CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`207154Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`MEMORANDUM
`REVIEW OF REVISED LABEL AND LABELING
`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)
`
`Date of This Memorandum:
`February 12, 2016
`Requesting Office or Division:
`Division of Dermatology and Dental Products
`Application Type and Number: NDA 207154
`Product Name and Strength:
`Aczone (dapsone) gel 7.5%
`Submission Date:
`February 11, 2016 and February 4, 2016
`Applicant/Sponsor Name:
`Allergan, Inc.
`OSE RCM #:
`2015-1106-1
`DMEPA Primary Reviewer:
`Hina Mehta, PharmD
`DMEPA Team Leader:
`Mishale Mistry, PharmD, MPH
`
`PURPOSE OF MEMO
`1
`The Division of Dermatology and Dental Products (DDDP) requested that we review the revised
`container label, carton labeling, and prescribing information for Aczone gel 7.5% (Appendix A)
`to determine if it is acceptable from a medication error perspective. The revisions are in
`response to recommendations that we made during a previous label and labeling review.1
`
` CONCLUSION
`2
`The revised container label, carton labeling, and prescribing information for Aczone gel 7.5% is
`acceptable from a medication error perspective. We have no further recommendations at this
`time.
`
`
`1 Mehta, H. Label, Labeling and Packaging Review for Aczone gel 7.5% (NDA 207154). Silver Spring (MD): Food and
`Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Division of
`Medication Error Prevention and Analysis (US); 2015 Nov 30. 17 p. OSE RCM No.: 2015-1065.
`
`Reference ID: 3887287
`
`1
`
`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/
`----------------------------------------------------
`
`HINA S MEHTA
`02/12/2016
`
`MISHALE P MISTRY
`02/12/2016
`
`Reference ID: 3887287
`
`

