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

`

`
`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`
`Iication:
`
`Stamp Date:
`
`
`Regulatory:
`
`Applicant:
`
`NDA 22501/000
`
`26-MAR-2009
`
`21-OCT-2010
`
`WARNER CHILCOTT CO
`
`
`100 ENTERPRISE DR STE 280
`
`
`
`
`ROCKAWAY, NJ 07866
`
`
`
`Action Goal:
`
`District Goal:
`
`
`Brand Name:
`
`Estab. Name:
`
`
`Generic Name:
`
`
`22—AUG-201 0
`
`(‘3) (4)
`
`norethindrone acetate and ethinyl estradiol
`
`
`
`
`tablets, ethinyl estradiol tablets,
`
`
`
`
`Priority:
`
`Org. Code:
`
`
`38
`580
`
`Application Comment:
`
`
`
`
`
`
`I
`
`..
`
`I
`
`'7
`
`
`
`
`
`
`
`Product Number; Dosage Form; Ingredient; Strengths
`
`
`001; TABLET; NORETHINDRONE ACETATE; 1MG
`001; TABLET; ETHINYL ESTRADIOL; 10UGM
`
`
`
`
`003; TABLET; FERROUS FUMARATE; POTENCY NOT GIVEN
`
`
`
`
`
`
`002; TABLET; ETHINYL ESTRADIOL; 10UGM
`
`
`
`
`THIS NDA IS FOR A LOW DOSE ORAL CONTRACEPTIVE, CONSISTING OF 10 MCG OF ETHINYL ESTRADIOL USP (EE)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`AND 1 MG OF NORETHINDRONE ACETATE USP (NA) DAILY FOR 24 DAYS, FOLLOWED BY A DAILY DOSE OF 10 MCG
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`OF ETHINYL ESTRADIOL USP FOR 2 DAYS, THEN FERROUS FUMARATE FOR 2 DAYS. (on 29-APR-2009 by J. DAVID
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`() 301-796—4247)
`
`FDA Contacts:
`
`
`THIS IS AN NDA RESUBMISSION (CLASS 2, 6 MONTH REVIEW CLOCK). THE NDA PDUFA GOAL DATE IS: 21—OCT-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`2010. (on 03-MAY—2010 by J. DAVID () 301-796—4247)
`
`
`
`
`
`
`
`
`
`
`
`
`C. TRAN-ZWAN ETZ
`Project Manager
`Y. TANG
`Review Chemist
`
`
`D. CHRISTNER
`Team Leader
`301-796-1341
`
`
`
`
`(HFD-800)
`
`301-796-3877
`
`301-796-2457
`
`Overall Recommendation:
`
`
`ACCEPTABLE
`
`on 26-MAY-2010
`
`
`by A. INYARD
`
`
`
`()
`
`301-796-3334
`(HFD-320)
`WlTHHOLD
`by E. JOHNSON
`on 19-JAN-2010
`
`
`
`
`October 15, 2010 11 :49 AM
`
`
`
`
`
`
`FDA Confldentlal - Internal Distrlbution Only
`
`
`
`
`
`Page 1 of 9
`
`
`(b) (4)
`
`

