CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`22-228
`
`
`APPLICA TI0N NUMBER:
`
`PROPRIETARY NAME REVIEW(S)
`PROPRIETARY NAME REVIEW! S}
`
`
`
`
`
`
`
`22-228
`
`

`

`
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`
`
`
`August 31, 2009
`
`Wiley Chambers, M.D., Acting Director
`Division of Anti-Infective & Ophthalmology Products
`Laura Pincock, Pharm.D., Acting Team Leader
`Denise Toyer, Pharm.D., Deputy Director
`Carol Holquist, RPh, Director
`Division of Medication Error Prevention and Analysis
`Raichell S. Brown, Pharm.D., J.D., Safety Evaluator
`Division of Medication Error Prevention and Analysis
`
`Proprietary Name Review
`
`Drug Name(s):
`
`Bepreve (Bepotastine Besilate) Ophthalmic Solution 1.5%
`
`Application Type/Number: NDA 22-288
`
`Applicant:
`
`OSE RCM #:
`
`ISTA Pharmaceuticals
`
`2009-260
`
`
`*** This document contains proprietary and confidential information that should not be released to
`the public.***
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`CONTENTS
`INTRODUCTION................................................................................................................... 3
`1
`2 METHODS AND RESULTS.................................................................................................. 3
`3 CONCLUSIONS AND RECOMMENDATIONS.................................................................. 3
`4 REFERENCES........................................................................................................................ 3
`
`
`
`
`
`2
`
`

`

`
`
` 1
`
`
`INTRODUCTION
`This review is written in response to the anticipated approval of this NDA within 90 days from the date of this
`review. DMEPA found the proposed name, Bepreve, acceptable in OSE Review #2008-1987, dated February
`9, 2009. Since that review, none of Bepreve’s product characteristics have been altered. Additionally, the
`Division of Drug Marketing, Advertising and Communications (DDMAC) found the name acceptable from a
`promotional perspective on June 16, 2009. Furthermore, the Review Division did not have any concerns with
`the proposed name, Bepreve, during our initial review.
`
`2 METHODS AND RESULTS
`For the proposed proprietary name, DMEPA staff searched a standard set of databases and information sources
`(see Section 4) to identify names with orthographic and/or phonetic similarity to the proposed name that have
`been approved since the previous OSE proprietary name review. Because none of the proposed product
`characteristics were altered, we did not re-evaluate previous names of concern. Additionally, DMEPA
`searched the USAN stem list to determine if the name contains any USAN stems as of the last USAN update.
`DMEPA bases the overall risk assessment on the findings of a Failure Mode Effects Analysis (FMEA) of the
`proposed proprietary name, and focuses on the avoidance of medication errors.
`The searches of the databases yielded three new names, Agenerase, Hepsera, and Hiprex, thought to look
`similar to Bepreve and represent a potential source of drug name confusion. These names were evaluated using
`FMEA. The findings of the FMEA indicate that the proposed name, Bepreve, is not likely to result in name
`confusion with Agenerase, Hepsera, and Hiprex for the reasons presented in Appendices A and B.
`
`3 CONCLUSIONS AND RECOMMENDATIONS
`The Proprietary Name Risk Assessment findings indicate that the proposed name, Bepreve, is not vulnerable to
`name confusion that could lead to medication errors nor is the name considered promotional. Thus, the
`Division of Medication Error Prevention and Analysis (DMEPA) has no objection to the proprietary name,
`Bepreve, for this product at this time.
`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 Anti-Infective and Ophthalmology Products should notify DMEPA because
`the proprietary name must be re-reviewed prior to the new approval date.
`
`4 REFERENCES
`1.
`OSE Review # 2008-1987. Proprietary Name Review of Bepreve, Raichell S. Brown. February 5,
`2009.
`
`Drugs@FDA (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm)
`2.
`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.
`
`Electronic online version of the FDA Orange Book (http://www.fda.gov/cder/ob/default.htm)
`3.
`The FDA Orange Book provides a compilation of approved drug products with therapeutic equivalence
`evaluations.
`
`
`
`3
`
`

