CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`203752Orig1s000
`
`
`OTHER REVIEW(S)
`
`
`
`
`
`
`
`
`
`
`
`

`

`SEALD Addendum: Selected Requirements of Prescribing Information
`Review of the End-of—Cycle Prescribing Information
`
`
`
`
`
`NIINIVELLE (estradiol transdermal system)
`
`I
`
`Product Title
`
`
`Applicant
`Noven Pharmaceuticals, Inc.
`Application/Supplement Number NDA 203752
`
`Type of Application
`Original
`Indication(3)
`For the treatment ofmoderate to severe vasomotor symptoms
`due to menopause
`%—
`Estrogen
`_ Established Pharmacologic Class
`I
`|
`|
`
`Office/Division
`ODE III/DRUP
`
`Division Project Manager
`Samantha Bell
`Date FDA Received Application
`December 29, 2011
`Goal Date
`October 29, 2012
`
`
`
`I
`
`
`| Date PI Received by SEALD
`| October 25, 2012
`
`SEALD Addendum Review Date October 29, 2012
`
`I SEALD Labeling Team Leader
`I Eric Brodsky
`I
`P1 = prescribing information
`1 The established pharmacologic class (EPC) that appears in the final draft PI.
`
`|
`
`The Study Endpoints and Labeling Development (SEALD) team performed a Selected
`Requirements of Prescribing Information (SRPI) review of the end-of-cycle, final agreed-upon
`Minivelle prescribing information (PI) on October 26, 2012. The review noted several format
`items that should be corrected prior to approval of the Minivelle PI.
`
`This addendum review amends one of the SRPI items from the October 26, 2012 review (Item
`#15). Therefore, Item #15 (length of the Boxed Warning in Highlights) does not need to be
`corrected prior to application approval.
`
`Guide to the SRPI Checklist: For each SRPI item, one of the following 3 response options is
`selected:
`
`NO: The PI does not meet the requirement for this item (deficiency).
`
`YES: The PI meets the requirement for this item (not a deficiency).
`0 N/A (not applicable): This item does not apply to the specific Plunder review.
`
`Highlights (HL)
`HIGHLIGHTS DETAILS
`
`Boxed Warning
`15. Must be limited in length to 20 lines (this does not include the heading and statement “Seefull
`- prescribing informationfor complete boxed warning. ”)
`Comment: The length ofthe Boxed Warning in Highlights is 22 lines and is greater than the 20 line
`limit. However, the length ofthe Boxed Warning in Highlights in the Minivelle PI is acceptable at
`this time (there is noformat deficienqv).
`
`Reference ID: 3209830
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ERIC R BRODSKY
`10/29/2012
`
`Reference ID: 3209830
`
`

`

`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
`
`Date:
`
`Reviewer:
`
`Team Leader:
`
`Drug Name:
`
`Labeling Memo
`
`October 26, 2012
`
`Walter Fava, RPh, MSEd, Safety Evaluator
`Division of Medication Error Prevention and Analysis
`
`Zachary Oleszczuk, PhaimD, Team Leader
`Division of Medication Error Prevention and Analysis
`
`Minivelle (Estradiol Transdennal System)
`W" 0.0375 mg/day, 0.05 mg/day, 0.075 mg/day,
`0.] mg/day
`
`Application Type/Number: NDA 203752
`
`Applicant/Sponsor:
`
`Noven Pharmaceuticals, Inc.
`
`OSE RCM #:
`
`2012-134
`
`*** This document contains proprietary and confidential information that should not be
`released to the public.***
`
`Reference ID: 3209485
`
`