`

`
`
`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`
`blishment:
`
`CFN:
`
`
`
`(b) (4)
`(b) (4)
`
`.
`
`FEI:
`
`(b) (4)
`
`_
`
`DMF No:
`
`
`Responsibilities:
`
`
`Estab- Comment
`
`Profile:
`
`AADA:
`
`DRUG SUBSTANCE OTHER TESTER
`
`
`
`FINISHED DOSAGE OTHER TESTER
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`THIS SITE IS FOR CONTRACT ANALYTICAL TESTING OF DRUG SUBSTANCES AND INACTIVE COMPONENTS. (on 29—
`~ --
`APR-2009 by J. DAVID () 301—796-4247)
`»
`.
`--
`-
`-
`.
`
`
`
`
`
`THE ADDRESS GIVEN FOR THIS SITE IN THE NDA IS:
`(‘3) (4)
`
`
`
`
`
`
`
`
`
`
`0’) <4)
`(THE ADDRESS
`THIS ADDRESS IS CONFIRMED ON THE FIRM‘S WEBSITE FOR ANALYTICAL TESTING.
`
`
`
`
`
`
`
`
`
`
`
`
`
`<b> <4) ADDRESS.) THE FULL EMAIL FOR THE CONTACT AT THIS SITE GIVEN IN THE NDA IS:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(b) <4) (on 03-MAY-2010 by J. DAVID () 301—796-4247)
`
`
`
`
`
`
`
`
`
`OAI Status:
`NONE
`
`
`
`CONTROL TESTING LABORATORY
`
`
`
`
`
`
`
`Creator
`Planned Completion Decision
`Reguest Tme
`Milestone Date
`Milestone Name
`
`
`Comment
`Reason
`SUBMITTED TO 00
`DAVlDJE
`
`
`
`29-APR-2009
`
`OC RECOMMENDATION
`
`
`01—MAY-2009
`
`
`
`
`
`
`
`
`SUBMITTED TO OC
`
`
`
`03-MAY-2010
`
`OC RECOMMENDATION
`
`
`O3—MAY—2010
`
`ACCEPTABLE
`
`BASED ON PROFILE
`
`
`
`FERGUSONS
`
`DAVlDJE
`
`STOCKM
`
`
`ACCEPTABLE
`BASED ON PROFILE
`
`
`
`
`
`
`
`
`
`
`October 15, 2010 11:49 AM
`
`
`
`
`
`FDA Confidential - Internal Distribution Only
`
`
`Page 2 of 9
`
`(b) (4)
`
`(
`
`
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`
`Tblishment:
`
`CFN:
`
`
`
`<b><4>
`
`>
`
`DMF No:
`
`
`<b><4>
`(b) (4)
`
`PEI;
`
`
`
`W4)
`
`..
`
`<b><4>
`
`H._
`
`<b><4>
`
`AADA:
`
`Responsibilities:
`
`Estab. Comment:
`
`
`Profile:
`
`DRUG SUBSTANCE MANUFACTURER
`
`
`
`THIS SITE Is FOR DRUG SUBSTANCE MANUFACTURE FOR ETHINYL ESTRADIOL USP AND NORETHINDRONE ACETATE
`
`
`
`
`
`
`
`
`
`
`
`
`
`USP. (on 24-APR-2009 by J.DAVID () 301-796-4247)
`
`
`
`
`
`THE FEI NUMBER PROVIDED IN THE NDA IS
`
`
`
`
`
`
`
`
`IN THE NDA IS:
`
`
`
`
`
`(9 ('4) (NOT FOUND IN EES DATABASEI. THE FULL ADDRESS GIVEN
`
`
`
`
`
`
`
`
`
`0’) <4)
`
`(b) (4). (on O3-MAY—2010 by J. DAVID () 301-796-4247)
`
`
`
`
`
`
`
`NON-STERILE BULK BY CHEMICAL SYNTHESIS
`OAI Status:
`
`
`
`
`
`
`NONE
`
`
`
`
`
`
`
`
`Planned Completion Decision
`Reguest Tyge
`Milestone Date
`Milestone Name
`
`
`Comment
`Reason
`SUBMITTED TO 00
`
`
`
`29—APR-2009
`
`SUBMITTED TO DO
`
`
`
`O1-MAY-2009
`
`10-Day Letter”.
`
`
`
`
`
`._
`
`. L.
`
`ASSIGNED INSPECTION TO IB
`
`
`
`
`04-MAY-2009
`
`
`GMP Inspection
`
`
`DO RECOMMENDATION
`
`
`19-JAN-2010
`
`CC RECOMMENDATION
`
`
`19—JAN-2010
`
`Creator
`
`DAVIDJE
`
`STOCKM
`
`JOHNSONE
`
`
`JOHNSONE
`WITHHOLD
`PEND REG ACTION - WARNING LTR
`
`
`
`
`
`
`JOHNSONE
`WITHHOLD
`DISTRICT RECOMMENDATION
`
`
`INSPECTION PERFORMED
`
`See EIR in Turbo.
`
`
`
`
`12-FEB-2010
`
`12-FEB-2010
`
`MCASALE
`
`DO RECOMMENDATION
`
`
`OS-APR-20’IO
`
`OC RECOMMENDATION
`
`
`12-APR-2010
`
`SUBMITTED TO OC
`
`
`
`03'-MAY-2010
`
`'
`
`-
`
`OC RECOMMEN DATION
`
`
`03—MAY—201 0
`
`
`
`f‘f‘f’f
`
`7"
`
`‘
`
`'
`
`'
`
`JOHNSONE
`ACCEPTABLE
`
`BASED ON FILE REVIEW
`
`
`
`
`JOHNSONE
`ACCEPTABLE
`
`DISTRICT RECOMMENDATION
`
`
`
`
`"
`
`
`ACCEPTABLE
`BASED ON PROFILE
`
`
`
`DAVIDJE
`
`STOCKM
`
`
`
`
`
`
`
`
`October 15, 2010 11:49 AM
`
`
`
`
`
`FDA Confidential - Internal Distribution Only
`
`
`Page 3 of 9
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`
`ablishment:
`
`CFN:
`
`
`
`(b) (4)
`
`.
`
`.
`
`(b)(4)
`
`._
`
`.
`
`FEI:
`,
`..,
`
`(b) (4)
`I
`
`.
`
`‘
`
`,
`
`DMF No:
`
`
`(b) (4)
`(b) (4)
`
`MBA:
`
`Responsibilities:
`
`DRUG SUBSTANCE
`
`
`
`
`(b) (4)
`
`
`
`
`
`
`
`
`
`
`
`
`
`(1’)“) FOR ETHINYL ESTRADIOL USP AND NORETHINDRONE
`THIS SITE IS FOR DRUG SUBSTANCE
`ACETATE USP. (on 24-APR-2009 by J. DAVID () 301—796-4247)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`THE FULL ADDRESS GIVEN IN THE NDA‘IS
`
`
`
`
`
`
`-
`0’) <4). (on 03-MAY-2010 by J. DAVID () 301-796-4247)
`
`
`
`
`
`
`OAI Status:
`NON-STERILE BULK BY CHEMICAL SYNTHESIS
`NONE
`
`,
`
`(b) ‘4)
`
`
`Estab. Comment:
`
`Profile:
`
`
`Milestone Name
`Comment
`
`
`SUBMITTED TO 00
`
`
`Milestone Date
`
`
`
`. Reguest Tme
`
`
`
`
`
`Planned Comgletion Decision
`Reason
`
`29-APR-2009
`
`
`OC RECOMMENDATION
`INSPECTION CONDUCTED
`
`
`
`
`
`01-MAY-2009
`(b) <4> COVERED THE CSN PROFILE; CLASSIFIED NAI.
`
`
`
`
`
`
`
`
`ACCEPTABLE
`BASED ON PROFILE
`
`
`
`SUBMITTED TO 00
`
`
`
`03-MAY-201O
`
`
`OC RECOMMENDATION
`
`03-MAY-201‘0
`
`
`ACCEPTABLE
`BASED ON PROFILE
`
`
`
`Creator
