CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`203496Orig1s000
`
`PROPRIETARY NAME REVIEW(S)
`
`
`
`
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`Office of Medication Error Prevention and Risk Management
`
`Date:
`
`Reviewer:
`
`Team Leader:
`
`Drug Name and Strength:
`
`Application Type/Number:
`Applicant:
`OSE RCM #:
`
`Proprietary Name Review
`
`November 27, 2013
`
`Loretta Holmes, BSN, PharmD
`Division of Medication Error Prevention and Analysis
`Irene Z. Chan, PharmD, BCPS
`Division of Medication Error Prevention and Analysis
`Orenitram (Treprostinil) Extended-release Tablets
`0.125 mg, 0.25 mg, 1 mg, and 2.5 mg
`NDA 203496
`United Therapeutics Corporation
`2013-2111
`
`*** This document contains proprietary and confidential information that should
`not be released to the public.***
`
`Reference ID: 3414629
`
`

`

`CONTENTS
`
`1
`
`INTRODUCTION....................................................................................................... 3
`1.1
`Background .......................................................................................................... 3
`1.2
`Product Information ............................................................................................. 3
`2 RESULTS.................................................................................................................... 4
`2.1
`Promotional Assessment ...................................................................................... 4
`2.2
`Safety Assessment................................................................................................ 4
`3 CONCLUSIONS ......................................................................................................... 6
`3.1
`Comments to the Applicant.................................................................................. 7
`4 REFERENCES ............................................................................................................ 8
`APPENDICES .................................................................................................................. 11
`
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`1
`
`INTRODUCTION
`
`This review evaluates the proposed proprietary name, Orenitram, from a safety and
`promotional perspective. The sources and methods used to evaluate the proposed name
`are outlined in the reference section and Appendix A, respectively.
`
`The Division of Medication Error Prevention and Analysis previously reviewed the
`proposed names
`M4) (OSE Review 20912-533, dated May 17, 2012) and
`mo
`(OSE Review 2012-1321, dated September 4, 2012) for this NDA and found both names
`unacceptable.
`
`1.1
`
`BACKGROUND
`
`United Therapeutics is the Applicant for the following products:
`
`0 Remodulin (Treprostinil) hijection (NDA 021272), approved on May 21, 2002
`
`o Tyvaso (Treprostinil) Solution for Inhalation (NDA 022387), approved on July
`30, 2009
`
`Orenitram (Treprostinil) Extended-release Tablet is the third dosage form for Treprostinil
`introduced by United Therapeutics for the indication of treatment of Puhnonary Arterial
`Hypertension G’AH) World Health Organization WHO) group 1. Remodulin and
`Tyvaso are considered dual proprietary names since they contain the same active
`ingredient marketed by the same manufacturer. If granted, Orenitram would be the third
`proprietary name for the same active ingredient (Treprostinil), for the same indication
`(PAH), by the same Applicant (United Therapeutics). DMEPA previously evaluated the
`appropriateness of a third proprietary name. We determined that a third proprietary
`name is acceptable.
`
`1.2
`
`PRODUCT INFORMATION
`
`The following was provided in the November 27, 2013 submission of product
`characteristics information. If approved, this will be the first oral formulation of
`Treprostinil.
`
`Table l. Orenitram Product Characteristics
`
`Acuvemreaiem
`
`
`
`Indication of Use
`
`Treatment of pulmonary hypertension (WHO Group 1) to
`imrove exercise ca aci
`.
`RouteorAammsn-auon _
`Extended-release Tablets
`M01251]: 0.25m 1m and2_.5m
`
`Dose and Frequency
`
`Take Orenitram with food. Swallow Orenitram intact; use only
`intact tablets.
`
`The recommended starting dose of Orenitram is 0.25 mg twice
`dail
`(BID) with food. taken a roximatel 12 hours a art.
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`Increase the dose as tolerated to achieve optimal clinical
`response. The recommended increment is 0.25 or 0.5 mg BID
`every 3 to 4 days. If 0.25 mg BID dose increments are not
`tolerated consider titrating slower. The total daily dose can be
`divided and given three times daily with food (TID;
`approximately 8 hours apart), titrating by increments of
`0.125 mg TID.
`The mean dose in a controlled clinical trial at 12 weeks was
`3.4 mg BID. Maximum doses studied were 12 mg BID in the
`12-week blinded study and up to 21 mg BID in an open-label
`long-term study.
