CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 204630Orig1s000 PROPRIETARY NAME REVIEW(S) PROPRIETARY NAME REVIEW Division of Medication Error Prevention and Analysis (DMEPA) Office of Medication Error Prevention and Risk Management (OMEPRM) Office of Surveillance and Epidemiology (OSE) Center for Drug Evaluation and Research (CDER) *** This document contains proprietary information that cannot be released to the public*** Date of This Review: February 19, 2016 Application Type and Number: NDA 204630 Product Name and Strength: ProvayBlue (Methylene Blue) Injection, 50 mg/10 mL (5 mg/mL) Total Product Strength: 50 mg/10 mL Product Type: Single-Ingredient Product Rx or OTC: Rx Applicant/Sponsor Name: Provepharm SAS Panorama #: 2016-2493314 DMEPA Primary Reviewer: Nicole Garrison, PharmD, BCPS DMEPA Team Leader: Yelena Maslov, PharmD Reference ID: 3890234 Contents 1 INTRODUCTION........................................................................................................1 1.1 Regulatory History................................................................................................1 1.2 Product Information ..............................................................................................1 2 RESULTS.....................................................................................................................1 2.1 Misbranding Assessment ......................................................................................1 2.2 Safety Assessment.................................................................................................2 3 CONCLUSIONS..........................................................................................................4 3.1 Comments to the Applicant...................................................................................5 4 REFERENCES.............................................................................................................6 APPENDICES .....................................................................................................................7 Reference ID: 3890234 1 INTRODUCTION This review evaluates the proposed proprietary name, (b) (4) , from a safety and misbranding perspective. The sources and methods used to evaluate the proposed name are outlined in the reference section and Appendix A respectively. The Applicant did not submit an external name study for this proposed proprietary name. 1.1 REGULATORY HISTORY The Applicant previously submitted the proposed proprietary name, (b) (4) on October 31, 2013. However, the Office of Prescription Drug Promotion (OPDP) found the name, (b) (4) unacceptable because it was misleading in OSE Review #2013- 2553, dated November 26, 2013. Thus, the Applicant submitted the name, (b) (4) for review on March 13, 2014. The application received a CR and was re-submitted for review on October 9, 2015. However, DMEPA found the name, (b) (4) unacceptable in OSE Review #2015- 1719756, dated December 21, 2015. Thus, the Applicant submitted the name, ProvayBlue, for review on January 11, 2016. 1.2 PRODUCT INFORMATION The following product information is provided in the January 11, 2016 proprietary name submission. • Intended Pronunciation: (/proh/-/vay/-/bloo/) • Active Ingredient: Methylene Blue • Indication of Use: Antidote for the treatment of acquired methemoglobinemia • Route of Administration: Intravenous • Dosage Form: Injection • Strength: 50 mg/mL (5 mg/mL) • Recommended Dose and Frequency in Adults and Children (b) (4) o 1 mg/kg (b) (4) intravenously over a period of 5 minutes o A repeat dose of up to 1 mg/kg (b) (4) may be given one hour after the first dose (b) (4) • How Supplied: 10 mL ampules Reference ID: 3890234 1 • Storage: Store at 20°C to 25°C (68°F to 77°F) 2 RESULTS The following sections provide information obtained and considered in the overall evaluation of the proposed proprietary name. 2.1 MISBRANDING ASSESSMENT The Office of Prescription Drug Promotion (OPDP) determined that the proposed name would not misbrand the proposed product. DMEPA and the Division of Hematology Products (DHP) concurred with the findings of OPDP’s 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 There is no USAN stem present in the proprietary name1. 2.2.2 Components of the Proposed Proprietary Name The Applicant indicated in their submission that the proposed name, ProvayBlue, is a derivation of the company name, Provepharm, plus the established name of the drug substance (USAN) name, methylene blue. This proprietary name is comprised of a multiple words that do not contain any components (i.e. a modifier, route of administration, dosage form, etc.) that are misleading or can contribute to medication error. 