`
`DAVIDJE
`
`STOCKM
`
`DAVIDJE
`
`STOCKM
`
`
`
`
`
`
`
`
`October 15, 2010 11:49 AM
`
`
`
`
`
`FDA Confidential - Internal Distribution Only
`
`Page 4 of 9
`
`
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`
`Vblishment:
`
`CFN:
`
`
`
`(b) (4)
`
`AADA:
`
`DRUG SUBSTANCE OTHER TESTER
`
`
`
`FINISHED DOSAGE OTHER TESTER
`
`
`
`
`THE FULL ADDRESS GIVEN IN THE NDA IS:
`
`
`
`
`
`
`
`
`
`DMF No:
`
`
`Responsibilities:
`
`
`Estab- Comment:
`
`Profile:
`
`(‘3) <4)
`
`(b) <4> (on 03—MAY-2010 by J. DAVID () 301-796-4247)
`
`
`
`
`
`
`THIS SlTE IS FOR CONTRACT ANALYTICAL TESTING OF DRUG SUBSTANCES AND INACTIVE COMPONENTS. THIS SITE
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IS ALSO FOR
`0’) (4);. (on 24—APR—2009 by J.
`DAVID () 301-796-4247)
`
`
`
`CONTROL TESTING LABORATORY
`
`
`
`
`
`
`OAI Status:
`
`NONE
`
`
`
`
`
`
`
`Creator
`Planned Completion Decision
`Reguest Type
`Milestone Date
`Milestone Name
`
`
`v
`Comment
`~
`Reason
`SUBMlTTED TO 00
`DAVlDJE
`
`
`
`29-APR-2009
`
`OC RECOMMENDATlON
`
`
`01-MAY-2009
`.. ...... u.» r
`
`
`
`
`
`
`
`..-
`
`
`
`
`
`
`
`
`
`ACCEPTABLE
`—-BASEDONPROF|LE
`
`
`FERGUSONS
`
`SUBMITTED TO 00
`
`
`
`03-MAY-2010
`
`0C RECOMMENDATION
`
`
`O3-MAY-2010
`
`DAVlDJE
`
`STOCKM
`
`
`ACCEPTABLE
`BASED ON PROFILE
`
`
`
`
`
`
`
`
`
`
`October 15, 2010 11:49 AM
`
`
`
`
`
`FDA Confidential - Internal Distribution Only
`
`Page 5 of 9
`
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`ablishment:
`
`CFN:
`
`
`
`(b) (4)
`
`
`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`(b) (4)
`
`FEI:
`
`
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`AADA:
`
`DRUG SUBSTANCE MANUFACTURER
`
`
`DRUG SUBSTANCE
`
`
`
`(b) (4)
`
`DMF No:
`
`
`'
`
`Responsibilities:
`
`
`Estab- Comment:
`
`Profile:
`
`
`Milestone Name
`Comment
`
`
`SUBMITTED TO 00
`
`-
`
`
`
`
`
`
`
`
`
`THE FULL ADDRESS PROVIDED IN THE NDA IS:
`
`
`
`
`
`_
`(1W4) (on 03—MAY-2010 by J. DAVID () 301-796-4247)
`03) (4) FOR ETHINYL ESTRADIOL USP AND
`THIS SITE IS FOR DRUG SUBSTANCE MANUFACTURE AND
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`NORETHINDRONE ACETATE USP. (on 24-APR-2009 by J. DAVID () 301-796-4247)
`
`
`
`
`
`NON-STERILE BULK BY CHEMICAL SYNTHESIS
`OAI Status:
`
`7
`
`,(b) (4),
`
`
`Milestone Date
`
`
`Reguest Txge
`
`
`
`29-APR-2009
`
`
`
`Planned Completion Decision
`Reason
`
`
`
`NONE
`
`Creator
`
`DAVIDJE
`
`STOCKM
`
`DAVIDJE
`
`STOCKM
`
`
`OI—MAY-ZOOQ
`OC RECOMMENDATION
`(b) (4) CLASSIFIED VAI AND COVERED THE CSN PROFILE.‘ '
`INSPECTION CONDUCTED
`
`
`
`
`
`
`
`
`FIRM'S RESPONSE TO RAI LETTER REVIEWED BY HM AND DEEMED ACCEPTABLE.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`ACCEPTABLE
`‘BASED ON PROFILE
`
`
`
`
`SUBMITTED TO OC
`
`
`
`08-MAY-2010
`
`
`OC RECOMMENDATION
`
`03-MAY—2010
`
`
`ACCEPTABLE
`BASED ON PROFILE
`
`
`
`
`
`
`
`
`
`
`
`
`October 15, 2010 11:49 AM
`
`
`
`
`
`FDA Confidential - Internal Distribution Only
`
`Page 6 of 9
`
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`\blishment:
`
`CFN:
`
`
`
`(b) (4)
`
`
`
`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`(b) (4)
`
`FE:
`
`(b) (4)
`
`(b) (4)
`
`DMF No:
`
`
`(b) (4)
`(b) (4)
`
`MBA:
`
`DRUG SUBSTANCE MANUFACTURER
`
`
`DRUG SUBSTANCE
`
`
`
`(b) (4)
`
`THE FULL ADDRESS PROVIDED IN THE NDA is:
`
`
`
`
`
`
`
`
`(b) <4> (on O3-MAY-2010 by J. DAVID () 301-796-4247)
`
`
`
`
`
`
`(‘3) (4) FOR ETHlNYL ESTRADIOL'USP AND
`THIS SITE IS FOR DRUG SUBSTANCE MANUFACTURE AND
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`NORETHINDRONE ACETATE USP. (on 24-APR-2009 by J. DAVID () 301-796-4247)
`
`
`
`
`
`
`NON-STERILE BULK BY CHEMICAL SYNTHESIS
`OAI Status:
`
`NONE
`
`
`
`,(b) (4).
`
`Responsibilities:
`
`
`Estab- Comment:
`
`Profile:
`
`
`Milestone Name
`Comment
`
`
`SUBMITTED TO 00
`
`
`Milestone Date
`
`
`Reguest Tyge
`
`
`
`
`
`Planned Completion Decision
`_.
`Reason
`
`29-APR-2009
`
`
`
`O1-MAY—2009
`OC RECOMMENDATION
`
`
`
`
`
`
`
`
`
`<b> <4) CLASSIFIED VAI AND COVERED THE CSNPROFILE.
`INSPECTION CONDUCTED
`FlRM'S RESPONSE TO RAI LETTER ADEQUATELY ADDRESSED ISSUES. COMPLIANCE
`
`
`
`
`
`
`
`REVIEW DONE BY HM.
`
`
`
`
`ACCEPTABLE
`
`
`BASED ON PROFILE
`
`
`
`SUBMITTED TO OC
`
`
`
`03-MAY—2010
`
`
`OC RECOMMENDATION
`
`03-MAY-2010
`
`’
`
`'
`
`
`ACCEPTABLE
`BASED ON PROFILE
`
`
`
`Creator
`
`DAVIDJE
`
`STOCKM
`
`DAVlDJE
`
`STOCKM
`
`
`
`
`
`
`
`
`October 15, 2010 11:49 AM
`
`
`
`
`
`FDA Confidential - internal Distribution Only
`
`Page 7 of 9
`
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`
`Vblishment:
`
`DMF No:
`
`
`Responsibilities:
`
`CFN: 2619635
`
