CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`022501Orig1s000
`
`
`OTHER REVIEW(S)
`
`
`
`
`

`

`NDA 022501 (Lo Loestrin Fe)
`Labeling Review
`
`NDA 022501 Labeling Review
`Memo to File
`
`
`
`The labeling, as submitted by the Sponsor on October 19, 2010, is acceptable to the
`Division.
`
`
`
`Ronald J. Orleans, M.D.
`Medical Officer
`
`October 21, 2001
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RONALD J ORLEANS
`10/21/2010
`
`LISA M SOULE
`10/21/2010
`
`Reference ID: 2853112
`
`

`

`
`
`SEALD LABELING: FINAL SIGN-OFF REVIEW
`
`
`
`
`APPLICATION NUMBER
`APPLICANT
`DRUG NAME
`
`NDA 22-501
`Warner Chilcott, Inc.
`Lo Loestrin Fe (norethindrone acetate and ethinyl estradiol
`tablets, ethinyl estradiol tablets, and ferrous fumarate
`tablets)
`April 20, 2010
`October 21, 2010
`October 19, 2010
`Ann Marie Trentacosti for Laurie Burke
`
`SUBMISSION DATE
`PDUFA DATE
`SEALD REVIEW DATE
`OND ASSOCIATE DIRECTOR
`FOR LABELING OR DESIGNEE
`
`
`
`
`
`This review confirms that the final draft labeling meets the minimum requirements of 21
`CFR 201.56 and 201.57 and related CDER labeling policies.
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ANN M TRENTACOSTI
`10/19/2010
`Signing for Laurie Burke
`
`Reference ID: 2852194
`
`

`

`
`
`SEALD LABELING REVIEW
`
`
`This review identifies aspects of the draft labeling that do not meet the requirements of 21 CFR
`201.56 and 201.57 and related CDER labeling policies.
`
`
`APPLICATION NUMBER
`APPLICANT
`DRUG NAME
`
`NDA 22-501
`Warner Chilcott Co, Inc.
`
`Lo Loestrin Fe (norethindrone acetate and ethinyl estradiol
`tablets, ethinyl estradiol tablets, and ferrous fumarate
`tablets)
`April 20, 2010
`October 21, 2010
`October 19, 2010
`Jun Yan, Pharm.D.
`
`SUBMISSION DATE
`PDUFA DATE
`SEALD REVIEW DATE
`SEALD LABELING
`REVIEWER(S)
`
`
`Outlined below are the following outstanding labeling issues that must be corrected before the
`final draft labeling is approved. Issues are listed in the order mandated by the regulations or
`guidance.
`
`If there are no issues for a particular heading in highlights (HL) or for sections in the full
`prescribing information (FPI), “none” is stated. If clearly inapplicable sections are omitted from
`the FPI, “not applicable” is stated. In addition, “not applicable” is stated if optional headings
`(i.e., Drug Interactions or Use in Specific Populations) are omitted from HL.
`
`
`Highlights (HL):
`
`
`• Highlights Limitation Statement: None.
`
`• Product Title Line: None.
`
`• Initial U.S. Approval: None.
`
`• Boxed Warning: None.
`
`• Recent Major Changes: None.
`
`• Indications and Usage: None.
`
`• Dosage and Administration: None.
`
`• Dosage Forms and Strengths: None.
`
`
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`

`

`
`
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`
`
`SEALD LABELING REVIEW
`
`• Contraindications: None.
`
`• Warnings and Precautions: None.
`
`• Adverse Reactions: None.
`
`• Drug Interactions: None.
`
`• Use in Specific Populations: None.
`
`• Patient Counseling Information Statement: None.
`
`• Revision Date: None.
`
`
`
`Table of Contents (TOC):
`
`
`• Please ensure the Full Prescribing Information title begins on a new page and is separated
`from the TOC with a horizontal line. See 21 CFR 201.57(d)(2).
`
`
`Full Prescribing Information (FPI):
`
`
`Boxed Warning: None.
`
`1 Indications and Usage: None.
`
`2 Dosage and Administration: None.
`
`3 Dosage Forms and Strengths: None.
`
`4 Contraindications: None.
`
`5 Warnings and Precautions: None.
`
`6 Adverse Reactions: None.
`
`7 Drug Interactions: None.
`
`8 Use in Specific Populations: None.
`
`9 Drug Abuse and Dependence: Not applicable.
`
`10 Overdosage: None.
`
`11 Description: None.
`
`2
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`SEALD LABELING REVIEW
`
`12 Clinical Pharmacology: None.
`
`13 Nonclinical Toxicology: None.
`
`14 Clinical Studies: None.
`
`15 References: None.
`
`16 How Supplied/Storage and Handling: None.
`
`17 Patient Counseling Information: None.
`
`3
`
`
`
`
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`JUN YAN
`10/19/2010
`
`Reference ID: 2851995
`
`

