CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`
`22-024
`
`APPLICATION NUMBER:
`
`PROPRIETARY NAME REVIEW(S)
`PROPRIETARY NAME REVIEW! S}
`
`
`
`
`
`
`
` 22-024
`
`

`

`
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`Drug Name(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
`
`
`
`April 30, 2009
`
`Mary Parks, M.D., Director
`Division of Metabolism and Endocrinology Products
`
`Kellie Taylor, Pharm.D., Team Leader
`Denise Toyer, Pharm.D., Deputy Director
`Carol Holquist, RPh, Director
`Division of Medication Error Prevention and Analysis (DMEPA)
`
`Cathy A. Miller, M.P.H., Safety Evaluator
`Division of Medication Error Prevention and Analysis (DMEPA)
`
`Proprietary Name Review
`
`ActoPlus Met XR
`(Pioglitazone HCl and Metformin HCl Extended-release)
`Tablets 15 mg/1000 mg and 30 mg/1000 mg
`
`Application Type/Number: NDA 22-024
`
`Applicant/Applicant:
`
`Takeda Global Research and Development Center, Inc.
`
`OSE RCM #:
`
`2009-566
`
`
`*** This document contains proprietary and confidential information that should not be
`released to the public.***
`
`
`
`

`

`CONTENTS
`EXECUTIVE SUMMARY............................................................................................................. 3
`1 BACKGROUND..................................................................................................................... 3
`1.1
`Product Information....................................................................................................... 3
`2 METHODS AND MATERIALS ............................................................................................ 3
`2.1
`Search Criteria................................................................................................................ 4
`3 RESULTS................................................................................................................................ 5
`3.1
`Database and Information Sources................................................................................. 5
`3.2
`Expert Panel Discussion................................................................................................. 5
`3.3
`Safety Evaluator Risk Assessment................................................................................. 5
`4 CONCLUSIONS and recommendations................................................................................. 6
`4.1
`Comments To the Division ............................................................................................ 6
`5 REFERENCES........................................................................................................................ 6
`APPENDICES................................................................................................................................. 9
`
`
`
`
`
`2
`
`

`

`EXECUTIVE SUMMARY
`This re-assessment of the proprietary name is written in response to a notification that new drug
`application (NDA 22-024) will be approved within 90 days. The Division of Medication Error
`Prevention and Analysis (DMEPA) found the proposed proprietary name, ActoPlus Met XR,
`acceptable in OSE Review# 05-0034 dated August 19, 2005 and again in OSE Review #06-0201
`dated August 25, 2006. Since that review, none of the ActoPlus Met XR product characteristics
`have changed.
`During this re-review we identified six new names for their similarity to ActoPlus Met XR The
`results of the Failure Mode Effects Analysis found that the proposed name, ActoPlus Met XR, is
`not vulnerable to name confusion that could lead to medication errors with any of six names.
`Thus, the Division of Medication Error Prevention and Analysis does not object to the use of the
`proprietary name, ActoPlus Met XR, 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 Metabolism and Endocrinology should notify
`DMEPA because the proprietary name must be re-reviewed prior to the new approval date.
`
`1 BACKGROUND
`
`1.1 PRODUCT INFORMATION
`Actoplus Met XR is an oral antihypoglycemic agent indicated as an adjunct to diet and exercise
`to improve glycemic control in patients with type 2 diabetes mellitus. It is an extension of the
`Actoplus Met product line. Actoplus Met, approved on August 29, 2005, is an immediate-
`release combination tablet of Pioglitazone Hydrochloride and Metformin Hydrochloride
`indicated for the treatment of patients with type 2 diabetes. Actoplus Met is available in
`15 mg/500 mg and 15 mg/850 mg tablets. Actoplus Met may be dosed once or twice daily.
`Actoplus Met XR is for use in patients who are already treated with a combination of
`Pioglitazone Hydrochloride and Metformin Hydrochloride or whose diabetes is not adequately
`controlled with Metformin Hydrochloride alone. Actoplus Met XR will be available as a
`combination tablet containing an immediate-release active ingredient (Pioglitazone
`Hydrochloride) and an extended-release active ingredient (Metformin Hydrochloride).
`Actoplus Met XR will be available in two different strengths: 15 mg/1000 mg and
`30 mg/1000 mg. This product is indicated as a once-daily product, but the dosage should be
`individualized based on a patient’s current treatment with each drug component or based on a
`patient’s treatment requirements for effectiveness and tolerability. The commercial product will
`be supplied in 30, 60, and 90 count bottles.
`
`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 re-assessment of a proprietary
`name 90 days prior to approval of an application. Section 2.1 identifies the specific search
`criteria associated with the proposed proprietary name, ActoPlus Met XR.
`
`3
`
`

