CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`22-350
`
`PROPRIETARY NAME REVIEW! SQ
`
`

`

`7/2/ 0‘7
`
`
`
`Department of Health and Human Services
`Public Health Service
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`
`July 2, 2009
`
`Mary Parks , Director
`Division of Metabolism and Endocrinology Products
`
`Carol Holquist, R.Ph. Director
`Division of Medication Error Prevention and Analysis
`
`Melina Griffis, R.Ph., Acting Team Leader
`Division of Medication Error Prevention and Analysis
`
`Proprietary Name Review
`
`Onglyza (saxagliptin) Tablets, 5 mg and /
`NDA 22-350
`
`Through:
`
`From:
`
`Subj ect:
`
`Drug Name(s):
`
`Application Type/Number:
`
`Applicant/sponsor:
`OSE RCM #:
`
`Bristol-Myers Squibb
`2009—994
`
`

`

`1
`
`INTRODUCTION
`
`This review was written in response to notification that the Division of Metabolism and
`Endocrinology Products is going to take an approval action on this application. The
`proprietary name Onglyza was last reviewed on February 11, 2009 and found to be
`acceptable (see OSE review 2008-967).
`
`1.1
`
`PRODUCT DESCRIPTION
`
`Onglyza (Saxagliptin tablets) is a dipeptidyl peptidase 4 (DPP4) inhibitor indicated as an
`adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.
`The recommended dose of Onglyza is 5 mg once daily with or without food. A single
`dosage adjustment of 2.5 mg daily is recommended for patients with moderate or severe
`renal impairment, or end stage renal disease. Onglyza will be available as 2.5 mg and
`5 mg oral film-coated tablets. All strengths of Onglyza will be available in bottles of 30
`and 90 tablets, and the 5 mg tablets will be available in 500 count bottles and blister
`packs of 100. Additionally, physicians will be given seven day sample packs of the 5 mg
`tablets.
`
`2
`
`DISCUSSION
`
`During our final review of the proposed proprietary name, Onglyza, DMEPA identified
`13 names not previously reviewed in OSE review 2008-967 (listed in Appendix A). Our
`FMEA determined that the 13 identified names were unlikely to result in medication
`errors with Onglyza. Therefore, we have concluded that the proposed proprietary name
`Onglyza remains acceptable for this product.
`
`3
`
`CONCLUSIONS AND RECOMMENDATIONS
`
`We have completed our review of the proposed proprietary name, Onglyza, and have
`concluded that it is acceptable. However, if the product approval is delayed beyond 90
`day from the date of this memo, the proposed name must be resubmitted for evaluation.
`
`If you have further questions or need clarifications, please contact Mildred Wright,
`project manager, at 301-796-1027.
`
`

`

`Appendix A: Additional names identified and reason to discard
`
`eta
`
`Unapproved orphan designated drug product
`
`Unapproved orphan designated drug product
`
`Proposed trademarks listed in USPTO but not located in any
`other drug database
`
`
`
`Originally identified in Micromedix however, unable to
`locate in any pharmaceutical database including Micromedix
`
`International brand for Amiodarone (marketed in Brazil)
`
`Withdrawn by Commissioner on 7/24/1970
`
`Unapproved drug product as of 4-"
`in DSS
`
`no recent activity
`
`Although there is an overlap in dose (5 mg and 10 mg)
`between Abilify and Onglyza orthographic differences in the
`names will likely minimize the risk of medication errors.
`[Abilify contains 3 cross-stokes letters vs 1 for Onglyza.
`Additionally, Onglyza does not contain any dotted letters
`and contains one additional downstoke. These names when
`written are of different shapes]
`
`Although there is a numerical overlap in dose (5 mg vs 0.5
`mg) between Abilify and Agrylin orthographic differences
`in the names will likely minimize the risk of medication
`errors. [Abilify contains 3 cross-stokes letters vs 1 for
`Agrylin. Additionally, Agrylin contains one additional
`downstoke. These names when written are of different
`shapes.)
`
`Different strength availability, dosage form and route of
`administration
`
`Ony-Clear ( 1%
`benzalkonium topical
`solution)
`
`