`

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`
`PMR/PMC Development Template
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`This template should be completed by the PMR/PMC Development Coordinator and included for each
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`PMR/PMC in the Action Package. _
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`NDA/BLA #
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`Product Name:
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`207154
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`Aczone (dapsone) topical gel, 7.5%
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`PMR/PMC Description:
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`PMR: Conduct an open-label trial to assess safety, pharmacokinetics, and
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`treatment effect of ACZONE (dapsone) gel, 7.5% in 100 pediatric subjects
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`aged 9 years to 11 years 11 months with acne vulgaris. Pharmacokinetic
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`assessments will be done in at least 16 evaluable subjects under maximal use
`conditions.
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`PMR/PMC Schedule Milestones: Final Protocol Submission:
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`Study Completion:
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`Final Report Submission:
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`06/3 0/2016
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`03/31/2019
`11/30/2019
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`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a pre-approval
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`requirement. Check type below and describe.
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`{:1 Unmet need
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`El Life-threatening condition
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`[:I Long—term data needed
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`D Only feasible to conduct post-approval
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`El Prior clinical experience indicates safety
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`E] Small subpopulation affected
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`[:1 Theoretical concern
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`X Other
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`Data in subjects 12 years of age and older is ready for approval.
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`PMR/PMC Development Template
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`Last Updated 1/21/2016
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`Page 1 of4
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`Reference ID: 3875284
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`Reference ID: 3897159
`Reference ID: 3897159
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`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is a
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`FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new safety
`information.”
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`This trial will evaluate the safety, systemic bioavailability, and treatment effect of Aczone gel, 7.5%,
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`applied once daily, in pediatric subjects 9 years to llyears and 11 months of age and who have acne
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`vulgaris.
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`3.
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`If the study/clinical trial is a PMR. check the applicable regulation.
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`If not a PMR. skip to 4.
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`— Which regulation ?
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`I:I Accelerated Approval (subpart H/E)
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`I:I Animal Efficacy Rule
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`g Pediatric Research Equity Act
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`El FDAAA required safety study/clinical trial
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`If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
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`El Assess a known serious risk related to the use of the drug?
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`E] Assess signals of serious risk related to the use of the drug?
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`E] Identify an unexpected serious risk when available data indicate the potential for a serious risk?
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`If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
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`D Analysis of spontaneous postmarketing adverse events?
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`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to assess
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`E] Analysis using pharmacovigilance system?
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`Do not select the above study/clinical trial type if. the new pharmacovigilance system that the FDA
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`is required to establish under section 505(k)(3) has not yet been established and is thus not sufficient
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`to assess this known serious risk, or has been established but is nevertheless not sufficient to assess
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`{3 Study: all other investigations, such as investigations in humans that are not clinical trials as defined
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`below (e.g., observational epidemiologic studies), animal studies, and laboratory experiments?
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`Do not select the above study type if. a study will not be sufficient to identify or assess a serious
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`D Clinical trial: any prospective investigation in which the sponsor or investigator determines the
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`method of assigning investigational product or other interventions to one or more human subjects?
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`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the study
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`or trial will be performed in a subpopulation, list here.
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`An open-label trial to assess safety, pharmacokinetics, and treatment effect of Aczone gel, 7.5%
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`in 100 pediatric subjects age 9 years to 11 years 1 1 months with acne vulgaris. Pharmacokinetic
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`assessments will be done in at least 16 evaluable subjects under maximal use conditions.
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`PMR/PMC Development Template
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`Reference !D: 3875284
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`Reference ID: 3897159
`Reference ID: 3897159
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`Regui red
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`[I Observational pharmacoepidemiologic study
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`El Registry studies
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`[:1 Primary safety study or clinical trial
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`[3 Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
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`[:1 Thorough Q-T clinical trial
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`I:I Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
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`I:| Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
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`E] Drug interaction or bioavailability studies or clinical trials
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`El Dosing trials
`Continuation 0
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`[3 Additional data or analysis required for a pretdously submitted or expected study/clinical trial
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`(provide explanation)
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`El Meta-analysis or pooled analysis of previous studies/clinical trials
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`El Immunogenicity as a marker of safety
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`[3 Other (provide explanation)
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`Agreed upon:
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`El Quality study without a safety endpoint (e.g., manufacturing, stability)
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`I:] Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease, background
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`rates of adverse events)
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`El Clinical trials primarily designed to further define efficacy (e.g., in another condition, different disease
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`severity, or subgroup) that are NOT required under Subpart H/E
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`El Dose-response study or clinical trial performed for effectiveness
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`El Nonclinical study, not safety-related (specify)
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`El Other
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`5.
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`Is the PMR/PMC clear, feasible, and appropriate?
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`x]: Does the study/clinical trial meet criteria for PMRs or PMCs?
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`xl:l Are the objectives clear from the description of the PMR/PMC?
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`XE] Has the applicant adequately justified the choice of schedule milestone dates?
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`XI: Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine feasibility,
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`and contribute to the development process?
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`[3 Check if this form describes a FDAAA PMR that is a randomized controlled clinical trial
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`If so, does the clinical trial meet the following criteria?
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`I: There is a significant question about the public health risks of an approved drug
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`[:I There is not enough existing information to assess these risks
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`D Information cannot be gained through a different kind of investigation
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`D The trial will be appropriately designed to answer question about a drug’s efficacy and safety, and
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`[j The trial will emphasize risk minimization for participants as the protocol is developed
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`PMR/PMC Development Template
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`Last Updated 1/21/2016
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`Reference ID: 3875284
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`Reference ID: 3897159
`Reference ID: 3897159
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`

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`PMR/PMC Development Coordinator:
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`XE This PMR/PMC has been reviewedfor clarity and consistency, and is necessary to further refine the
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`safety, eflicacy, 0r optimal use of a drug, or to ensure consistency and reliability of drug quality.
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`(signature line for BLAS)
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`PMR/PMC Development Template
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`Last Updated 1/21/2016
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`Reference ID: 3875284
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`Reference ID: 3897159
`Reference ID: 3897159
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`

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`This is a representation of an electronic record that was signed
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`electronically and this page is the manifestation of the electronic
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`signature.
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`STROTH ER D DIXON
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`
`01/21/2016
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`TATIANA OUSSOVA
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`01/29/2016
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`Reference ID: 3875284
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`Reference ID: 3897159
`Reference ID: 3897159
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`