`

`2.1 SEARCH CRITERIA
`For this review, particular consideration was given to drug names beginning with the letter ‘A’
`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 ActoPlus Met XR, 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 (13 letters), upstrokes (8 letters
`including uppercase letters ‘A’, ‘P’, ‘M’, ‘X’ and ‘R’ and two lowercase letter ‘t’s and one ‘l’),
`downstrokes (one ‘p’ if scripted in lowercase form rather than capitalized), cross strokes (two
`lowercase letter ‘t’s and one capital letter ‘X’), and dotted (none). Additionally, several letters in
`ActoPlus Met XR may be vulnerable to ambiguity when scripted, including the capital letter ‘A’
`may appear as capital letters ‘O’ or ‘Cl’; lower case ‘’c’ may look like lower case ‘r’ or ‘n’;
`lower case ‘t’ may look like lower case ‘l’or ‘e’; lowercase letter ‘o’ may appear as lower case
`‘a’ or ‘u’; when scripted with capitalization, the capital letter ‘P’ may appear as uppercase letter
`‘F’ or ‘B’ and when written as lowercase letter ‘p’ may appear as lowercase letter ‘f’ or ‘z’;
`lower case ‘l’ may appear as lowercase letter ‘t’ or ‘e’; lowercase letter ‘u’ may appear as
`lowercase letter ‘o’, ‘v’ or ‘n’; lowercase letter ‘s’ may appear as lowercase letter ‘r’ or ‘n’;
`capital letter ‘M’ may appear as uppercase letter ‘N’ or ‘W’; lowercase letter ‘e’ may appear as
`lowercase letter ‘i’ or ‘l’; capital letter ‘X’ may appear as uppercase letter ‘V’ and capital letter
`‘R’ may appear as uppercase letter ‘K’ or ‘P’. As a result, the DMEPA staff also considers
`these alternate appearances when identifying drug names that may look similar to ActoPlus Met
`XR. Additionally, DMEPA considers the potential for confusion that may occur because the
`proprietary name has three sections ‘ActoPlus’, ‘Met, and ‘XR’. Therefore, DMEPA considers
`possible drug names that begin with the letters ‘M’ and ‘X’.
`When searching to identify potential names that may sound similar to ActoPlus Met XR, the
`DMEPA staff search for names with similar number of syllables (six), stresses (ACT- o-plus-
`met-xr, act-O-plus-met-xr, act-o-PLUS-met-xr and act-o-plus-MET-xr), and placement of vowel
`and consonant sounds. Additionally, the DMEPA staff considers that pronunciation of parts of
`the name can vary such as ‘Act’ can sound like ‘Ax’, ‘Met’ can sound like ‘Med’ and ‘XR’ can
`sound like ‘exar’. The Applicant did not provide their intended pronunciation of the proprietary
`name in the proposed name submission and, therefore, it could not be taken into consideration.
`Moreover, names are often mispronounced and/or spoken with regional accents and dialects, so
`other potential pronunciations of the name are considered.
`
`
`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)
`
`4
`
`

`

`3 RESULTS
`
`3.1 DATABASE AND INFORMATION SOURCES
`The searches of the databases listed in Section 6 yielded a total of seven names as having some
`similarity to the name ActoPlus Met XR.
`One of the names was thought to look like ActoPlus Met XR: Actophlem. Five names were
`thought to look and sound similar to ActoPlus Met XR. These names include Act Plus, Actonel
`Plus Calcium, ActoPlus Met, Actos and Octaplex. The remaining name, Metformin, was thought
`to look and sound similar to one of the two active ingredients in the established name,
`(Pioglitazone and Metformin).
`Additionally, DMEPA staff did not identify any United States Adopted Names (USAN) stems in
`the proposed proprietary name, as of April 15, 2009.
`
`3.2 EXPERT PANEL DISCUSSION
`The Expert Panel, as described in Appendix A, section 2, reviewed the pool of names identified
`by DMEPA staff (See Section 3.1 above) and noted no additional names thought to have
`orthographic or phonetic similarity to ActoPlus Met XR.
`DDMAC had no concerns regarding the proposed name from a promotional perspective, and did
`not offer any additional comments relating to the proposed name.
`
`3.3 SAFETY EVALUATOR RISK ASSESSMENT
`Independent searches by the primary Safety Evaluator resulted in two additional names
`(Anzemet and Aptivus) which were thought to look similar to ActoPlus Met XR and represent a
`potential source of drug name confusion. Therefore, a total of nine names were assessed for
`their potential to cause confusion that could lead to medication errors.
`Three of the names that were identified (Actonel Plus Calcium, ActoPlus Met and Actos) were
`reviewed in the previous proprietary name reviews for ActoPlus Met XR (OSE Review
`#05-0034 and #06-0201). Since none of the product characteristics have changed for these
`names, our original assessment is maintained that no vulnerabilities were identified that could
`lead to medication errors. (See Appendix B)
`As assessed in our previous OSE reviews, DMEPA evaluated the Applicant’s proposed use of
`the modifier ‘XR’. DMEPA noted that, although there is potential for confusion to occur
`between the regular (ActoPlus Met) and the extended-release product (ActoPlus Met XR),
`utilizing the modifier ‘XR’ to denote an extended-release to an existing product line is common
`for oral dosage forms. Additionally, the modifier ‘XR’ is well established and well recognized
`by healthcare practitioners and patients to designate extended-release and therefore, DMEPA
`found the modifier ‘XR’ acceptable. As such, DMEPA will not revisit these issues in this
`review.
`
`5
`
`