`

`USAN Stems (http://www.ama-assn.org/ama/pub/category/4782.html)
`4.
`USAN Stems List contains all the recognized USAN stems.
`
`APPENDICES
`Appendix A: Products that lack convincing orthographic or phonetic similarity to Bepreve.
`
`Product Name Identified to have Potential for
`Confusion
`orthographic
`Agenerase
`Appendix B: Single strength products with multiple differentiating product characteristics.
`
`Similarity to Bepreve.
`
`Differentiating Product
`Characteristics
`(Bepreve vs. Product)
`N/A
`
`DOSAGE FORM:
`Bepreve- Ophthalmic Drop
`Hiprex- Oral Tablet
`ROUTE OF
`ADMINISTRATION:
`Bepreve- Topical to the eye(s)
`Hiprex- Oral
`DOSAGE FORM:
`Bepreve- Ophthalmic Drop
`Hepsera- Oral Tablet
`ROUTE OF
`ADMINISTRATION:
`Bepreve- Topical to the eye(s)
`Hepsera- Oral
`FREQUENCY OF
`ADMINISTRATION:
`Bepreve- Twice daily
`Hepsera- Once daily
`
`Product name
`with potential
`for confusion
`
`Bepreve
`(Bepotastine)
`Ophthalmic
`Solution
`
`Hiprex
`(Methenamine)
`Tablet
`
`Hepsera
`(Adefovir)
`Tablet
`
`Similarity
`to Bepreve
`
`Strengt
`h
`
`Indication for
`Use
`
`Usual Dose
`(if applicable)
`
`N/A
`
`1.5%
`
`orthographic 1 gram
`
`orthographic 10 mg
`
`Itching
`associated with
`allergic
`conjunctivitis
`
`One drop in
`affected
`eye(s) twice a
`day
`
`1 gram by
`mouth twice
`daily
`
`Prophylactic or
`suppressive
`treatment or
`frequently
`recurring urinary
`tract infections
`
`Treatment of
`chronic
`Hepatitis B in
`patients 12 years
`of age or older
`
`10 mg by
`mouth once
`daily
`
`
`
`
`
`
`
`4
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAICHELL S Brown
`09/01/2009
`
`LAURA L PINCOCK
`09/01/2009
`
`CAROL A HOLQUIST
`09/01/2009
`
`

`

`
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`
`
`
`February 5, 2009
`
`Wiley Chambers, M.D., Acting Director
`Division of Anti-Infective & Ophthalmology Products
`
`Todd Bridges, R.Ph., Team Leader
`Denise Toyer, Pharm.D., Deputy Director
`Carol Holquist, RPh, Director
`Division of Medication Error Prevention and Analysis (DMEPA)
`
`Raichell S. Brown, Pharm.D., J.D., Safety Evaluator
`Division of Medication Error Prevention and Analysis (DMEPA)
`
`Proprietary Name Review
`
`Drug Name(s):
`
`Bepreve (Bepotastine Besilate Ophthalmic Solution) 1.5%
`
`Application Type/Number: NDA 22-288
`
`Applicant:
`
`OSE RCM #:
`
`ISTA Pharmaceuticals
`
`2008-1987
`
`
`*** This document contains proprietary and confidential information that should not be
`released to the public.***
`
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`CONTENTS
`EXECUTIVE SUMMARY............................................................................................................. 3
`1 BACKGROUND..................................................................................................................... 3
`1.1
`Introduction.................................................................................................................... 3
`1.2
`Product Information....................................................................................................... 3
`2 METHODS AND MATERIALS ............................................................................................ 3
`2.1
`Proprietary Name Risk Assessment............................................................................... 4
`3 RESULTS................................................................................................................................ 9
`3.1
`Proprietary Name Risk Assessment............................................................................... 9
`4 DISCUSSION ....................................................................................................................... 10
`4.1
`Proprietary Name Risk Assessment............................................................................. 10
`5 CONCLUSIONS and recommendations............................................................................... 11
`5.1
`Comments To the Division .......................................................................................... 11
`5.2
`Comments To The Applicant....................................................................................... 11
`6 REFERENCES...................................................................................................................... 11
`APPENDICES............................................................................................................................... 14
`
`
`
`
`
`2
`
`

