CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`204654Orig1s000
`
`PROPRIETARY NAME REVIEW(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
`Office of Medication Error Prevention and Risk Management
`
`Proprietary Name Review
`
`Date:
`
`July 9, 2013
`
`Manizheh Siahpoushan, PharmD
`Reviewer:
`Division of Medication Error Prevention and Analysis
`
`James Schlick, RPh, MBA
`Acting Team Leader:
`Division of Medication Error Prevention and Analysis
`
`Carol Holquist, RPh
`Division Director:
`Division of Medication Error Prevention and Analysis
`
`Lo Minastrin Fe
`Drug Name and Strength:
`(Norethindrone Acetate and Ethinyl Estradiol Chewable
`
`Tablets, Ethinyl Estradiol Tablets, and Ferrous Fumarate
`
`Tablets)
`
`1 mg/10 mcg and 10 mcg and 75 mg
`
`Application Type/Number: NDA 204654
`Applicant/Sponsor:
`Warner Chilcott
`OSE RCM #:
`2013-1522
`
`*** This document contains proprietary and confidential information that should not be
`released to the public.
`
`
`
`
`
`Reference ID: 3338192
`
`

`

`
`
`CONTENTS
`
`1
`
`INTRODUCTION................................................................................................................... 1
`1.1
`Regulatory History .......................................................................................................... 1
`1.2
`Product Information......................................................................................................... 1
`2 RESULTS................................................................................................................................ 2
`2.1
`Promotional Assessment ................................................................................................. 2
`2.2
`Safety Assessment........................................................................................................... 2
`3 CONCLUSIONS ..................................................................................................................... 6
`3.1
`Comments to the Applicant............................................................................................. 6
`4 REFERENCES........................................................................................................................ 7
`APPENDICES............................................................................................................................... 10
`
`
`
`
`
`
`Reference ID: 3338192
`
`1
`
`

