CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`22-3 87
`
`PROPRIETARY NAME REVIEW; S)
`
`

`

`Department of Health and Human Services
`
`Public Health Service
`
` Office of Surveillance and Epidemiology -
`
`Food and Drug Administration
`
`Center for Drug Evaluation and Research
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`June 29, 2009
`
`Norman Stockbridge, MD
`Director, Division of Cardiovascular and Renal Products
`
`\
`
`Carlos Mena-Grillasca, RPh, Acting Team Leader
`Denise Toyer, PharmD, Deputy Director
`Division of Medication Error Prevention and Analysis
`
`Judy Park, PharmD, Safety Evaluator
`Division of Medication Error Prevention and Analysis
`
`Final Proprietary Name Review
`
`Drug Name(s):
`
`Tyvaso (Treprostinil) Inhalation Solution 0.6 mg/mL
`
`ApplicatiOn Type/Number: NDA 22-3 87
`
`Applicant:
`
`United Therapeutics Corporation
`
`0813 RCM #2
`
`2009-814 -
`
`“Note: This review contains proprietary and confidential information that should not be
`released to the public?”-
`
`

`

`CONTENTS
`
`2
`
`EXECUTIVE SUMMARY ............................................................................................................. 3
`1 METHODS AND MATERIALS ............................................................................................ 3
`1.1
`Proprietary Name Risk Assessment ............................................................................... 3
`RESULTS ................................................................................................................................ 4
`2.1
`Database and Information Sources................................................................................. 4
`2.2
`Expert Panel Discussion................................................................................................. 4
`2.3
`Safety Evaluator Risk Assessment................................................................................. '4
`DISCUSSION ......................................................................................................................... 4
`3
`CONCLUSIONS AND RECOMMENDATIONS.................................:................................ 5
`4
`REFERENCES ........................................................................................................................ 6
`5
`APPENDICES ................................................................................................................................. 8
`
`

`

`EXECUTIVE SUMMARY
`
`This re—assessment of this proprietary name is written in response to a notification that
`treprostinil will be approved within 90 days. DMEPA found the proposed proprietary name,
`Tyvaso, acceptable in OSE Review #2008-1113 on February 19, 2009. Since that review, none
`of Tyvaso’s product characteristics have changed.
`
`During this re-review we identified 9 new names for their similarity to Tyvaso. The results of
`the Failure Mode Effects Analysis found that the proposed name, Tyvaso, is not vulnerable to
`name confusion that could lead to medication errors with any of 9 names. Thus, the Division of
`Medication Error Prevention and Analysis does not object to the use of the proprietary name,
`Tyvaso, for this product.
`
`DMEPA considers this a final review, however, if approval of the NDA is delayed beyond 90
`days from the date of this review, the Division of Tyvaso should notify DMEPA because the
`proprietary name must be re—reviewed prior to the new approval date.
`
`1 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 re-assessrnent of a proprietary
`name 90 days prior to approval of an application. Section 1.1 identifies the specific search
`criteria associated with the proposed proprietary name, Tyvaso.
`
`l .1
`
`PROPRIETARY NAME RISK ASSESSMENT
`
`For this review, particular consideration was given to drug names beginning with the letter "T
`when searching to identify potentially similar drug names, as 75% of the confiised 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 Tyvaso, DMEPA also consider the orthographic
`appearance of the name on lined and unlined orders. Specific attributes taken into consideration
`include the length of the name (six letters), upstrokes (one, capital letter ‘T’), downstokes (lower
`case ‘y’), cross-strokes (none), and dotted letters (none). Additionally, several letters in Tyvaso
`may be vulnerable to ambiguity when scripted, including the letter ‘T’ may appear as ‘F,’ ‘L,’
`‘S,’ ‘Z,’ or ‘A’; lower case "y may appear as a lower case "g or ";p lower case ‘v? may appear
`as ‘c,’ ‘r,’ ‘s,’ or ”z,‘and a’ and‘ 0’ may appear as ‘,a ’ ‘e, ’ ‘i,’ ‘0,” or ‘u’. As such, the staffalso
`considers these alternate appearances when identifying drug names that may look similar to
`Tyvaso.
`
`When searching to identify potential names that may sound similar to Tyvaso, the DMEPA staff
`searches for names with similar number of syllables (three), stresses (ty-VA-so or TY-va-so),
`and placement of vowel and consonant sounds. Additionally, several letters in Tyvaso may be
`
`1 Institute for Safe Medication Practices. Confirsed Drug name List (1996-2006). Available at
`htt
`://www. ism .orofTools/confuseddru names. df
`
`
`2 Kondrack, G and Dorr, B Automatic Identification of Confusable Drug Names. Artifical Inteligence1n Medicine
`(2005)
`
`

