CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`203567Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`PMR/PMC Development Template
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`NDA/BLA #
`Product Name:
`
`203567
`Jublia (efinaconazole) topical solution, 10%
`
`PMR/PMC Description: A Multicenter, Randomized, Double-Blind Study Evaluating the
`Safety, Efficacy and Pharmacokinetics of Jublia Topical Solution, 10%
`versus Vehicle in Pediatric Subjects ages 12 to 17 years with
`Onychomycosis of the Toenails
`
`PMR/PMC Schedule Milestones: Final Protocol Submission:
`Study/Trial Completion:
`Final Report Submission:
`Other:
`
`09/30/2014
`03/31/2018
`09/30/2018
`MM/DD/YYYY
`
`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a pre-approval
`requirement. Check type below and describe.
`Unmet need
`Life-threatening condition
`Long-term data needed
`Only feasible to conduct post-approval
`Prior clinical experience indicates safety
`Small subpopulation affected
`Theoretical concern
`Other
`
`There is insufficient data provided by the sponsor for subjects ages 12 through 17. Therefore additional
`studies are required under PREA. Since the adult studies are completed and Jublia is ready for approval,
`then a deferral of PREA studies is appropriate.
`
`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is a
`FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new safety
`information.”
`
`PMR/PMC Development Template
`
`Last Updated 5/28/2014
`
`Page 1 of 4
`
`Reference ID: 3513844
`
`

`

`This application triggers PREA. The goal of the pediatric study is to obtain pediatric safety data.
`
`3.
`
`If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
`Accelerated Approval (subpart H/E)
`Animal Efficacy Rule
`Pediatric Research Equity Act
`FDAAA required safety study/clinical trial
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
`Assess a known serious risk related to the use of the drug?
`Assess signals of serious risk related to the use of the drug?
`Identify an unexpected serious risk when available data indicate the potential for a serious risk?
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
`Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to assess
`or identify a serious risk
`
`Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the FDA
`is required to establish under section 505(k)(3) has not yet been established and is thus not sufficient
`to assess this known serious risk, or has been established but is nevertheless not sufficient to assess
`or identify a serious risk
`
`Study: all other investigations, such as investigations in humans that are not clinical trials as defined
`below (e.g., observational epidemiologic studies), animal studies, and laboratory experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a serious
`risk
`
`Clinical trial: any prospective investigation in which the sponsor or investigator determines the
`method of assigning investigational product or other interventions to one or more human subjects?
`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the study
`or trial will be performed in a subpopulation, list here.
`The pediatric trial will enroll subjects 12 years and older and pharmacokinetics will be assessed
`under maximal use conditions.
`
`PMR/PMC Development Template
`
`Last Updated 5/28/2014
`
`Page 2 of 4
`
`Reference ID: 3513844
`
`

`

`Required
`Observational pharmacoepidemiologic study
`Registry studies
`Primary safety study or clinical trial
`Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
`Thorough Q-T clinical trial
`Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
`Pharmacokinetic studies or clinical trials
`Drug interaction or bioavailability studies or clinical trials
`Dosing trials
`Continuation of Question 4
`
`Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
`Meta-analysis or pooled analysis of previous studies/clinical trials
`Immunogenicity as a marker of safety
`Other (provide explanation)
`
`Agreed upon:
`Quality study without a safety endpoint (e.g., manufacturing, stability)
`Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease, background
`rates of adverse events)
`Clinical trials primarily designed to further define efficacy (e.g., in another condition, different disease
`severity, or subgroup) that are NOT required under Subpart H/E
`Dose-response study or clinical trial performed for effectiveness
`Nonclinical study, not safety-related (specify)
`
`Other
`
`5.
`
`Is the PMR/PMC clear, feasible, and appropriate?
`Does the study/clinical trial meet criteria for PMRs or PMCs?
`Are the objectives clear from the description of the PMR/PMC?
`Has the applicant adequately justified the choice of schedule milestone dates?
`Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine feasibility,
`and contribute to the development process?
`
`Check if this form describes a FDAAA PMR that is a randomized controlled clinical trial
`
`If so, does the clinical trial meet the following criteria?
`
`There is a significant question about the public health risks of an approved drug
`There is not enough existing information to assess these risks
`Information cannot be gained through a different kind of investigation
`The trial will be appropriately designed to answer question about a drug’s efficacy and safety, and
`The trial will emphasize risk minimization for participants as the protocol is developed
`
`PMR/PMC Development Template
`
`Last Updated 5/28/2014
`
`Page 3 of 4
`
`Reference ID: 3513844
`
`