`

`M E M O R A N D U M
`
` DEPARTMENT OF HEALTH AND HUMAN SERVICES
`PUBLIC HEALTH SERVICE
`FOOD AND DRUG ADMINISTRATION
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`DATE:
`
`TO:
`
`FROM:
`
`THROUGH:
`
`CLINICAL INSPECTION SUMMARY
`January 12, 2016
`
`Strother Dixon, Regulatory Project Manager
`Patricia Brown, M.D., Medical Officer
`Gordana Diglisic, M.D., Medical Team Leader
`Division of Dermatology and Dental Products
`
`Roy Blay, Ph.D.
`Good Clinical Practice Assessment Branch
`Division of Clinical Compliance Evaluation
`Office of Scientific Investigations
`
`Janice Pohlman, M.D., M.P.H
`Team Leader
`Good Clinical Practice Assessment Branch
`Division of Clinical Compliance Evaluation
`Office of Scientific Investigations
`
`Kassa Ayalew, M.D., M.P.H.
`Branch Chief
`Good Clinical Practice Assessment Branch
`Division of Clinical Compliance Evaluation
`Office of Scientific Investigations
`
`SUBJECT:
`
`Evaluation of Clinical Inspections
`
`NDA:
`
`207154
`
`APPLICANT:
`
` Allergan, Inc.
`
`DRUG:
`
`NME:
`
`Aczone® Gel (Dapsone gel 7.5%)
`
`No
`
`THERAPEUTIC
`CLASSIFICATION: Standard Review
`
`INDICATION:
`
`Treatment of acne vulgaris in patients 12 years of age and older
`
`
`
`Reference ID: 3873026
`
`

`

`Page 2- NDA 207154 Aczone– Clinical Inspection Summary
`CONSULTATION REQUEST DATE:
`July 1, 2015
`CLINICAL INSPECTION SUMMARY DATE:
`January 19, 2016
`DIVISION ACTION GOAL DATE:
`February 12, 2016
`PDUFA DATE:
`February 28, 2016
`
`I. BACKGROUND:
`
`The Applicant submitted this NDA to support the use of Aczone Gel (Dapsone gel 7.5%) for
`the treatment of acne vulgaris in patients 12 years of age and older
`
`The identical pivotal studies, Protocols 225678-006 and 225678-007, entitled, “A Safety and
`Efficacy Study to Compare Dapsone Dermal Gel with Vehicle Control in Patients with Acne
`Vulgaris” were inspected in support of this application.
`
`Dr. Flores’s site was selected for inspection because it was one of the larger enrolling sites.
`
`Dr. Forsha’s site was selected for inspection because there was a large treatment effect
`(59.6% vs. 24.2% for GAAS success (score of 0 or 1) at Week 12).
`
`Dr. Klein’s site was selected for inspection because there was a large treatment effect with
`none of the placebo just achieving GAAS success (score 0 or1) at Week 12.
`
`Dr. Parish’s site was selected for inspection because while there was a large treatment effect
`for success on GAAS (75.7% vs. 45.1%), there wasn’t a treatment effect for change in lesion
`counts. Generally, a large treatment effect for success on GAAS translates to large treatment
`effect for change in lesion counts; therefore, the results from this center were not consistent.
`
`II. RESULTS (by Site):
`
`Name of CI, Location
`
`Francisco Flores, M.D.
`FXM Research Miramar
`14601 SW 29th Street , Suite 208
`Miramar, FL 33027
`Douglass Forsha, M.D.
`Jordan Valley Dermatology
`3570 West 9000 South, Suite 220
`West Jordan, UT 84088
`Tracy Klein, M.D.
`Heartland Research Associates, LLC
`1709 South Rock Road
`Wichita, KS 67207
`Jennifer Parish, M.D.
`Paddington Testing Company
`1845 Walnut Street, Suite 1650
`Philadelphia, PA 19103
`
`Protocol #/
`Site #/
`# of Subjects
`(enrolled)
`225678-007/
`27032/
`66
`
`225678-006/
`16062/
`50
`
`225678-006/
`16030/
`53
`
`225678-007/
`27084/
`88
`
`Inspection Dates
`
`Final
`Classification
`
`10-21 Aug 2015
`
`NAI
`
`19-28 Oct 2015
`
`21-24 Jul 2015
`
`Pending
`(Preliminary
`Classification
`VAI)
`NAI
`
`27 Jul –3 Aug 2015
`
`NAI
`
`Reference ID: 3873026
`
`