`

`vulnerable to misinterpretation when spoken, including ‘Ty’ may be interpreted as ‘Zy’; ‘v’ may
`be interpreted as ‘b’ and ‘3’ may be interpreted as ‘c’ or ‘2’. As such, the staff also considers
`these alternate pronunciations when identifying drug names that may sound similar to Tyvaso.
`The Applicant’s intended pronunciation of the proprietary name could not be expressly taken
`into consideration, as this was not provided with the proposed name submission.
`
`2 RESULTS
`
`2.1
`
`DATABASE AND INFORMATION SOURCES
`
`The searches of the databases listed in Section 6 yielded a total of 19 names as having some
`similarity to the name Tyvaso.
`'
`
`Seventeen of the 19 names were thought to look like Tyvaso, which include: Lyrica, Lysine,
`
`
`44 Tazorac, Tequin,
`. Tyrazol, Tyrex, Tyrex-Z,
`Tysabri, Tyverb,
`Tyzeka, Tyzine, Vyvanse, Zyrona, and Zyvox. One additional name, Tri—Vi-Sol, was thought to
`sound similar to Tyvaso. One name, Travasol, was thought to look and sound similar to Tyvaso.
`
`M4)
`
`A search of the United States Adopted Names (USAN) stem list on June 22, 2009 identified no
`USAN stems contained in the proposed name, Tyvaso.
`
`2.2
`
`EXPERT PANEL DISCUSSION
`
`The Expert Panel reviewed the pool of names identified by the DMEPA staff (see section 2.1
`above), and noted no additional names thought to have orthographic or phonetic similarity to
`Tyvaso.
`
`DDMAC had no concerns regarding the proposed name from a promotiOnal perspective, and did
`not offer any additional comments relating to the proposed name.
`
`2.3
`
`SAFETY EVALUATOR RISK ASSESSMENT
`
`Independent searches by the primary Safety Evaluator did not identify any additional names
`thought to look similar to Tyvaso and represent a potential source of drug name confusion.
`
`Ten of the 19 names were identified in the previous Tyvaso proprietary name review (See
`Appendix B). None Of Tyvaso’s product characteristics have changed since the previous review.
`Therefore, the original assessment is maintained. Please see OSE #2008-1113 for a detailed
`analysis of these names.
`
`3 DISCUSSION
`
`Nine names were evaluated for their potential similarity to the proposed name, Tyvaso. Four
`names lacked orthographic and/or phonetic similarity to Tyvaso and were not evaluated firrther
`(See Appendix C).
`
`Failure mode and effect analysis (FMEA) was then applied to determine if the proposed name
`could potentially be confused with the remaining 5 names and lead to medication errors. This
`analysis determined that the name similarity between Tyvaso was unlikely to result in
`medication errors with any Of the 5 products for the reasons presented in Appendices D and E.
`
`m This review contains proprietary and confidential information that should not be released to the public.
`
`

`

`4 CONCLUSIONS AND RECOMIMENDATIONS
`
`The Proprietary Name Risk Assessment findings indicate that the proposed name, Tyvaso, is not
`vulnerable to name confusion that could lead to medication errors. As such, we do not object to
`the use of the proprietary name, Tyvaso, for this product. Additionally, DDMAC does not object
`to the proposed name, Tyvaso, from a promotional perspective.
`
`DMEPA considers this a final review; however, if approval of the NDA is delayed beyond 90
`days from the date of this review, the Division of Cardiovascular and Renal Products should
`notify DMEPA because the proprietary name must be re~reviewed prior to the new approval
`date.
`
`We are willing to meet with the Division for further discussion, if needed. If you have further
`questions or need clarifications, please contact Sean Bradley, OSE project manager, at 301-796-
`1332.
`
`