`Hepatic impairment:
`In patients with mild hepatic
`impairment (Child Pugh Class A) start at 0.125 mg BID with
`0.125 mg BID dose increments every 3 to 4 days. Avoid use
`of Orenitram in patients with moderate hepatic impairment
`(Child Pugh Class B). Orenitram is contraindicated in patients
`with severe hepatic impairment (Child Pugh Class C).
`Concomitant administration with CYP2C8 inhibitors:
`When co-administered with strong CYP2C8 inhibitors the
`initial dose is 0.125 mg BID with 0.125 mg BID dose
`increments every 3 to 4 days.
`100-count bottles with
`Store at 25°C (77°F); excursions 15°C to 30°C (59°F to 86°F)
`[See USP controlled room temperature].
`
`How Supplied
`Storage
`
`Container and Closure
`System
`
`HDPE bottles with
`
`2 RESULTS
`The following sections provide information obtained and considered in the overall
`evaluation of the proposed proprietary name.
`
`PROMOTIONAL ASSESSMENT
`2.1
`The Office of Prescription Drug Promotion (OPDP) determined the proposed name is
`acceptable from a promotional perspective. The Division of Medication Error Prevention
`and Analysis (DMEPA) and the Division of Cardiovascular and Renal Products (DCRP)
`concurred with the findings of OPDP’s promotional assessment of the proposed name.
`
`SAFETY ASSESSMENT
`2.2
`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 proposed proprietary Orenitram.1
`
`1 USAN stem list searched October 11, 2013.
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`(b) (4)
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`(b) (4)
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`2.2.2 Components of the Proposed Proprietary Name
`The Applicant did not provide the derivation or intended meaning of the name,
`Orenitram, in their submission. Orenitram is an extended-release formulation comprised
`of one active ingredient, Treprostinil. The Applicant does not include a modifier with the
`name (e.g., ER, XR, XL) to convey that Orenitram is an extended-release dosage form.
`In OSE Review 2012-1321, dated September 4, 2012, DMEPA evaluated the necessity of
`having a modifier in the name of this product to convey its extended-release dosage form.
`We determined a modifier was unnecessary..
`
`2.2.3 FDA Name Simulation Studies
`Seventy-eight practitioners participated in DMEPA’s prescription studies. The
`interpretations did not overlap with currently marketed products nor did they appear or
`sound similar to any currently marketed products or products pending in the pipeline.
`The written prescription studies indicate the letters “O” and “m” and can be
`misinterpreted as the letters “A” and “n”, respectively. The verbal prescription study
`indicates that “i” can be misheard as “a”. We have considered these variations in our
`look-alike and sound-alike searches and analysis (see Appendix B). Appendix C contains
`the results of the verbal and written prescription studies.
`
`2.2.4 Comments from Other Review Disciplines
`In response to the OSE, September 25, 2013 e-mail, the Division of Cardiovascular and
`Renal Products (DCRP) did not forward any comments or concerns relating to the
`proposed name at the initial phase of the proprietary name review.
`
`2.2.5 Failure Mode and Effects Analysis of Similar Names
`The potential letter and letter string variations listed in Appendix B were used to search
`for names with possible orthographic and phonetic similarity to the proposed proprietary
`name, Orenitram (Table 1).
`Our analysis of the 28 names contained in Table 1 considered the information obtained in
`the previous sections along with their product characteristics. We determined all
`28 names will not pose a risk for confusion as described in Appendices D through E.
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`Table 1: Collective List of Potentially Similar Names from the Expert Panel Discussion
`(EPD) and Primary Safety Evaluator
`
`Quintabs
`
`Oratanem
`
`EPD
`
`EPD
`
`Orathccin***
`
`EPD
`
`Asena . 1ne
`
`Acitretin
`
`Oxacillin
`
`Orencia
`
`EPD
`
`Urealac
`
`EPD
`
`EPD
`
`EPD
`
`EPD
`
`
`
`Questran
`
`Quinidine
`
`EPD
`
`Orvatcn
`
`EPD
`
`Dronedarone
`EPD
`Oxsoralen
`___
`___
`
`Quenalin
`
`Cannustine
`
`Granisetron
`
`Safety
`Evaluator
`
`Evaluator
`
`2.2.6 Communication ofDMEPA ’s Analysis at Midpoint ofReview
`
`DMEPA communicated our findings to the Division of Cardiovascular and Renal
`Products (DCRP) via e-mail on November 5, 2012. At that time we also requested
`additional information or concerns that could inform our review. Per e-mail
`
`correspondence from the Division of Cardiovascular and Renal Products on November 5,
`2013, they stated no additional concerns with the proposed proprietary name, Orenitram.
