CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
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`APPLICATION NUMBER:
`0201280Orig1s000
`
`PROPRIETARY NAME REVIEW(S)
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`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`
`
`
`Date:
`
`Through:
`
`From:
`
`Subject:
`
`May 12, 2011
`
`Carol Holquist, RPh, Division Director
`Division of Medication Error Prevention and Analysis
`(DMEPA)
`
`Denise V. Baugh, PharmD, BCPS, Safety Evaluator
`Division of Medication Error Prevention and Analysis
`
`Proprietary Name Review
`
`Xarelto (Rivaroxaban) Tablets
`10 mg
`NDA 022406 (Division of Hematology Products)
`
`Xarelto (Rivaroxaban) Tablets
` 20 mg
`NDA 202439 (Division of Cardio-Renal Products)
`
`Johnson & Johnson Pharmaceutical Research &
`Development, LLC on behalf of Ortho-McNeil-Janssen-
`Pharmaceuticals, Inc.
`
`2011-512
`2011-437
`
`*** Note: This review contains proprietary and confidential information that should not be
`released to the public.**
`
`
`
`Drug Name and
`Strengths, Application
`Types/Numbers:
`
`Applicant:
`
`OSE RCM #:
`
`Reference ID: 2946218
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`(b) (4)
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`CONTENTS
`
`EXECUTIVE SUMMARY............................................................................................................. 1
`1 BACKGROUND..................................................................................................................... 1
`1.1
`Introduction.................................................................................................................... 1
`1.2
`Regulatory History......................................................................................................... 1
`1.3
`Product Information ....................................................................................................... 1
`2 METHODS AND MATERIALS ............................................................................................ 2
`2.1
`Search Criteria................................................................................................................ 2
`2.2
`FDA Prescription Analysis Studies................................................................................ 3
`3 RESULTS................................................................................................................................ 4
`3.1
`Data base and information sources ................................................................................ 4
`3.2
`CDER Expert panel discussion ...................................................................................... 4
`3.3
`FDA Prescription analysis studies ................................................................................. 4
`3.4
`Comments from the Division of Hematology Products (DHP) ..................................... 4
`3.5
`Comments from the Division of Cardiovascular and Renal Products ........................... 5
`3.6
`Safety evaluator risk assessment.................................................................................... 5
`4 DISCUSSION ......................................................................................................................... 5
`4.1
`Promotional Assessment................................................................................................ 5
`4.2
`Safety Assessment.......................................................................................................... 5
`5 CONCLUSIONS AND RECOMMENDATIONS.................................................................. 6
`6
`Prior OSE Review ................................................................................................................... 7
`7 REFERENCES........................................................................................................................ 7
`APPENDICES................................................................................................................................. 9
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`EXECUTIVE SUMMARY
`This review summarizes DMEPA’s evaluation of the proposed proprietary name, Xarelto for
`Rivaroxaban Tablets. Our evaluation did not identify concerns that would render the name
`unacceptable based on the product characteristics and safety profile known at the time of this
`review. Thus, DMEPA finds the proposed proprietary name, Xarelto, acceptable for this product.
`DMEPA will notify the Applicant of these findings via letter
`
`1 BACKGROUND
`
`1.1
`INTRODUCTION
`This review responds to a request received from Johnson & Johnson Pharmaceutical
`Research & Development, LLC on behalf of Ortho-McNeil-Janssen-Pharmaceuticals,
`Inc., submitted February 18, 2011, to evaluate the proposed proprietary name, Xarelto, regarding
`promotional concerns and potential name confusion with other proprietary or established drug
`names based on the product characteristics provided by the Applicant.
`The Applicant also submitted container labels and carton labeling which will be reviewed under
`separate cover (OSE Review #2011-438 and #2011-513).