`

`
`
`1
`INTRODUCTION
`This review evaluates the proposed proprietary name, Lo Minastrin Fe, from a safety and
`promotional perspective. The sources and methods used to evaluate the proposed name
`are outlined in the reference section and Appendix A respectively.
`
`1.1
`REGULATORY HISTORY
`Warner Chilcott LLC submitted a request for proprietary name review for Lo Minastrin
`Fe (Norethindrone Acetate and Ethinyl Estradiol Chewable Tablets, Ethinyl Estradiol
`Tablets, and Ferrous Fumarate Tablets) for NDA 204654 on June 27, 2013. The first
`proposed proprietary name,
`was found unacceptable in OSE
`Review #2013-860 dated June 12, 2013.
`The New Drug Application for this product was submitted by the Applicant under
`Section 505(b)(1) on September 28, 2012. This NDA provides for a new method of
`administration for low dose oral contraception consisting of mint-flavored, chewable
`tablets. The proposed regimen is the same as the approved regimen for Lo Loestrin Fe
`(NDA 022501, approved October 21, 2010) by Applicant holder, Warner Chilcott LLC.
`The main difference with NDA 204654 is that the first 24 active tablets may be chewed
`before swallowing and followed with liquid
`. Once
`approved, the Applicant plans to discontinue Lo Loestrin Fe.
`Additionally, the Applicant submitted labels and labeling on June 27, 2013 which will be
`reviewed by DMEPA under a separate cover in OSE Review #2013-1-1.
`
`1.2
`PRODUCT INFORMATION
`The following product information is provided in the June 27, 2013 proprietary name
`submission.
`• Active Ingredient: Norethindrone Acetate and Ethinyl Estradiol Chewable
`Tablets, Ethinyl Estradiol Tablets and Ferrous Fumarate Tablets
`•
`Indication of Use: Prevention of Pregnancy
`• Route of Administration: Oral
`• Dosage Form: Chewable Tablets and Tablets
`• Strength: 1 mg/10 mcg, 10 mcg, and 75 mg
`• Dose and Frequency: Take one tablet by mouth at the same time every day. The
`blue tablet may be
` chewed and swallowed. If the blue tablet
`is chewed, the patient should drink a full glass (8 ounces) of liquid immediately
`after swallowing. The white tablet and the brown tablet are swallowed.
`• How Supplied: Carton of 5 blister cards; each blister card contains 24 blue, round
`(active) chewable tablets containing 1 mg norethindrone and 10 mcg ethinyl
`estradiol, 2 white hexagonal (active) tablets containing 10 mcg ethinyl estradiol,
`and 2 brown, round (non-hormonal placebo) tablets containing 75 mg ferrous
`fumarate.
`
`Reference ID: 3338192
`
`
`1
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`0
`
`Storage: Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F)
`
`0 Container and Closure System: Primary packaging consists of unit-dose blisters
`consisting of
`(ma) blister film and an aluminum foil/vinyl heat-seal
`coated lidding. Secondary packaging consists of a rigid (m4) card bonded to the
`unit-dose blister, prescriber and patient package inserts, and aw’board cartons.
`
`2 RESULTS
`
`The following sections provide information obtained and considered in the overall
`evaluation of the proposed proprietary name.
`
`2.1
`
`PROMOTIONAL ASSESSMENT
`
`The Office of Prescription Drug Promotion OPDP determined the proposed name is
`acceptable from a promotional perspective. DMEPA and the Division Of Bone,
`Reproductive, and Urologic Products concurred with the findings of OPDP’s promotional
`assessment Of the proposed name.
`
`2.2
`
`SAFETY ASSESSMENT
`
`The following aspects were considered in the safety evaluation of the name.
`
`2.2.1 United States Adopted Names (USAN) SEARCH
`
`The June 28, 2013 search of the United States Adopted Name (USAN) stems did not
`identify that a USAN stem is present in the proposed proprietary name.
`
`2.2.2 Components ofthe Proposed Proprietary Name
`
`The proprietary name is comprised of the root name ‘Minastrin’ and the modifiers ‘Lo’
`and ‘Fe’. The Applicant indicated in their submission that a derivation of the proposed
`proprietary name has not been determined. They further indicate that the modifier ‘Lo’
`denotes the low dose of estrogen in this product, and the modifier ‘Fe’ denotes the
`Ferrous Fumarate tablets (non-hormonal) provided to complete a 28-day cycle.
`
`The Applicant did not provide data to support the use of these modifiers, nor provide data
`to support that these modifiers would not inadvertently introduce a source of error.
`However, the Applicant followed the same naming convention for the proposed name, Lo
`Minastrin Fe, as that Of the reference listed drug, Lo Loestrin Fe.
`
`The ‘Fe’ modifier in oral contraceptive products has consistently meant 75 mg of Ferrous
`Fumarate. The Applicant is proposing to use the modifier ‘Fe’ consistently with how it is
`used in the reference listed drug. Similarly, the ‘Lo’ modifier is used for other approved
`oral contraceptive products to represent lower estrogen content or lower estrogen and
`progestin content. The Applicant is proposing to use the modifier ‘Lo’ consistently with
`how it is used in the reference listed drug, and the amount of Ethinyl Estradiol in the
`proposed product, Lo Minastrin Fe is indeed less than that found in the Applicant’s other
`proposed Minastrin product (i.e., Minastrin 24 Few) which is currently under review by
`the Agency. Additionally, DIVIEPA has previously reviewed and permitted the modifiers
`‘Lo’ and ‘Fe’ into the marketplace in the past. Table 1 provides a comparison of Warner
`Chilcott’s Loestrin product line as well as their new proposed products, Minastrin 24
`
`Reference ID: 3338192
`
`2
`
`