`

`1
`INTRODUCTION
`This memo responds to a request from the Division of Reproductive and Urologic
`Products (DRUP) for a review of the revised carton labeling and container labels for
`Minivelle (Estradiol Transdermal System). DMEPA’s initial review comments for the
`proposed labels and labeling submitted on April 27, 2012, were communicated to the
`Division on August 15, 2012, via e-mail. Some of DMEPA’s review comments were
`included in an Advice Letter sent to the Applicant on September 24, 2012 (See Appendix
`A). The Applicant responded to the recommendations in the Advice Letter and submitted
`revised carton labeling and container labels on October 15, 2012. DMEPA reviewed the
`revised carton labeling and container labels and provided comments to the Division via e-
`mail on October 24, 2012. In response to those comments, the Applicant sent
`representative revised carton labeling and container labels via e-mail on October 26,
`2012.
`
`2 MATERIAL REVIEWED
`DMEPA reviewed the representative revised Minivelle 0.5 mg/day carton labeling and
`pouch labels received via e-mail on October 26, 2012 (see Appendix B).
`
`3 CONCLUSIONS AND RECOMMENDATIONS
`Review of the revised representative carton labeling and pouch labels show that the
`Applicant accepted DMEPA’s recommendations and we find the representative revisions
`acceptable for implementation for each strength. We have no additional
`recommendations at this time.
`Please copy the Division of Medication Error Prevention and Analysis on any
`communication to the Applicant with regard to this review. If you have further questions
`or need clarifications on this review, please contact the OSE Regulatory Project Manager,
`Marcus Cato at 301-796-3903.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3209485
`
`1
`
`

`

`Apnendix A: Original carton labeling and container label comments provided to
`the Division of Reproductive and Urologic Products via e-mail on August 15, 2012
`
`DMEPA would like to provide the following preliminary comments to the Applicant to minimize
`the number of changes needed when they submit revised labels and labeling for Minivelle.
`
`1. Ensure that the established name is printed in letters that are at least half as large as the letters
`comprising the proprietary name and has the same prominence commensurate with the
`proprietary name taking into account typography. layout. contrast. and other printing features per
`21 CFR 201.10(g)(2).
`
`2. Ensure that every presentation of the strength statement on the carton and pouch labeling
`includes the units of measure (mg/day) and is preceded by the proprietary and established names.
`
`3. Increase the prominence of the strength statement following the proprietary and established
`name on the principal display panel and remove the bolded strength statement from the upper
`right hand corner of the carton and pouch labeling. The multiple presentation of the strength
`statement is redundant.
`
`3. Use different backgrormd colors on the carton and pouch labeling for each product strength to
`minimize the risk of product strength selection errors. It is also important to make sure the carton
`color matches the pouch color for each strength. As currently presented, the cartons and the
`pouches for each strength are very similar in color and can contribute to confusion that may lead
`to product strength selection errors as illustrated in the
`“""and 0.0375 mg/day carton
`and pouch
`
`10 Page(s) of Draft Labeling has been VWthheld in Full as B4 (CCIITS) immediately
`following his page
`
`Reference ID: 3209485
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`WALTER L FAVA
`10/26/2012
`
`WALTER L FAVA on behalf of ZACHARY A OLESZCZUK
`10/26/2012
`
`Reference ID: 3209485
`
`

