CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`214187Orig1s000
`
`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 2, 2021
`Application Type and Number: NDA 214187
`Product Name and Strength:
`Epclusa (sofosbuvir and velpatasvir) oral pellets,
`200 mg/50 mg and 150 mg/37.5 mg
`Multiple Ingredient Product
`Prescription (Rx)
`Gilead Sciences
`2020-44675936
`Melina Fanari, RPh
`Sevan Kolejian, PharmD, MBA, BCPPS
`
`Product Type:
`Rx or OTC:
`Applicant/Sponsor Name:
`Panorama #:
`DMEPA Safety Evaluator:
`DMEPA Team Leader:
`
`Reference ID: 4755232
`
`

`

`1
`
`Contents
`INTRODUCTION....................................................................................................................1
`1.1
`Regulatory History............................................................................................................1
`1.2
`Product Information ..........................................................................................................1
`2 RESULTS.................................................................................................................................1
`2.1 Misbranding Assessment ..................................................................................................2
`2.2
`Safety Assessment.............................................................................................................2
`3 CONCLUSION ........................................................................................................................4
`3.1
`Comments to the Applicant/Sponsor ................................................................................4
`4 REFERENCES.........................................................................................................................4
`APPENDICES .................................................................................................................................6
`
`
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`Reference ID: 4755232
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`