`

`Fe... and Lo Minastrin Fe.
`
`Table 1: Loestrin
`
`Loestrin
`Product Name Lo
`Loestrin Minastrin 24 Fe
`
`Fe
`
`Feififiii.
`
`
`
`Combination
`tablets
`
`Norethiudrone
`
`NAlmg/
`EB") "“3
`(24 tablets)
`
`NAlmg/
`5520““
`(24 tablets)
`
`NAlmg/ musing NAlmg/
`EEZOmcg
`EE30mcg
`EE20 mcg
`(21 tablets)
`(21 tablets)
`(21 tablets)
`
`NAl.5mg/
`EE30mcg
`(21 tablets)
`
`acetate (NA)
`
`and Ethinyl
`estradiol
`
`Ethinyl
`estradiol (EE)
`tablets
`
`Ferrous
`fumarate
`
`tablets
`
`Monthly
`estrogen
`content
`
`DMEPA conducted a search of the FDA Adverse Event Reporting System G‘AERS) on
`July 2, 2013 to identify potential problems with the nomenclature of the Loestrin product
`line. This search identified the same number of relevant cases related to the Loestrin
`
`product line that were identified in OSE Review #2009-2349 dated January 19, 2010 (Lo
`Loestrin Fe Proprietary Name Review), OSE Review #2012- 1408, 2012- 1409 dated
`March 21, 2013
`(m4) Proprietary Name Review) and OSE
`Review #2013-1 dated May 21, 2013
`”(oLabel, Label, and Packaging Review). All
`of these cases were wrong drug errors and included eight reports of confusion between
`the strengths of the Loestrin Fe products (i.e., Loestrin Fe 1/20, which are represented by
`numerical modifiers (e.g. 1/20 and 1.5/30), and two reports of confusion between
`Loestrin Fe 24 and Lo Loestrin Fe. No cases of confusion between Loestrin Fe and the
`
`non-iron containing Loestrin products were identified, which helps to support the safety
`of the “Fe” modifier. No additional cases of wrong drug errors have been reported since
`July 9, 2012. See Appendix G for a list of the case numbers retrieved from the
`July 2, 2013 FAERS search.
`
`In our assessment of the modifiers ‘Lo’ and ‘Fe’, we also considered the possibility of
`these modifiers being omitted from prescriptions or medication orders. The results of our
`written prescription studies identified three participants who omitted the ‘Fe’ modifier on
`the medication order. However, none of the participants omitted the ‘L0’ modifier. This
`
`883
`
`This document contains proprietary and confidential information that should not be released to the
`public.
`
`Reference ID: 3338192
`
`3
`
`