`WARNER CHILCOTT COMPANY, INC.
`
`
`
`RD 195 KM 1.1
`-
`
`
`
`FAJARDO, PR 00738
`
`
`
`FEI: 2619635
`
`
`AADA:
`
`DRUG SUBSTANCE OTHER TESTER
`
`
`
`FINISHED DOSAGE MANUFACTURER
`
`
`FINISHED DOSAGE OTHER TESTER
`
`
`
`FINISHED DOSAGE PACKAGER
`
`
`
`
`Estab. Comment:
`
`Profile:
`
`THIS SITE IS FOR ANALYTICAL TESTING AND RELEASE OF THE DRUG SUBSTANCE AND INACTIVE COMPONENTS.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`THIS SITE IS ALSO FOR MANUFACTURING, IN-PROCESS TESTING, AND PACKAGING OF THE DRUG PRODUCT. (on 24-
`APR—2009 by J. DAVID () 301-796—4247)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`THE FULL ADDRESS GIVEN FOR THIS SITE IN THE NDA IS: WARNER CHILCOT COMPANY, LLC, ROAD 195 (UNION
`STREET) KM 1.1, ARJARDO, PR 00738-1005. (on 03-MAY—2010 by J. DAVID () 301-796-4247)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`OAI Status:
`NONE
`TABLETS, PROMPT RELEASE
`
`
`
`
`
`Planned Completion
`Reguest Tyge
`Milestone Name’
`Milestone’Date
`
`
`Comment
`SUBMITTED TO 00
`29-APR-2009
`
`
`
`
`
`SUBMITTED TO DO
`
`
`
`01-MAY-2009
`
`10-Day L'etfer’ "“ I” “ '
`‘T ‘
`
`
`
`
`.2.
`
`
`Mn—__ Creator
`Reason
`
`DAVIDJE
`
`FERGUSONS
`
`DO RECOMMENDATION
`
`
`ACCEPTABLE RECOMMENDATION-BASED ON PREVIOUS INSPECTION RESULTS (NAI
`
`
`
`
`
`
`
`INSPECTION DATES: 08/1809 TO 09/15/08)
`
`
`
`
`
`18-MAY-2009
`
`RHERNAND
`ACCEPTABLE
`
`BASED ON FILE REVIEW
`
`
`
`
`QECOMMENDATION
`
`19—MAY-2009
`
`SUBMITTED TO OC
`
`
`
`SUBMITTED TO DO
`
`
`
`O3-MAY-201O
`
`03-MAY—201 0
`
`10-Day Letter
`
`
`DO RECOMMENDATION
`
`
`ACCEPTABLE RECOMMENDATION BASED ON FIRM PREVIOUS INSPECTION
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`CLASSIFICATION, VAI DATED 12/29/2009. PROFILE CLASS TCM IS CLASSIFIED AS
`ACCEPTABLE IN FACTS
`'
`
`
`
`26-MAY-2010
`
`OC RECOMMENDATION
`
`
`26-MAY-2010
`
`STOCKM
`ACCEPTABLE
`
`DISTRICT RECOMMENDATION
`
`
`DAVIDJE
`
`STOCKM
`
`RHERNAND
`ACCEPTABLE
`
`BASED ON FILE REVIEW
`
`
`
`
`INYARDA
`ACCEPTABLE
`
`DISTRICT RECOMMENDATION
`
`
`
`
`October 15, 2010 11:49 AM
`
`
`
`
`
`
`
`
`
`
`FDA Confidential - Internal Distribution Only
`
`Page 8 of 9
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`
`FDA CDER EES
`
`
`ESTABLISHMENT EVALUATION REQUEST
`
`DETAIL REPORT
`
`'
`I
`CFN:
`WARNER CHILCOTT UK LTD
`
`
`
`OLD BELFAST ROAD
`
`
`LARNE, , UNITED KINGDOM BT40 28H '
`
`
`
`
`FEI: 3007097388
`
`
`,
`‘
`‘
`‘
`AADA:
`
`FINISHED DOSAGE RELEASE TESTER
`
`
`
`FINISHED DOSAGE STABILITY TESTER
`
`
`
`
`'blishment:
`
`DMF No:
`
`
`Responsibilities:
`
`
`Estab. Comment:
`
`Profile:
`
`
`
`THE FULL ADDRESS GIVEN FOR THIS SITE IN THE NDA IS: WARNER CHILCOTT UK LIMITED, OLD BELFAST ROAD,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`MILLBROOK, LARNE, NORTHERN IRELAND BT40 28H. (on 03-MAY-2010 by J. DAVID () 301—796—4247)
`
`
`
`
`
`
`
`
`
`
`
`
`THIS SITE IS FOR IN-PROCESS CHEMICAL TESTING (NO MANUFACTURING FUNCTION), RELEASE AND STABILITY
`
`
`
`
`
`
`
`
`
`
`
`
`TESTING OF THE DRUG PRODUCT. (on 03-MAY-2010 by J. DAVID () 301-796-4247)
`
`
`
`
`
`
`
`
`
`
`THIS SITE IS FOR BACK-UP lN-PROCESS, RELEASE AND STABILITY TESTING OF THE DRUG PRODUCT. (on 16-JUN-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`2009 by J. DAVID () 301—796—4247) ~ -~
`~- ~-
`-
`‘
`‘
`
`
`
`
`
`CONTROL TESTING LABORATORIES "ALSO" (DRUGS)
`
`
`
`
`
`OAI Status:
`
`
`
`
`NONE
`
`
`
`
`Planned Completion Decision
`Reguest Type
`Milestone Date
`Milestone Name
`
`Comment—__________— Reason
`
`SUBMITTED TO 00
`. 16-JUN-2009
`.
`,
`
`Creator V
`
`_
`
`DAVIDJE
`
`OC RECOMMENDATION
`
`
`16—JUN-2009
`
`SUBMITTED TO OC
`
`
`03—MAY-2010
`
`
`SUBMITTED TO DO
`
`
`O3-MAY-2010
`
`GMP Inspection
`
`
`RECOMMENDATION
`
`06-MAY—2010
`
`,
`
`ACCEPTABLE
`BASED ON PROFILE
`
`
`
`JOHNSONE
`
`DAVIDJE
`
`STOCKM
`
`I
`
`JOHNSONE
`ACCEPTABLE
`BASED ON FILE REVIEW
`
`
`
`
`00 RECOMMENDATION
`
`
`STOCKM
`ACCEPTABLE
`DISTRICT RECOMMENDATION
`
`
`
`11-MAY-2010
`
`
`
`
`
`October 15, 2010 11:49 AM
`
`‘
`
`FDA Confidential - Internal Distribution Only
`
`
`
`
`
`Page 9 of 9
`
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`
`
`
`
`NDA 22-501
`
`Lo Loestrin® Fe*
`(norethindrone acetate and ethinyl estradiol
`tablets, ethinyl estradiol tablets
`and ferrous fumarate tablets)
`
`* The previous proprietary name stated in Review #1 was
`
`
`Warner Chilcott Company, Inc.
`
`
`
`
`Yubing Tang, Ph.D.
`
`Branch VI, Division of New Drug Quality Assessment II
`Office of New Drug Quality Assessment
`
`
`
`CMC Review of NDA 22-501
`For Division of Reproductive and Urologic Products
`
`
`
`
`
`Page 1 of 16
`
`(b
`)
`
`(
`
`