`

`
`
`
`
`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Translational Science
`Office of Biostatistics
`
`
`ADDENDUM TO LABELIBNG REVIEW
`
`NDA/Serial Number:
`Drug Name:
`
`Indication(s):
`Applicant:
`Date(s):
`
`Review Priority:
`
`22-501 / Resubmission
`LO LOESTRIN FE (Norethindrone acetate and Ethinyl Estradiol tablets, and
`Ferrous Fumarate tablets)
`Prevention of Pregnancy
`
`Warner Chilcott Company, Inc.
`
`Submission Date: 4/21/2010
`PDUFA Due Date: 10/21/2010
`Priority
`
`
`
`
`
`Biometrics Division:
`Division of Biometrics III
`Statistical Reviewer:
`Kate Dwyer, Ph.D.
`Concurring Reviewers: Mahboob Sobhan, Ph.D.
`
`
`Medical Division:
`Clinical Team:
`
`Project Manager:
`
`
`Keywords: Labeling review
`
`
`
`
`
`
`Division of Reproductive and Urologic Drug Products
`
`Ronald Orleans, M.D., Medical Reviewer
`Lisa Soule, M.D., Team Leader
`Karl Stiller
`
`

`

`
`This addendum updates the labeling review of this NDA resubmission for LO LOESTRIN FE,
`an oral contraceptive. This reviewer agrees with the final version of the labeling change.
`
`
`
`
`2
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`KATE L DWYER
`10/15/2010
`
`Reference ID: 2850994
`
`

`

`MEMORANDUM
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`
`***PRE-DECISIONAL AGENCY MEMO***
`
`
`Date: October 4, 2010
`
`To:
`
`
`
` Karl Stiller
` Regulatory Project Manager
`Division of Reproductive and Urologic Products (DRUP)
`
`
`From:
`
`
`Re:
`
`Janice Maniwang, Pharm.D., M.B.A., Regulatory Review Officer
`Carrie Newcomer, Pharm.D., Regulatory Review Officer
`Division of Drug Marketing, Advertising, and Communications (DDMAC)
`
` NDA: 022501
`DDMAC labeling comments for Lo Loestrin Fe (norethindrone acetate and
`ethinyl estradiol tablets, ethinyl estradiol tablets and ferrous fumarate tablets)
`
`
`
`Background
`
`This consult is in response to DRUP’s August 6, 2010 request for DDMAC’s review on
`labeling materials for Lo Loestrin Fe (norethindrone acetate and ethinyl estradiol tablets,
`ethinyl estradiol tablets and ferrous fumarate tablets) DDMAC has reviewed the
`following labeling materials for Lo Loestrin Fe:
`
`Healthcare Provider Directed:
`• Prescribing Information (PI)
`
`
`Consumer Directed:
`• Patient Product Information (PPI)
`
`
`Please note that our comments are based on the substantially complete version of the
`draft label sent to DDMAC on September 29, 2010. In addition, we have considered the
`Loestrin 24 Fe PI (approved February 2006) and the Natazia PI (approved May 2010) in
`our review of the draft Lo Loestrin Fe labeling.
`
`We offer the following comments:
`
`
`
`
`
`
`

`

`Page 2
`
`PI & PPI
`
`Please see our attached comments.
`
`DDMAC appreciates the opportunity to provide comments on these materials. If you
`have any questions, please contact:
`
`
`• Janice Maniwang (Professional directed materials)
`(301) 796-3821, or janice.maniwang@fda.hhs.gov
`
`
`
`
`
`• Carrie Newcomer (Consumer directed materials)
`(301) 796-1233, or carrie.newcomer@fda.hhs.gov
`
`
`
`
`
`30 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/
`----------------------------------------------------
`
`JANICE L MANIWANG
`10/04/2010
`
`CARRIE A NEWCOMER
`10/04/2010
`
`Reference ID: 2844790
`
`