`
`3 CONCLUSIONS
`
`The proposed proprietary name is acceptable from both a promotional and safety
`perspective.
`
`If you have further questions or need clarifications, please contact Cherye Milburn,
`OSE Project Manager, at 301-796-2084.
`
`:33
`
`This document contains proprietary and confidential information that should not be released to the
`public . * * *
`
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`3.1 COMMENTS TO THE APPLICANT
`We have completed our review of the proposed proprietary name, Orenitram, and have
`concluded that this name is acceptable.
`If any of the proposed product characteristics as stated in your November 27, 2013
`submission are altered, the name must be resubmitted for review.
`
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`4 REFERENCES
`
`1. Micromedex Integrated Index (http://csi.micromedex.com)
`Micromedex contains a variety of databases covering pharmacology, therapeutics,
`toxicology and diagnostics.
`
`2. Phonetic and Orthographic Computer Analysis (POCA)
`POCA is a database which was created for the Division of Medication Error
`Prevention and Analysis, FDA. As part of the name similarity assessment, proposed
`names are evaluated via a phonetic/orthographic algorithm. The proposed proprietary
`name is converted into its phonemic representation before it runs through the phonetic
`algorithm. Likewise, an orthographic algorithm exists which operates in a similar
`fashion.
`
`3. Drug Facts and Comparisons, online version, St. Louis, MO
`(http://factsandcomparisons.com)
`Drug Facts and Comparisons is a compendium organized by therapeutic course; it
`contains monographs on prescription and OTC drugs, with charts comparing similar
`products. This database also lists the orphan drugs.
`
`4. FDA Document Archiving, Reporting & Regulatory Tracking System [DARRTS]
`DARRTS is a government database used to organize Applicant and Sponsor
`submissions as well as to store and organize assignments, reviews, and
`communications from the review divisions.
`
`5. 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.
`
`6. Drugs@FDA (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm)
`Drugs@FDA contains most of the drug products approved 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, generic drugs, therapeutic biological
`products, prescription and over-the-counter human drugs and discontinued drugs and
`“Chemical Type 6” approvals.
`7. U.S. Patent and Trademark Office (http://www.uspto.gov)
`USPTO provides information regarding patent and trademarks.
`
`8. Clinical Pharmacology Online (www.clinicalpharmacology-ip.com)
`Clinical Pharmacology contains full monographs for the most common drugs in
`clinical use, plus mini monographs covering investigational, less common,
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`combination, nutraceutical and nutritional products. It also provides a keyword search
`engine.
`
`9. Natural Medicines Comprehensive Databases (www.naturaldatabase.com)
`Natural Medicines contains up-to-date clinical data on the natural medicines, herbal
`medicines, and dietary supplements used in the western world.
`
`10. Access Medicine (www.accessmedicine.com)
`Access Medicine® from McGraw-Hill contains full-text information from
`approximately 60 titles; it includes tables and references. Among the titles are:
`Harrison’s Principles of Internal Medicine, Basic & Clinical Pharmacology, and
`Goodman and Gilman’s The Pharmacologic Basis of Therapeutics.
`
`11. USAN Stems (http://www.ama-assn.org/ama/pub/about-ama/our-people/coalitions-
`consortiums/united-states-adopted-names-council/naming-guidelines/approved-
`stems.shtml)
`USAN Stems List contains all the recognized USAN stems.
`
`12. Red Book (www.thomsonhc.com/home/dispatch)
`Red Book contains prices and product information for prescription, over-the-counter
`drugs, medical devices, and accessories.
`
`13. Lexi-Comp (www.lexi.com)
`Lexi-Comp is a web-based searchable version of the Drug Information Handbook.
`
`14. Medical Abbreviations (www.medilexicon.com)
`Medical Abbreviations dictionary contains commonly used medical abbreviations and
`their definitions.