`

`EXECUTIVE SUMMARY
`Our Proprietary Name Risk Assessment considered the potential similarity of 39 names to the proposed
`name, Bepreve. However, we concluded that these names would not render the proposed name, Bepreve,
`vulnerable to name confusion that could lead to medication errors. Thus, DMEPA has no objection to the
`use of the proprietary name Bepreve for this product. The Division of Anti-Infective & Ophthalmology
`Products concurs with this assessment.
`However, if any of the proposed product characteristics as stated in this review are altered prior to
`approval of the product, DMEPA rescinds this Risk Assessment finding and recommends that the name
`be resubmitted for review. In the event that our Risk Assessment finding is rescinded, the evaluation of
`the name on resubmission is independent of the previous Risk Assessment, and as such, the conclusions
`on re-review of the name are subject to change.
`In addition, the proposed name must be reevaluated 90 days before the expected approval date of the
`NDA, even if the proposed product characteristics as stated in this review are not altered.
`
`1 BACKGROUND
`
`1.1
`INTRODUCTION
`This review is in response to a request from the Division of Anti-Infective & Ophthalmology Products for
`an assessment of the proposed proprietary name, Bepreve, regarding potential name confusion with other
`proprietary or established drug names in normal practice settings. Labels and labeling were also
`submitted and will be evaluated in separate forthcoming review (OSE Review 2008-1998).
`
`1.2 PRODUCT INFORMATION
`Bepreve is the proposed proprietary name for bepotastine besilate ophthalmic solution 1.5%. Bepreve is
`intended for treatment of itching associated with allergic conjunctivitis in patients 3 (three) years of age or
`older. Bepreve is dosed as one drop into affected eye(s) twice a day. Bepreve is proposed to be marketed
`in plastic squeeze bottles in the following sizes: 2.5 mL, 5 mL, and 10 mL. The recommended storage
`condition is 15 degrees Celsius to 25 degrees Celsius (59 degrees Fahrenheit to 77 degrees Fahrenheit).
`
`2 METHODS AND MATERIALS
`This section describes the methods and materials used by DMEPA staff conducting a proprietary name
`risk assessment (See 2.1 Proprietary Name Risk Assessment). The primary objective of the assessment
`is to identify and remedy potential sources of medication error prior to drug approval. 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. 1
`
`
`
`
`
`
`
`1 National Coordinating Council for Medication Error Reporting and Prevention.
`http://www.nccmerp.org/aboutMedErrors html. Last accessed 12/22/2008.
`
`

`

`
`
`2.1 PROPRIETARY NAME RISK ASSESSMENT
`FDA’s Proprietary Name Risk Assessment considers the potential for confusion between the proposed
`proprietary name, Bepreve, and the proprietary and established names of drug products existing in the
`marketplace and those pending IND, NDA, and ANDA products currently under review by CDER.
`For the proprietary name, Bepreve, the DMEPA staff searched a standard set of databases and
`information sources to identify names with orthographic and phonetic similarity (See 2.1.1 for details)
`and held a CDER Expert Panel discussion to gather professional opinions on the safety of the proposed
`proprietary name (See 2.1.1.2). DMEPA also conducts internal CDER prescription analysis studies.
`When provided, external prescription analysis studies results are considered and incorporated 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 (See
`2.1.2 for details). The overall risk assessment is based on the findings of a Failure Mode and Effects
`Analysis (FMEA) of the proprietary name, and is focused on the avoidance of medication errors.
`FMEA is a systematic tool for evaluating a process and identifying where and how it might fail. 2 FMEA
`is used to analyze whether the drug names identified with orthographic or phonetic similarity to the
`proposed name could cause confusion that subsequently leads to medication errors in the clinical setting.
`DMEPA uses the clinical expertise of the medication error 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 medication error 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 drug name include, but are not limited to, established name of the proposed
`product, the proposed indication, 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 considers the potential for confusion
`throughout the entire U.S. medication use process, including drug procurement, prescribing and ordering,
`dispensing, administration, and monitoring the impact of the medication.3
`
`
`
`
`
`2 Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston. IHI:2004.
`3 Institute of Medicine. Preventing Medication Errors. The National Academies Press: Washington DC. 2006.
`
`4
`
`