`

`
`
`
`
`RPM FILING REVIEW
`(Including Memo of Filing Meeting)
`To be completed for all new NDAs, BLAs, and Efficacy Supplements (except SE8 and SE9)
`
`Application Information
`NDA Supplement #:S-
`Efficacy Supplement Type SE-
`NDA # 022501
`BLA STN #
`BLA#
`Proprietary Name: not established
`Established/Proper Name: norethindrone acetate (NA) and ethinyl
`estradiol tablets (EE), ethinyl estradiol tablets, and ferrous fumarate
`Dosage Form: tablet
`Strengths: 1 mg NA/10 mcg EE, 10 mcg EE
`Applicant: Warner Chilcott Company, Inc.
`Agent for Applicant (if applicable): N/A
`Date of Application: March 26, 2009
`Date of Receipt: March 26, 2009
`Date clock started after UN: N/A
`PDUFA Goal Date: January 26, 2010
`
`
`
` 505(b)(1)
` 505(b)(2)
` 505(b)(1)
` 505(b)(2)
`
` Standard
` Priority
`
`Action Goal Date (if different):
`
`Date of Filing Meeting: April 30, 2009
`Filing Date: May 25, 2009
`Chemical Classification: (1,2,3 etc.) (original NDAs only) Type 3
`Proposed indication(s)/Proposed change(s): Prevention of pregnancy
`
`Type of Original NDA:
`AND (if applicable)
`Type of NDA Supplement:
`
`If 505(b)(2): Draft the “505(b)(2) Assessment” form found at:
`http://inside.fda.gov:9003/CDER/OfficeofNewDrugs/ImmediateOffice/ucm027499.html
`and refer to Appendix A for further information.
`Review Classification:
`
`If the application includes a complete response to pediatric WR, review
`classification is Priority.
`
`If a tropical disease priority review voucher was submitted, review
`classification is Priority.
`
`Resubmission after withdrawal?
`Part 3 Combination Product?
`
`If yes, contact the Office of Combination
`Products (OCP) and copy them on all Inter-
`Center consults
` Fast Track
` Rolling Review
` Orphan Designation
`
`
`
`
` Tropical Disease Priority
`Review Voucher submitted
`
`
`
`Resubmission after refuse to file?
` Drug/Biologic
` Drug/Device
` Biologic/Device
`
`
`
` PMC response
` PMR response:
` FDAAA [505(o)]
` PREA deferred pediatric studies [21 CFR
`314.55(b)/21 CFR 601.27(b)]
` Accelerated approval confirmatory studies (21 CFR
`314.510/21 CFR 601.41)
` Animal rule postmarketing studies to verify clinical
`
`
`
`
`
` Rx-to-OTC switch, Full
` Rx-to-OTC switch, Partial
` Direct-to-OTC
`
`Version: 9/9/09
`
`1
`
`

`

`
`
`YES NO NA Comment
`X
`
`
`
`
`
`
`X
`
`X
`
`
`
`
`
`
`
`Correction requested
`
`
`
`YES NO NA Comment
`
`
`
`X
`
`
`
`
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`
`
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`
`X
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`
`YES NO NA Comment
`X
`
`
`
`
`benefit and safety (21 CFR 314.610/21 CFR 601.42)
`Other:
`Collaborative Review Division (if OTC product):
`List referenced IND Number(s): IND 073510
`Goal Dates/Names/Classification Properties
`PDUFA and Action Goal dates correct in tracking system?
`
`If not, ask the document room staff to correct them immediately.
`These are the dates used for calculating inspection dates.
`Are the proprietary, established/proper, and applicant names
`correct in tracking system?
`
`If not, ask the document room staff to make the corrections. Also,
`ask the document room staff to add the established/proper name
`to the supporting IND(s) if not already entered into tracking
`system.
`Are all classification properties [e.g., orphan drug, 505(b)(2)]
`entered into tracking system?
`
`If not, ask the document room staff to make the appropriate
`entries.
`Application Integrity Policy
`Is the application affected by the Application Integrity Policy
`(AIP)? Check the AIP list at:
`http://www.fda.gov/ICECI/EnforcementActions/ApplicationIntegr
`ityPolicy/default.htm
`If yes, explain in comment column.
`
`If affected by AIP, has OC/DMPQ been notified of the
`submission? If yes, date notified:
`
`
`
`User Fees
`Is Form 3397 (User Fee Cover Sheet) included with
`authorized signature?
`
`
`User Fee Status
`
`If a user fee is required and it has not been paid (and it
`is not exempted or waived), the application is
`unacceptable for filing following a 5-day grace period.
`Review stops. Send UN letter and contact user fee staff.
`
`
`
`If the firm is in arrears for other fees (regardless of
`whether a user fee has been paid for this application),
`the application is unacceptable for filing (5-day grace
`period does not apply). Review stops. Send UN letter
`and contact the user fee staff.
`Note: 505(b)(2) applications are no longer exempt from user fees pursuant to the passage of FDAAA. All 505(b)
`applications, whether 505(b)(1) or 505(b)(2), require user fees unless otherwise waived or exempted (e.g., small
`business waiver, orphan exemption).
`
`Payment for this application:
`
`
` Paid
` Exempt (orphan, government)
` Waived (e.g., small business, public health)
` Not required
`Payment of other user fees:
`
`
` Not in arrears
` In arrears
`
`Version: 9/9/09
`
`2
`
`