`

`INTRODUCTION
`1
`This review evaluates the proposed proprietary name, Epclusa, 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. Gilead submited an external
`name study for this proposed proprietary name that was previously reviewed by DMEPA.
`
`REGULATORY HISTORY
`1.1
`Epclusa (sofosbuvir and velpatasvir) tablet was approved on June 28, 2016 under NDA 208341
`for the treatment of adult patients with chronic hepatitis C virus infection.
`Gilead is pursuing a oral pellet formulation in patients 3 years and older, therefore submitted the
`name, Epclusa, for review under NDA 214187 on December 15, 2020.
`
`PRODUCT INFORMATION
`1.2
`The following product information is provided in the proprietary name submission received on
`December 15, 2020.
`Table 1. Relevant product information for Epclusa Pellets and Epclusa tableta
`Epclusa Pellets
`Epclusa tablet
`
`Initial Approval
`Date
`
`Intended
`Pronunciation
`
`Active
`Ingredient
`
`Indication
`
`Route of
`Administration
`
`Dosage Form
`Strength
`
`N/A
`
`June 28, 2016
`
`Ep-KLOO-suh
`
`sofosbuvir and velpatasvir
`
`EPCLUSA is indicated for the treatment of
`adults and pediatric patients 3 years of age and
`older with chronic hepatitis C virus (HCV)
`genotype 1, 2, 3, 4, 5, or 6 infection.
`
`EPCLUSA is indicated for the treatment of
`adults and pediatric patients 6 years of age
`and older or weighing at least 17 kg with
`chronic hepatitis C virus (HCV) genotype 1,
`2, 3, 4, 5, or 6 infection.
`
`Oral
`
`Oral pellets
`
`Oral tablets
`
`150 mg/37.5 mg and 200 mg/50 mg
`
`200 mg/50 mg and 400 mg/100 mg
`
`a Epclusa Product information obtained at https://dailymed nlm nih.gov/dailymed/drugInfo.cfm?setid=7f30631a-
`ee3b-4cfe-866b-964df3f0a44f Accessed February 18, 2021.
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`Dose and
`Frequency
`
`Recommended Dosage in Pediatric Patients
`3 Years and Older
`
`Recommended Dosage in Adult and
`Pediatric Patients 6 Years and Older or
`Weighing at Least 17 kg
`
`Less than 17 kg- One 150 mg/37.5 mg packet
`of pellets once daily
`
`17 kg to less than 30 kg- One 200 mg/50
`mg tablet once daily
`
`17 kg to less than 30 kg- One 200 mg/50 mg
`tablet or one 200 mg/50 mg packet of pellets
`once daily.
`
`30 kg and up- One 400 mg/100 mg tablet
`(or two 200 mg/50 mg tablets) once daily
`
`At least 30 kg- One 400 mg/100 mg tablet (or
`two 200 mg/50 mg tablets or two 200 mg/50
`mg packets of pellets) once daily
`
`(How Supplied
`
`Cartons of 28 packets
`
`Bottles of 28 tablets
`
`Storage
`
`Store below 30℃ (86℉)
`
`2 RESULTS
`The following sections provide information obtained and considered in the overall evaluation of
`the proposed proprietary name, Epclusa.
`
`2.1 MISBRANDING ASSESSMENT
`The Office of Prescription Drug Promotion (OPDP) determined that Epclusa would not misbrand
`the proposed product. The Division of Medication Error Prevention and Analysis (DMEPA) and
`the Division of Antivirals (DAV) concurred with the findings of OPDP’s assessment for Epclusa.
`
`2.2 SAFETY ASSESSMENT
`The following aspects were considered in the safety evaluation of the proposed proprietary name,
`Epclusa.
`
`2.2.1 United States Adopted Names (USAN) Search
`There is no USAN stem present in the proposed proprietary name1F
`
`b.
`
`2.2.2 Components of the Proposed Proprietary Name
`Gilead did not provide a derivation or intended meaning for the proposed proprietary name,
`Epclusa, in their submission. This proprietary name is comprised of a single word that does not
`
`b USAN stem search conducted on November 30, 2020.
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`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, Janaury 25, 2021 e-mail, the Division of Antivirals (DAV) did not
`forward any comments or concerns relating to Epclusa at the initial phase of the review.
`
`2.2.4 Medication Error Data Selection of Cases
`On February 18, 2021, we searched the FDA Adverse Event Reporting System (FAERS)
`database using the strategy listed in Table 2 for name confusion errors involving Epclusa that
`would be relevant for this review.
`
`Table 2. FAERS Search Strategy
`FAERS Field
`Initial FDA Receive Dates
`Product Name
`Verbatim Name(s)
`Product Active Ingredient
`
`Epclusa
`July 1, 2016 – February 18, 2021
`Epclusa
`n/a
`Sofosbuvir/Velpatasvir
`
`n/a
`Medication errors(narrow)
`
`Drug Role
`Event
`USA
`Country (derived)
`Each report was reviewed for relevancy and duplication. Duplicates were merged into a single
`case. The NCC MERP Taxonomy of Medication Errors was used to code the case outcome and
`error root causes when provided by the reporter.
`After individual review, no relevent reports related to name confusion with Epclusa were
`retrieved.
`
`2.2.5 Safety Assessment of the Proposed Name, Epclusa
`The Applicant proposes a new dosage form, oral pellets (150 mg sofosbuvir and 37.5 mg of
`velpatasvir or 200 mg sofosbuvir and 50 mg of velpatasvir per packet), as a product line
`extension. The proposed formulation shares the same active ingredients as the approved Epclusa
`tablet product (200 mg sofosbuvir and 50 mg of velpatasvir or 400 mg sofosbuvir and 100 mg of
`velpatasvir per tablet) and an overlapping strength (200 mg/50 mg), but differ in the fact that the
`oral pellet formulation is not available in a 400 mg/100 mg strength but is available in a lower
`strength (150 mg/37.5 mg) (see Table 1 for more information). In addition, feedback from the
`clinical pharmacology team has determined that the oral pellets and tablet dosage forms are
`equivalent on a milligram-per-milligram basis. We considered whether these products sharing
`the same proprietary name, Epclusa, may lead to medication errors. However, since the dosage
`forms are equivalent, we determined that label and labeling mitigations may adequately address
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`any residual risk of product confusion. In this specific case, we have determined that the
`different dosage forms and strengths can be managed under a single proprietary name. Therefore,
`we do not have concerns with the use of Epclusa as the proprietary name for the proposed oral
`pellet formulation.
`
`2.2.6 Communication of DMEPA’s Analysis at Midpoint of Review
`DMEPA communicated our findings to the Division of Antivirals (DAV) via e-mail on February
`24, 2021. At that time, we also requested additional information or concerns that could inform
`our review. Per e-mail correspondence from the Division of Antivirals (DAV) on March 1,
`2021, they stated no additional concerns with the proposed proprietary name, Epclusa.
`
`3 CONCLUSION
`The proposed proprietary name, Epclusa, is acceptable.
`If you have any questions or need clarifications, please contact Mammah Borbor, OSE project
`manager, at 301-796-7731.
`
`COMMENTS TO GILEAD SCIENCES
`3.1
`We have completed our review of the proposed proprietary name, Epclusa, and have concluded
`that this name is acceptable.
`If any of the proposed product characteristics as stated in your submission, received on
`December 15, 2020, are altered prior to approval of the marketing application, the name must be
`resubmitted for review.
`
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`4
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`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.
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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
`c
`
`c 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.
` 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 F
`d. 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.
`
`d 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: 4755232
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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 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%).
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`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?
`Y/N 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?
`
`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.
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`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: 4755232
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`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`MELINA N FANARI
`03/02/2021 07:22:59 AM
`
`SEVAN H KOLEJIAN
`03/02/2021 07:22:59 AM
`
`Reference ID: 4755232
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`(
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