`

`SEALD Director Sign-Off Review of the End-of—Cycle Prescribing
`Information: Outstanding Format Deficiencies
`
`——
`
`Product Title
`
`Applicant
`
`MINIVELLE (estradiol transdermal system)
`
`Noven Pharmaceuticals, Inc.
`
` Application/Supplement Number
`
`Type of Application
`
`NDA 203752
`Original
`For the treatment of moderate to severe vasomotor symptoms
`due to menopause
`Estrogen
`Established Phannacologic ClassI
`1::
`
`Office/Division
`ODE III/DRUP
`
`Indication(s)
`
`Division Project Manager
`
`Samantha Bell
`
`
`
`Goal Date
`
`October 29, 2012
`
`| Date PI Received by SEALD
`I October 25, 2012
`
`SEALD Review Date
`October 26, 2012
`SEALD Labelin Reviewer
`Abimbola Adebowale
`SEALD Division Director
`
`I
`
`I
`
`P1 = prescribing information
`1 The established pharmacologic class (EPC) that appears in the final draft PI.
`
`This Study Endpoints and Labeling Development (SEALD) Director Sign-Off review of the end-of—
`cycle, draft prescribing information (PI) for critical format elements reveals outstanding labeling
`format deficiencies that must be corrected before the final PI is approved. Afier these outstanding
`labeling format deficiencies are corrected, the SEALD Director will have no objection to the
`approval of this PI.
`
`The critical format elements include labeling regulation (21 CFR 201.56 and 201.57), labeling
`guidance, and best labeling practices (see list below). This review does not include every
`regulation or guidance that pertains to P1 format.
`
`Guide to the Selected Reguirements of Prescribing Information (SRPI) Checklist: For each SRPI
`item, one of the following 3 response options is selected:
`
`NO: The PI does not meet the requirement for this item (deficiency).
`
`YES: The PI meets the requirement for this item (not a deficiency).
`0 N/A (not applicable): This item does not apply to the specific PI under review.
`
`Reference ID: 3209548
`
`Page 1 of 8
`
`

`

`Selected Requirements of Prescribing Information
`
`
`
`
`Highlights (HL)
`GENERAL FORMAT
`1. Highlights (HL) must be in two-column format, with ½ inch margins on all sides and in a
`minimum of 8-point font.
`Comment: From e-mail PI copy (dated 10/25/2012), the margins are not a ½ inch on all sides
`2. The length of HL must be less than or equal to one-half page (the HL Boxed Warning does not
`count against the one-half page requirement) unless a waiver has been is granted in a previous
`submission (i.e., the application being reviewed is an efficacy supplement).
`Instructions to complete this item: If the length of the HL is less than or equal to one-half page
`then select “YES” in the drop-down menu because this item meets the requirement. However, if
`HL is longer than one-half page:
`(cid:190) For the Filing Period (for RPMs)
`(cid:131) For efficacy supplements: If a waiver was previously granted, select “YES” in the drop-
`down menu because this item meets the requirement.
`(cid:131) For NDAs/BLAs and PLR conversions: Select “NO” in the drop-down menu 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.
`(cid:190) For the End-of Cycle Period (for SEALD reviewers)
`(cid:131) The SEALD reviewer documents (based on information received from the RPM) that a
`waiver has been previously granted or will be granted by the review division in the
`approval letter.
`Comment:
`3. All headings in HL must be presented in the center of a horizontal line, in UPPER-CASE letters
`and bolded.
`Comment:
`4. White space must be present before each major heading in HL.
`Comment: Insert a white space between the following: (1) Highlights Limitation Statement and
`the Product Title and (2) Initial U.S. Approval and the Boxed Warning.
`5. Each summarized statement in HL must reference the section(s) or subsection(s) of the Full
`Prescribing Information (FPI) that contains more detailed information. The preferred format is
`the numerical identifier in parenthesis [e.g., (1.1)] at the end of each information summary (e.g.
`end of each bullet).
`Comment: Insert the reference to the more detailed information in the FPI at the end of the
`summarized statement under the “Dosage Forms and Strengths” heading.
`6. Section headings are presented in the following order in HL:
`Section
`Required/Optional
`• Highlights Heading
`Required
`• Highlights Limitation Statement
`Required
`Required
`• Product Title
`• Initial U.S. Approval
`Required
`
`NO
`
`YES
`
`YES
`
`NO
`
`NO
`
`YES
`
`
`
` Page 2 of 8
`
`Reference ID: 3209548
`
`

`

`
`
`
`
`Selected Requirements of Prescribing Information
`
`• Boxed Warning
`Required if a Boxed Warning is in the FPI
`• Recent Major Changes
`Required for only certain changes to PI*
`• Indications and Usage
`Required
`• Dosage and Administration
`Required
`• Dosage Forms and Strengths
`Required
`• Contraindications
`Required (if no contraindications must state “None.”)
`• Warnings and Precautions
`Not required by regulation, but should be present
`• Adverse Reactions
`Required
`• Drug Interactions
`Optional
`• Use in Specific Populations
`Optional
`• Patient Counseling Information Statement Required
`• Revision Date
`Required
`* RMC only applies to the Boxed Warning, Indications and Usage, Dosage and Administration, Contraindications,
`and Warnings and Precautions sections.
`Comment:
`7. A horizontal line must separate HL and Table of Contents (TOC).
`Comment:
`
`
`HIGHLIGHTS DETAILS
`Highlights Heading
`8. At the beginning of HL, the following heading must be bolded and appear in all UPPER CASE
`letters: “HIGHLIGHTS OF PRESCRIBING INFORMATION”.
`Comment:
`
`
`Highlights Limitation Statement
`9. The bolded HL Limitation Statement must be on the line immediately beneath the HL heading
`and must state: “These highlights do not include all the information needed to use (insert
`name of drug product in UPPER CASE) safely and effectively. See full prescribing
`information for (insert name of drug product in UPPER CASE).”
`Comment:
`
`Product Title
`10. Product title in HL must be bolded.
`Comment:
`
`Initial U.S. Approval
`11. Initial U.S. Approval in HL must be placed immediately beneath the product title, bolded, and
`include the verbatim statement “Initial U.S. Approval:” followed by the 4-digit year.
`Comment:
`
`Boxed Warning
`12. All text must be bolded.
`Comment:
`13. Must have a centered 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”).
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`
`
`Reference ID: 3209548
`
`
`
`Page 3 of 8
`
`

`

`
`
`
`
`Selected Requirements of Prescribing Information
`
`Comment:
`14. Must always have the verbatim statement “See full prescribing information for complete boxed
`warning.” in italics and centered immediately beneath the heading.
`Comment:
`15. Must be limited in length to 20 lines (this does not include the heading and statement “See full
`prescribing information for complete boxed warning.”)
`Comment: Boxed Warning is 22, not 20 lines
`16. Use sentence case for summary (combination of uppercase and lowercase letters typical of that
`used in a sentence).
`Comment:
`
`
`Recent Major Changes (RMC)
`17. Pertains to only the following five sections of the FPI: Boxed Warning, Indications and Usage,
`Dosage and Administration, Contraindications, and Warnings and Precautions.
`Comment:
`18. Must be listed in the same order in HL as they appear in FPI.
`Comment:
`19. Includes heading(s) and, if appropriate, subheading(s) of labeling section(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, “Dosage and Administration, Coronary Stenting (2.2) --- 3/2012”.
`Comment:
`20. 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
`21. If a product belongs to an established pharmacologic class, the following statement is required in
`the Indications and Usage section of HL: “(Product) is a (name of established pharmacologic
`class) indicated for (indication)”.
`Comment:
`
`Dosage Forms and Strengths
`22. For a product that has several dosage forms, bulleted subheadings (e.g., capsules, tablets,
`injection, suspension) or tabular presentations of information is used.
`Comment:
`
`YES
`
`NO
`
`YES
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`YES
`
`N/A
`
`YES
`
`
`Contraindications
`23. All contraindications listed in the FPI must also be listed in HL or must include the statement
`“None” if no contraindications are known.
`Comment:
`
`
`
`Reference ID: 3209548
`
`
`
`Page 4 of 8
`
`