2.2.3 FDA Name Simulation Studies Sixty-four practitioners participated in DMEPA’s prescription studies. One practitioner misinterpreted the voice prescription as “Pronate”, which is a close variation of the marketed product, Prenate. See section 2.2.6 for further discussion for this name. Voice prescriptions had the most varied interpretations. Appendix B contains the results from the verbal and written prescription studies. 2.2.4 Comments from Other Review Disciplines at Initial Review In response to the OSE, January 19, 2016 e-mail, the Division of Hematology Products (DHP) did not forward any comments or concerns relating to the proposed proprietary name at the initial phase of the review. 2.2.5 Phonetic and Orthographic Computer Analysis (POCA) Search Results Table 1 lists the number of names with the combined orthographic and phonetic score of ≥50% retrieved from our POCA search2 organized as highly similar, moderately similar 1USAN stem search conducted on January 12, 2016. Reference ID: 3890234 2 or low similarity for further evaluation. Table 1 also includes names identified from the FDA Prescription Simulation Study. Table 1. POCA Search Results Number of Names Highly similar name pair: 4 combined match percentage score ≥70% Moderately similar name pair: 107 combined match percentage score ≥50% to ≤ 69% Low similarity name pair: 0 combined match percentage score ≤49% 2.2.6 Safety Analysis of Names with Potential Orthographic, Spelling, and Phonetic Similarities In the voice study, 1 participant misinterpreted ProvayBlue for “Pronate”. Pronate is a close variation to the marketed product, Prenate. Despite the misinterpretation in the FDA Rx Study, we do not think that the name pair ProvayBlue and Prenate, has a potential for confusion in the acutal use environment for the following reasons: 1. ProvayBlue and Prenate (Combined POCA 49% and Orthographic POCA 58%) have signficant orthographic and phonetic differences. ProvayBlue has one downstroke in the sixth position compared to Prenate, which does not contain a downstroke. ProvayBlue contains 10 letters versus Prenate which contains 7 letters. The infixes and suffixes of this name pair has sufficient orthographic differences. 2. ProvayBlue has 3 syllables and Prenate has 2 syllables (Phonetic POCA 40%). 3. Additionally, this name does not share any overlapping product characteristics. Our analysis of the 111 names contained in Table 1 determined 111 names will not pose a risk for confusion as described in Appendices C through H. 2.2.7 Communication of DMEPA’s Analysis at Midpoint of Review DMEPA communicated our findings to the Division of Hematology Products (DHP) via e-mail on February 17, 2016. At that time we also requested additional information or concerns that could inform our review. Per e-mail correspondence from the DHP on February 18, 2016, they stated no additional concerns with the proposed proprietary name, ProvayBlue. 3 CONCLUSIONS The proposed proprietary name is acceptable. 2 POCA search conducted on January 11, 2016. Reference ID: 3890234 3 If you have any questions or need clarifications, please contact Sarah Harris, OSE project manager, at 240-402-4774. 3.1 COMMENTS TO THE APPLICANT We have completed our review of the proposed proprietary name, ProvayBlue, and have concluded that this name is acceptable. If any of the proposed product characteristics as stated in your January 11, 2016 submission are altered prior to approval of the marketing application, the name must be resubmitted for review. 4 REFERENCES 1. USAN Stems (http://www.ama-assn.org/ama/pub/physician-resources/medical- science/united-states-adopted-names-council/naming-guidelines/approved-stems.page) USAN Stems List contains all the recognized USAN stems. 2. Phonetic and Orthographic Computer Analysis (POCA) POCA is a system that FDA designed. As part of the name similarity assessment, POCA is used to evaluate proposed names via a phonetic and orthographic algorithm. The proposed proprietary name is converted into its phonemic representation before it runs through the phonetic algorithm. Likewise, an orthographic algorithm exists that operates in a similar fashion. POCA is publicly accessible. Drugs@FDA Drugs@FDA is an FDA Web site that contains most of the drug products approved in the United States 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 and generic drugs; therapeutic biological products, prescription and over-the-counter human drugs; and discontinued drugs (see Drugs @ FDA Glossary of Terms, available at http://www.fda.gov/Drugs/InformationOnDrugs/ucm079436.htm#ther