`

`can be attributed to the fact that based on post-marketing reports of medication errors
`resulting from practitioners dropping the modifier ‘Lo’ when it appears at the end of the
`name, DMEPA now recommends incorporating the modifier ‘Lo’ at the beginning of the
`name or within the name. The name submitted by the Applicant follows this
`recommendation which should help prevent the modifier ‘Lo’ from being overlooked
`when included on a prescription. Therefore, even if the modifier ‘Fe’ is omitted from a
`prescription order that is intended for L0 Minastrin Fe, the presence of the modifier ‘Lo’
`can help differentiate this product from the other Minastrin products (i.e., Minastrin 24
`Fe-'-).
`
`Although confusion between products with similar root names but differing modifiers
`(i.e., Lo Minastrin Fe and Minastrin 24 Few) is a possibility, the Applicant is proposing
`to use the modifiers ‘Lo’ and ‘Fe’ in the proposed product, Lo Minastrin Fe, as they are
`consistently used in the oral contraceptive marketplace. Additionally, adequate
`differentiation of the labels and labeling associated with the Minastrin products may help
`minimize confusion, especially if the
`(m4)
`Thus, in consideration of the
`
`total data available, DMEPA does not object to the use of the modifiers, ‘Lo’ and ‘Fe’.
`
`2.2.3 FDA Name Simulation Studies
`
`Thirty-two practitioners participated in DMEPA’s prescription studies. The
`interpretations did not overlap with any currently marketed products nor did the
`misinterpretations sound or look similar to any currently marketed products or any
`products in the pipeline. Thirteen out of thirty-two prescription study participants
`interpreted the name correctly as Lo Minastrin Fe (9 outpatient and 4 inpatient
`participants). All ten voice prescription study participants misinterpreted the modifier
`‘Lo’. The misinterpretations included the following: ‘Blo’, ‘Blu’, ‘Bo’, and ‘Bul’.
`Other misinterpretations included confusing the second position vowel ‘i’ as ‘e’, the
`t
`3
`€"
`‘
`, ",
`fourth position vowel ‘a’ as e ,
`1 , and ‘u’, and the eighth position vowel ‘i’ as a ,
`1 ,
`‘o’, ‘u’, ‘e’, and ‘ai’, in the root name Minastrin in the voice and inpatient prescription
`studies. Three inpatient prescription study participants omitted the ‘Fe’ modifier. We
`have considered these variations including those related to the modifier ‘L0’ in our look—
`alike and sound—alike searches and analysis (see Appendix B). See Appendix C for the
`complete listing of interpretations from the verbal and written prescription studies.
`
`2.2.4 Comments from Other Review Disciplines at Initial Review
`
`In response to the OSE, July 5, 2013 e-mail, the Division of Bone, Reproductive, and
`Urologic Products, (DBRUP) did not forward any comments or concerns relating to the
`proposed proprietary name at the initial phase of the review.
`
`2.2.5 Failure Mode and Effects Analysis ofSimilar Names
`
`Appendix B lists possible orthographic and phonetic misinterpretations of the letters
`appearing in the proposed proprietary name, Lo Minastrin Fe. Table 2 lists the names
`
`383
`
`This document contains proprietary and confidential information that should not be released to the
`public.
`
`Reference ID: 3338192
`
`4
`
`

`

`with orthographic, phonetic, or spelling similarity to the proposed proprietary name, Lo
`Minastrin Fe identified by the primary reviewer and the Expert Panel Discussion (EPD),
`which were not previously identified and evaluated in OSE Review #2013-1490. Since
`our evaluation found that none of the product characteristics have changed, we did not re-
`evaluate the previously identified names. See Appendix F for a list of these names.
`
`Table 2: Collective List of Potentially Similar Names (DMEPA and EPD)
`
`Look Similar
`
`Name
`
`Source
`
`Name
`
`Source
`
`Name
`
`Source
`
`Lorna
`
`Asthma
`
`EPD
`
`Lomustine
`
`EPD
`
`Lovastatin
`
`EPD
`
`Name
`
`Source
`
`Name
`
`Source
`
`Name
`
`Source
`
`Look and Sound Similar
`
`(m4)
`
`EPD
`
`(mo
`
`EPD
`
`Our analysis of the five names contained in Table 2 considered the information obtained
`in the previous sections along with their product characteristics. We determined none of
`the five names will pose a risk for confusion as described in Appendices D through E.
`
`2.2. 6 Communication ofDMEPA ’s Analysis at Midpoint ofReview
`
`DMEPA communicated our findings to the Division of Bone, Reproductive, and
`Urologic Products via e—mail on July 8, 2013. At that time we also requested additional
`information or concerns that could inform our review. Per e-mail correspondence from
`the Division of Bone, Reproductive, and Urologic Products on July 9, 2013, they stated
`no additional concerns with the proposed proprietary name, Lo Minastrin Fe.
`
`383
`
`This document contains proprietary and confidential information that should not be released to the
`public.
`
`Reference ID: 3338192
`
`5
`
`

`

`
`
`3 CONCLUSIONS
`The proposed proprietary name is acceptable from both a promotional and safety
`perspective.
`If you have further questions or need clarifications, please contact Marcus Cato, OSE
`project manager, at 301-796-3903.
`
`3.1
`COMMENTS TO THE APPLICANT
`We have completed our review of the proposed proprietary name, Lo Minastrin Fe, and
`have concluded that this name is acceptable.
`The proposed proprietary name must be re-reviewed 90 days prior to approval of the
`NDA. The results are subject to change. If any of the proposed product characteristics as
`stated in your June 27, 2013 submission are altered, the name must be resubmitted for
`review.
`
`
`Reference ID: 3338192
`
`
`6
`
`