`

`
`
`YES NO NA Comment
`
`
`505(b)(2)
`(NDAs/NDA Efficacy Supplements only)
`Is the application for a duplicate of a listed drug and eligible
`for approval under section 505(j) as an ANDA?
`Is the application for a duplicate of a listed drug whose only
`difference is that the extent to which the active ingredient(s)
`is absorbed or otherwise made available to the site of action
`less than that of the reference listed drug (RLD)? (see 21
`CFR 314.54(b)(1)).
`Is the application for a duplicate of a listed drug whose only
`difference is that the rate at which the proposed product’s
`active ingredient(s) is absorbed or made available to the site
`of action is unintentionally less than that of the listed drug
`(see 21 CFR 314.54(b)(2))?
`
`Note: If you answered yes to any of the above questions, the
`application may be refused for filing under 21 CFR 314.101(d)(9).
`Is there unexpired exclusivity on the active moiety (e.g., 5-
`year, 3-year, orphan or pediatric exclusivity)? Check the
`Electronic Orange Book at:
`http://www.fda.gov/cder/ob/default.htm
`
`If yes, please list below:
`Exclusivity Expiration
`Exclusivity Code
`Drug Name
`Application No.
`
`
`
`
`
`
`
`
`
`
`
`
`If there is unexpired, 5-year exclusivity remaining on the active moiety for the proposed drug product, a 505(b)(2)
`application cannot be submitted until the period of exclusivity expires (unless the applicant provides paragraph IV
`patent certification; then an application can be submitted four years after the date of approval.) Pediatric
`exclusivity will extend both of the timeframes in this provision by 6 months. 21 CFR 108(b)(2).Unexpired, 3-year
`exclusivity will only block the approval, not the submission of a 505(b)(2) application.
`Exclusivity
`YES NO NA Comment
`Does another product have orphan exclusivity for the same
`
`X
`
`
`indication? Check the Electronic Orange Book at:
`http://www.fda.gov/cder/ob/default.htm
`If another product has orphan exclusivity, is the product
`considered to be the same product according to the orphan
`drug definition of sameness [21 CFR 316.3(b)(13)]?
`
`If yes, consult the Director, Division of Regulatory Policy II,
`Office of Regulatory Policy (HFD-007)
`Has the applicant requested 5-year or 3-year Waxman-Hatch
`exclusivity? (NDAs/NDA efficacy supplements only)
`
`If yes, # years requested: 3
`
`Note: An applicant can receive exclusivity without requesting it;
`therefore, requesting exclusivity is not required.
`
`
`
`
`
`
`
`
`
`
`
`X
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`X
`
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`
`
`
`
`
`
`
`
`
`
`
`
`Version: 9/9/09
`
`3
`
`