`

`
`
`
`
`
`
`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`
`
`Chemistry Review Data Sheet
`
`
`
`
`
`
`
`
`
`22-501
`
`#2
`
`September 14, 2010
`
`Yubing Tang, Ph.D.
`
`
`1. NDA:
`
`
`2. REVIEW:
`
`
`3. REVIEW DATE :
`
`
`4. REVIEWER:
`
`
`5. PREVIOUS DOCUMENTS:
` NDA 22-501, CMC Review #1, January 07, 2010
` Addendum to NDA 22-501 CMC Review #1, January 22, 2010
`
`6. SUBMISSION(S) BEING REVIEWED:
`
`
`Submission(s) Reviewed
`Resubmission
`
`
`7. NAME & ADDRESS OF APPLICANT:
`
`
`
`
`
`
`
`
`
`
`Document Date
`April 20, 2010
`
`Name: Warner Chilcott Co., Inc.
`Address: Union Street, Rd. 195 Km 1.1
`Fajardo, PR 00738-1005
`Representative: 100 Enterprise Drive
`Rockaway, NJ 07866
`Telephone: 973-442-3200
`
`
`8. DRUG PRODUCT NAME/CODE/TYPE:
`
`
`a) Proprietary Name:
`Lo Loestrin® Fe
`(Note: Lo Loestrin® Fe is the proprietary name in the resubmission. Formerly, the
` and was not accepted by DMEPA.)
`proprietary name was
`
`b) Non-Proprietary Name (USAN):
`c) Code Name/# (ONDQA only):
`
`norethindrone acetate/ethinyl estradiol
`none
`
`Page 2 of 16
`
`(b) (4)
`
`

`

`
`
`
`
`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`
`d) Chem. Type/Submission Priority (ONDQA only):
`• Chem. Type:
`
`
`5
`
`• Submission Priority:
`
`S
`
`505 (b) (1)
`
`Prevention of Pregnancy
`
`
`
`tablets
`
`
`9. LEGAL BASIS FOR SUBMISSION:
`
`
`10. PHARMACOL CATEGORY:
`
`
`
`11. DOSAGE FORM:
`
`
`12. STRENGTH/POTENCY: 1mg norethindrone acetate /10mcg ethinyl
`estradiol, 10mcg ethinyl estradiol
`
`
`
`
`
`oral
`
`
`
`13. ROUTE OF ADMINISTRATION:
`
`
`14. Rx/OTC DISPENSED: _x_Rx _ _ OTC
`
`
`15. SPOTS (SPECIAL PRODUCTS ON-LINE TRACKING SYSTEM):
`
`
`
` SPOTS product – Form Completed
`
` x Not a SPOTS product
`
`
`16. CHEMICAL NAME, STRUCTURAL FORMULA, MOLECULAR
`FORMULA, MOLECULAR WEIGHT:
`Chemical
`Norethindrone acetate: (17α)-17-(acetyloxy)-19-norpregn-4-
`Name:
`en-20-yn-3-one
`Ethinyl Estradiol: (17α)-19-Norpregna-1,3,5(10)-trien-20-
`yne-3,17-diol
`
`
`
`Page 3 of 16
`
`

`

`
`
`
`
`Structure
`Formula:
`
`
`
`Molecular
`Formula:
`
`
`Molecular
`Weight:
`
`
`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`
`
`• Norethindrone Acetate: C22H28O3
`• Ethinyl Estradiol: C20H24O2
`
`
`
`
`
`• Norethindrone acetate: 340.46
`• Ethinyl Estradiol: 296.40
`
`
`
`17. RELATED/SUPPORTING DOCUMENTS:
`
`
`A. DMFs:
`
`TYPE HOLDER
`
`
`DMF
`#
`
`
`
`
`
`
`
`II
`
`II
`
`II
`
`
`
`II
`
`
`
`
`
`III
`
`III
`
`ITEM
`REFERENCED CODE1 STATUS2
`Drug Substance
`(ethinyl
`estradiol)
`Drug Substance
`(norethindrone
`acetate)
`Drug Substance
`(ethinyl
`estradiol)
`Drug Substance
`(norethindrone
`acetate)
`
`3
`
`3
`
`3
`
`adequate
`
`adequate
`
`adequate
`
`3
`
`adequate
`
`COMMENTS
`
`DATE
`REVIEW
`COMPLETED
`July 07, 2010 Reviewed by
`Dr. J. Ping
`
`August 01,
`2008
`
`Reviewed by
`Dr. J. Chang
`
`March 10,
`2010
`
`Reviewed by
`Dr. J. Chang
`
`June 27, 2010 Reviewed by
`Dr. Z. Bahar
`
`1
`
`
`3
`
`adequate November 30,
`2009
`
`Reviewed by
`Dr. Y. Tang
`
`adequate
`
`August 04,
`2008
`
`Reviewed by
`Dr. J. Chang
`
`
`
`1 Action codes for DMF Table:
`
`Page 4 of 16
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`
`
`
`
`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`
`1 – DMF Reviewed.
`Other codes indicate why the DMF was not reviewed, as follows:
`2 –Type 1 DMF
`3 – Reviewed previously and no revision since last review
`4 – Sufficient information in application
`5 – Authority to reference not granted
`6 – DMF not available
`7 – Other (explain under “Comments”)
`
` 2
`
` Adequate, Inadequate, or N/A (There is enough data in the application, therefore the DMF did
`not need to be reviewed)
`
`DESCRIPTION
`Loestrin® 24 Fe was approved
`under NDA 21-871, which uses
`the same drug substances for the
`same indication, and is sponsored
`by the same applicant. NDA 22-
`501 is cross-referenced to NDA
`21-871.
`
`
`
`
`
`B. Other Documents:
`
`DOCUMENT
`
`APPLICATION NUMBER
`
`CMC Review #1,
`Feb. 16, 2006
`
`NDA 21-871
`
`
`
`18. CONSULTS/CMC-RELATED REVIEWS:
`
`Not applicable.
`
`
`
`Page 5 of 16
`
`