`

`Page 3- NDA 207154 Aczone– Clinical Inspection Summary
`Key to Classifications
`NAI = No deviation from regulations.
`VAI = Deviation(s) from regulations.
`OAI = Significant deviations from regulations. Data unreliable.
`Pending = Preliminary classification based on information in Form FDA 483 or preliminary communication
`with the field; EIR has not been received from the field or complete review of EIR is pending.
`
`1. Francisco Flores, M.D.
`
`a. What was inspected: At this site for Protocol 225678-007, 69 subjects were
`screened, 66 subjects were enrolled, and 64 subjects completed the study. The records
`of 36 subjects were reviewed. Source records were compared against data listings.
`Records reviewed included, but were not limited to, IRB and sponsor monitoring
`documentation, financial disclosure, inclusion/exclusion criteria, primary endpoints,
`protocol deviations, adverse event reporting, concomitant medications, and drug
`accountability.
`
`b. General observations/commentary: Signed informed consent was obtained from all
`screened subjects prior to study entry. Subjects 5844 and 7566 had Week 1 lesion
`counts and Global Acne Assessment Scores (GAAS) assessments performed and
`entered into the eCRFs but this information was not reflected in the line listings. Loss
`of this data appeared to stem from a synchronization glitch between computers at the
`site and the sponsor. A Form FDA 483 was not issued at the conclusion of the
`inspection. Review of the records noted above revealed no significant discrepancies
`or regulatory violations.
`
`c. Assessment of data integrity: The study appears to have been conducted adequately,
`and the data generated by this site appear acceptable in support of the respective
`indication.
`
`2. Douglass Forsha, M.D.
`
`a. What was inspected: At this site for Protocol 225678-006, 52 subjects were
`screened, and 50 subjects were enrolled in the study. Study record data were reviewed
`for 22 subjects. Adherence to protocol-required procedures and evaluations including
`physical examinations, test article administration, lesion counts, and medical histories
`was reviewed. Other records reviewed included, but were not limited to, financial
`disclosure, training documentation, delegation logs, IRB documentation, enrollment
`logs, protocol deviations, and adverse events.
`
`b. General observations/commentary: All study subjects signed consent forms prior to
`screening procedures. A Form FDA 483 was issued at the conclusion of the
`inspection noting numerous study deficiencies including lack of adherence to the
`protocol, and inadequate documentation of adverse events (AEs), concomitant
`medications, informed consent or assent, and drug accountability.
`
`Reference ID: 3873026
`
`

`

`Page 4- NDA 207154 Aczone– Clinical Inspection Summary
`Specific deficiencies included, but were not limited to, (1) study enrollment of
`Subject 2144 without pregnancy testing as required by the protocol (a negative
`pregnancy test was noted in the CRF but was lacking in the source documentation),
`(2) the lack of complete documentation of AEs for Subjects 2844, 1484, 3210, 1974,
`2706, and 3200 (AEs included stomach pain, back pain, hot flashes, headache, fever,
`head colds, tooth infection, common cold, sore throat, etc.) with respect to start of the
`AE, its resolution, its relationship to drug treatment, or the assessment of the outcome
`of the AE, (3) the lack of documentation of concomitant medications used by
`Subjects 1974, 2706, 2844, and 3210 (medications included Dayquil, Alavert, Nyquil,
`Benadryl, ibuprofen, etc.), (4) inadequate documentation of the Informed Assent
`Forms (IAF) since the CI did not sign the assent form for Subjects 2706, 3177, and
`3200, (5) inadequate completion of Informed Consent Forms (ICFs) for Subjects
`1484, 3073, and 3102, and (6) inadequate documentation of dispensation or return of
`investigational product for Subjects 1547, 1642, and 3175.
`
`Dr. Forsha, in his written response dated November 17, 2015, acknowledged the
`deficiencies observed during the inspection and established a Corrective Action Plan
`(CAP) to help ensure proper study conduct. The CAP notes the hiring of a new Site
`Director and a full time Data Entry Manager, the retraining and certifications of the
`clinical staff, the implementation of weekly meetings, the use of spot checks to ensure
`data integrity, and the dual review of drug disposition records. Standard Operating
`Procedures (SOPs) were submitted as attachments to the written response in support
`of the actions taken by this clinical site to correct the observed deficiencies.
`
`c. Assessment of data integrity: Although numerous deficiencies were observed
`during the inspection of Dr. Forsha’s site, they would not appear to affect subject
`safety or data integrity. The proper implementation of the CAP should help ensure
`that similar deficiencies do not occur in subsequent studies. The study appears to have
`been conducted adequately, and the data generated by this site appear acceptable in
`support of the respective indication.
`
`3. Tracy Klein, M.D.
`
`a. What was inspected: At this site for Protocol 225678-006, 56 subjects were
`screened, 53 subjects were enrolled, and 46 subjects completed the study. The records
`of 24 subjects were reviewed. Source records were compared against Case Report
`Forms (CRFs). Records reviewed included, but were not limited to, IRB and sponsor
`monitoring documentation, financial disclosure, inclusion/exclusion criteria, study
`blinding, co-primary endpoints, protocol deviations, adverse event reporting, and
`drug accountability and storage.
`
`b. General observations/commentary: Signed informed consent was obtained from all
`screened subjects prior to study entry. A Form FDA 483 was not issued at the
`conclusion of the inspection. Review of the records noted above revealed no
`significant discrepancies or regulatory violations.
`
`c. Assessment of data integrity: The study appears to have been conducted adequately,
`and the data generated by this site appear acceptable in support of the respective
`indication.
`
`Reference ID: 3873026
`
`