`
`15. CVS/Pharmacy (www.CVS.com)
`This database contains commonly used over the counter products not usually
`identified in other databases.
`
`16. Walgreens (www.walgreens.com)
`This database contains commonly used over the counter products not usually
`identified in other databases.
`
`17. Rx List (www.rxlist.com)
`RxList is an online medical resource dedicated to offering detailed and current
`pharmaceutical information on brand and generic drugs.
`
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`18. Dogpile (www.dogpile.com)
`Dogpile is a Metasearch engine that searches multiple search engines including
`Google, Yahoo! and Bing, and returns the most relevant results to the search.
`
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`APPENDICES
`Appendix A
`FDA’s Proprietary Name Risk Assessment considers the promotional and safety aspects
`of a proposed proprietary name. The promotional review of the proposed name is
`conducted by OPDP. OPDP evaluates proposed proprietary names to determine if they
`are overly fanciful, so as to misleadingly imply unique effectiveness or composition, as
`well as to assess whether they contribute to overstatement of product efficacy,
`minimization of risk, broadening of product indications, or making of unsubstantiated
`superiority claims. OPDP provides their opinion to DMEPA for consideration in the
`overall acceptability of the proposed proprietary name.
`The safety assessment is conducted by DMEPA. DMEPA staff search a standard set of
`databases and information sources to identify names that are similar in pronunciation,
`spelling, and orthographically similar when scripted to the proposed proprietary name.
`Additionally, 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.).
`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. 2
`Following the preliminary screening of the proposed proprietary name, DMEPA gathers
`to discuss their professional opinions on the safety of the proposed proprietary name.
`This meeting is commonly referred to the Center for Drug Evaluation and Research
`(CDER) Expert Panel discussion. DMEPA also considers other aspects of the name that
`may be misleading from a safety perspective. DMEPA staff conducts a prescription
`simulation studies using FDA health care professionals. 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. DMEPA bases the overall risk assessment
`on the findings of a Failure Mode and Effects Analysis (FMEA) of the proprietary name
`and misleading nature of the proposed proprietary name with a focus on the avoidance of
`medication errors.
`DMEPA uses the clinical expertise of its staff to anticipate the conditions of the clinical
`setting where the product is likely to be used based on the characteristics of the proposed
`product. DMEPA considers the product characteristics associated with the proposed
`product throughout the risk assessment because the product characteristics of the
`proposed may provide a context for communication of the drug name and ultimately
`determine the use of the product in the usual clinical practice setting.
`
`2 National Coordinating Council for Medication Error Reporting and Prevention.
`http://www nccmerp.org/aboutMedErrors html. Last accessed 10/11/2007.
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`Typical product characteristics considered when identifying drug names that could
`potentially be confused with the proposed proprietary name include, but are not limited
`to; established name of the proposed product, proposed indication of use, dosage form,
`route of administration, strength, unit of measure, dosage units, recommended dose,
`typical quantity or volume, frequency of administration, product packaging, storage
`conditions, patient population, and prescriber population. DMEPA considers how these
`product characteristics may or may not be present in communicating a product name
`throughout the medication use system. Because drug name confusion can occur at any
`point in the medication use process, DMEPA considers the potential for confusion
`throughout the entire U.S. medication use process, including drug procurement,
`prescribing and ordering, dispensing, administration, and monitoring the impact of the
`medication.3
`The DMEPA considers the spelling of the name, pronunciation of the name when spoken, and
`appearance of the name when scripted. DMEPA compares the proposed proprietary name
`with the proprietary and established name of existing and proposed drug products and names
`currently under review at the FDA. DMEPA compares the pronunciation of the proposed
`proprietary name with the pronunciation of other drug names because verbal communication
`of medication names is common in clinical settings. DMEPA examines the phonetic
`similarity using patterns of speech. If provided, DMEPA will consider the Sponsor’s intended
`pronunciation of the proprietary name. However, DMEPA also considers a variety of
`pronunciations that could occur in the English language because the Sponsor has little control
`over how the name will be spoken in clinical practice. The orthographic appearance of the
`proposed name is evaluated using a number of different handwriting samples. DMEPA
`applies expertise gained from root-cause analysis of postmarketing medication errors to
`identify sources of ambiguity within the name that could be introduced when scripting
`(e.g.,“T” may look like “F,” lower case ‘a’ looks like a lower case ‘u,’ etc). Additionally,
`other orthographic attributes that determine the overall appearance of the drug name when
`scripted (see Table 1 below for details).