`

`
`
`
`
`
`
`CHEMISTRY REVIEW
`Executive Summary Section
`The Chemistry Review for NDA 22-501
`
`The Executive Summary
`
` I. Recommendations
`
`
`
`
`A. Recommendation and Conclusion on Approvability
`
`
`The previous Review #1 noted that this NDA has provided sufficient information to
`assure identity, strength, purity, and quality of the drug product with adequate
`information on labels and labeling, except for an overall “Withhold” recommendation
`from the Office of Compliance.
`
`Now, the Office of Compliance has made the overall “Acceptable” recommendation.
`
`Therefore, from the CMC perspective, this NDA is recommended for approval.
`
`B. Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements,
`and/or Risk Management Steps, if Approvable
`
`
`
`
`
`Not applicable.
`
`
`II. Summary of Chemistry Assessments
`
`A. Description of the Drug Product(s) and Drug Substance(s)
`
`1) Drug Product
`
`The proposed drug product, Lo Loestrin® Fe (norethindrone acetate and ethinyl estradiol
`tables, ethinyl estradiol tablets and ferrous fumarate tables), is a low dose oral
`contraceptive consisting of new dose and new regimen of the combination of norethindrone
`acetate (NA) and ethinyl estradiol (EE). Lo Loestrin® Fe is packaged in a unit-dose
`blister card (dispensers) containing 24 blue active tablets, 2 white active tablets and 2
`brown placebo tablets.
`• Each blue, round tablet contains 1 mg of norethindrone acetate, USP and 10 mcg of
`ethinyl estradiol, USP and is imprinted with WC on one side and 421 on the other.
`• Each white, hexagonal tablet contains 10 mcg of ethinyl estradiol, USP and is
`imprinted with WC on one side and 422 on the other.
`• Each brown, round placebo tablet contains 75 mg ferrous fumarate, USP and is
`imprinted with WC on one side and 624 on the other. The ferrous fumarate tablets
`are non-hormonal and non- therapeutic, present to facilitate ease of drug
`administration via a 28-day regimen.
`
`
`
`Page 6 of 16
`
`

`

`
`
`
`
`CHEMISTRY REVIEW
`Executive Summary Section
`
`
`The following compendial excipients are contained in Lo Loestrin® Fe: mannitol, USP,
`microcrystalline cellulose, NF, FD&C Blue No. 1 Aluminum Lake (FD&C certified),
`sodium starch glycolate, NF, magnesium stearate, NF, povidone, USP, vitamin E, USP,
`lactose monohydrate, NF and sucralose, NF. The spearmint flavor in ferrous fumarate
`tablets is the only non-compendial excipient; however contains GRAS ingredients and has
`been used in other FDA approved drug products.
`
`Lo Loestrin® Fe active tablets are manufactured using a
`estradiol, USP is
`
`
`
`
`
`
`
`
`
`
`
` process. Ethinyl
`
`
`
`
`
`
` cartons.
`
`
`Container closure system for Lo Loestrin® Fe tablet regimen is a unit-dose blister
`consisting of a
` blister lidding and aluminum foil/
` backing. Non-functional secondary packaging components consist of a rigid
` to the unit-dose blister, a
`card
`pouch, a
`overwrap film,
`prescriber and patient package inserts and
`
`Based on the provided stability study data, the proposed 24 months expiration dating period
`is granted for Lo Loestrin® Fe tablets under the labeled storage conditions (stored at 25ºC
`(77ºF); excursion permitted to 15 - 30ºC (59 - 86ºF )).
`
`2) Drug Substance
`
`There are two drug substances in Lo Loestrin® Fe, Norethindrone acetate, USP and ethinyl
`estradiol, USP. The drug substances are synthetic hormones widely used as components of
`combination oral contraceptives. The NA and EE used in Lo Loestrin® Fe tablets are
`sourced from
`
`. Information about the manufacture, characterization, quality control, container
`closure system and stability for each drug substance from each manufacturer is contained in
`drug master files
`. LOAs (Letter of Authorization) from the
`holders of DMFs are provided. All DMFs have been recently reviewed and found to be
`adequate.
`
`B. Description of How the Drug Product Is Intended to Be Used
`
`
`
`Lo Loestrin® Fe is indicated for the prevention of pregnancy in women
`
`. The dosage of Lo Loestrin® Fe is one
`blue tablet containing norethindrone acetate and ethinyl estradiol daily for 24 consecutive
`days, followed by one white tablet containing ethinyl estradiol daily for 2 consecutive days,
`followed by one brown non-hormonal (placebo) tablet containing ferrous fumarate daily for
`2 consecutive days. The ferrous fumarate tablets do not serve any therapeutic purpose.
`
`Page 7 of 16
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`
`
`
`
`CHEMISTRY REVIEW
`Executive Summary Section
`
`
`
`
`C. Basis for Approvability or Not-Approval Recommendation
`
`This NDA provided adequate information on the raw material controls, manufacturing
`process, specifications, and container/closure system. It also provided sufficient stability
`data to assure identity, strength, purity and quality of the drug product during the expiration
`dating period. Labels have required information. The Office of Compliance has issued the
`overall “Acceptable” recommendation for all manufacturing and testing facilities.
`
`III. Administrative
`
`
`A. Reviewer’s Signature:
`
`
`In DARRTS
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`B. Endorsement Block:
`
`
`
`
`
`
`
`
`
`
`C. CC Block:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` _____________________
` Yubing Tang, Ph.D.
`
` Chemist, Branch VI/DNDQAII/ONDQA
`
`In DARRTS
`
` _____________________
` Moo-Jhong Rhee, Ph.D.
`
`Branch Chief, Branch IV/DNDQAII/ONDQA
`
`
`
`
`In DARRTS
`
`Page 8 of 16
`
`8 Page(s) have been Withheld in Full as b4 (CCI/TS) immediately
`following this page
`
`