`

`Page 5- NDA 207154 Aczone– Clinical Inspection Summary
`4. Jennifer Parish, M.D.
`
`a. What was inspected: At this site for Protocol 225678-007, 88 subjects were
`screened, 88 subjects were enrolled, and 79 subjects completed the study. The records
`of 45 subjects were reviewed. Source records were compared against data listings for
`the Global Acne Assessment Scale (GAAS) and Lesion Counts. Records reviewed
`included, but were not limited to, financial disclosure, IRB, sponsor, and monitor
`correspondence, inclusion/exclusion criteria, blinding, randomization, source
`documents, primary efficacy and safety endpoints, adverse events, protocol
`deviations, subject discontinuations, and drug accountability and storage.
`
`b. General observations/commentary: Signed informed consent was obtained from all
`screened subjects prior to study entry. A Form FDA 483 was not issued at the
`conclusion of the inspection. Review of the records noted above revealed no
`significant discrepancies or regulatory violations.
`
`c. Assessment of data integrity: The study appears to have been conducted adequately,
`and the data generated by this site appear acceptable in support of the respective
`indication.
`
`III.OVERALL ASSESSMENT OF FINDINGS AND RECOMMENDATIONS
`
`The clinical sites of Drs. Flores, Forsha, Klein, and Parish were inspected in support of this
`NDA. The sites of Drs. Flores, Klein, and Parish were not issued Form FDA 483s. The final
`classification of these inspections was No Action Indicated (NAI).
`
`The site of Dr. Forsha was issued a Form FDA 483 noting deficiencies including a lack of
`adherence to the protocol, and inadequate documentation of adverse events (AEs),
`concomitant medications, informed consent or assent, and drug accountability. Although
`deficiencies were noted, they would not appear to affect subject safety or data integrity. Dr.
`Forsha submitted a corrective action plan to prevent such deficiencies from occurring in
`future clinical trials. The preliminary classification of this inspection is Voluntary Action
`Indicated (VAI); final classification is pending receipt and review of the EIR.
`
`Reference ID: 3873026
`
`

`

`Page 6- NDA 207154 Aczone– Clinical Inspection Summary
`The study appears to have been conducted adequately, and the data generated by these sites
`appear acceptable in support of the respective indication.
`
`{See appended electronic signature page}
`
`Roy Blay, Ph.D.
`Good Clinical Practice Assessment Branch
`Division of Clinical Compliance Evaluation
`Office of Scientific Investigations
`
`CONCURRENCE:
`
`{See appended electronic signature page}
`
`Janice Pohlman, M.D., M.P.H.
`Team Leader
`Good Clinical Practice Assessment Branch
`Division of Clinical Compliance Evaluation
`Office of Scientific Investigations
`
`{See appended electronic signature page}
`
`Kassa Ayalew, M.D., M.P.H.
`Branch Chief
`Good Clinical Practice Assessment Branch
`Division of Clinical Compliance Evaluation
`Office of Scientific Investigation
`
`Reference ID: 3873026
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ROY A BLAY
`01/13/2016
`
`JANICE K POHLMAN
`01/13/2016
`
`KASSA AYALEW
`01/13/2016
`
`Reference ID: 3873026
`
`