`
`1.2 REGULATORY HISTORY
`Rivaroxaban is the established name for the proposed proprietary name, Xarelto, previously
`found acceptable by DMEPA (OSE Review # 2007-1832 dated April 30, 2009) under IND#
`64,892. At that time the dose was 10 mg taken orally once daily and the indication was for the
`prophylaxis of deep vein thrombosis and pulmonary embolism in patients undergoing hip
`replacement or knee replacement surgery. No other indication or treatment regimen was
`proposed at that time.
`
`1.3 PRODUCT INFORMATION
`Xarelto is a new molecular entity which will have two different indications and corresponding
`treatment regimens. Details are described below.
`
`1.3.1 Prophylaxis of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)
`Xarelto (Rivaroxaban Tablets) is indicated for the prophylaxis of deep vein thrombosis and
`pulmonary embolism in patients undergoing hip replacement or knee replacement surgery. The
`recommended oral dose is 10 mg taken once daily with or without food. The initial dose should
`be taken at least 6 to 10 hours after surgery once hemostasis has been established. Xarelto should
`be used with caution in patients with CrCl 15 mL/minute to less than 30 mL/minute. It is not
`recommended in patients with CrCl less than 15 mL/minute. The treatment duration is 35 days
`(hip surgery) to 14 days (knee surgery). Xarelto will be supplied in bottles of 30 and in a
` carton containing 10 blister cards of 10 tablets each.
`
`
`
`1.3.2 Prevention of Stroke and Systemic Embolism
`Xarelto (Rivaroxaban Tablets) is indicated for the prevention of stroke and systemic embolism in
`patients with non-valvular atrial fibrillation.
`
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`Reference ID: 2946218
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`2 METHODS AND MATERIALS
`Appendix A describes the general methods and materials used by the Division of Medication
`Error Prevention and Analysis (DMEPA) when conducting a proprietary name risk assessment
`for all proprietary names. Sections 2.1 and 2.2 identify specific information associated with the
`methodology for the proposed proprietary name, Xarelto.
`
`2.1 SEARCH CRITERIA
`For this review, particular consideration was given to drug names beginning with the letter ‘X’
`when searching to identify potentially similar drug names, as 75% of the confused drug names
`reported by the USP-ISMP Medication Error Reporting Program involve pairs beginning with the
`same letter.1,2
`To identify drug names that may look similar to ‘Xarelto’, the DMEPA staff also considers the
`orthographic appearance of the name on lined and unlined orders. Specific attributes taken into
`consideration include the length of the name (seven letters), upstrokes (three, upper case ‘X’,
`lower case ‘l’ and ‘t’), down-strokes (none), cross-strokes (two, upper case ‘X’ and lower case
`‘t’) and dotted letters (none). Additionally, several letters in Xarelto may be vulnerable to
`ambiguity when scripted (see Appendix B). As such, the DMEPA staff also considers these
`alternate appearances when identifying drug names that may look similar to Xarelto.
`When searching to identify potential names that may sound similar to Xarelto, the DMEPA staff
`searches for names with similar number of syllables (three), stresses (XA-rel-to, xa-REL-to, or
`za-rel-TO), and placement of vowel and consonant sounds. Additionally, the DMEPA staff
`considers that pronunciation of parts of the name can vary, such as the letter ‘x’ which may be
`interpreted as ‘z’ and the letters ‘to’ may be interpreted as ‘tow’.
`
`
`1 Institute for Safe Medication Practices. Confused Drug name List (1996-2006). Available at
`http://www.ismp.org/Tools/confuseddrugnames.pdf
`2 Kondrack, G and Dorr, B. Automatic Identification of Confusable Drug Names. Artificial Intelligence in
`Medicine (2005)
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`The Applicant’s intended pronunciation (zah-REL-toe) was also taken into consideration, as it
`was included in the Proprietary Name Review Request. However, names are often
`mispronounced and/or spoken with regional accents and dialects, so other potential
`pronunciations of the name are considered.
`
`2.2 FDA PRESCRIPTION ANALYSIS STUDIES
`In order to evaluate the potential for misinterpretation of the proposed proprietary name in
`handwriting and verbal communication of the name, the following inpatient medication order,
`outpatient and verbal prescriptions were communicated during the FDA prescription studies.