`

`PMR/PMC Development Coordinator:
`This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine the
`safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug quality.
`_______________________________________
`(signature line for BLAs)
`
`PMR/PMC Development Template
`
`Last Updated 5/28/2014
`
`Page 4 of 4
`
`Reference ID: 3513844
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`STROTHER D DIXON
`05/28/2014
`
`DAVID L KETTL
`05/29/2014
`
`TATIANA OUSSOVA
`05/30/2014
`
`Reference ID: 3513844
`
`

`

`REGULATORY PROJECT MANAGER
`PHYSICIAN’S LABELING RULE (PLR) FORMAT REVIEW
`OF THE PRESCRIBING INFORMATION
`
`Complete for all new NDAs, BLAs, Efficacy Supplements, and PLR Conversion Labeling Supplements
`
`Application: NDA 203567
`
`Application Type: New NDA (Resubmission)
`
`Name of Drug/Dosage Form: Jublia (efinaconazole) topical solution, 10%
`
`Applicant: Dow Pharmaceutical Sciences
`
`Receipt Date: December 20, 2013
`
`Goal Date: June 20, 2014
`
`1. Regulatory History and Applicant’s Main Proposals
`The sponsor originally submitted NDA 203567 (efinaconazole) topical solution, 10% on July 25,
`2012. The Division of Dermatology and Dental Products issued the sponsor a complete response
`letter on May 13, 2013 due to Chemistry, Manufacturing and Controls (CMC) deficiencies. The
`sponsor resubmitted the NDA on December 20, 2013.
`
`2. Review of the Prescribing Information
`This review is based on the applicant’s submitted Word format of the prescribing information (PI).
`The applicant’s proposed PI was reviewed in accordance with the labeling format requirements listed
`in the “Selected Requirements for Prescribing Information (SRPI)” checklist (see the Appendix).
`
`3. Conclusions/Recommendations
`SRPI format deficiencies were identified in the review of this PI. For a list of these deficiencies see
`the Appendix.
`
`All SRPI format deficiencies of the PI will be conveyed to the applicant via email and in an attached
`red-lined label. The applicant will be asked to correct these deficiencies and resubmit the PI in Word
`format by May 16, 2014. The resubmitted PI will be used for further labeling review.
`
`Reference ID: 3493586
`
`