`

`This is a representation 'of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Melina Griffis
`-
`7/2/2009 08:24:25 AM
`DRUG SAFETY OFFICE REVIEWE
`
`Carol Holquist
`7/2/2009 08:58:12 AM
`DRUG SAFETY OFFICE REVIEWER
`
`

`

`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:
`
`Thm:
`
`From:
`
`February 11, 2009
`
`Mary Parks, MD, Director
`Division of Metabolism and Endocrinology Products
`
`Kristina Amwine, PharmD, Team Leader
`Denise Toyer, PharmD, Deputy Director
`Carol Holquist, RPh, Director
`Division of Medication Error Prevention and Analysis
`
`Anne Crandall, PharmD, Safety Evaluator
`Division of Medication Error Prevention and Analysis
`
`Subject:
`
`Proprietary Name, Label and Labeling Review
`
`Drug Name(s):
`
`Onglyza (Saxagliptin) Tablets
`
`Application
`Type/Number:
`
`2.5 mg and 5 mg
`
`NDA # 22-350
`
`Applicant/sponsor:
`
`Bristol Myer Squibb
`
`OSE RCM #:
`
`2008-967, 2008-1199
`
`*** This document contains proprietary and confidential information that should not
`be released to the public. ***
`
`

`

`CONTENTS
`
`EXECUTIVE SUMMARY ................................................................................................ 1
`
`1
`
`BACKGROUND ......................................................................................................... 1
`
`l . 1
`
`1.2
`1.3
`
`Introduction ......................................................................................................... l
`
`Regulatory History...........................................I................................................... 1
`Product Information ............................................................................................ 1
`
`.2 METHODS AND MATERIALS ................................................................................ 2
`
`2.1
`
`Proprietary Name Risk Assessment .................................................................... 2
`
`Label and Labeling Risk Assessment ................................................................. 9 '
`2.2
`RESULTS .................................................................................................................... 9
`
`3
`
`3.1
`
`Proprietary Name Risk Assessment .................................................................... 9
`
`Label and Labeling Risk Assessment ............................................................... 10
`3.2
`4 DISCUSSION ............................................................................................................ 11
`
`Proprietary Name Risk Assessment .................................................................. 1 1
`4.1
`CONCLUSIONS ....................................................................................................... 12
`
`5
`
`5.1 Comments to the Division ..................................................................................... 12
`
`5.2 Comments to the Applicant ................................................................................... 13
`
`A.
`
`B.
`6
`
`Proposed Proprietary Name Review ..................................................................... 13
`
`Label and Labeling Risk Assessment ................................................................... l3
`REFERENCES .......................................................................................................... 14
`
`APPENDICES .......................’........................................................................................... 13
`
`

`

`EXECUTIVE SUMlVIARY
`
`The Proprietary Name Risk Assessment found that the proposed name, Onglyza is not
`vulnerable to name confusion that could lead to medication errors. Thus, the Division of
`Medication Error Prevention and Analysis does not object to the use of the proprietary
`name Onglyza for this product. If any of the proposed product characteristics as stated in
`this review are altered prior to approval of the product, we rescind this Risk Assessment
`finding, and recommend that the name be resubmitted for review. Additionally, if the
`product approval is delayed beyond 90 days from the signature date of this review, the
`proposed name must be resubmitted for evaluation.
`
`In addition, as part of a proprietary name review, the Division of Medication Error
`Prevention and Analysis reviewed the container labels, carton and insert labeling and noted
`that improvements could be made to the carton labeling and container label to decrease the
`potential for selection errors, to mimimize confusion with dosing, and to increase
`readability of information presented on the labeling. DMEPA believes the risks we have
`identified can be addressed and mitigated prior to drug approval, and provides
`recommendations in Section 6 that aim at reducing the risk of medication errors.
`
`1 BACKGROUND
`
`1 .1 INTRODUCTION
`
`This consult was written in response to a request from the Division of Metabolism and
`Endocrinology Products (DMEP) to evaluate the proposed name, Onglyza, for its potential
`to contribute to medication errors.
`
`1.2 REGULATORY HISTORY
`
`The IND 63,634 was submitted by Bristol-Myers Squibb on November 8, 2001. The NDA
`22—350 for this product was submitted on June 30, 2008. The Division of Medication Error
`Prevention and Analysis (DMEPA) was consulted on June 11, 2008 to review the proposed
`proprietary name, Onglyza. Another consult was received from the Division of Metabolism
`and Endocrine Products on July 23, 2008 to review the label and labeling for Onglyza.
`
`1.3 PRODUCT INFORMATION
`
`Onglyza (Saxagliptin tablets) is a dipeptidyl peptidase 4 (DPP4) inhibitor indicated as an
`adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. The
`recommended dose of Onglyza is 5 mg once daily with or without food. A single dosage
`adjustment of 2.5 mg daily is recommended for patients with moderate or severe renal
`impairment, or end stage renal disease. Onglyza will be available as 2.5 mg and 5 mg oral
`film-coated tablets. All strengths of Onglyza will be available in bottles of 30 and 90
`tablets, and the 5 mg tablets will be available in 500 count bottles and blister packs of 100.
`Additionally, physicians will be given seven day sample packs of the 5 mg tablets.
`
`