`

`
`
`
`Is the proposed product a single enantiomer of a racemic drug
`previously approved for a different therapeutic use (NDAs
`only)?
`If yes, did the applicant: (a) elect to have the single
`enantiomer (contained as an active ingredient) not be
`considered the same active ingredient as that contained in an
`already approved racemic drug, and/or (b): request
`exclusivity pursuant to section 505(u) of the Act (per
`FDAAA Section 1113)?
`
`If yes, contact Mary Ann Holovac, Director of Drug Information,
`OGD/DLPS/LRB.
`
`
`
`
`
`Do not check mixed submission if the only electronic component
`is the content of labeling (COL).
`
`
`If mixed (paper/electronic) submission, which parts of the
`application are submitted in electronic format?
`Overall Format/Content
`If electronic submission, does it follow the eCTD
`guidance1?
`If not, explain (e.g., waiver granted).
`Index: Does the submission contain an accurate
`comprehensive index?
`Is the submission complete as required under 21 CFR 314.50
`(NDAs/NDA efficacy supplements) or under 21 CFR 601.2
`(BLAs/BLA efficacy supplements) including:
`
`
` legible
` English (or translated into English)
` pagination
` navigable hyperlinks (electronic submissions only)
`
`
`If no, explain.
`Controlled substance/Product with abuse potential:
`Is an Abuse Liability Assessment, including a proposal for
`scheduling, submitted?
`
`
`
`If yes, date consult sent to the Controlled Substance Staff:
`BLAs only: Companion application received if a shared or
`divided manufacturing arrangement?
`
`If yes, BLA #
`
`
`
`Format and Content
`
`
`
`
`
`X
`
`
`
`
`
`X
`
`
`
`
`
` All paper (except for COL)
` All electronic
` Mixed (paper/electronic)
`
` CTD
` Non-CTD
` Mixed (CTD/non-CTD)
`
`
`
`
`
`YES NO NA Comment
`
`X
`
`
`
`X
`
`X
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`No navigable
`hyperlinks in
`portions
`submitted
`electronically,
`but information
`is made available
`in application.
`
`X
`
`X
`
`
`
`
`
`Version: 9/9/09
`
`4
`
`

`

`
`
`YES NO NA Comment
`X
`
`
`
`
`X
`
`
`
`All establishment
`information included
`in application
`YES NO NA Comment
`
`
`
`Forms and Certifications
`Electronic forms and certifications with electronic signatures (scanned, digital, or electronic – similar to DARRTS,
`e.g., /s/) are acceptable. Otherwise, paper forms and certifications with hand-written signatures must be included.
`Forms include: user fee cover sheet (3397), application form (356h), patent information (3542a), financial
`disclosure (3454/3455), and clinical trials (3674); Certifications include: debarment certification, patent
`certification(s), field copy certification, and pediatric certification.
`Application Form
`Is form FDA 356h included with authorized signature?
`
`If foreign applicant, both the applicant and the U.S. agent must
`sign the form.
`Are all establishments and their registration numbers listed
`on the form/attached to the form?
`Patent Information
`(NDAs/NDA efficacy supplements only)
`Is patent information submitted on form FDA 3542a?
`
`Financial Disclosure
`Are financial disclosure forms FDA 3454 and/or 3455
`included with authorized signature?
`
`Forms must be signed by the APPLICANT, not an Agent.
`
`Note: Financial disclosure is required for bioequivalence studies
`that are the basis for approval.
`Clinical Trials Database
`Is form FDA 3674 included with authorized signature?
`
`Debarment Certification
`Is a correctly worded Debarment Certification included with
`authorized signature? (Certification is not required for
`supplements if submitted in the original application)
`
`If foreign applicant, both the applicant and the U.S. Agent must
`sign the certification.
`
`Note: Debarment Certification should use wording in FD&C Act
`section 306(k)(l) i.e.,“[Name of applicant] hereby certifies that it
`did not and will not use in any capacity the services of any person
`debarred under section 306 of the Federal Food, Drug, and
`Cosmetic Act in connection with this application.” Applicant may
`not use wording such as, “To the best of my knowledge…”
`
`
`
`X
`
`
`
`
`
`
`
`YES NO NA Comment
`X
`
`
`
`
`YES NO NA Comment
`X
`
`
`
`
`YES NO NA Comment
`X
`
`
`
`
`Version: 9/9/09
`
`5
`
`