`

`Selected Requirements of Prescribing Information
`
`Appendix
`
`The Selected Requirement of Prescribing Information (SRPI) is a 42-item, drop-down checklist of
`important format elements of the prescribing information (PI) based on labeling regulations (21 CFR
`201.56 and 201.57) and guidances.
`
`Highlights
`
`See Appendix A for a sample tool illustrating the format for the Highlights.
`
`HIGHLIGHTS GENERAL FORMAT and HORIZONTAL LINES IN THE PI
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`1. Highlights (HL) must be in a minimum of 8-point font and should be in two-column format, with
`½ inch margins on all sides and between columns.
`Comment:
`2. The length of HL must be one-half page or less (the HL Boxed Warning does not count against
`the one-half page requirement) unless a waiver has been granted in a previous submission (e.g.,
`the application being reviewed is an efficacy supplement).
`Instructions to complete this item: If the length of the HL is one-half page or less, then select
`“YES” in the drop-down menu because this item meets the requirement. However, if HL is
`longer than one-half page:
` For the Filing Period:
` For efficacy supplements: If a waiver was previously granted, select “YES” in the drop-
`down menu because this item meets the requirement.
` For NDAs/BLAs and PLR conversions: Select “NO” because this item does not meet the
`requirement (deficiency). The RPM notifies the Cross-Discipline Team Leader (CDTL) of
`the excessive HL length and the CDTL determines if this deficiency is included in the 74-
`day or advice letter to the applicant.
` For the End-of-Cycle Period:
` Select “YES” in the drop down menu if a waiver has been previously (or will be) granted
`by the review division in the approval letter and document that waiver was (or will be)
`granted.
`Comment:
`3. A horizontal line must separate HL from the Table of Contents (TOC). A horizontal line must
`separate the TOC from the FPI.
`Comment:
`4. All headings in HL must be bolded and presented in the center of a horizontal line (each
`horizontal line should extend over the entire width of the column as shown in Appendix A). The
`headings should be in UPPER CASE letters.
`Comment:
`5. White space should be present before each major heading in HL. There must be no white space
`between the HL Heading and HL Limitation Statement. There must be no white space between
`
`SRPI version 3: October 2013
`
`Reference ID: 3493586
`
`Page 2 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`the product title and Initial U.S. Approval. See Appendix A for a sample tool illustrating white
`space in HL.
`
`Comment:
`
`YES 6. Each summarized statement or topic in HL must reference the section(s) or subsection(s) of the
`Full Prescribing Information (FPI) that contain more detailed information. The preferred format
`is the numerical identifier in parenthesis [e.g., (1.1)] at the end of each summarized statement or
`topic.
`
`Comment:
`
`YES
`
`7. Section headings must be presented in the following order in HL:
`M
`
`
`
`* RMC only applies to the BOXED WARNING. INDICATIONS AND USAGE. DOSAGE AND
`ADMINISTRATION. CONTRAINDICATIONS. and WARNINGS AND PRECAUTIONS sections.
`
`Comment:
`
`HIGHLIGHTS DETAILS
`
`Highlights Heading
`
`YES 8. At the beginning of HL, the following heading must be bolded and should appear in all UPPER
`CASE letters: “HIGHLIGHTS OF PRESCRIBING INFORMATION”.
`Comment:
`
`Highlights Limitation Statement
`
`YES 9. The bolded HL Limitation Statement must include the following verbatim statement: “These
`highlights do not include all the information needed to use (insert name of drug product)
`safely and effectively. See full prescribing information for (insert name of drug product).”
`The name of drug product should appear in UPPER CASE letters.
`
`Comment:
`
`Product Title in Highlights
`
`YES 10. Product title must be bolded.
`
`SRPIvcrsion 3: October 2013
`
`Reference ID: 3493586
`
`Page 3 0f 10
`
`

`

`Selected Requirements of Prescribing Information
`
`Comment:
`
`YES
`
`Initial U.S. Approval in Highlights
`11. Initial U.S. Approval in HL must be bolded, and include the verbatim statement “Initial U.S.
`Approval:” followed by the 4-digit year.
`Comment:
`
`Boxed Warning (BW) in Highlights
`12. All text in the BW must be bolded.
`Comment:
`13. The BW must have a heading in UPPER CASE, containing the word “WARNING” (even if
`more than one warning, the term, “WARNING” and not “WARNINGS” should be used) and
`other words to identify the subject of the warning (e.g., “WARNING: SERIOUS
`INFECTIONS and ACUTE HEPATIC FAILURE”). The BW heading should be centered.
`Comment:
`14. The BW must always have the verbatim statement “See full prescribing information for
`complete boxed warning.” This statement should be centered immediately beneath the heading
`and appear in italics.
`Comment:
`15. The BW must be limited in length to 20 lines (this includes white space but does not include the
`BW heading and the statement “See full prescribing information for complete boxed
`warning.”).
`Comment:
`
`Recent Major Changes (RMC) in Highlights
`16. RMC pertains to only the following five sections of the FPI: BOXED WARNING,
`INDICATIONS AND USAGE, DOSAGE AND ADMINISTRATION,
`CONTRAINDICATIONS, and WARNINGS AND PRECAUTIONS. RMC must be listed in
`the same order in HL as the modified text appears in FPI.
`Comment:
`17. The RMC must include the section heading(s) and, if appropriate, subsection heading(s) affected
`by the recent major change, together with each section’s identifying number and date
`(month/year format) on which the change was incorporated in the PI (supplement approval date).
`For example, “Warnings and Precautions, Acute Liver Failure (5.1) --- 9/2013”.
`Comment:
`18. The RMC must list changes for at least one year after the supplement is approved and must be
`removed at the first printing subsequent to one year (e.g., no listing should be one year older than
`revision date).
`Comment:
`
`Indications and Usage in Highlights
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`YES
`
`SRPI version 3: October 2013
`
`Reference ID: 3493586
`
`Page 4 of 10
`
`