`Figure 1. Xarelto Prescription Study (conducted on April 26, 2011)
`
`HANDWRITTEN
`VERBAL PRESCRIPTION
`PRESCRIPTION and
`MEDICATION ORDER
`
`Inpatient Prescription:
`
`“Xarelto 10 mg orally daily”
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`Outpatient Prescription:
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` 3
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` RESULTS
`The following sections describe DMEPA’s findings from the database searches, CDER Expert
`Panel Discussion, and FDA prescription analysis studies.
`
`3.1 DATA BASE AND INFORMATION SOURCES
`The DMEPA safety evaluator searches yielded a total of 20 names as having some similarity to
`the proposed proprietary name Xarelto.
`Sixteen of the 20 names (Kalbitor, Kaletra, Kariva, Parafon Forte DSC, Ramelteon, Varicella,
`Verdeso, Vivella Dot, Voltaren, Xalatan,
`, Xeroflo, Xiaflex***, Xodol, Zarelix, and
`Zometa) were thought to look like Xarelto. One name (Zarontin) was thought to sound like
`Xarelto and three names Lorelco, Xarelto, and Xeloda were thought to look and sound like
`Xarelto.
`A search of the United States Adopted Name stem list on April 26, 2011, did not identify any
`United States Adopted Names (USAN) stem within the proposed name, Xarelto.
`
`3.2 CDER EXPERT PANEL DISCUSSION
`The Expert Panel reviewed the pool of names identified by DMEPA safety evaluators (See
`Section 3.1 above) and did not identify additional names which were thought to have phonetic or
`orthographic similarity to Xarelto.
`DDMAC had no concerns regarding the proposed name from a promotional perspective, and did
`not offer any additional comments relating to the proposed proprietary name.
`
`3.3 FDA PRESCRIPTION ANALYSIS STUDIES
`A total of 41 practitioners responded and none of the names overlapped with existing names.
`Twenty-five (n = 25) of the participants interpreted the name correctly as ‘Xarelto’ with correct
`interpretation occurring in the inpatient (n = 10), outpatient (n = 13), and verbal studies (n = 2).
`The remainder of the responses misinterpreted the drug name. Common misinterpretations
`included mistaking the first letter ‘X’ for the letter ‘C’, ‘S’ or ‘Z’ and the lower case ‘a’ for ‘e’,
`‘y’, ‘o’ or ‘u’. See Appendix C for the complete listing of interpretations from the verbal and
`written prescription studies.
`
`3.4 COMMENTS FROM THE DIVISION OF HEMATOLOGY PRODUCTS (DHP)
`
`3.4.1 Initial Phase of Review
`In response to the OSE March 3, 2011, e-mail, the Division of Hematology Products stated that
`they concur with DDMAC.
`
`3.4.2 Midpoint of Review
`On May 9, 2011, DMEPA notified DHP via e-mail that we find the name, Xarelto, acceptable.
`Per e-mail correspondence from DHP on May 12, 2011, they “had no objections” to Xarelto.
`
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`*** This is proprietary and confidential information that should not be released to the public.***
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`Reference ID: 2946218
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`3.5 COMMENTS FROM THE DIVISION OF CARDIOVASCULAR AND RENAL PRODUCTS
`
`3.5.1 Initial Phase of Review
`
`In response to the OSE March 3, 2011, e-mail, the Division of Cardiovascular and Renal Products
`(DCRP) stated that they had no objections to the proposed name, Xarelto.
`
`3.5.2 Midpoint of Review
`On May 9, 2011, DMEPA notified DCRP via e-mail that we find the name, Xarelto, acceptable.
`Per e-mail correspondence from DCRP on May 9, 2011, they “have no objections to Xarelto”.