`

`YES
`
`NO
`
`
`
`Selected Requirements of Prescribing Information
`
`
`24. Each contraindication is bulleted when there is more than one contraindication.
`Comment:
`
`Adverse Reactions
`25. 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: Change www.fda.gov\medwatch to www.fda.gov/medwatch. Delete “Vivelle” from
`the first sentence in the “Adverse Reactions (AR)” Section in Highlights as shown below:
`“Most common adverse reactions (≥5 percent) with Vivelle are: headache, breast
`tenderness, back pain, pain in limb, and nasopharyngitis, dyspepsia, nausea,
`sinusitis, intermenstrual bleeding. (6.1)”
`
`
`This is because the regulations state that ARs should be from the drug. The prescriber can use
`the reference to Section 6.1 and learn that the AR profile is from Vivelle. The Highlights does
`not need the detail of whether these AR are from Minivelle or Vivelle.
`
`YES
`
`Patient Counseling Information Statement
`26. Must include one of the following three bolded verbatim statements (without quotation marks):
`
`
`
`
`
`
`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
`
`YES
`
`YES
`
`Revision Date
`27. Bolded revision date (i.e., “Revised: MM/YYYY or Month Year”) must be at the end of HL.
`Comment:
` Contents: Table of Contents (TOC)
`
`
`
`
`GENERAL FORMAT
`28. A horizontal line must separate TOC from the FPI.
`Comment:
`29. The following bolded heading in all UPPER CASE letters must appear at the beginning of TOC:
`“FULL PRESCRIBING INFORMATION: CONTENTS”.
`Comment:
`
`
`
`Reference ID: 3209548
`
`
`
`Page 5 of 8
`
`

`

`
`
`Selected Requirements of Prescribing Information
`
`
`30. The section headings and subheadings (including title of the Boxed Warning) in the TOC must
`match the headings and subheadings in the FPI.
`Comment: Boxed warning title in the FPI does not match the title of the boxed warning in the
`TOC
`31. The same title for the Boxed Warning that appears in the HL and FPI must also appear at the
`beginning of the TOC in UPPER-CASE letters and bolded.
`Comment: The title for the boxed warning in the TOC needs to be in upper-case letters to match
`the same title that appears in the HL and FPI
`32. All section headings must be bolded and in UPPER CASE.
`Comment:
`33. All subsection headings must be indented, not bolded, and in title case.
`Comment:
`34. When a section or subsection is omitted, the numbering does not change.
`Comment:
`35. 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:
`
`
`
`Full Prescribing Information (FPI)
`GENERAL FORMAT
`36. The following heading must appear at the beginning of the FPI in UPPER CASE and bolded:
`“FULL PRESCRIBING INFORMATION”.
`Comment:
`37. All section and subsection headings and numbers must be bolded.
`Comment:
`
`38. The bolded section and subsection headings must be named and numbered in accordance with
`21 CFR 201.56(d)(1) as noted below. If a section/subsection is omitted, the numbering does not
`change.
`
`NO
`
`
`
`NO
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`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
`
`
`
`
`
`Reference ID: 3209548
`
`
`
`Page 6 of 8
`
`

`

`
`
`
`
`Selected Requirements of Prescribing Information
`
`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:
`
`
`39. 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 patient labeling must appear at the end of the PI upon approval.
`Comment:
`40. The preferred presentation for cross-references in the FPI is the section heading (not subsection
`heading) followed by the numerical identifier in italics. For example, “[see Warnings and
`Precautions (5.2)]”.
`Comment:
`41. 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
`Boxed Warning
`42. All text is bolded.
`Comment:
`43. 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”).
`Comment:
`44. Use sentence case (combination of uppercase and lowercase letters typical of that used in a
`sentence) for the information in the Boxed Warning.
`
`
`
`YES
`
`YES
`
`N/A
`
`YES
`
`YES
`
`YES
`
`
`
`Reference ID: 3209548
`
`
`
`Page 7 of 8
`
`

`

`
`
`
`
`Selected Requirements of Prescribing Information
`
`Comment:
`Contraindications
`45. If no Contraindications are known, this section must state “None”.
`Comment:
`
`N/A
`
`YES
`
`
`
`N/A
`
`YES
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Adverse Reactions
`46. When clinical trials adverse reactions data is 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 clinical practice.”
`Comment:
`47. When postmarketing adverse reaction data is 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
`48. Must reference any FDA-approved patient labeling, include the type of patient labeling, and use
`one of the following statements at the beginning of Section 17:
`• “See FDA-approved patient labeling (Medication Guide)”
`• “See FDA-approved patient labeling (Medication Guide and Instructions for Use)”
`• “See FDA-approved patient labeling (Patient Information)"
`• “See FDA-approved patient labeling (Instructions for Use)"
`• “See FDA-approved patient labeling (Patient Information and Instructions for Use)”
`Comment:
`
`
`
`Reference ID: 3209548
`
`
`
`Page 8 of 8
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ABIMBOLA O ADEBOWALE
`10/26/2012
`
`LAURIE B BURKE
`10/26/2012
`
`Reference ID: 3209548
`
`