`

`2 METHODS AND MATERIALS
`
`This section consists of methods and materials used by medication error staff conducting a
`proprietary name risk assessment (see 2.1 Proprietary Name Risk Assessment) and label,
`labeling, and/or packaging risk assessment (see 2.2 Label and Labeling Risk Assessment).
`The primary focus for this 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.l
`
`2.1 PROPRIETARY NAME RISK ASSESSMENT
`
`FDA’s Proprietary Name Risk Assessment considers the potential for confusion between
`the proposed proprietary name, Onglyza, and the proprietary and established names of drug
`products existing in the marketplace and those pending IND, BLA, NBA, and ANDA
`products. currently under review by CDER.
`
`For the proprietary name, Onglyza, the medication error staff of DMEPA search a standard
`set of databases and information sources to identify names with orthographic and phonetic
`similarity (see Sections 2.1.1 for detail) and held an CDER Expert Panel discussion to
`gather professional opinions on the safety of the proposed proprietary name (see 2.1.1.2).
`The Division also conducts internal FDA prescription analysis studies (see 2.1.2), and,
`when provided, external prescription analysis studies results are considered and
`incorporated into the overall risk assessment (see detail 2.1.4).
`
`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 detail 2.1.4). 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. ‘ FMEA is used to analyze whether the drug
`names identified with look- or sound-alike similarity to the proposed name could cause
`confiision 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 that the product is likely to be used in 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. As such, the Staff considers the product characteristics associated with the
`proposed drug throughout the risk assessment, since 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.
`
`
`
`I Institute for Healthcare Improvement (1H1). Failure Mode and Effects Analysis. Boston. 11-11:2004.
`
`

`

`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, desage 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, the Division of Medication Error Prevention and
`Analysis considers the potential for confiision throughout the entire US. medication use
`process, including drug procurement, prescribing and ordering, dispensing, administration,
`and monitoring the impact of the medication.2
`
`2.1.1
`
`Search Criteria
`
`The medication error 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
`‘0’ 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.34
`-
`
`To identify drug names that may look similar to Onglyza, the staff also consider the
`orthographic appearance of the name on lined and unlined orders. Specific attributes taken
`into consideration include the length of the name (7 letters), upstrokes (two, capital letter
`‘0’, and ‘1’), downstrokes (two, ‘g’, ‘y’, possibly three, ‘2’), cross-strokes (‘2’, depending
`on how scripted), and dotted letters (none). Additionally, several letters in Onglyza may
`be vulnerable to ambiguity when scripted, including the letter ‘0’ may appear as ‘A’;
`,‘,
`"7"
`lower case ‘n’ appears as a lower case ‘v , r , or ‘s’; lower case ‘g’ may appear as lower
`4""
`case, J , q or ‘y’, ; lower case ‘1’ may appear as lower case ‘t’ or ‘f’; lower case ‘y’ may
`‘
`,
`6
`’
`appear as lower case _]
`, q or ‘g’; lower case ‘2’ may appear as ‘m’; and lower case ‘a’
`appears as lower case e , 0 or ‘u’. As such, the staff also considers these alternate
`appearances when identifying drug names that may look similar to Onglyza.
`
`When searching to identify potential names that may sound similar to Onglyza, the
`medication error staff search for names with similar number of syllables (three), stresses
`(ON-gly—za, on—GLY-za or on-gly—ZA), and placement of vowel and consonant sounds. In
`addition, several letters in Onglyza may be subject to interpretation when spoken,
`including the letter ‘0’ may be interpreted as ‘A’ or ‘U’; the letter ‘n’ may be interpreted
`as ‘m’; the letter ‘y’ may be interpreted as ‘i’ or the letter ‘2’ may be interpreted as ‘s’ or
`‘c’. The Applicant’s intended pronunciation of the proprietary (on-GLY-zah) was also
`
`
`
`2 Institute of Medicine. Preventing Medication Errors. The National Academies Press: Washington DC.
`2006.
`
`3 Institute for Safe Medication Practices. Confiised Drug name List (1996-2006). Available at
`hgpzl/wwszmporgz I ools/confuseddrugnamespdf
`4 Kondrack, G and Dorr, B. Automatic ldentification of Confusable Drug Names. Artifical lnteligence in
`Medicine (2005)
`
`