`

`4 DISCUSSION
`Six new names were evaluated for their potential similarity to the proposed name, ActoPlus Met
`XR. Failure mode and effect analysis (FMEA) was then applied to determine if the proposed
`name could potentially be confused with the six names and lead to medication errors. This
`analysis determined that the name similarity between ActoPlus Met XR was unlikely to result in
`medication errors with any of the six products for the reasons presented in Appendices C
`through F.
`
`5 CONCLUSIONS AND RECOMMENDATIONS
`The Proprietary Name Risk Assessment findings indicate that the proposed name,
`ActoPlus Met XR, is not vulnerable to name confusion that could lead to medication errors.
`Thus the Division of Medication Error Prevention and Analysis (DMEPA) has no objection to
`the proprietary name, ActoPlus Met XR, for this product at this time. Additionally, DDMAC
`does not object to the proposed name, ActoPlus Met XR 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 Metabolism and Endocrinology should notify
`DMEPA because the proprietary name must be re-reviewed prior to the new approval date.
`
`5.1 COMMENTS TO THE DIVISION
`We are willing to meet with the Division for further discussion, if needed. If you have further
`questions or need clarifications, please contact Cheryl Campbell of OSE Project MANAGER,
`Project Manager, at 301-796-0723.
`
`6 REFERENCES
`REVIEWS
`1. OSE Proprietary Name Reviews for ActoPlus Met XR, Reviews #05-0034 dated August 19,
`2005 and #06-0201 dated August 25, 2006
`
`Micromedex Integrated Index (http://csi.micromedex.com)
`1.
`Micromedex contains a variety of databases covering pharmacology, therapeutics, toxicology
`and diagnostics.
`
`Phonetic and Orthographic Computer Analysis (POCA)
`2.
`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.
`
`6
`
`

`

`AMF Decision Support System [DSS]
`4.
`DSS is a government database used to track individual submissions and assignments in review
`divisions.
`
`Division of Medication Errors Prevention and Analysis proprietary name consultation
`5.
`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)
`6.
`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.
`
`U.S. Patent and Trademark Office (http://www.uspto.gov)
`8.
`USPTO provides information regarding patent and trademarks.
`
`Clinical Pharmacology Online (www.clinicalpharmacology-ip.com)
`9.
`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.
`
`Stat!Ref (www.statref.com)
`12.
`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.
`
`7
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`

`

`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.
`
`8
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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.
`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, DMEPA staff considers the
`potential for confusion throughout the entire U.S. medication use process, including drug
`
`
`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.
`
`
`
`9
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`

`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.
`
`
`5 Institute of Medicine. Preventing Medication Errors. The National Academies Press: Washington DC. 2006.
`
`
`
`10
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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
`
`Type of
`similarity Potential causes
`of drug name
`similarity
`
`Attributes examined to identify
`similar drug names
`
`Potential Effects
`
`Similar spelling
`
`
`Identical prefix
`Identical infix
`Identical suffix
`Length of the name
`Overlapping product characteristics
`
`
`
`
`
`
`Look-
`alike
`
`Orthographic
`similarity
`
`Sound-
`alike
`
`Phonetic similarity
`
`
`• 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
`
`Similar spelling
`Length of the name
`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, 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-
`
`
`
`11
`
`

`

`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 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:
`
`
`6 Institute for Healthcare Improvement (IHI). Failure Mode and Effects Analysis. Boston. IHI:2004.
`
`
`
`12
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`

`“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?”
`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 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.
`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 Risk Assessment:
`a. 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)].
`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)].
`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 errors. Such errors may not necessarily involve confusion between the
`proposed drug and another drug product.
`If DMEPA