`
`3.6 SAFETY EVALUATOR RISK ASSESSMENT
`The primary safety evaluator performed an independent search for names that would represent a
`potential source of drug name confusion. Additionally, although there were five names (Kaletra,
`Kariva, Xeroflo, Lorelco, and Zarontin) identified in our databases as well as in our previous
`review (OSE# 2009-637 dated April 30, 2009), we re-evaluated all the names for their potential
`for confusion as a result of the change in product characteristics for Xarelto. Furthermore, we
`considered the vulnerability to confusion that this name would pose if it were available as a single
`strength product (10 mg).
`) thought to look
`We identified four additional names (Zaditor, Xiral Zimulti***,
`similar to Xarelto and represent a potential source of drug name confusion.
`As such, a total of 32 names were further analyzed to determine if the drug names could be
`confused with Xarelto and if the drug name confusion would likely result in a medication error in
`the usual practice setting. Thirteen names were identified in our previous review, fifteen new
`names were identified in our database search, and four were identified in our independent search.
`
`4 DISCUSSION
`The proposed name, Xarelto, was evaluated from a safety and promotional perspective based on
`the product characteristics provided by the Applicant. Furthermore, we sought input from
`pertinent disciplines involved with the review of this application and considered it accordingly.
`
`4.1 PROMOTIONAL ASSESSMENT
`DDMAC had no concerns regarding the proposed name from a promotional perspective, and did
`not offer any additional comments relating to the proposed name. The Division of Hematology
`Products, the Division of Cardiovascular Renal Products, and DMEPA concurred with the
`promotional assessment.
`
`4.2 SAFETY ASSESSMENT
`DMEPA identified 19 new names for their potential similarity to the proposed name, Xeralto. No
`other aspect of the name was identified as a potential source of confusion. Upon evaluation of the
`similar names, four of the 19 were eliminated from further consideration for the following
`reasons: two names lacked sufficient orthographic and/or phonetic similarity (Appendix D), one
`name was identified in our database search and found to be the subject of this review (Appendix
`E), and one name is a foreign name (Appendix F).
`Failure mode and effects analysis (FMEA) was then applied to determine if the proposed
`proprietary name could potentially be confused with the remaining fifteen names and lead to
`medication errors. This analysis determined that the name similarity between Xeralto and the
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`identified names was unlikely to result in medication errors with all of the products identified for
`the reasons presented in Appendix G.
`
`5 CONCLUSIONS AND RECOMMENDATIONS
`The Proprietary Name Risk Assessment findings indicate that the proposed name, Xeralto, is not
`vulnerable to name confusion that could lead to medication errors, nor is it considered
`promotional. Thus, the Division of Medication Error Prevention and Analysis (DMEPA) has no
`objection to the proposed proprietary name, Xeralto, for this product at this time. DMEPA will
`notify the Applicant of this determination via letter.
`If any of the proposed product characteristics as stated in this review are altered, DMEPA
`rescinds this finding and the name must be resubmitted for review. The conclusions upon re-
`review are subject to change.
`If you have further questions or need clarifications, please contact Sue Kang, OSE Project
`Manager for the Division of Hematology Products, at 301-796-4216 or Nina Ton, OSE Project
`Manager for the Division of Cardiovascular and Renal Products, at 301-796-1648.
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` 6
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` PRIOR OSE REVIEW
`OSE Review# 2009-637. DMEPA Proprietary Name Review for Xarelto (Rivaroxaban) Tablets
`10 mg, Tselaine Jones Smith; April 30, 2009.
`
`7 REFERENCES
`
`1.
`
`2.
`
`Micromedex Integrated Index (http://csi.micromedex.com)
`Micromedex contains a variety of databases covering pharmacology, therapeutics, toxicology
`and diagnostics.
`
`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.
`
` FDA Document Archiving, Reporting & Regulatory Tracking System
`4.
`[DARRTS]
`DARRTS is a government database used to organize Applicant and Applicant submissions as
`well as to store and organize assignments, reviews, and communications from the review
`divisions.
`
`5.
`
`6.
