s value is
`greater than its true functional role in the formulation (21 CFR 201.10(c)(4)).
`Y/N Does the proprietary name include combinations of active ingredients?
`Proprietary names of fixed combination drug products should not include or
`suggest the name of one or more, but not all, of its active ingredients (see 21 CFR
`201.6(b)).
`Y/N Is there a United States Adopted Name (USAN) stem in the proprietary name?
`Proprietary names should not incorporate a USAN stem in the position that USAN
`designates for the stem.
`Y/N Is this proprietary name used for another product that does not share at least
`one common active ingredient?
`Drug products that do not contain at least one common active ingredient should not
`use the same (root) proprietary name.
`Y/N Is this a proprietary name of a discontinued product?
`Proprietary names should not use the proprietary name of a discontinued product if
`that discontinued drug product does not contain the same active ingredients.
`
`b. 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%.
`• Low similarity: combined match percentage score ≤54%.
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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.
`(cid:3) 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 o. 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.
`(cid:3) 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.
`
`o 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: 4742630Reference ID: 4772718
`
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`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 propriet