`

`
`
`
`Field Copy Certification
`(NDAs/NDA efficacy supplements only)
`For paper submissions only: Is a Field Copy Certification
`(that it is a true copy of the CMC technical section) included?
`
`Field Copy Certification is not needed if there is no CMC
`technical section or if this is an electronic submission (the Field
`Office has access to the EDR)
`
`If maroon field copy jackets from foreign applicants are received,
`return them to CDR for delivery to the appropriate field office.
`
`
`Pediatrics
`PREA
`
`Does the application trigger PREA?
`
`If yes, notify PeRC RPM (PeRC meeting is required)
`
`Note: NDAs/BLAs/efficacy supplements for new active ingredients,
`new indications, new dosage forms, new dosing regimens, or new
`routes of administration trigger PREA. All waiver & deferral
`requests, pediatric plans, and pediatric assessment studies must be
`reviewed by PeRC prior to approval of the application/supplement.
`If the application triggers PREA, are the required pediatric
`assessment studies or a full waiver of pediatric studies
`included?
`
`If studies or full waiver not included, is a request for full
`waiver of pediatric studies OR a request for partial waiver
`and/or deferral with a pediatric plan included?
`
`If no, request in 74-day letter
`If a request for full waiver/partial waiver/deferral is
`included, does the application contain the certification(s)
`required under 21 CFR 314.55(b)(1), (c)(2), (c)(3)/21 CFR
`601.27(b)(1), (c)(2), (c)(3)
`
`If no, request in 74-day letter
`BPCA (NDAs/NDA efficacy supplements only):
`
`Is this submission a complete response to a pediatric Written
`Request?
`
`If yes, notify Pediatric Exclusivity Board RPM (pediatric
`exclusivity determination is required)
`
`
`YES NO NA Comment
`
`X
`
`
`
`
`
`
`
`YES NO NA Comment
`X
`
`
`
`
`
`
`X
`
`X
`
`X
`
`
`
`
`
`
`
`X
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Version: 9/9/09
`
`6
`
`

`

`
`
`
`Proprietary Name
`Is a proposed proprietary name submitted?
`
`If yes, ensure that it is submitted as a separate document and
`routed directly to OSE/DMEPA for review.
`Prescription Labeling
`Check all types of labeling submitted.
`
`
`
`
`Is Electronic Content of Labeling (COL) submitted in SPL
`format?
`
`If no, request in 74-day letter.
`Is the PI submitted in PLR format?
`
`If PI not submitted in PLR format, was a waiver or
`deferral requested before the application was received or in
`the submission? If requested before application was
`submitted, what is the status of the request?
`
`If no waiver or deferral, request PLR format in 74-day letter.
`All labeling (PI, PPI, MedGuide, IFU, carton and immediate
`container labels) consulted to DDMAC?
`MedGuide, PPI, IFU (plus PI) consulted to OSE/DRISK?
`(send WORD version if available)
`
`REMS consulted to OSE/DRISK?
`
`Carton and immediate container labels, PI, PPI sent to
`OSE/DMEPA?
`
`OTC Labeling
`Check all types of labeling submitted.
`
`
`Is electronic content of labeling (COL) submitted?
`
`If no, request in 74-day letter.
`
`YES NO NA Comment
`X
`
`
`Final approve
`proprietary name
`pending (4-Jan-10).
`
` Not applicable
` Package Insert (PI)
` Patient Package Insert (PPI)
` Instructions for Use (IFU)
` Medication Guide (MedGuide)
` Carton labels
` Immediate container labels
` Diluent
` Other (specify)
`YES NO NA Comment
`X
`
`
`
`
`X
`
`
`
`X
`
`X
`
`
`
`X
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`X
`
`
`
`
`
`X
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Not Applicable
` Outer carton label
` Immediate container label
` Blister card
` Blister backing label
` Consumer Information Leaflet (CIL)
` Physician sample
` Consumer sample
` Other (specify)
`YES NO NA Comment
`
`
`
`
`
`Version: 9/9/09
`
`7
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Are annotated specifications submitted for all stock keeping
`units (SKUs)?
`
`If no, request in 74-day letter.
`If representative labeling is submitted, are all represented
`SKUs defined?
`
`If no, request in 74-day letter.
`All labeling/packaging, and current approved Rx PI (if
`switch) sent to OSE/DMEPA?
`Consults
`Are additional consults needed? (e.g., IFU to CDRH; QT
`study report to QT Interdisciplinary Review Team)
`
`If yes, specify consult(s) and date(s) sent:
`
`
`Meeting Minutes/SPAs
`End-of Phase 2 meeting(s)?
`Date(s):
`
`If yes, distribute minutes before filing meeting
`Pre-NDA/Pre-BLA/Pre-Supplement meeting(s)?
`Date(s):
`
`If yes, distribute minutes before filing meeting
`Any Special Protocol Assessments (SPAs)?
`Date(s):
`
`If yes, distribute letter and/or relevant minutes before filing
`meeting
`1http://www fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072349
`.pdf
`
`
`YES NO NA Comment
`
`X
`
`
`
`YES NO NA Comment
`
`X
`
`
`
`
`
`
`
`X
`
`X
`
`
`
`
`
`
`
`
`
`Version: 9/9/09
`
`8
`
`