`

`N/A
`
`YES
`
`YES
`
`YES
`
`Selected Requirements of Prescribing Information
`
`19. If a product belongs to an established pharmacologic class, the following statement is required
`under the Indications and Usage heading in HL: “(Product) is a (name of established
`pharmacologic class) indicated for (indication)”.
`Comment:
`
`Dosage Forms and Strengths in Highlights
`20. For a product that has several dosage forms (e.g., capsules, tablets, and injection), bulleted
`subheadings or tabular presentations of information should be used under the Dosage Forms and
`Strengths heading.
`Comment:
`
`Contraindications in Highlights
`21. All contraindications listed in the FPI must also be listed in HL or must include the statement
`“None” if no contraindications are known. Each contraindication should be bulleted when there
`is more than one contraindication.
`Comment:
`
`Adverse Reactions in Highlights
`22. For drug products other than vaccines, the verbatim bolded statement must be present: “To
`report SUSPECTED ADVERSE REACTIONS, contact (insert name of manufacturer) at
`(insert manufacturer’s U.S. phone number) or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch”.
`Comment:
`
`Patient Counseling Information Statement in Highlights
`23. The Patient Counseling Information statement must include one of the following three bolded
`verbatim statements that is most applicable:
`If a product does not have FDA-approved patient labeling:
` “See 17 for PATIENT COUNSELING INFORMATION”
`If a product has FDA-approved patient labeling:
` “See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling”
` “See 17 for PATIENT COUNSELING INFORMATION and Medication Guide”
`Comment:
`
`YES
`
`Revision Date in Highlights
`24. The revision date must be at the end of HL, and should be bolded and right justified (e.g.,
`“Revised: 9/2013”).
`Comment: The date will be reflected as "MM/2014" until the time of action.
`
`SRPI version 3: October 2013
`
`Reference ID: 3493586
`
`Page 5 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`Contents: Table of Contents (TOC)
`
`See Appendix A for a sample tool illustrating the format for the Table of Contents.
`
`YES
`
`YES
`
`N/A
`
`YES
`
`YES
`
`YES
`
`YES
`
`25. The TOC should be in a two-column format.
`Comment:
`26. The following heading must appear at the beginning of the TOC: “FULL PRESCRIBING
`INFORMATION: CONTENTS”. This heading should be in all UPPER CASE letters and
`bolded.
`Comment:
`27. The same heading for the BW that appears in HL and the FPI must also appear at the beginning
`of the TOC in UPPER CASE letters and bolded.
`Comment:
`28. In the TOC, all section headings must be bolded and should be in UPPER CASE.
`Comment:
`29. In the TOC, all subsection headings must be indented and not bolded. The headings should be in
`title case [first letter of all words are capitalized except first letter of prepositions (through),
`articles (a, an, and the), or conjunctions (for, and)].
`Comment:
`30. The section and subsection headings in the TOC must match the section and subsection headings
`in the FPI.
`Comment:
`31. In the TOC, when a section or subsection is omitted, the numbering must not change. If a section
`or subsection from 201.56(d)(1) is omitted from the FPI and TOC, the heading “FULL
`PRESCRIBING INFORMATION: CONTENTS” must be followed by an asterisk and the
`following statement must appear at the end of TOC: “*Sections or subsections omitted from the
`full prescribing information are not listed.”
`Comment:
`
`SRPI version 3: October 2013
`
`Reference ID: 3493586
`
`Page 6 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`Full Prescribing Information (FPI)
`
`FULL PRESCRIBING INFORMATION: GENERAL FORMAT
`
`YES
`
`32. The bolded section and subsection headings in the FPI must be named and numbered in