`

`Application
`Type/Number
`--------------------
`NDA-22501
`
`Submission
`Type/Number
`--------------------
`ORIG-1
`
`Submitter Name
`
`Product Name
`
`--------------------
`WARNER
`CHILCOTT CO INC
`
`------------------------------------------
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`YUBING TANG
`09/16/2010
`Thanks.
`
`MOO JHONG RHEE
`09/16/2010
`Chief, Branch IV
`
`(b) (4)
`
`

`

`MEMORANDUM
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`DATE:
`
`TO:
`
`FROM:
`
`
`
`THROUGH:
`
`
`
`
`CC:
`
`
`SUBJECT:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`PUBLIC HEALTH SERVICE
`FOOD AND DRUG ADMINISTRATION
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`January 22, 2010
`
`NDA 22-501, CMC Review #1
`
`Yubing Tang, Ph.D., Chemist
`(ONDQA Division of Pre-Marketing assessment II)
`
`Moo-Jhong Rhee, Ph.D., Chief, Branch III
`(ONDQA Division of Pre-Marketing assessment II)
`
`Donna Christner, Ph.D., Pharmaceutical Assessment Lead
`(ONDQA Division of Pre-Marketing assessment II)
`
`CMC Recommendation for NDA 22-501 due to
`Recent Notification of Unacceptable cGMP
`Compliance
`
`
`
`CMC Review #1 was completed on 08-JAN-2010 with all CMC issues resolved except for the
`absence of an overall “Acceptable” recommendation from the Office of Compliance.
`
`Now the Office of Compliance has issued an overall rating of “Withhold” on 19-JAN-2010 (see
`attached EES summary report).
`
`Therefore, from a CMC perspective, this NDA is recommended not to approve in its present
`form until all the facilities involved are fully in compliance with cGMP requirements to assure
`the identity, strength, purity, and quality of the drug product.
`
`
` 1 of 5
`
`