`
`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.
`
`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.
`
`Electronic online version of the FDA Orange Book
`(http://www.fda.gov/cder/ob/default.htm)
`The FDA Orange Book provides a compilation of approved drug products with therapeutic
`equivalence evaluations.
`
`Reference ID: 2946218
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`8.
`
`9.
`
`U.S. Patent and Trademark Office (http://www.uspto.gov)
`USPTO provides information regarding patent and trademarks.
`
`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, combination, nutraceutical and
`nutritional products. It also provides a keyword search engine.
`
`10.
`
`Data provided by Thomson & Thomson’s SAEGIS ™ Online Service, available
`at (www.thomson-thomson.com)
`The Pharma In-Use Search database contains over 400,000 unique pharmaceutical trademarks
`and trade names that are used in about 50 countries worldwide. The data is provided under
`license by IMS HEALTH.
`
`Natural Medicines Comprehensive Databases (www.naturaldatabase.com)
`11.
`Natural Medicines contains up-to-date clinical data on the natural medicines, herbal
`medicines, and dietary supplements used in the western world.
`
`12.
`
`Stat!Ref (www.statref.com)
`Stat!Ref contains full-text information from approximately 30 texts; it includes tables and
`references. Among the database titles are: Handbook of Adverse Drug Interactions, Rudolphs
`Pediatrics, Basic Clinical Pharmacology, and Dictionary of Medical Acronyms
`Abbreviations.
`
`USAN Stems (http://www.ama-assn.org/ama/pub/category/4782.html)
`13.
`USAN Stems List contains all the recognized USAN stems.
`
`Red Book Pharmacy’s Fundamental Reference
`14.
`Red Book contains prices and product information for prescription, over-the-counter drugs,
`medical devices, and accessories.
`
`Lexi-Comp (www.lexi.com)
`15.
`Lexi-Comp is a web-based searchable version of the Drug Information Handbook.
`
`16. Medical Abbreviations Book
`Medical Abbreviations Book contains commonly used medical abbreviations and their
`definitions
`
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`APPENDICES
`Appendix A:
`FDA’s Proprietary Name Risk Assessment considers the potential for confusion between the
`proposed proprietary name and the proprietary and established names of drug products existing in
`the marketplace and those pending IND, NDA, BLA, and ANDA products currently under review
`by the Center. 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. 3
`For the proposed proprietary name, DMEPA staff search a standard set of databases and
`information sources to identify names with orthographic and phonetic similarity and hold a
`Center for Drug Evaluation and Research (CDER) Expert Panel discussion to gather professional
`opinions on the safety of the proposed proprietary name. DMEPA staff also conducts internal
`CDER prescription analysis studies. When provided, DMEPA considers external prescription
`analysis study results and incorporate into the overall risk assessment.
`The Safety Evaluator assigned to the Proprietary Name Risk Assessment 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 focuses on the avoidance of
`medication errors.
`FMEA is a systematic tool for evaluating a process and identifying where and how it might fail. 4
`DMEPA uses FMEA to analyze whether the drug names identified with orthographic or phonetic
`similarity to the proposed proprietary name could cause confusion that subsequently leads to
`medication errors in the clinical setting. 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.
`In addition, the product characteristics provide the context for the verbal and written
`communication of the drug names and can interact with the orthographic and phonetic attributes
`of the names to increase the risk of confusion when there is overlap or, in some instances,
`decrease the risk of confusion by helping to differentiate the products through dissimilarity.
`Accordingly, the DMEPA staff considers the product characteristics associated with the proposed
`drug 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.
`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. Because drug name confusion can occur at any point in the medication use process,
`
`
`3 National Coordinating Council for Medication Error Reporting and Prevention.
`http://www.nccmerp.org/aboutMedErrors.html. Last accessed 10/11/2007.
`4 Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston.
`IHI:2004.
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`DMEPA staff 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.5 DMEPA provides the product characteristics
`considered for this review in section one.