`

`5 REFERENCES
`
`I.
`
`Micromedex Integrated Index (http://weblern/l
`
`Contains a variety of databases covering pharmacology, therapeutics, toxicology and diagnostics.
`
`2.
`
`Phonetic and Orthographic Computer Analysis (POCA)
`
`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. This is a database which was created for the
`Medication Error Prevention Staff, FDA.
`
`3.
`
`Drug Facts and Comparisons, online version, St. Louis, MO (http://weblern/l
`
`Drug Facts and Comparisons is a compendium organized by therapeutic Course; contains
`monographs on prescription and OTC drugs, with charts comparing similar products.
`
`4.
`
`AMF Decision Support System [DSS]
`
`DSS is a government database used to track individual submissions and assignments in review
`divisions.
`
`Division ofMedication Error Prevention proprietary name consultation requests
`5.
`This is a list of proposed and pending names that is generated by the Medication Error
`Prevention Staff from the Access database/tracking system.
`
`6.
`
`Drugs@FDA (ht! .'//www. acce
`ssdata. iia. ov/scri ts/cder/dru sat da/z'ndex.c n
`
`
`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
`M and generic drugs and therapeutic biological_products; mscrjption and over-the—counter
`human drugs and therapeutic biologicals, discontinued drugs and “Chemical Type 6” approvals.
`
`7.
`(hit
`
`Electronic online version of the FDA Orange Book
`://mvw. do. ov/cder/ob/de aulthtm
`
`
`Provides a compilation of approved drug products with therapeutic equivalence evaluations.
`
`8.
`
`US Patent and Trademark Oflice location http://mvw. usgto. gov.
`
`Provides information regarding patent and trademarks.
`
`9.
`
`Clinical Pharmacology Online (http://weblern/l
`
`Contains full monographs for the most common drugs in clinical use, plus mini monographs
`covering investigational, less common, combination, nutraceutical and nutritional products.
`Provides a keyword search engine.
`
`

`

`Data provided by Thomson & Thomson ’s SAEGIS TM Online Service, available at
`10.
`www.thornson-z‘homsoncom
`
`The Pharma In—Use Search database contains over 400,000 unique pharmaceutical trademarks
`and tradenames that are used in about 50 countries worldwide. The data is provided under license
`by IMS HEALTH.
`'
`
`11.
`
`Natural Medicines Comprehensive Databases (httQ://weblern_,/)
`
`Contains up—to-date clinical data on the natural medicines, herbal medicines, and dietary
`supplements used in the western world.
`
`12.
`
`Stat!Ref (httQ ://weblern_,/)
`
`Contains full-text information from approximately 30 texts. 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.
`
`13.
`
`USAN Stems (hit .'//www.ama-
`
`
`assnor /am(1/ ub/cate or 2/47821711721
`
`
`List contains all the recognized USAN stems.
`
`14.
`
`Red Book Pharmacy ’s Fundamental Reference
`
`Contains prices and product information for prescription, over-the-counter drugs, medical
`devices, and accessories.
`
`15.
`
`Lexi-Comp (www, pharmacist. com)
`
`A web-based searchable version of the Drug Information Handbook.
`
`16. Medical Abbreviations Book
`
`Contains commonly used medical abbreviations and their definitions.
`
`1 7.
`
`PriorOSE Review
`
`OSE Review #2008-1 113. DMEPA Proprietary Name Review for Tyvaso (Treprostinil)
`Inhalation Solution, 0.6 mg/mL, Judy Park; February 19, 2009.
`
`

`

`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 (CDBR) Expert Panel discussion to gather professional
`opinions on the safety of the proposed proprietary name.
`
`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 FMBA 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,
`DMEPA staff considers the potential for confirsion throughout the entire US. medication use
`process, including drug procurement, prescribing and ordering, dispensing, administration, and
`
`3 National Coordinating Council for Medication Error Reporting and Prevention.
`htt
`://»vww.nccmer .ora/aboutMedErrorertml. Last accessed 10/11/2007.
`
`
`
`4 Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston. IHI:2004.
`
`