`

`
`
` 4
`
` REFERENCES
`OSE Review #2013-1490, Minastrin 24 Fe Proprietary Name Review, Siahpoushan, M.,
`July 1, 2013.
`Label, Labeling, and Packaging Review, Park, A.,
`OSE Review #2013-1,
`Siahpoushan, M., May 21, 2013
`OSE Review #2012-78/2012-79, 2012-65/2012-66, 2012-110/2012-111, 2012-
`
`1408/2012/1409,
`Proprietry name, Label, Labeling, and Packaging Review, Brody, S., March 21, 2013.
`OSE Review #2009-2349, Lo Loestrin Fe Proprietary Name Review, Turner, T.,
`January 19, 2010.
`
`1. Micromedex Integrated Index (http://csi.micromedex.com)
`Micromedex contains a variety of databases covering pharmacology, therapeutics,
`toxicology and diagnostics.
`
`2. Phonetic and Orthographic Computer Analysis (POCA)
`POCA is a database which was created for the Division of Medication Error
`Prevention and Analysis, FDA. As part of the name similarity assessment, proposed
`names are evaluated via a phonetic/orthographic algorithm. The proposed proprietary
`name is converted into its phonemic representation before it runs through the phonetic
`algorithm. Likewise, an orthographic algorithm exists which operates in a similar
`fashion.
`
`3. Drug Facts and Comparisons, online version, St. Louis, MO
`(http://factsandcomparisons.com)
`Drug Facts and Comparisons is a compendium organized by therapeutic course; it
`contains monographs on prescription and OTC drugs, with charts comparing similar
`products. This database also lists the orphan drugs.
`
`4. FDA Document Archiving, Reporting & Regulatory Tracking System [DARRTS]
`DARRTS is a government database used to organize Applicant and Sponsor
`submissions as well as to store and organize assignments, reviews, and
`communications from the review divisions.
`
`5. Division of Medication Errors Prevention and Analysis proprietary name
`consultation requests
`This is a list of proposed and pending names that is generated by the Division of
`Medication Error Prevention and Analysis from the Access database/tracking system.
`
`Reference ID: 3338192
`
`
`7
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`6. Drugs@FDA (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm)
`Drugs@FDA contains most of the drug products approved since 1939. The majority of
`labels, approval letters, reviews, and other information are available for drug products
`approved from 1998 to the present. Drugs@FDA contains official information about FDA
`approved brand name, generic drugs, therapeutic biological products, prescription and over-
`the-counter human drugs and discontinued drugs and “Chemical Type 6” approvals.
`7. U.S. Patent and Trademark Office (http://www.uspto.gov)
`USPTO provides information regarding patent and trademarks.
`
`8. Clinical Pharmacology Online (www.clinicalpharmacology-ip.com)
`Clinical Pharmacology contains full monographs for the most common drugs in
`clinical use, plus mini monographs covering investigational, less common,
`combination, nutraceutical and nutritional products. It also provides a keyword search
`engine.
`
`9. Natural Medicines Comprehensive Databases (www.naturaldatabase.com)
`Natural Medicines contains up-to-date clinical data on the natural medicines, herbal
`medicines, and dietary supplements used in the western world.
`
`10. Access Medicine (www.accessmedicine.com)
`Access Medicine® from McGraw-Hill contains full-text information from
`approximately 60 titles; it includes tables and references. Among the titles are:
`Harrison’s Principles of Internal Medicine, Basic & Clinical Pharmacology, and
`Goodman and Gilman’s The Pharmacologic Basis of Therapeutics.
`
`11. USAN Stems (http://www.ama-assn.org/ama/pub/about-ama/our-people/coalitions-
`consortiums/united-states-adopted-names-council/naming-guidelines/approved-
`stems.shtml)
`USAN Stems List contains all the recognized USAN stems.
`
`12. Red Book (www.thomsonhc.com/home/dispatch)
`Red Book contains prices and product information for prescription, over-the-counter
`drugs, medical devices, and accessories.
`
`13. Lexi-Comp (www.lexi.com)
`Lexi-Comp is a web-based searchable version of the Drug Information Handbook.
`
`14. Medical Abbreviations (www.medilexicon.com)
`Medical Abbreviations dictionary contains commonly used medical abbreviations and
`their definitions.
`
`Reference ID: 3338192
`
`
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`

`
`
`15. CVS/Pharmacy (www.CVS.com)
`This database contains commonly used over the counter products not usually
`identified in other databases.
`
`16. Walgreens (www.walgreens.com)
`This database contains commonly used over the counter products not usually
`identified in other databases.
`
`17. Rx List (www.rxlist.com)
`RxList is an online medical resource dedicated to offering detailed and current
`pharmaceutical information on brand and generic drugs.
`
`18. Dogpile (www.dogpile.com)
`Dogpile is a Metasearch engine that searches multiple search engines including
`Google, Yahoo! and Bing, and returns the most relevant results to the search.
`
`19. Natural Standard (http://www.naturalstandard.com)
`Natural Standard is a resource that aggregates and synthesizes data on complementary
`and alternative medicine.
`
`Reference ID: 3338192
`
`
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`

`
`
`APPENDICES
`Appendix A
`FDA’s Proprietary Name Risk Assessment considers the promotional and safety aspects
`of a proposed proprietary name. The promotional review of the proposed name is
`conducted by OPDP. OPDP evaluates proposed proprietary names to determine if they
`are overly fanciful, so as to misleadingly imply unique effectiveness or composition, as
`well as to assess whether they contribute to overstatement of product efficacy,
`minimization of risk, broadening of product indications, or making of unsubstantiated
`superiority claims. OPDP provides their opinion to DMEPA for consideration in the
`overall acceptability of the proposed proprietary name.
`The safety assessment is conducted by DMEPA. DMEPA staff search a standard set of
`databases and information sources to identify names that are similar in pronunciation,
`spelling, and orthographically similar when scripted to the proposed proprietary name.
`Additionally, we consider inclusion of USAN stems or other characteristics that when
`incorporated into a proprietary name may cause or contribute to medication errors (i.e.,
`dosing interval, dosage form/route of administration, medical or product name
`abbreviations, names that include or suggest the composition of the drug product, etc.).
`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
`Following the preliminary screening of the proposed proprietary name, DMEPA gathers
`to discuss their professional opinions on the safety of the proposed proprietary name.
`This meeting is commonly referred to the Center for Drug Evaluation and Research
`(CDER) Expert Panel discussion. DMEPA also considers other aspects of the name that
`may be misleading from a safety perspective. DMEPA staff conducts a prescription
`simulation studies using FDA health care professionals. When provided, DMEPA
`considers external proprietary name studies conducted by or for the Applicant/Sponsor
`and incorporates the findings of these studies into the overall risk assessment.
`The DMEPA primary reviewer assigned to evaluate the proposed proprietary name 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 misleading nature of the proposed proprietary name with a focus on the avoidance of
`medication errors.
`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. DMEPA considers the product characteristics associated with the proposed
`product 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.
`
`1 National Coordinating Council for Medication Error Reporting and Prevention.
`http://www nccmerp.org/aboutMedErrors html. Last accessed 10/11/2007.
`
`Reference ID: 3338192
`
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`