`

`taken into consideration, as this was provided by Q
`name review.
`
`Din the submitted
`
`The staff also considers the product characteristics associated with the proposed drug
`throughout the identification of similar drug names, since the product characteristics of the
`proposed drug ultimately determine the use of the product in the clinical practice setting.
`For this review, the medication error staff were provided with the following information
`about the proposed product:
`the proposed proprietary name (Onglyza), the established
`name (Saxagliptin), indication (adjunct therapy for type 2 diabetes), strength (2.5 mg, 5
`mg), dose (2.5 mg, 5 mg), frequency of administration (once daily), route of administration
`(oral) and dosage form of the product (film-coated tablet). Appendix A provides a more
`detailed listing of the product characteristics the medication error staff general takes into
`consideration.
`‘
`
`Lastly, the medication error staff also considers the potential for the proposed name to
`inadvertently function as a source of error for reasons other than name confusion.
`Postmarketing experience has demonstrated that proprietary names (or components of the
`proprietary name) can be a source of error in a variety of ways. As such, 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 experience with medication errors.
`
`2.1.1.1 Database and Information Sources
`
`The proposed proprietary name, Onglyza, was provided to the medication error staff of
`DMEPA 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 were
`not identified in the previous reviews that may sound—alike or look-alike to Onglyza 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 medication error staff uses a
`computerized method of identifying phonetic and orthographic similarity between
`medication names. The program, Phonetic and Orthographic Computer Analysis (POCA),
`uses complex algorithms to select a list of names from a database that have some similarity
`(phonetic, orthographic, or both) to the trademark being evaluated. Lastly, the medication
`error staff reviews the USAN stem list to determine if any USAN stems are present within
`the proprietary name. The findings of the individual Safety Evaluators were then pooled
`and presented to the Expert Panel.
`
`2.1.1.2 CDER Expert Panel Discussion
`
`An Expert Panel Discussion is held by the Division of Medication Error Prevention and
`Analysis to gather CDER professional opinions on the safety of the product and the
`proprietary name, Onglyza. Potential concerns regarding drug marketing and promotion
`related to the proposed names are also discussed. This group is composed of the DMEPA
`staff and representatives from the Division of Drug Marketing, Advertising, and
`Communications (DDMAC).
`
`The pooled results of the medication error staff were 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 Onglyza with marketed US.
`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 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 Onglyza 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 prescriptions are optically scanned and
`one prescription is delivered to a random sample of 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 medication
`error staff.
`
`-
`
`'
`
`’ VERBAL
`PRESCRIPTION
`
`
`
`
`
`Fi
` ure 1. 0702 Stud
`conducted on Jul 11 2008
`
`
`»
`HANDWRITTEN PRESCRIPITON AND ‘
`
`
`MEDICATION ORDER
`‘
`
`
`
`Inpatient Medication order:
`
`
`
`
`One tablet by mouth once
`daily
`
`
` Out atient Medication Order:
`
`
`W / /
`/¢é~ fl ”6%
`
`Onglyza 5 mg
`
`
`
`2.1.3
`
`External Proprietary Name Risk Assessments
`
`For this product, the Applicant submitted two name validation studies to evaluate the
`proposed proprietary name Onglyza. One study was conducted by. L
`
`.3
`
`[1(4)
`
`