`

`monitoring the impact of the medications 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.
`
`Considerations when searching the databases
`
`
`
`
`Potential Effects
`:15? of
`Potential causes Attributes examined to identz'fi/
`
`
`similar drug names
`arlty
`ofdrug name
`
`
`
`
`similarity
`
`
` Identical prefix
`0 Names may appear similar in print or
`
`Similar spelling
`Identical infix
`electronic media and lead to drug name
`
`Identical suffix
`
`confusion in printed or electronic
`
`
`communication
`Length of the name
`
`Overlapping product characteristics
`
`
`0 Names may look similar when scripted
`
`
`and lead to drug name confusion in written
`
`
`communication
`
`
`Similar spelling
`0 Names may look similar when scripted,
`
`
`Orthographic
`
`
`Length of the name
`and lead to drug name confusion in written
`
`
`
`'
`similarity
`communication
`
`Upstrokes
`
`
`Down strokes
`
`
`Cross-stokes
`
`Dotted letters
`
`Ambiguity introduced by scripting letters
`
`Overla. -_in roduct characteristics
`
`
`
`
`
`
`5 Institute of Medicine. Preventing Medication Errors. The National Academies Press: Washington DC.
`2006.
`
`

`

`Phonetic similarity
`
`0 Names may sound similar when
`pronounced and lead to drug name
`confusion in verbal communication
`
`Identical prefix
`Identical infix
`Identical suffix
`Number of syllables
`Stresses
`Placement of vowel sounds
`Placement of consonant sounds
`
`Overla- ting nroduct characteristics
`
`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. 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, conducts a Failure Mode and Effects Analysis, and provides
`an overall risk assessment of name confusion. Failure Mode and Effects Analysis (FMEA) is a
`
`10
`
`

`

`systematic tool for evaluating a process and identifying where and how it might fail.6 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 characteristics listed in Section one.
`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 proposedproprietary name convincingly similar to another drug name, which
`may cause practitioners to become confused at any point in the usual practice setting?”
`
`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. If the answer to the question is no, the Safety Evaluator is not
`convinced that the names posses 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 eflect of the drug name confusion, by asking:
`
`“Could the confusion ofthe drug names conceivably result in medication errors in the
`usualpractice 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.
`
`DMEPA will obj ect to the use of proposed proprietary name when the primary Safety Evaluator
`identifies one or more of the following conditions in the Risk Assessment:
`
`1. DDMAC finds the proposed proprietary name misleading from a promotional perspective,
`and the Review Division concurs with DDMAC’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)].
`
`6 Institute for Healthcare Improvement (IHI). Failure Mode and Effects Analysis. Boston. IHI:2004.
`
`11
`
`