`

`
`
`ATTACHMENT
`
`MEMO OF FILING MEETING
`
`
`
`DATE: April 30, 2009
`
`BLA/NDA/Supp #: NDA 022501
`
`
`PROPRIETARY NAME: not established (Warner Chilcott internal name – WC3016)
`
`ESTABLISHED/PROPER NAME: norethindrone acetate (NA) and ethinyl estradiol tablets
`(EE), ethinyl estradiol tablets, and ferrous fumarate tablets
`
`DOSAGE FORM/STRENGTH: tablets
`
`APPLICANT: Warner Chilcott Company, Inc.
`
`PROPOSED INDICATION(S)/PROPOSED CHANGE(S): Prevention of pregnancy
`
`BACKGROUND: Warner Chilcott has submitted a new drug application for WC3016
`(norethindrone acetate and ethinyl estradiol tablets, ethinyl estradiol tablets and ferrous fumarate
`tablets). WC3016 is a low dose oral contraceptive consisting of a new dose and new regimen of
`the combination of NA and EE. The combination of 10 mcg of EE and 1 mg of NA (or WC3016
`1/10 tablets) is taken daily for 24 days followed by a daily dose of 10 mcg of EE (or WC3016
`EE10 tablets) for 2 days and then ferrous fumarate tablets (75 mg) for 2 days during a 28-day
`regimen. The dose may be taken without regard to meals (per draft labeling).
`
`REVIEW TEAM:
`
`
`Discipline/Organization
`
`Names
`
`Regulatory Project Management
`
`
`Cross-Discipline Team Leader (CDTL)
`
`Clinical
`
`
`Social Scientist Review (for OTC
`products)
`
`
`OTC Labeling Review (for OTC
`products)
`
`
`RPM:
`CPMS/TL:
`
`Lisa Soule
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Karl Stiller
`Jennifer Mercier/Margaret
`Kober / Lisa Soule
`
`Ron Orleans
`
`Lisa Soule
`
`
`
`
`
`
`
`
`
`Present at
`filing
`meeting?
`(Y or N)
`Y
`Y/N/Y
`
`Y
`
`Y
`
`Y
`
`
`
`
`
`
`
`
`
`Version: 9/9/09
`
`9
`
`

`

`
`
`Clinical Microbiology (for antimicrobial
`products)
`
`
`
`Clinical Pharmacology
`
`
`Biostatistics
`
`
`Nonclinical
`(Pharmacology/Toxicology)
`
`Statistics (carcinogenicity)
`
`
`Immunogenicity (assay/assay
`validation) (for BLAs/BLA efficacy
`supplements)
`
`Product Quality (CMC)
`
`
`Quality Microbiology (for sterile
`products)
`
`CMC Labeling Review (for BLAs/BLA
`supplements)
`
`Facility Review/Inspection
`
`OSE/DMEPA (proprietary name)
`
`OSE/DRISK (REMS)
`
`
`Reviewer:
`
`TL:
`
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`
`
`
`
`
`Sandhya Apparaju
`
`Myong-Jin Kim
`
`Kate Dwyer
`
`Mahboob Sobhan
`
`Krishan Raheja
`
`Lynnda Reid
`
`
`
`
`
`
`
`
`
`Yubing Tang
`
`Moo Jhong Rhee
`
`
`
`
`
`
`
`
`
`
`
`
`
`Tara Turner
`
`Kellie Taylor
`
`
`
`
`
`
`
`
`
`Y
`
`N
`
`Y
`
`N
`
`Y
`
`Y
`
`
`
`
`
`
`
`
`
`Y
`
`N
`
`
`
`
`
`
`
`
`
`
`
`
`
`N
`
`N
`
`
`
`
`
`Version: 9/9/09
`
`10
`
`