`

`11(4)
`
`and one study was conducted byWW
`.The Division of Medication Error Prevention and Analysis conducts an
`independent analysis and evaluation of the data provided, and responds to the overall
`findings of the assessments. When the external proprietary name risk assessment identifies
`potentially confiising names that were not captured in the Division’s medication error
`staff’s database searches or in the Expert Panel Discussion, these names are included in the
`Safety Evaluator’s Risk Assessment and analyzed independently by the Safety Evaluator to
`determine if the potentially confusing name could lead to medication errors in usual
`practice settings.
`
`After the Safety Evaluator has determined the overall risk assessment of the proposed
`name, the Safety Evaluator compares the findings of their overall risk assessment with the
`findings of the proprietary name risk assessment submitted by the Sponsor. The Safety
`Evaluator then determines whether the Division’s risk assessment concurs or differs with
`the findings. When the proprietary name risk assessments differ, DMEPA provides a
`detailed explanation of these differences.
`
`2.1.4
`
`Safety Evaluator Risk Assessment ofthe Proposed Proprietary Name
`
`Based on the criteria set forth in Section 2.1.1, 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)1s a systematic tool for evaluating
`a process and identifying where and how it might fail.5 When applying FMEA to assess
`the risk of a proposed proprietary name, the Division of Medication Error Prevention and
`Analysis seeks to evaluate the potential for a proposed name to be confiised 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.
`
`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
`Onglyza convincingly similar to another drug name, which may cause practitioners to
`become confused at any point in the usual practice setting?” An affirmative answer
`
`5 Institute for Healthcare Improvement (1H1). Failure Mode and Effects Analysis. Boston. IHI:200_4.
`
`

`

`indicates a failure mode and represents a potential for Onglyza 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 and 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, such as 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.
`
`The Division of Medication Error Prevention and Analysis 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. The Division of Medication Error Preventionand Analysis 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 confirsion 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 confiision 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 identifies a potential source of medication error within the proposed
`proprietary name. 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 the Division of Medication Error Prevention and Analysis objects to the
`use of the proposed proprietary name, based upon the potential for confusion with another
`
`

`

`proposed (but not yet approved) proprietary name, the Division 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 the Division will recommend that the second product to
`reach approval seek an alternative name.
`
`If none of these conditions are met, then the Division of Medication Error Prevention and
`Analysis will not object to the use of the proprietary name. If any of these conditions are
`met, then the Division will object to the use of the proprietary name. The threshold set for
`objection to the proposed proprietary name may seem low to the Sponsor; 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, JCAHO, and ISMP, 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, the Division of Medication Error Prevention and Analysis 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
`efforts and so on are low-leverage strategies that have proven to have limited effectiveness
`at alleviating the 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 Sponsor, 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 Sponsor’s have changed a product’s proprietary
`name in the post-approval phase, it is difficult to eradicate the original proprietary name
`p from practitioner’s vocabulary, and as such, the Agency has continued to receive reports of
`drug name confusion long after a name change in some instances. Therefore, the Division
`of Medication Error Prevention and Analysis 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 limitations of the
`process).
`
`If the Division of Medication Error Prevention and Analysis objects to a proposed
`proprietary name on the basis that drug name confiision could lead to medication errors,
`the FMEA process is used to identify strategies to reduce the risk of medication errors.
`The Division of Medication Error Prevention and Analysis is likely to recommend that the
`Sponsor select an alternative proprietary name and submit the alternate name to the
`Agency for the Division of Medication Error Prevention and Analysis to review.
`However, in rare instances FMEA may identify plausible strategies that could reduce the
`risk of medication error of the currently proposed name, and so the Division of Medication
`Error Prevention and Analysis may be able to provide the Sponsor with recommendations
`that reduce or eliminate the potential for error would render the proposed name acceptable.
`
`

`

`2.2
`
`LABEL AND LABELING RISK ASSESSMENT
`
`The label and labeling of a drug product are the primary means by which