`accordance with 21 CFR 201.56(d)(1) as noted below (section and subsection headings should
`be in UPPER CASE and title case, respectively). If a section/subsection required by regulation
`is omitted, the numbering must not change. Additional subsection headings (i.e., those not
`named by regulation) must also be bolded and numbered.
`
`BOXED WARNING
`1 INDICATIONS AND USAGE
`2 DOSAGE AND ADMINISTRATION
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`6 ADVERSE REACTIONS
`7 DRUG INTERACTIONS
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Labor and Delivery
`8.3 Nursing Mothers
`8.4 Pediatric Use
`8.5 Geriatric Use
`9 DRUG ABUSE AND DEPENDENCE
`9.1 Controlled Substance
`9.2 Abuse
`9.3 Dependence
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`12.4 Microbiology (by guidance)
`12.5 Pharmacogenomics (by guidance)
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`13.2 Animal Toxicology and/or Pharmacology
`14 CLINICAL STUDIES
`15 REFERENCES
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`Comment:
`33. The preferred presentation for cross-references in the FPI is the section (not subsection)
`heading followed by the numerical identifier. The entire cross-reference should be in italics and
`enclosed within brackets. For example, “[see Warnings and Precautions (5.2)]” or “[see
`Warnings and Precautions (5.2)]”.
`Comment:
`
`YES
`
`SRPI version 3: October 2013
`
`Reference ID: 3493586
`
`Page 7 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`N/A
`
`34. If RMCs are listed in HL, the corresponding new or modified text in the FPI sections or
`subsections must be marked with a vertical line on the left edge.
`Comment:
`
`FULL PRESCRIBING INFORMATION DETAILS
`
`FPI Heading
`35. The following heading must be bolded and appear at the beginning of the FPI: “FULL
`PRESCRIBING INFORMATION”. This heading should be in UPPER CASE.
`Comment:
`
`BOXED WARNING Section in the FPI
`36. In the BW, all text should be bolded.
`Comment:
`37. The BW must have a heading in UPPER CASE, containing the word “WARNING” (even if
`more than one Warning, the term, “WARNING” and not “WARNINGS” should be used) and
`other words to identify the subject of the Warning (e.g., “WARNING: SERIOUS
`INFECTIONS and ACUTE HEPATIC FAILURE”).
`Comment:
`CONTRAINDICATIONS Section in the FPI
`38. If no Contraindications are known, this section must state “None.”
`Comment:
`ADVERSE REACTIONS Section in the FPI
`39. When clinical trials adverse reactions data are included (typically in the “Clinical Trials
`Experience” subsection of ADVERSE REACTIONS), the following verbatim statement or
`appropriate modification should precede the presentation of adverse reactions:
`“Because clinical trials are conducted under widely varying conditions, adverse reaction rates
`observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
`of another drug and may not reflect the rates observed in practice.”
`Comment: Added "observed" and deleted
`40. When postmarketing adverse reaction data are included (typically in the “Postmarketing
`Experience” subsection of ADVERSE REACTIONS), the following verbatim statement or
`appropriate modification should precede the presentation of adverse reactions:
`
`“The following adverse reactions have been identified during post-approval use of (insert drug
`name). Because these reactions are reported voluntarily from a population of uncertain size, it is
`not always possible to reliably estimate their frequency or establish a causal relationship to drug
`exposure.”
`Comment:
`PATIENT COUNSELING INFORMATION Section in the FPI
`41. Must reference any FDA-approved patient labeling in Section 17 (PATIENT COUNSELING
`INFORMATION section). The reference should appear at the beginning of Section 17 and
`
`YES
`
`N/A
`
`N/A
`
`YES
`
`NO
`
`N/A
`
`YES
`
`SRPI version 3: October 2013
`
`Reference ID: 3493586
`
`Page 8 of 10
`
`(b) (4)
`
`