`
`
`3 Institute of Medicine. Preventing Medication Errors. The National Academies Press: Washington DC.
`2006.
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`Table 1. Criteria Used to Identify Drug Names that Look- or Sound-Similar to a
`Proposed Proprietary Name.
`
`Considerations when Searching the Databases
`
`Attributes Examined to Identify
`Similar Drug Names
`
`Potential Effects
`
`Identical prefix
`Identical infix
`Identical suffix
`Length of the name
`Overlapping product
`characteristics
`
` Names may appear similar
`in print or electronic media
`and lead to drug name
`confusion in printed or
`electronic communication
` Names may look similar
`when scripted and lead to
`drug name confusion in
`written communication
` Names may look similar
`when scripted, and lead to
`drug name confusion in
`written communication
`
` Names may sound similar
`when pronounced and lead
`to drug name confusion in
`verbal communication
`
`Type of
`Similarity
`
`Potential
`Causes of Drug
`Name
`Similarity
`
`Similar spelling
`
`Look-
`alike
`
`Orthographic
`similarity
`
`Sound-
`alike
`
`Phonetic
`similarity
`
`Similar spelling
`Length of the name/Similar
`shape
`Upstrokes
`Down strokes
`Cross-strokes
`Dotted letters
`Ambiguity introduced by
`scripting letters
`Overlapping product
`characteristics
`Identical prefix
`Identical infix
`Identical suffix
`Number of syllables
`Stresses
`Placement of vowel sounds
`Placement of consonant sounds
`Overlapping product
`characteristics
`Lastly, DMEPA considers the potential for the proposed proprietary name to
`inadvertently function as a source of error for reasons other than name confusion. Post-
`marketing experience has demonstrated that proprietary names (or components of the
`proprietary name) can be a source of error in a variety of ways. Consequently, DMEPA
`considers and evaluates these broader safety implications of the name throughout this
`assessment and the medication error staff provides additional comments related to the
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`safety of the proposed proprietary name or product based on professional experience with
`medication errors.
`
`1. Database and Information Sources
`DMEPA searches the internet, several standard published drug product reference texts,
`and FDA databases to identify existing and proposed drug names that may sound-alike or
`look-alike to the proposed proprietary name. A standard description of the databases
`used in the searches is provided in the reference section of this review. To complement
`the process, the DMEPA uses a computerized method of identifying phonetic and
`orthographic similarity between medication names. The program, Phonetic and
`Orthographic Computer Analysis (POCA), uses complex algorithms to select a list of
`names from a database that have some similarity (phonetic, orthographic, or both) to the
`trademark being evaluated. Lastly, DMEPA reviews the USAN stem list to determine if
`any USAN stems are present within the proprietary name. The individual findings of
`multiple safety evaluators are pooled and presented to the CDER Expert Panel. DMEPA
`also evaluates if there are characteristics included in the composition that may render the
`name unacceptable from a safety perspective (abbreviation, dosing interval, etc.).
`
`2. Expert Panel Discussion
`DMEPA gathers gather CDER professional opinions on the safety of the proposed
`product and discussed the proposed proprietary name (Expert Panel Discussion). The
`Expert Panel is composed of Division of Medication Errors Prevention (DMEPA) staff
`and representatives from the Office of Prescription Drug Promotion (OPDP). We also
`consider input from other review disciplines (OND, ONDQA/OBP). The Expert Panel
`also discusses potential concerns regarding drug marketing and promotion related to the
`proposed names.
`The primary Safety Evaluator presents the pooled results of the database and information
`searches to the Expert Panel for consideration. Based on the clinical and professional
`experiences of the Expert Panel members, the Panel may recommend additional names,
`additional searches by the primary Safety Evaluator to supplement the pooled results, or
`general advice to consider when reviewing the proposed proprietary name.
`
`3. FDA Prescription Simulation Studies
`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
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`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.
`
`4. 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.
`
`5. Safety Evaluator Risk Assessment of the Proposed Proprietary Name
`The primary Safety Evaluator applies his/her individual expertise gained from evaluating
`medication errors reported to FDA, considers all aspects of the name that may be
`misleading or confusing, conducts a Failure Mode and Effects Analysis, and provides an
`overall decision on acceptability dependent on their risk assessment of name confusion.