`

`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`Division of Professional Drug Promotion/Division of Consumer Drug
`Promotion
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`
`
`
`Memorandum
`
`October 23, 2012
`
`
`
`
`
`
`
`
`
`Date:
`
`To:
`Samantha Bell
`Regulatory Project Manager
`
`
`Division of Reproductive and Urologic Products (DRUP)
`
`
`
`
`
`From: Melinda McLawhorn, PharmD, BCPS
`
`
`Regulatory Review Officer
`
`
`Division of Prescription Drug Promotion (DPDP)
`
`
`Office of Prescription Drug Promotion (OPDP)
`
`
`
`
`
`Carrie Newcomer, PharmD
`Regulatory Review Officer
`Division of Consumer Drug Promotion (DCDP)
`OPDP
`
`
`CC:
`
`
`
`Subject: NDA 203752
`MINIVELLE™(estradiol transdermal system)
`
`Mathilda Fienkeng, PharmD, Team Leader (Acting) (DPDP)
`Mike Sauers, Team Leader (DCDP)
`
`
`
`
`
`Background
`
`On March 30, 2012, DRUP consulted OPDP to review the proposed package insert (PI),
`patient package insert (PPI), and carton/container labeling for the original NDA
`submission for MINIVELLE™ (estradiol transdermal system) (Minivelle).
`
`DPDP and DCDP reviewed the PI, PPI, and Instructions for Use (IFU) from the proposed
`substantially complete version retrieved from the eRoom on September 28, 2012, and
`provided comments to DRUP on October 9, 2012.
`
`DPDP and DCDP have reviewed the substantially complete version of the carton and
`container submitted to the electronic document room (EDR Location:
`\\CDSESUB1\EVSPROD\NDA203752\203752.enx) on October 15, 2012.
`1
`
`
`Reference ID: 3207289
`
`

`

`Attachment 1 includes our comments on the following proposed materials:
`All Strength Trade Carton
`All Strength Sample Carton
`“m" mg Trade Carton
`W" mg Sample Carton Packer
`“m" mg Sample Carton
`0.05 mg Early Experience Kit Sample
`0.05 mg and 0.01 mg Early Experience Kit Sample Carton Inside Print
`"m" mg Pouch Stock
`
`“M" mg Pouch
`We note that Noven did not submit the back view of the proposed "
`Stock", therefore, OPDP’s evaluation and comments apply to the front view only.
`
`Please apply these comments to the carton and container labeling for the following
`dosage strengths: 0.05 mg, 0.01 mg, 0.075 mg and 0.0375 mg.
`
`Proposed “Placebo Pouch Stock" (see Attachment 2)
`
`To prevent confusion with the demonstration sample and the trade product, we
`recommend the following:
`
`Increase the prominence of the statement “Contains no active ingredient”
`0 Present the statement “Contains no active ingredient” in conjunction with the
`proprietary and the established names.
`
`0
`
`Increase the prominence of the statement “Demonstration Sample — Placebo”
`
`We also recommend that the statement, “Contains no active ingredient" be
`prominently presented on the placebo patch. Lastly, since Noven did not submit the
`back view of the proposed “Placebo Pouch Stock”, OPDP’s evaluation and
`comments apply to the front view only.
`
`If you have any questions, please contact Melinda
`Thank you for your consult.
`McLawhorn at 6-7559 or at Melinda.McLawhorn@fda.hhs.gov or Carrie Newcomer
`at 6—1233 or at Carrie.Newcomer@fda.hhs.gov.
`
`9 Page(s) of Draft Labeling has been Withheld in Full as B4 (CCIITS) immediately
`following this page
`
`Reference ID: 3207289
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MELINDA W MCLAWHORN
`10/23/2012
`
`CARRIE A NEWCOMER
`10/23/2012
`
`Reference ID: 3207289
`
`