`The Division of Medication Error Prevention and Analysis considers the spelling of the name,
`pronunciation of the name when spoken, and appearance of the name when scripted. DMEPA also
`compares the spelling of the proposed proprietary name with the proprietary and established name of
`existing and proposed drug products because similarly in spelled names may have greater likelihood
`to sound similar to one another when spoken or look similar to one another when scripted. DMEPA
`staff also examines the orthographic appearance of the proposed name using a number of different
`handwriting samples. Handwritten communication of drug names has a long-standing association
`with drug name confusion. Handwriting can cause similarly and even dissimilarly spelled drug name
`pairs to appear very similar to one another. The similar appearance of drug names when scripted has
`led to medication errors. The DMEPA staff applies expertise gained from root-cause analysis of such
`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). In addition, the DMEPA staff 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. If provided, DMEPA will consider the
`Applicant’s intended pronunciation of the proprietary name. However, DMEPA also considers a
`variety of pronunciations that could occur in the English language because the Applicant has little
`control over how the name will be spoken in clinical practice.
`Table 1. Criteria used to identify drug names that look- or sound-similar to a proposed
`proprietary name.
`
`Type of
`similarity Potential causes
`of drug name
`similarity
`
`Considerations when searching the databases
`
`Attributes examined to identify
`similar drug names
`
`Potential Effects
`
`
`
`
`
`
`Look-
`alike
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`Similar spelling
`
`
`Identical prefix
`Identical infix
`Identical suffix
`Length of the name
`Overlapping product characteristics
`
`Orthographic
`similarity
`
`Similar spelling
`Length of the name
`Upstrokes
`Down strokes
`Cross-strokes
`Dotted letters
`Ambiguity introduced by scripting
`
`• 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
`
`
`5 Institute of Medicine. Preventing Medication Errors. The National Academies Press:
`Washington DC. 2006.
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`Sound-
`alike
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`Phonetic similarity
`
`
`
`
`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
`
`• Names may sound similar when
`pronounced and lead to drug name
`confusion in verbal communication
`
`
`Lastly, the DMEPA staff also 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 safety of the proposed proprietary name or product
`based on professional experience with medication errors.
`
`1. Database and Information Sources
`DMEPA staff conducts searches of 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 using the criteria outlined in
`Section 2.1. Section 6 provides a standard description of the databases used in the searches.
`To complement the process, the DMEPA staff use 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, the DMEPA staff review 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.
`
`2. CDER Expert Panel Discussion
`DMEPA conducts an Expert Panel Discussion to gather CDER professional opinions on the
`safety of the proposed product and the proposed proprietary name. The Expert Panel is
`composed of Division of Medication Errors Prevention (DMEPA) staff and representatives
`from the Division of Drug Marketing, Advertising, and Communications (DDMAC). 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 DMEPA staff to the Expert
`Panel for consideration. Based on the clinical and professional experiences of the Expert
`Panel members, the Panel may recommend the addition of 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 Analysis 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
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`Reference ID: 2946218
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`marketed U.S. drug names (proprietary and established) due to similarity in visual appearance
`with handwritten prescriptions or verbal pronunciation of the drug name. The studies employ
`healthcare professionals (pharmacists, physicians, and nurses), and attempts to simulate the
`prescription ordering process. The primary Safety Evaluator uses the results to identify
`orthographic or phonetic vulnerability of the proposed name to be misinterpreted by
`healthcare practitioners.
`In order to evaluate the potential for misinterpretation of the proposed proprietary name in
`handwriting and verbal communication of the name, inpatient medication orders and/or
`outpatient prescriptions are written, each consisting of a combination of marketed and
`unapproved drug products, including the proposed name. These orders are optically scanned
`and one prescription is delivered to a random sample of the 123 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 send their interpretations of the orders via e-mail to
`DMEPA.
`
`4. Safety Evaluator Risk Assessment of the Proposed Proprietary Name
`The primary Safety Evaluator applies his/her individual expertise gained from