`
`
`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. DMEPA considers how these
`product characteristics may or may not be present in communicating a product name
`throughout the medication use system. 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.2
`The DMEPA considers the spelling of the name, pronunciation of the name when spoken, and
`appearance of the name when scripted. DMEPA compares the proposed proprietary name
`with the proprietary and established name of existing and proposed drug products and names
`currently under review at the FDA. DMEPA 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. DMEPA examines the phonetic
`similarity using patterns of speech. If provided, DMEPA will consider the Sponsor’s intended
`pronunciation of the proprietary name. However, DMEPA also considers a variety of
`pronunciations that could occur in the English language because the Sponsor has little control
`over how the name will be spoken in clinical practice. The orthographic appearance of the
`proposed name is evaluated using a number of different handwriting samples. DMEPA
`applies expertise gained from root-cause analysis of postmarketing 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).
`
`
`
`
`
`
`
`
`
`
`2 Institute of Medicine. Preventing Medication Errors. The National Academies Press: Washington DC.
`2006.
`
`Reference ID: 3338192
`
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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
`
`Attributes Examined to Identify
`Similar Drug Names
`
`Potential Effects
`
`Potential
`Causes of Drug
`Name
`Similarity
`
`Similar spelling
`
`
`Type of
`Similarity
`
`
`
`
`
`
`Look-
`alike
`
`Orthographic
`similarity
`
`Identical prefix
`Identical infix
`Identical suffix
`Length of the name
`Overlapping product
`characteristics
`
`• 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
`
`Similar spelling
`Length of the name/Similar
`shape
`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, DMEPA 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
`
`Sound-
`alike
`
`Phonetic
`similarity
`
`
`• Names may sound similar
`when pronounced and lead
`to drug name confusion in
`verbal communication
`
`Reference ID: 3338192
`
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`
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`safety of the proposed proprietary name or product based on professional experience with
`medication errors.
`
`1. Database and Information Sources
`DMEPA searches the internet, several standard published drug product reference texts,
`and FDA databases to identify existing and proposed drug names that may sound-alike or
`look-alike to the proposed proprietary name. A standard description of the databases
`used in the searches is provided in the reference section of this review. To complement
`the process, the DMEPA 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, DMEPA reviews 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. DMEPA
`also evaluates if there are characteristics included in the composition that may render the
`name unacceptable from a safety perspective (abbreviation, dosing interval, etc.).
`
`2. Expert Panel Discussion
`DMEPA gathers gather CDER professional opinions on the safety of the proposed
`product and discussed the proposed proprietary name (Expert Panel Discussion). The
`Expert Panel is composed of Division of Medication Errors Prevention (DMEPA) staff
`and representatives from the Office of Prescription Drug Promotion (OPDP). We also
`consider input from other review disciplines (OND, ONDQA/OBP). 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 database and information
`searches to the Expert Panel for consideration. Based on the clinical and professional
`experiences of the Expert Panel members, the Panel may recommend additional names,
`additional searches by the primary Safety Evaluator to supplement the pooled results, or
`general advice to consider when reviewing the proposed proprietary name.
`
`3. FDA Prescription Simulation Studies
`Three separate studies are conducted within the Centers of the FDA for the proposed
`proprietary name to determine the degree of confusion of the proposed proprietary name
`with marketed U.S. drug names (proprietary and established) due to similarity in visual
`appearance with handwritten prescriptions or verbal pronunciation of the drug name. The
`studies employ healthcare professionals (pharmacists, physicians, and nurses), and
`attempts to simulate the prescription ordering process. The primary Safety Evaluator
`uses the results to identify orthographic or phonetic vulnerability of the proposed name to
`be misinterpreted by healthcare practitioners.
`In order to evaluate the potential for misinterpretation of the proposed proprietary name
`in handwriting and verbal communication of the name, inpatient medication orders and/or
`outpatient prescriptions are written, each consisting of a combination of marketed and
`unapproved drug products, including the proposed name. These orders are optically
`
`Reference ID: 3338192
`
`
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`

`
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`scanned and one prescription is delivered to a random sample of 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 record their interpretations of the orders which
`are recorded electronically.
`
`4. Comments from Other Review Disciplines
`DMEPA requests the Office of New Drugs (OND) and/or Office of Generic Drugs
`(OGD), ONDQA or OBP for their comments or concerns with the proposed proprietary
`name, ask for any clinical issues that may impact the DMEPA review during the