`

`2. 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)].
`
`3. FMEA identifies the potential for confusion between the proposed proprietary name and
`other proprietary or established drug narne(s), a_nd demonstrates that medication errors are
`likely to result from the drug name confusion under the conditions of usual clinical practice.
`4. The proposed proprietary name contains an USAN (United States Adopted Names) stem.
`5. 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 errors. Such errors may not necessarily involve
`confusion between the proposed drug and another drug product.
`
`If DMEPA objects to a proposed proprietary name on the basis that drug name confusion could
`lead to medication errors, the primary Safety Evaluator uses the FMEA process to identify
`strategies to reduce the risk of medication errors. DMEPA is likely to recommend that the
`Applicant select an alternative proprietary name and submit the alternate name to the Agency for
`DMEPA to review. However, in rare instances FMEA may identify plausible strategies that
`could reduce the risk of medication error of the currently proposed name. In that instance,
`DMEPA may be able to provide the Applicant with recommendations that reduce or eliminate the
`potential for error and, thereby, would render the proposed name acceptable.
`
`In the event that DMEPA objects to the use of the proposed proprietary name, based upon the
`potential for confusion with another proposed (but not yet approved) proprietary name, DMEPA
`,will provide a contingency objection based on the date of approval. Whichever product, the
`Agency approves first has the right to use the proprietary name, while DMEPA will recommend
`that the second product to reach approval seek an alternative name.
`
`The threshold set for objection to the proposed proprietary name may seem low to the Applicant.
`However, the safety concerns set forth in criteria a through e are supported either by FDA
`regulation or by external healthcare authorities, including the Institute of Medicine (IOM), World
`Health Organization (WHO), Joint Commission on Accreditation of Hospitals (JCOAH), and the
`Institute for Safe Medication Practices (ISMP). These organizations have examined medication
`errors resulting from look- or sound-alike drug names and called for regulatory authorities to
`address the issue prior to approval. Additionally, DMEPA contends that the threshold set for the
`Proprietary Name Risk Assessment is reasonable because proprietary drug name confusion is a
`predictable and a preventable source of medication error that, in many instances, the Agency
`and/or Applicant can identify and rectify prior to approval to avoid patient harm.
`
`Furthermore, post-marketing experience has demonstrated that medication errors resulting from
`drug name confusion are notoriously difficult to rectify post-approval. Educational and other
`post-approval efforts are low-leverage strategies that have had limited effectiveness at alleviating
`medication errors involving drug name confusion. Applicants have undertaken higher—leverage
`strategies, such as drug name changes, in the past but at great financial cost to the Applicant and
`at the expense of the public welfare, not to mention the Agency’s credibility as the authority
`responsible for approving the error—prone proprietary name. Moreover, even after Applicants’
`have changed a product’s proprietary name in the post-approval phase, it is difficult to eradicate
`the original proprietary name from practitioners’ vocabulary, and as a result, the Agency has '
`continued to receive reports of drug name confusion long after a name change in some instances.
`Therefore, DMEPA believes that post—approval efforts at reducing name confusion errors should
`be reserved for those cases in which the potential for name confusion could not be predicted prior
`to approval.
`. (See Section 4 for limitations of the process).
`
`12
`
`

`

`Appendix B: Names previously reviewed and determined not to pose a safety risk.
`
`
`
`
`
`
`
`Lysine
`
`Travasol
`
`
`
`
`
`
`Tyverb
`
`
`
`Tyzeka
`
`
`
`
`
`
`
`Appendix C: Proprietary names with minimal orthographic and/or phonetic similarity
`
`2!
`
`
`
`
`
`
` Look
`
`
`M4)
`
`Appendix D: Proprietary names used only in foreign countries
`
`_Look
`
`-yrona
`
`
`
`" This review contains proprietary and confidential information that should not be released to the public.
`
`13
`
`

`

`Appendix E: Products with no overlap in strength or dose
`
`Similarity to
`Product name
`. Proposed
`.
`with potential,
`for confusion _ Proprietary Name
`
`Strength
`
`Usual'Dose (if applicable)
`‘
`
`Dimesylate)
`
`Vyvanse
`(Lisdexamfetamine
`
`20 mg, 30 mg, 40 mg, 50 mg,
`60 mg, 70 mg
`
`30 mg (1 tablet) by mouth once in the
`“101'ng
`
`% m
`
`This review contains proprietary and confidential information that should not be released to the public.
`
`14
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Judy Park
`6/29/2009 02:34:36 PM
`DRUG SAFETY OFFICE REVIEWER
`
`Carlos M Mena—Grillasca
`6/29/2009 03:31:11 PM
`DRUG SAFETY OFFICE REVIEWER
`
`Denise Toyer
`7/1/2009 03:57:02 PM
`DRUG SAFETY OFFICE REVIEWER
`
`

`

`
`
`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:
`
`To:
`
`Through:
`
`From:
`
`February 18, 2009
`
`Norman Stockbridge, MD
`Director, Division of Cardiovascular and Renal Products
`
`Kellie Taylor, thD, MPH, Team Leader
`Denise Toyer, PharmD, Deputy Director
`Carol Holquist, RPh, Director
`‘
`Division of Medication Error Prevention and Analysis
`
`Judy Park, PharmD, Safety Evaluator
`Division of Medication Error Prevention and Analysis
`
`Subject:
`
`Proprietary Name Review-
`
`Drug Name(s):
`
`Tyvaso (Treprostinil Sodium) Inhalation Solution 0.6 mg/mL
`
`Application Type/Number: NDA 22—387
`
`Applicant:
`
`United Therapeutics
`
`OSE RCM #:
`
`2008-1113
`
`*“Note: This review contains proprietary and confidential information that shouid not be
`retcased to the public.”
`
`

`

`