`

`Selected Requirements of Prescribing Information
`
`YES
`
`include the type(s) of FDA-approved patient labeling (e.g., Patient Information, Medication
`Guide, Instructions for Use).
`Comment:
`42. FDA-approved patient labeling (e.g., Medication Guide, Patient Information, or Instructions for
`Use) must not be included as a subsection under section 17 (PATIENT COUNSELING
`INFORMATION). All FDA-approved patient labeling must appear at the end of the PI upon
`approval.
`Comment:
`
`SRPI version 3: October 2013
`
`Reference ID: 3493586
`
`Page 9 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`Appendix A: Format of the Highlights and Table of Contents
`
`SRPI version 3: October 2013 Page 10 of 10
`
`Reference ID: 3493586
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`STROTHER D DIXON
`04/22/2014
`
`BARBARA J GOULD
`04/30/2014
`
`Reference ID: 3493586
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy
`
`PATIENT LABELING REVIEW
`
`March 31, 2014
`
`Susan Walker, MD
`Director
`Division of Dermatology and Dental Products (DDDP)
`
`LaShawn Griffiths, MSHS-PH, BSN, RN
`Associate Director for Patient Labeling
`Division of Medical Policy Programs (DMPP)
`
`Barbara Fuller, RN, MSN, CWOCN
`Team Leader, Patient Labeling
`Division of Medical Policy Programs (DMPP)
`
`Nathan Caulk, MS, BSN, RN
`Patient Labeling Reviewer
`Division of Medical Policy Programs (DMPP)
`Puja Shah, PharmD
`Regulatory Reviewer Office
`Office of Prescription Drug Promotion (OPDP)
`Review of Patient Labeling: Patient Package Insert (PPI)
`
`JUBLIA (efinaconazole)
`
`
`topical solution, 10%
`NDA 203-567
`
`Dow Pharmaceutical Sciences
`
`
`
`
`
`Reference ID: 3480561
`
`
`
`
`Date:
`
`To:
`
`
`Through:
`
`
`From:
`
`Subject:
`
`Drug Name (established
`name):
`
`Dosage Form and Route:
`Application
`Type/Number:
`Applicant:
`
`
`
`
`
`

`

`1
`
`INTRODUCTION
`On December 20, 2013, Dow Pharmaceutical Sciences submitted for the Agency’s
`review a New Drug Application (NDA) 203-567 for JUBLIA (efinaconazole) topical
`solution in response to a Complete Response (CR) letter issued on May 13, 2013.
`This Class 2 resubmission includes updated labels and responses to the product
`quality and labeling deficiencies. The proposed indication for JUBLIA
`(efinaconazole) topical solution is for the topical treatment of onychomycosis of the
`toenails due to Trichophyton mentagrophytes and Trichophyton rubrum.
`This collaborative review is written by the Division of Medical Policy Programs
`(DMPP) and the Office of Prescription Drug Promotion (OPDP) in response to a
`request by the Division of Dermatology and Dental Products (DDDP) on January 24,
`2014, for DMPP and OPDP to review the Applicant’s proposed Patient Package
`Insert (PPI) for JUBLIA (efinaconazole) topical solution.
`
`
`
`2 MATERIAL REVIEWED
`• Draft JUBLIA (efinaconazole) topical solution PPI received on December 20,
`2013, revised by the Review Division throughout the review cycle, and received
`by DMPP on January 24, 2014.
`• Draft JUBLIA (efinaconazole) topical solution PPI received on December 20,
`2013, revised by the Review Division throughout the review cycle, and received
`by OPDP on March 17, 2014.
`• Draft JUBLIA (efinaconazole) topical solution Prescribing Information (PI)
`received on December 20, 2013, revised by the Review Division throughout the
`review cycle, and received by DMPP and OPDP on March 17, 2014.
`• Draft KERYDIN (tavaborole) comparator labeling dated February 18, 2014.
`
`3 REVIEW METHODS
`To enhance patient comprehension, materials should be written at a 6th to 8th grade
`reading level, and have a reading ease score of at least 60%. A reading ease score of
`60% corresponds to an 8th grade reading level. In our review of the PPI the target
`reading level is at or below an 8th grade level.
`Additionally, in 2008 the American Society of Consultant Pharmacists Foundation
`(ASCP) in collaboration with the American Foundation for the Blind (AFB)
`published Guidelines for Prescription Labeling and Consumer Medication
`Information for People with Vision Loss. The ASCP and AFB recommended using
`fonts such as Verdana, Arial or APHont to make medical information more
`accessible for patients with vision loss. We have reformatted the PPI document
`using the Verdana font, size 10.
`In our collaborative review of the PPI we have:
`simplified wording and clarified concepts where possible
`•
`ensured that the PPI is consistent with the Prescribing Information (PI)
`•
`
`
`
`
`
`Reference ID: 3480561
`
`
`
`