`

`FDA CDER EES
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`
`Application:
`Org. Code:
`
`Priority:
`
`Stamp Date:
`pDUFA Date:
`Action Goal:
`
`District Goal:
`
`FDA Contacts:
`
`NDA 22501.?000
`530
`
`BS
`
`26-MAR-2009
`25._|AN.2010
`
`27-Nov-2009
`
`J. DAVID
`Y. TANG
`D. CHRISTNER
`
`Sponsor:
`
`WARNER CHILCOTT CO
`100 ENTERPRISE DR STE 280
`
`ROCKAWAY. NJ ONES
`
`Brand Name:
`Estab. Name:
`Generic Name:
`
`(‘3) (4)
`norethindrone acetate and ethinyl estradiol tablets.
`ethinyl estradiol tablets.
`
`Product Number. Dosage Form: Ingredient; Strengths
`001: TABLET: NORETHINDRONE ACETATE: IMG
`001: TABLET: ETHINYL ESTRADIOL:1DUGM
`002: TABLET: ETHINYL ESTRADIOL:1DUGM
`003: TABLET: FERROUS FUMARATE.‘ POTENCY NOT GIVEN
`301—?96424?
`301-?96-245?
`301—?96-1341
`
`Project Manager
`Review Chemist
`Team Leader
`
`Overall Recommendatlon:
`WITHHOLD
`on 19-JAN-2DID
`by E. JOHNSON
`{HFD-3ZD)
`301-795-3334
`
`
`Establishment:
`
`CFN'.
`
`(b) (4)
`
`FEI:
`
`(b) (4)
`
`(b) (4)
`
`DMF No:
`
`Responsibilities:
`
`Profile:
`
`Last Milestone:
`
`Milestone Date:
`
`DBCISIOI'I:
`
`Reason:
`
`Establishment:
`
`DRUG SUBSTANCE OTHER TESTER
`FINISHED DOSAGE OTHER TESTER
`CONTROL TESTING LABORATORY
`
`OC RECOMMENDATION
`
`0 1 —M A‘r‘ 2009
`
`ACC E PTAB LE
`
`BASED ON PROFILE
`
`CFN'.
`
`(b) (4)
`
`FEI:
`
`(b) (4)
`
`AADA:
`
`OAI Status:
`
`NONE
`
`DMF No:
`
`(b) (4)
`
`(b) (4)
`
`AADA:
`
`Responsibilities:
`Profile:
`
`Last Milestone:
`
`MIISSIODO Date:
`
`Decision:
`
`Reason:
`
`DRUG SUBSTANCE MANUFACTURER
`
`NON—STERILE BULK BY CHEMICAL SYNTHESIS
`
`OAI Status:
`
`OAI ALE RT
`
`DC RECOMMENDATION
`
`1Q—JAN-201D
`
`WITHHOLD
`
`DISTRICT RECOMMEN DATION
`
`January 25‘ 2010 8:36 AM
`
`FDA Con fidentlal - Internal Distribution Only
`
`Page ‘I ot 4
`
`
`
` 2 of 5
`20f5
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`Establlshme nt:
`
`CFN:
`
`FDA CDER EES
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`b 4
`(m
`
`0’) (4)
`
`FE|_
`'(b) (4)
`
`DMF Na:
`
`Responsibilities:
`
`DRUG SUBSTANCE OTHER TESTER
`FINISHED DOSAGE OTHER TESTER
`
`AADA:
`
`Profile:
`
`CONTROL TESTING LABORATORY
`
`OAI Status:
`
`NONE
`
`Last Mllasmne:
`
`Milestone Data:
`
`Decision:
`
`Reason:
`
`0C RECOMMENDATION
`
`01-MAY-2009
`
`ACCEPTABLE
`
`BASED ON PROFILE
`
`Establishment:
`
`CFN'.
`
`(b) (4)
`
`4
`03“ )
`
`FEI:
`(b) (4)
`
`DMF No:
`
`AADA:
`
`Responsibilitles:
`
`DRUG SUBSTANCE MANUFACTURER
`
`Profile:
`
`Last Milestone:
`
`Milestone Date:
`
`Dacislan:
`
`(b) (4)
`DRUG SUBSTANCE
`NON—STERILE BULK BY CHEMICAL SYNTHESIS
`
`CAI Status:
`
`NONE
`
`0:: RECOMMENDATION
`
`DT-MAY-2DOQ
`
`ACCEPTABLE
`
`Reason:
`BASED ON PROFILE
`
`Establishment:
`CFN:
`(b) (4)
`FEI:
`0’) (4)
`(b) (4)
`
`DMF No:
`
`Responsibilities:
`
`Profile:
`
`Last Milestone:
`
`Milestone Date:
`
`Decision:
`
`Reason:
`
`AADA:
`
`DRUG SUBSTANCE MANUFACTURER
`DRUG SUBSTANCE
`(1’)“)
`NON-STERILE BULK BY CHEMICAL SYNTHESIS
`
`OAI Status:
`
`NONE
`
`OC RECOMMENDATION
`
`01—MAY-2009
`
`ACC E PTAB LE
`
`BASED ON PROFILE
`
`January 25. 2010 8:36 AM
`
`FDA Confidential - Internal Distribution Only
`
`Page 2 0! 4
`
` 3 of 5
`3of5
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`FDA CDER EES
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`
`Establishment:
`
`CFN:
`
`0’) (4)
`
`(b) (4)
`
`FEI:
`(b) (4)
`
`DMF No:
`
`Responslbilltles:
`
`Profile:
`
`Last Milestone;
`
`Milestone Date:
`
`Decision:
`
`DRUG SUBSTANCE OTHER TESTER
`FINISHED DOSAGE OTHER TESTER
`
`CONTROL TESTING LABORATORY
`
`OC RECOMMENDATION
`
`21—SEP—2009
`
`WITHHOLD
`
`AADA:
`
`OAI Status:
`
`NONE
`
`Reason:
`DISTRICT RECOMMENDATION
`FIRM NOT READY
`
`Establishment:
`CFN:
`(b) (4)
`FEI:
`(b) (4)
`
`(b) (4)
`
`DMF No:
`
`Responslbilltles:
`Profile:
`
`Last Milestone;
`Milestone Date:
`
`Decision;
`
`AADA:
`
`0’) (4)
`DRUG SUBSTANCE
`NCN-STERILE BULK BY CHEMICAL SYNTHESIS
`
`OAI Status:
`
`NONE
`
`OC RECOMMENDATION
`01—MAY-2009
`
`ACCEPTABLE
`
`Reason:
`BASED ON PROFILE
`
`Establishment:
`CFN:
`2619635
`FEI:
`2619635
`
`DMF No:
`
`Responsibilities:
`
`Profile:
`
`Last Milestone:
`
`Milestone Date:
`
`Decision:
`
`WARNER CHILCOTT COMPANY. INC.
`RD 195 KM 1.1
`
`FAJARDO. PR UD?38
`
`DRUG SUBSTANCE OTHER TESTER
`FINISHED DOSAGE MAN UFACTU RER
`FINISHED DOSAGE PACKAGER
`
`AADA:
`
`TABLETS. PROMPT RELEASE
`
`OAI Status:
`
`NONE
`
`OC RECOMMENDATION
`
`‘I Q—M AY-2009
`
`ACCEPTABLE
`
`DISTRICT RECOMMENDATION
`Reason:
`
`
`.lat'luanlr 25. 2010 3:36 AM
`
`FDA Confidentlal - Internal Distrlbutlon Only
`
`Page 3 of 4
`
`
`
` 4 of 5
`4of5
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`FDA CDER EES
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`
`Establishment:
`
`DMF No:
`
`Responslbllitles:
`
`Profile:
`
`Last Milestone:
`
`Milestone Date:
`
`Decision:
`
`R9350":
`
`CFN.’
`WARNER CHILCOTT UK LTD
`OLD BELFAST ROAD
`
`FEI:
`
`3005206014
`
`LARNE. . UNITED KINGDOM BT40 28H
`
`FINISHED DOSAGE RELEASE TESTER
`FINISHED DOSAGE STABILITY TESTER
`
`CONTROL TESTING LABORATORIES "ALSO"
`[DRUGS]
`OC RECOMMENDATION
`
`16-JUN-2009
`
`ACCEPTABLE
`
`BASED ON PROFILE
`
`AADA:
`
`OAI Status:
`
`NONE
`
`January 25. 2010 8:36 AM
`
`FDA Confidentlal -|nterna| Distrlbution Only
`
`Paged oi-i
`
`
`
` 5 of 5
`50f5
`
`

`

`Application
`Type/Number
`--------------------
`NDA-22501
`
`Submission
`Type/Number
`--------------------
`ORIG-1
`
`Submitter Name
`
`Product Name
`
`--------------------
`WARNER
`CHILCOTT CO INC
`
`------------------------------------------
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`YUBING TANG
`01/25/2010
`
`MOO JHONG RHEE
`01/25/2010
`Chief, Branch III
`
`(b) (4)
`
`

`

`
`
`
`
`
`
`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`
`
`NDA 22-501
`
`
`
`(norethindrone acetate and ethinyl estradiol
`tablets, ethinyl estradiol tablets
`and ferrous fumarate tablets)
`
`
`Warner Chilcott Company, Inc.
`
`
`
`
`Yubing Tang, Ph.D.
`
`Branch III, Division of Pre-Marketing Assessment II
`Office of New Drug Quality Assessment
`
`
`
`CMC Review of NDA 22-501
`For Division of Reproductive and Urologic Products
`
`
`
`
`
`
`
`Page 1 of 71
`
`
`
`
`
`
`
`
`
`
`(b)
`(4)
`
`

`

`
`
`
`
`
`
`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`
`
`Table of Contents
`
`
`Table of Contents .........................