`

`2.1.1 Search Criteria
`The DMEPA staff considers the spelling of the name, pronunciation of the name when spoken, and
`appearance of the name when scripted as outlined in Appendix A.
`For this review, particular consideration was given to drug names beginning with the letter ‘Bb’ 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.4,5
`To identify drug names that may look similar to Bepreve, the staff also considered 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 (one, capital and lower case letter ‘Bb’), downstrokes
`(one, lower case ‘p’), cross-strokes (none), and dotted letters (none). In addition, several letters in
`Bepreve may be vulnerable to ambiguity when scripted, including the capital letter ‘B’ may appear as
`capital letters ‘P’, ‘D’, or ‘R’; lower case ‘b’ may look like lower case ‘l’ or ‘h’; lower case ‘e’ may look
`like lower case ‘a’ or ‘i’; lower case ‘p’ may look like lower case ‘j’ or ‘q’; lower case letters ‘re’ together
`may appear as lower case ‘u’; and lower case ‘v’ may appear as lower case ‘u’, ‘a’, ‘r’, or ‘n’. As a result,
`the medication error staff considers these alternate appearances when identifying drug names that may
`look similar to Bepreve.
`When searching to identify potential names that may sound similar to Bepreve, the DMEPA staff
`searched for names with similar number of syllables (two), stresses (BE-preve or Be-PREVE), and
`placement of vowel and consonant sounds. Additionally, the medication error staff considers that
`pronunciation of parts of the name can vary such as ‘Be-’ may sound like ‘Bi-’, ‘Ba-’, or ‘Bu-’. The
`Applicant’s intended pronunciation of the proprietary name, Bepreve, was not provided with the proposed
`name submission and, therefore, 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.
`The DMEPA staff also considers the product characteristics associated with the proposed drug throughout
`the identification of similar drug names because the product characteristics of the proposed drug
`ultimately determine the use of the product in the clinical practice setting. For this review, the DMEPA
`staff was provided with the following information about the proposed product: proposed proprietary name
`(Bepreve); proposed established name (bepotastine besilate ophthalmic solution); proposed indication of
`use (itching associated with allergic conjunctivitis); strength (1.5%); dose (one drop in affected eye);
`frequency of administration (twice daily); route (ophthalmic); and dosage form (solution). Appendix A
`provides a more detailed listing of product characteristics that the medication error staff generally takes
`into consideration.
`Lastly, the DMEPA staff considers the potential for the proposed 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, these broader safety implications of the name are considered and evaluated throughout this
`assessment and the medication error staff provides additional comments related to the safety of the
`proposed name or product based on their professional experiences with medication errors.
`
`
`
`
`4 Institute for Safe Medication Practices. Confused Drug name List (1996-2006). Available at
`http://www.ismp.org/Tools/confuseddrugnames.pdf
`5 Kondrack, G and Dorr, B. Automatic Identification of Confusable Drug Names. Artificial Intelligence in
`Medicine (2005)
`
`5
`
`

`

`2.1.1.1 Database and Information Sources
`The proposed proprietary name, Bepreve, was provided to the DMEPA staff to conduct a search 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 Bepreve using the criteria outlined in
`2.1.1. A standard description of the databases used in the searches is provided in Section 7. To
`complement the process, the DMEPA staff used 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. The medication error staff
`also reviewed the USAN stem list to determine if any USAN stems are present within the proprietary
`name. The individual findings of multiple safety evaluators were then pooled and presented to the CDER
`Expert Panel.
`
`2.1.1.2 CDER Expert Panel Discussion
`An Expert Panel Discussion was held to gather CDER professional opinions on the safety of the product
`and the proprietary name, Bepreve. The Expert Panel is composed of staff of the Division of Medication
`Error Prevention and Analysis (DMEPA) and representatives from the Division of Drug Marketing,
`Advertising, and Communications (DDMAC). Potential concerns regarding drug marketing and
`promotion related to the proposed names were also discussed.
`The pooled results of the DMEPA staff are presented 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 Safety Evaluator to supplement the pooled results, or
`general advice to consider when reviewing the proposed proprietary name.
`
`2.1.2 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 Bepreve with marketed U.S. drug names (proprietary and
`established) due to similarity in visual appearance with handwritten prescriptions or verbal pronunciation
`of the drug name. The studies employ a total of 123 (one hundred twenty-three) healthcare professionals
`(pharmacists, physicians, and nurses), and attempts to simulate the prescription ordering process. The
`results are used by the Safety Evaluator to identify any 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 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 the DMEPA staff.
`
`
`
`
`
`6
`
`