`Failure Mode and Effects Analysis (FMEA) is a systematic tool for evaluating a process
`and identifying where and how it might fail.4 When applying FMEA to assess the risk of
`a proposed proprietary name, DMEPA seeks to evaluate the potential for a proposed
`proprietary name to be confused with another drug name because of name confusion and,
`thereby, cause errors to occur in the medication use system. FMEA capitalizes on the
`predictable and preventable nature of medication errors associated with drug name
`confusion. FMEA allows the Agency to identify the potential for medication errors due
`to orthographically or phonetically similar drug names prior to approval, where actions to
`overcome these issues are easier and more effective than remedies available in the post-
`approval phase.
`In order to perform an FMEA of the proposed name, the primary Safety Evaluator must
`analyze the use of the product at all points in the medication use system. Because the
`proposed product is has not been marketed, the primary Safety Evaluator anticipates the
`use of the product in the usual practice settings by considering the clinical and product
`
`
`4 Institute for Healthcare Improvement (IHI). Failure Mode and Effects Analysis. Boston. IHI:2004.
`
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`

`characteristics listed in Section 1.2 of this review. The Safety Evaluator then analyzes
`the proposed proprietary name in the context of the usual practice setting and works to
`identify potential failure modes and the effects associated with the failure modes.
`In the initial stage of the Risk Assessment, the Safety Evaluator compares the proposed
`proprietary name to all of the names gathered from the above searches, Expert Panel
`Discussion, and prescription studies, external studies, and identifies potential failure
`modes by asking:
`“Is the proposed proprietary name convincingly similar to another drug name,
`which may cause practitioners to become confused at any point in the usual
`practice setting? And are there any components of the name that may function
`as a source of error beyond sound/look-alike?”
`An affirmative answer indicates a failure mode and represents a potential for the
`proposed proprietary name to be confused with another proprietary or established drug
`name because of look- or sound-alike similarity or because of some other component of
`the name. If the answer to the question is no, the Safety Evaluator is not convinced that
`the names possess similarity that would cause confusion at any point in the medication
`use system, thus the name is eliminated from further review.
`In the second stage of the Risk Assessment, the primary Safety Evaluator evaluates all
`potential failure modes to determine the likely effect of the drug name confusion, by
`asking:
`“Could the confusion of the drug names conceivably result in medication errors
`in the usual practice setting?”
`The answer to this question is a central component of the Safety Evaluator’s overall risk
`assessment of the proprietary name. If the Safety Evaluator determines through FMEA
`that the name similarity would not ultimately be a source of medication errors in the
`usual practice setting, the primary Safety Evaluator eliminates the name from further
`analysis. However, if the Safety Evaluator determines through FMEA that the name
`similarity could ultimately cause medication errors in the usual practice setting, the
`Safety Evaluator will then recommend the use of an alternate proprietary name.
`Moreover, DMEPA will object to the use of proposed proprietary name when the primary
`Safety Evaluator identifies one or more of the following conditions in the Overall Risk
`Assessment:
`a. OPDP finds the proposed proprietary name misleading from a promotional
`perspective, and the Review Division concurs with OPDP’s findings. The Federal
`Food, Drug, and Cosmetic Act provides that labeling or advertising can misbrand a
`product if misleading representations are made or suggested by statement, word,
`design, device, or any combination thereof, whether through a PROPRIETARY
`name or otherwise [21 U.S.C 321(n); See also 21 U.S.C. 352(a) & (n)].
`b. DMEPA identifies that the proposed proprietary name is misleading because of
`similarity in spelling or pronunciation to another proprietary or established name of a
`different drug or ingredient [CFR 201.10.(C)(5)].
`
`Reference ID: 3414629
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`c. FMEA identifies the potential for confusion between the proposed proprietary name
`and other proprietary or established drug name(s), and demonstrates that medication
`errors are likely to result from the drug name confusion under the conditions of usual
`clinical practice.
`d. The proposed proprietary name contains an USAN (United States Adopted Names)
`stem.
`e. DMEPA identifies a potential source of medication error within the proposed
`proprietary name. For example, the proprietary name may be misleading or,
`inadvertently, introduce ambiguity and confusion that leads to err