`

`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`
`Tara Turner, Pharm.D., MPH
`Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`
`Melinda McLawhorn, Pharm.D., BCPS, RAC, Team Leader, OPDP
`
`Strother Dixon
`Regulatory Project Manager
`Division of Dermatology and Dental Products (DDDP)
`
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`Memorandum
`
`Date:
`December 15, 2015
`
`
`To:
`
`
`
`
`
`
`From:
`
`
`
`
`
`CC:
`
`Subject:
`
`
`
`
`
`
`On May 12, 2015, DDDP consulted OPDP to review the draft Package Insert (PI), carton and
`container labeling, and Patient Package Insert (PPI) for ACZONE® (dapsone) Gel, 7.5%, for topical
`use (Aczone) for the original NDA submission. We note that this formulation is proposed for once
`daily dosing. Aczone is currently available in a 5% formulation which is dosed twice daily.
`
`OPDP reviewed the proposed substantially complete version of the PI provided by DDDP via e-mail
`on December 1, 2015. OPDP also reviewed the proposed carton and container labeling submitted to
`the electronic document room by the sponsor on April 28, 2015. The Division of Medical Policy
`Programs (DMPP) and OPDP will provide comments on the PPI for Aczone under separate cover.
`OPDP’s comments on the PI and carton and container labeling are provided below.
`
`Thank you for your consult. If you have any questions about OPDP’s comments, please contact Tara
`Turner at 6-2166 or at Tara.Turner@fda.hhs.gov.
`
`
`
`NDA 207154
`ACZONE® (dapsone) Gel, 7.5%, for topical use
`
`
`
`
`
`Reference ID: 3861175
`
`15 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/
`----------------------------------------------------
`
`TARA P TURNER
`12/15/2015
`
`Reference ID: 3861175
`
`

`

`
`Date:
`
`To:
`
`
`Through:
`
`
`From:
`
`Subject:
`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy
`
`PATIENT LABELING REVIEW
`
`December 9, 2015
`
`Kendall Marcus, 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)
`
`Tara Turner, Pharm.D., MPH
`Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`Review of Patient Labeling: Patient Package Insert (PPI)
`
`ACZONE (dapsone)
`Drug Name (established
`name):
`
`Dosage Form and Route: Gel, 7.5%, for topical use
`Application
`NDA 207154
`Type/Number:
`Applicant:
`
`
`
`
`
`Allergan, Inc.
`
`
`
`
`
`Reference ID: 3857722
`
`
`
`

`

`INTRODUCTION
`On April 28, 2015, Allergan, Inc. submitted for the Agency’s review an original New
`Drug Application (NDA) 207154 for ACZONE (dapsone) Gel, 7.5%. The purpose
`of this submission is to propose the indication for ACZONE (dapsone) Gel, 7.5% for
`the topical treatment of acne vulgaris in patients 12 years of age and older.
`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 May 12,
`2015, for DMPP and OPDP to review the Applicant’s proposed Patient Package
`Insert (PPI) for ACZONE (dapsone) Gel, 7.5%.
`
`1
`
` 2
`
` MATERIAL REVIEWED
`• Draft ACZONE (dapsone) Gel, 7.5% PPI received on April 28, 2015, and
`received by DMPP and OPDP on May 12, 2015.
`• Draft ACZONE (dapsone) Gel, 7.5% Prescribing Information (PI) received on
`April 28, 2015, revised by the Review Division throughout the review cycle, and
`received by DMPP and OPDP on December 1, 2015.
`
`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 Arial font, size 10.
`In our collaborative review of the PPI we have:
`
`
`
`
`
`
`
`•
`•
`•
`•
`
`•
`
`
`
`Reference ID: 3857722
`
`simplified wording and clarified concepts where possible
`ensured that the PPI is consistent with the Prescribing Information (PI)
`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)
`
`
`
`

`

`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: 3857722
`
`
`
`3 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
`12/09/2015
`
`TARA P TURNER
`12/09/2015
`
`BARBARA A FULLER
`12/10/2015
`
`LASHAWN M GRIFFITHS
`12/10/2015
`
`Reference ID: 3857722
`
`

`

`LABEL, LABELING AND PACKAGING 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:
`11