`

`•
`•
`
`•
`
`•
`
`removed unnecessary or redundant information
`ensured that the PPI is free of promotional language or suggested revisions to
`ensure that it is free of promotional language
`ensured that the PPI meets the criteria as specified in FDA’s Guidance for
`Useful Written Consumer Medication Information (published July 2006)
`ensured that the PPI is consistent with the approved comparator labeling where
`applicable.
`
`
`4 CONCLUSIONS
`The PPI is acceptable with our recommended changes.
`
` 5
`
` RECOMMENDATIONS
`• Please send these comments to the Applicant and copy DMPP and OPDP on the
`correspondence.
`• Our collaborative review of the PPI is appended to this memorandum. Consult
`DMPP and OPDP regarding any additional revisions made to the PI to determine
`if corresponding revisions need to be made to the PPI.
` Please let us know if you have any questions.
`
`
`
`
`
`Reference ID: 3480561
`
`
`
`6 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`NATHAN P CAULK
`03/31/2014
`
`PUJA J SHAH
`03/31/2014
`
`BARBARA A FULLER
`03/31/2014
`
`LASHAWN M GRIFFITHS
`03/31/2014
`
`Reference ID: 3480561
`
`

`

`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`Memorandum
`
`Date:
`March 28, 2014
`
`
`To:
`
`
`
`
`
`
`From:
`
`
`
`
`
`Through:
`
`
`
`Subject:
`
`
`
`
`
`Strother D. Dixon
`Regulatory Project Manager
`Division of Dermatology and Dental Products (DDDP)
`
`Puja Shah, PharmD
`Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`
`Lynn Panholzer, PharmD
`Regulatory Review Officer, OPDP
`
`NDA 203567
`JUBLIA TM (efinaconazole) topical solution, 10%
`
`
`
`
`Background
`
`This consult review is in response to DDDP’s January 24, 2014, request for OPDP’s
`review of the draft package insert (PI), carton/container labeling, and patient package
`insert (PPI) for JUBLIA TM (efinaconazole) topical solution, 10%. OPDP reviewed the
`substantially complete version of the draft PI provided by the Division of Medical Policy
`Programs (DMPP) on March 28, 2014, and the carton/container labeling accessed via
`eRooms on March 21, 2014. Our comments on the PI are included directly on the
`attached copy of the labeling, and our comments on the carton/container labeling are
`listed below.
`
`Carton/Container Labeling Comments
`
`
`
`
`
`
`• OPDP is concerned about the lack of prominence of the established name on the
`carton and container labeling. The JUBLIA tradename is in bolded font, while
`the established name is in unbolded font, and thus less prominent. We
`recommend that the applicant revise the established name to reflect comparable
`prominence as the JUBLIA tradename.
`
`
`
`
`Reference ID: 3480159
`
`1
`
`

`

`0 Furthermore, we note that the carton and container labeling includes an exact
`storage temperature of
`(mu) rather than the storage temperature range of
`20°C — 25°C (68°F — 77 F) in section 16 of the draft PI. Ifappropriate, OPDP
`recommends the applicant revise the carton and container labeling to fully reflect
`the temperature range.
`
`0 We note that carton and container labeling include the following (emphasis
`original):
`
`0 “Usual dosage: Apply to affected nail(s) once daily. See package insert
`for full Prescribing Information.
`
`WARNING: For use on nails and immediately adjacent skin only.”
`
`M4) to “toenails” to be consistent with the
`OPDP recommends changing
`INDICATIONS AND USAGE and DOSAGE AND ADMlNISTRATION
`
`sections of the proposed PI.
`
`Our review of the PPI and IFU was conducted jointly with DMPP and will be filed under
`
`separate cover.
`
`OPDP appreciates the opportimity to provide comments on these materials. Ifyou have
`any questions or concerns, please contact Puja Shah at 240-402-5040 or
`puja.shah@fda.hhs.gov
`
`12 Page(s) of Draft Labeling have been Wifliheld in Full as b4 (CCI/TS) immediately following this page
`
`Reference ID: 34801 59
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`PUJA J SHAH
`03/28/2014
`
`Reference ID: 3480159
`
`

`

`LABEL A