`

`Figure 1. Bepreve Study (conducted on December 31, 2008)
`
`
`HANDWRITTEN PRESCRIPTION AND
`MEDICATION ORDER
`
`VERBAL
`PRESCRIPTION
`
`Inpatient Medication Order:
`
`
`
`Outpatient Prescription:
`
`
`
`“Bepreve, number one,
`instill 1 drop into both eyes
`bid”
`
`
`
`
`
`
`
`2.1.3 Comments from the Division of Anti-Infective & Ophthalmology Products
`DMEPA requests the regulatory division in the Office of New Drugs responsible for the application for
`their comments and/or clinical/other concerns on the proposed proprietary name at the initial phase of the
`name review. Additionally, when applicable, at the same time DMEPA requests concurrence/non-
`concurrence with DDMAC’s decision on the name. Any comments or concerns are addressed in the
`safety evaluator’s assessment.
`The review division is contacted a second time following our analysis of the proposed name. At this
`point, DMEPA conveys our decision to accept or reject the name. The regulatory division is requested to
`concur /not concur with DMEPA’s final decision.
`
`2.1.4 Safety Evaluator Risk Assessment of the Proposed Proprietary Name
`Based on the criteria set forth in Section 2.1, the Safety Evaluator Risk Assessment applies their
`individual expertise gained from evaluating medication errors reported to FDA to conduct a Failure Mode
`and Effects Analysis and provide an overall risk 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 name to be confused with another drug name as a result of the name confusion and 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 look- or sound-alike drug names prior to approval, where actions to
`overcome these issues are easier and more effective then remedies available in the post-approval phase.
`In order to perform an FMEA of the proposed name, the Safety Evaluator must analyze the use of the
`product at all points in the medication use system. Because the proposed product is not yet marketed, the
`Safety Evaluator anticipates the use of the product in the usual practice settings by considering the clinical
`and product characteristics listed in Appendix A. 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.
`
`
`6 Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston. IHI:2004.
`
`7
`
`

`

`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 evaluation, and studies, and identifies
`potential failure modes by asking: “Is the name Bepreve 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 Bepreve to be confused with
`another proprietary or established drug name because of orthographic or phonetic 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, then the name is eliminated from
`further review.
`In the second stage of the Risk Assessment, all potential failure modes are evaluated 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 ultimately not be a source of
`medication errors in the usual practice setting, the name is eliminated 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 that an alternate
`proprietary name be used. In rare instances, the FMEA findings may provide other risk-reduction
`strategies; for example, product reformulation to avoid an overlap in strength or an alternate modifier
`designation may be recommended as a means of reducing the risk of medication errors resulting from
`drug name confusion.
`DMEPA will object to the use of proposed proprietary name when the one or more of the following
`conditions are identified in the Safety Evaluator’s 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 trade name or otherwise. [21 U.S.C 321(n); see also 21 U.S.C. 352(a) & (n)].
`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 potential for confusion between the proposed proprietary name and other
`proprietary or established drug names, and 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 stem, particularly in a manner that is
`contradictory to the USAN Council’s definition.
`5. DMEPA staff 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.
`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 is awarded approval first has the
`right to the use the name, while DMEPA will recommend that the second product to reach approval seek
`an alternative name.
`
`8
`
`

`

`If none of these criteria are met, then DMEPA will not object to the use of the proprietary name. If any of
`these criteria are met, then DMEPA will object to the use of the proposed proprietary 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 1 through 5 are supported either by FDA regulation or by external
`healthcare authorities, including the IOM, WHO, Joint Commission, and ISMP, who have examined
`medication errors resulting from look- or sound-alike drug names and called for regulatory authorities to
`address the issue prior to approval.
`Furthermore, DMEPA contends that the threshold set for the Proprietary Name Risk Assessment is
`reasonable because proprietary drug name confusion is a predictable and preventable source of
`medication error that, in many instances, can be identified and remedied prior to approval to avoid patient
`harm.
`Additionally, post-marketing experience has demonstrated that medication errors resulting from drug
`name confusion are notoriously difficult to remedy post-approval. Educational and other post-approval
`efforts are low-leverage strategies that have proven to have limited effectiveness at alleviating medication
`errors involving drug name confusion. Higher-leverage strategies, such as drug name changes, have been
`undertaken 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 the approving the error-prone
`proprietary name. Moreover, even after Applicants