`

`
`
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`Division of Professional Drug Promotion/Division of Consumer Drug
`Promotion
`
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`
`
`
`Memorandum
`
`October 9, 2012
`
`
`
`
`
`
`
`
`
`
`Carrie Newcomer, PharmD
`Regulatory Review Officer
`Division of Consumer Drug Promotion (DCDP)
`OPDP
`
`Mathilda Fienkeng, PharmD, Group Leader (DPDP)
`Michael Sauers, Group Leader (DCDP)
`
`Date:
`
`To:
`Samantha Bell
`Regulatory Project Manager
`
`
`Division of Reproductive and Urologic Products (DRUP)
`
`
`
`
`
`From: Melinda McLawhorn, PharmD, BCPS
`
`
`Regulatory Review Officer
`
`
`Division of Prescription Drug Promotion (DPDP)
`
`
`Office of Prescription Drug Promotion (OPDP)
`
`
`
`
`
`
`CC:
`
`
`
`Subject: NDA 203752
`MINIVELLE™(estradiol transdermal system)
`
`
`
`
`
`Background
`
`On March 30, 2012, DRUP consulted OPDP to review the proposed package insert (PI), patient
`package insert (PPI), and carton/container labeling for the original NDA submission for
`MINIVELLE™ (estradiol transdermal system) (Minivelle).
`
`DPDP reviewed the PI from the proposed substantially complete version retrieved from the
`eRoom on September 28, 2012. Our comments are provided below. DPDP will review the
`carton/container after the sponsor submits the complete versions.
`
`DCDP notes that the Division of Medical Policy Programs (DMPP) provided comments on the
`draft PPI and Instructions for Use (IFU) on October 1, 2012. DCDP agrees with DMPP’s
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3201109
`
`

`

`
`
`comments and has provided additional comments directly on DMPP’s review of the PPI and IFU
`(please see attached document below).
`
`Thank you for your consult. If you have any questions on the PI, please contact Melinda
`McLawhorn at 6-7559 or at Melinda.McLawhorn@fda.hhs.gov. If you have any questions
`on the PPI or IFU, please contact Carrie Newcomer at 6-1233 or at
`carrie.newcomer@fda.hhs.gov
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3201109
`
`43 Page(s) of Draft Labeling has 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/
`----------------------------------------------------
`
`MELINDA W MCLAWHORN
`10/09/2012
`
`CARRIE A NEWCOMER
`10/09/2012
`
`Reference ID: 3201109
`
`

`

`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`Drug Name:
`
`Application
`Type/Number:
`
`Applicant:
`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy Initiatives
`Division of Medical Policy Programs
`
`PATIENT LABELING REVIEW
`October 1, 2012
`
`Hylton V. Joffe, M.D., Director
`Division of Reproductive and Urologic Products (DRUP)
`
`LaShawn Griffiths, RN, MSHS-PH, BSN
`Associate Director, Patient Labeling Team
`Division of Medical Policy Programs (DMPP)
`
`Melissa Hulett, RN, BSN, MSBA
`Team Leader, Patient Labeling Team
`Division of Medical Policy Programs (DMPP)
`
`Twanda Scales, RN, MSN/Ed.
`Patient Labeling Reviewer
`Division of Medical Policy Programs (DMPP)
`
`DMPP Review of Patient Labeling (Patient Package Insert
`and Instructions for Use)
`Minivelle (estradiol transdermal system)
`
`Dosage Form and Route: Topical Patch
`
`
`NDA 203