`

`
`
`Bioresearch Monitoring (DSI)
`
`
`
`Other reviewers
`
`Other attendees
`
`
`FILING MEETING DISCUSSION:
`
`
`
`GENERAL
`
` •
`
` 505(b)(2) filing issues?
`
`
`
`
`
`
`
`
`
`
`If yes, list issues:
`
`• Per reviewers, are all parts in English or English
`translation?
`
`If no, explain:
`
`
`
`
`• Electronic Submission comments
`
`
`List comments:
`
`
`
`
`
`
`
`
`
`
`
`Reviewer:
`
`TL:
`
`
`
`
`
`
` Janice Maniwang, DDMAC
`
`
`
`
`
`
`
`N
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Not Applicable
` YES
` NO
`
` YES
` NO
`
` Not Applicable
`
` Not Applicable
` FILE
` REFUSE TO FILE
`
` Review issues for 74-day letter
`
` YES
` NO
`
` YES
`Date if known:
` NO
` To be determined
`
`
`
`
`Reason:
`o this drug/biologic is not
`the first in its class
`
`
`
`
`CLINICAL
`
`Comments: Potential Review Issues:
`Recalculation of the Pearl Index based on the Division’s
`definition of “on-drug pregnancies.” The Division
`defines “on-drug pregnancies” as all conceptions
`occurring from Day 1 (the initiation of taking study
`drug) to 7 days after the conclusion of the final pill
`packet.
`
`• Clinical study site(s) inspections(s) needed?
`
`
`If no, explain:
`
`
`
`
`• Advisory Committee Meeting needed?
`
`Comments:
`
`
`
`
`
`
`
`
`
`
`
`
`
`If no, for an original NME or BLA application, include the
`reason. For example:
`o this drug/biologic is not the first in its class
`
`Version: 9/9/09
`
`11
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Not Applicable
` YES
` NO
`
` Not Applicable
` FILE
` REFUSE TO FILE
`
` Review issues for 74-day letter
`
` Not Applicable
` FILE
` REFUSE TO FILE
`
` Review issues for 74-day letter
` YES
` NO
`
` Not Applicable
` FILE
` REFUSE TO FILE
`
` Review issues for 74-day letter
`
` Not Applicable
` FILE
` REFUSE TO FILE
`
` Review issues for 74-day letter
`
` Not Applicable
` FILE
` REFUSE TO FILE
`
` Review issues for 74-day letter
`
`o the clinical study design was acceptable
`o the application did not raise significant safety
`or efficacy issues
`o the application did not raise significant public
`health questions on the role of the
`drug/biologic in the diagnosis, cure,
`mitigation, treatment or prevention of a
`disease
`
`If the application is affected by the AIP, has the
`division made a recommendation regarding whether
`or not an exception to the AIP should be granted to
`permit review based on medical necessity or public
`health significance?
`
`Comments:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` •
`
`
`
`
`
`
`CLINICAL MICROBIOLOGY
`
`
`
`
`
`
`
`Comments:
`CLINICAL PHARMACOLOGY
`
`
`
`Comments: none
`• Clinical pharmacology study site(s) inspections(s)
`needed?
`
`
`
`
`BIOSTATISTICS
`
`
`
`Comments: none
`
`NONCLINICAL
`(PHARMACOLOGY/TOXICOLOGY)
`
`
`
`Comments: none
`
`IMMUNOGENICITY (BLAs/BLA efficacy
`supplements only)
`
`
`
`
`Version: 9/9/09
`
`12
`
`

`

` Not Applicable
` FILE
` REFUSE TO FILE
`
` Review issues for 74-day letter
`
` Not Applicable
`
` YES
` NO
`
` YES
` NO
`
` YES
` NO
`
` Not Applicable
`
` YES
` NO
`
` Not Applicable
`
` YES
` NO
`
` YES
` NO
`
` Not Applicable
` FILE
` REFUSE TO FILE
`
` Review issues for 74-day letter
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Comments:
`
`PRODUCT QUALITY (CMC)
`
`
`
`Comments: none
`
`
`Environmental Assessment
`
` •
`
` Categorical exclusion for environmental assessment
`(EA) requested?
`
`If no, was a complete EA submitted?
`
`
`
`
`If EA submitted, consulted to EA officer (OPS)?
`
`Comments:
`
`Quality Microbiology (for sterile products)
`
`
`
`
`
`
`
`
`
`
`
` •
`
` Was the Microbiology Team consulted for validation
`of sterilization? (NDAs/NDA supplements only)
`
`
`Comments:
`
`Facility Inspection
`
`
`
`
`
`
`
`
`
`
`
` •
`
` Establishment(s) ready for inspection?
`
` Establishment Evaluation Request (EER/TBP-EER)
`submitted to DMPQ?
`
`
`
` (cid:131)
`
`
`
`
`Comments:
`
`Facility/Microbiology Review (BLAs only)
`
`
`
`Comments:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Version: 9/9/09
`
`13
`
`

`

`
`
`CMC Labeling Review (BLAs/BLA supplements
`only)
`
`
`Comments:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Review issues for 74-day letter
`
`
`
`REGULATORY PROJECT MANAGEMENT
`
`
`
`
`
`
`
`
`
`
`
`
`Signatory Authority: George Benson
`
`21st Century Review Milestones (see attached) (optional):
`
`Comments: