CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`206439Orig1s000
`
`CHEMISTRY REVIEW(S)
`
`
`
`
`
`
`

`

`
`
`Chemistry Review Section
`
`NDA 206439
`
`MDX—8704 (Memantine HCl ER/ donepezil HCl fixed
`dose combination capsules 28/10mg and 14/10mg)
`
`Forest Laboratories Inc.
`
`Pei-I Chu, Ph.D.
`
`Office of New Drug Quality Assessment DPAl
`For Division of Neurology Products
`
`Review of Chemistry, Manufacturing, and Controls
`
`Reference ID: 3633270
`
`

`

`
`
`Chemistry Review Section
`
`Table of Contents
`
`Table of Contents ................................................................................................ 2
`
`Chemistry Review Data Sheet ........................................................................... 2
`
`The Executive Summary .................................................................................... 9
`
`1. Recommendations ........................................................................................... 9
`
`A. Recommendation and Conclusion on Approvability..........................................9
`
`B. Recommendation on Phase 4 (Post-Marketing) Commitments,
`
`Agreements, and/or Risk Management Steps, if Approvable.................................... 9
`
`II. Summary of Chemistry Assessments ................................................ 9
`
`A.
`
`B.
`
`C.
`
`Description of the Drug Product(s) and Drug Substance(s) .............................. 9
`
`Description of How the Drug Product is Intended to be Used .......................... 13
`
`Basis for Approvability or Not-Approval Recommendation ............................ 13
`
`III. Administrative ........................................................................ 13
`
`A.
`
`B.
`
`C.
`
`Reviewer’s Signature ........................................................................... 13
`
`Endorsement Block ............................................................................. 13
`
`CC Block ......................................................................................... 13
`
`Chemistry Assessment...................................................................14
`
`I. Review Of Common Technical Document-Quality (Ctd—Q) Module 3.2:
`
`Body Of Data ......................................................................... 14
`
`S DRUG SUBSTANCE [Name, Manufacturer] .................................................. 14
`
`P DRUG PRODUCT [Name, Dosage form] .................. ,,................................. 19
`
`A APPENDICES....................................................................................................................28
`
`R REGIONAL INFORMATION.........................................................................................64
`
`II- Review Of Common Technical Document-Quality (Ctd-Q) Module 1..-......65
`
`A.
`
`B.
`
`Labeling & Package Insert.................................................................... 65
`
`Environmental Assessment Or Claim Of Categorical Exclusion .......................68
`
`Reference ID: 3633270
`
`2
`
`

`

`f'"e"‘
`
`CHEMISTRY REVIEW
`
`Chemistry Review Section
`
`Chemistry Review Data Sheet
`
`“"5",
`
`1. NDA 206439
`
`2. REVIEW # 1
`
`3. REVIEW DATE: September 23, 2014
`
`4. REVIEWER: Pei-I Chu, Ph.D.
`
`5. PREVIOUS DOCUMENTS:
`
`Previous Documents
`
`Document Date
`
`6. SUBMISSION(S) BEING REVIEWED:
`
`Submission; s! Reviewed
`
`Document Date
`
`Original
`
`February 26, 2014
`
`7. NAME & ADDRESS OF APPLICANT:
`
`Name:
`
`Forest laboratories, Inc.
`
`Address:
`
`Harborside Financial Center, Plaza V,
`
`Suite 1900, Jersey City, USA, 07311
`
`Representative:
`
`Kathleen Waldron
`
`Telephone:
`
`201-386—21 15
`
`8. DRUG PRODUCT NAME/CODE/TYPE: N/A
`
`a) Proprietary Name: Namzaric
`b) Non-Proprietary Name (USAN): MDX-8704 (memantine HCl extended
`release/donepezil HCl capsules)
`c) Code Name/# (ONDC only): N/A
`(1) Chem. Type/Submission Priority (ONDC only):
`0 Chem. Type: 1
`
`0
`
`Submission Priority:
`
`Reference ID: 3633270
`
`

`

`
`
`Chemistry Review Section
`
`9. LEGAL BASIS FOR SUBMISSION: 505(b) (2)
`
`10
`
`ll
`
`12
`
`. PHARMACOL. CATEGORY: memantine: an orally active N-methyl—D-aspartate
`(NMDA) receptor antagonist, donepezil: an orally active reversible
`acetylcholinesterase inhibitor
`
`. DOSAGE FORM: Capsule
`
`. STRENGTH/POTENCY: 28mg memantine HCl ER/lOmg donepezil HCl and 14mg
`memantine HCl ER/lOmg donepezil HCl
`
`l3
`
`. ROUTE OF ADMINISTRATION: Oral
`
`14
`
`. Rx/OTC DISPENSED:
`
`X Rx
`
`OTC
`
`15
`
`X
`
`. SPOTS (SPECIAL PRODUCTS ON-LINE TRACKING SYSTEM):
`
`SPOTS product — Form Completed
`Not a SPOTS product
`
`16. CHEMICAL NANIE, STRUCTURAL FORMULA, MOLECULAR FORMULA,
`MOLECULAR WEIGHT:
`
`Chemical Name: donepezil hydrochloride
`(2 )-2.3-dihydro-5 .6-dimelhoxy2-[[ 1 -
`(phenyhnelhyl )4-piperidinyl]methyl]- lH-iudeu- l -
`one hydrochloride
`
`(1 )-2-[( l-Bcnzyl-4-piperidyl)methyll-S .6-
`dimethoxy-l.3-dihydroinden— 1 -one hydrochloride
`
`Molecular Formula: C24Hng03 .HCl
`
`Molecular Weight: 415.95 g/mol
`
`Structural Formula
`
`0- »'> E/ ,r‘\_
`\U 1—!
`I“) L
`I
`ll
`
`0
`
`I:
`
`Reference ID: 3633270
`
`

`

`
`
`Chemistry Review Section
`
`Chemical Name: memantine hydrochloride(salt)
`
`l-Amino-3.5-dimcthyladamantanc hydrochloride
`
`l-Amino-S.5-dimcthyltricyclo[3.3. 1 .13‘7] dccanc
`hydrochloride
`
`Molecular Formula: C 12H21NHC1
`
`Molecular Weight: 215.77 g/mol
`
`\n; ‘ nu
`
`Q.“
`
`"w
`
`Structural Formula:
`
`17. RELATED/SUPPORTING DOCUMENTS:
`
`Reference ID: 3633270
`
`

`

`— It. h
`
`A. DMFs:
`
`CHEMISTRY REVIEW
`
`Chemistry Review Section
`
`:-"'-T‘
`
`--__III Winformation in
`III Winformation in
`III
`
`: J-lication
`
`: J-lication
`
`Adequate
`
`09/10/2012
`
`Suficient
`information in
`
`: J-lication
`Suflicient
`information in
`
`
`
`I-- M in
`--- M in
`I-- m
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`
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`
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`Suficient
`
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`
`information in
`: J-lication
`
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`
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`Suficient
`
`4
`
`4
`
`4
`
`4
`
`--- M in
`I-- M in
`: J-lication
`—-——information in
`
`: J-lication
`Suficicnt
`
`: J-lication
`Suflicient
`
`Reference ID: 3633270
`
`

`

`
`
`a U n lication
`
`
`
`a y . lication
`
` a y . lication
`
`
`
`lAction codes for DMF Table:
`
`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)
`
`Reference ID: 3633270
`
`

`

`
`
`Chemistry Review Section
`
`B. Other Documents:
`
`APPLICATION
`
`
`
`22525
`
`21720
`
`21487
`
`18. STATUS:
`
`CONSULTS/
`
`CMC
`RELATED
`REVIEWS
`
`RECOMMENDATI
`ON
`
`DATE
`
`REVIEWER
`
`
`
`——N——
`Acceptable
`05/30/2014
`Ofiice of
`com 0 liance
`
`————
`—___NA—NA—I_
`LNChalm
`OPDRA —NA—NA—
`
`Methods Validation
`
`————
`Microbi010305/06/2014
`
`Reference ID: 3633270
`
`

`

`
`
`Chemistry Review Section
`
`The Chemistry Review for NDA 206439
`
`The Executive Summafl
`
`I.
`
`Recommendations
`
`A. Recommendation and Conclusion on Approvability
`
`MDX-8704 is a combination product of capsules containing two approved active ingredients
`(memantine and donepezil). Except for the dissolution specification. NDA 206439 has been
`reviewed for the chemistry, manufacturing and controls section. The Office of Compliance
`has determined that the drug substance, drug product and packaging facilities are acceptable
`based on profile. The approval from a CMC perspective is contingent upon an acceptable
`recommendation from the Biopharm reviewer for the dissolution specification. A separate
`memo will be put in DARRTS with final CMC recommendation on the adequacy of the
`dissolution specification and product shelf life.
`
`B. Recommendation on Phase 4 (Post-Marketing) Commitments,
`Agreements, and/or Risk Management Steps, if Approvable
`
`II.
`
`Summary of Chemistry Assessments
`
`A.
`
`Description of the Drug Product(s) and Drug Substance(s)
`
`Drug Product (MDX 8704)
`
`The drug product, memantine HCl ER/donepezil HCl (MDX8740) capsules. is developed as an oral
`capsule formulation containing a fixed dose combination of memantine HCl extended release (ER)
`and donepezil HCl
`“M”. The memantine ER “"9 have been manufactured commercially for
`Namenda XR® capsules which were approved in NDA 22525. They are sugar sphere
`
`M"
`
`(mo
`
`Donepezil is commercially
`M" formulation developed for MDX 8704 is
`available as tablets (Aricept®). The donepezil HCl
`similar to the Aricept tablet formulation which was approved in NDA 21720. The excipients consistoof
`
`Most of the excipients used in the donepezil HCl
`Aricept® tablet.
`
`(we) have been used in the approved
`
`The manufacturing process for memantine HCl ER/donepezil HCl capsules consists 01 M” distinct
`stages:
`on»
`
`“M" are encapsulated from a common ER om)
`Both Memantine strengths
`(mo Memantine HCl ER/Donepezil HCl
`formulation.
`Capsules. 14 mg/10 mg. are a locked size 2 light green opaque capsules. with black ‘FL 14/ 10’ radial
`imprint on the cap. Memantine HCl ER/Donepezil HCl Capsules, 28 mg/ 10 mg are locked, size 1 blue
`
`9
`
`Reference ID: 3633270
`
`

`

`
`
`Chemistry Review Section
`
`opaque capsules, with black ‘FL 28/10’ radial imprints on the caps. The commercial product is available
`in HDPE bottles with
`(”m caps
`(b)(4)_
`
`Forest has provided 12 month stability data and a complete regression analysis within 120 days post-
`submission of the original NDA. With the update, Forest has request a drug product shelf life of 18
`months.
`
`From the CMC perspective, the product quality risk is low. The memantine XR component of this
`product has been manufactured using the same commercial process as in the approved NDA 22525. The
`donepezil
`“M"
`
`Drug Substance
`
`Donepezil HCl, USP is off-white to cream colored crystalline powder with a melting point of 219.0°C to
`220.5°C. The water solubility at pH 7 is 0.15g/mL. DMF M" has been filed by the drug substance
`manufacturer
`“"0. This DMF has been reviewed and found to be adequate. The applicant has
`referred to DMF
`”(4’ for all manufacturing, control. testing and stability of the donepezil HCl drug
`substance.
`
`Memantine hydrochloride drug substance is currently approved for Namenda® tablets (NDA 21487),
`Namenda® Oral Solution (NDA 21627) and Namenda® XR extended release capsules (NDA 22525). It
`is a white
`M" powder with a melting point of greater than 220°C
`M"
`The solubility at pH 7 is 43.6 mg/mL.
`
`Reference ID: 3633270
`
`10
`
`

`

`‘
`.
`I I
`CHENIISTRY REVIEW
`‘.
`I
`
`Chemistry Review Section
`
`Risk Assessment — Memantine MCI and Donepezil HCI XR Capsules
`
`From Initial Quality Assessment
`
`Review Assessment
`
`Product
`
`Factors That Can
`
`Risk
`
`.
`
`. .
`
`.
`
`Risk
`
`Lifecycle Considerations!
`
`The applicant developed the memantine WW
`manufacturing process and gained commercial
`batch experience at the proposed manufacturing
`site. The formulation, manufacturing process and
`container closure selected will ensure that
`acceptable assay and stability will be obtained.
`
`Acceptable
`
`Any changes in the
`manufacturing process
`parameters could affect the
`assay and dissolution profile of
`the memantine ER (5)“)
`
`Assay
`(memantine),
`stability
`
`n
`
`y
`(donepezil),
`stability
`
`Physical
`stability
`memantine).
`solid state
`
`Physical
`stability
`(donepezil).
`solid state
`
`- Formulation
`- Container closure
`- Raw materials
`- Process parameters
`- Scale/equipment
`- Site
`
`- Formulation
`.
`Container closure
`' Raw materials
`- Process parameters
`- Scale/equipment
`- Site
`
`- Formulation
`- Raw materials
`- Process parameters
`- Scale/equipment
`- Site
`
`- Formulation
`- Raw materials
`- Process parameters
`- Scale/equipment
`- Site
`
`- Formulation
`- Raw materials
`
`and dissolution
`
`.
`The applicant has conducted DOE study to
`0""
`The capsules were 100% weight
`
`inspected
`
`Excipients selected for the memantine ER (5)“)
`were the same as the approved Namenda XR
`commercial product developed by Forest.
`Manufacturing process parameters and batch size
`were the same as the Namenda XR capsule .
`
`Acceptable
`
`Excipient compatibility study was conducted during
`development. Product stability data has been
`collected. The process was scaled up to the
`commercial size. Process parameters selected
`based on DOE study
`
`Acceptable
`
`.
`.
`The assay and dissolution
`profile of the donepezil may be
`affected
`9W)
`
`used
`
`The drug product is stable. Any
`changes of manufacturing
`process parameters could affect
`the dissolution profile of the
`memantine ER ‘5’“).
`
`The drug product is stable. Any
`changes
`(5)“)
`process parameters could affect
`the dissolution profile of the
`donepezil
`“M".
`
`The drug substance
`
`to ensure
`acceptable content uniformity
`
`Content
`uniformity
`(memantine)
`
`- Process parameters
`- Scale/equipment
`- Site
`
`Process parameters selected were based on
`previous manufacturing experience of the same
`product, release and stability data.
`
`Reference ID: 3633270
`
`11
`
`

`

`CHENIISTRY REVIEW
`
`Chemistry Review Section
`
`Risk Assessment - Memantine HCI and Donepezil l-lCl XR Capsules
`
`From Initial Quality Assessment
`
`Review Assessment
`
`Product
`
`Factors That Can
`
`Risk
`
`.
`
`.
`
`.
`
`.
`
`Risk
`
`Lifecycle Considerations]
`
`. Formulation
`- Raw materials
`
`- Process parameters
`- Scale/equipment
`- Site
`
`Content
`
`uniformity
`(donepezil)
`
`Microbial limits
`
`Dissolution
`
`(donepezil)
`
`Dissolution
`
`(memantine),
`
`- Formulation
`- Raw materials
`
`- Process parameters
`- Scale/equipment
`- Site
`- Formulation
`- Raw materials
`
`- Process parameters
`- Scale/equipment
`- Site
`
`. Formulation
`
`- Raw materials (rate
`controlling polymers)
`- API sources
`
`- Process parameters
`- Scale/equipment
`- Site
`
`The drug loading in the donepezil
`
`The
`
`Process parameters Acceptable
`selected were based on DOE study. The
`commercial equipment is considered the same as
`the registration batch according to SUPAC
`
`to
`
`ensure adequate content
`uniformity and dissolution
`profile.
`
`The applicant follows c-GMP procedure to maintain
`the facility and manufacture the product. Microbial
`data will be monitored at release and annually
`
`Acceptable
`
`Follow c-GMP procedure and
`adequately maintain the
`manufacturing facility
`
`09‘” should
`dissolution profile of the donepezil
`meet specification due to its high solubility and the
`00(4)
`
`Acceptable
`
`Refer to Biopharmaceutics
`Review
`
`(h) (4)
`
`The
`
`HDPE bottles.
`
`The roduct will be acka ed in
`p
`P
`g(b)(4)
`
`Acceptable
`
`If changes in the container
`closure system are to be made,
`adequate stability/dissolution
`data should be provided since
`the dissolution profile may be
`affected by the package
`components selected.
`
`Review
`
`Alcohol dose
`
`dumping
`(memantine)
`
`- Formulation
`
`- Process parameters
`- Scale/equipment
`- Site
`
`Even though the product has a pronounced effect
`in dose dumping with 40% alcohol, clinical trials
`suggested that the adverse events were mild for
`doses up to 100mg
`
`Acceptable
`
`Refer to Biopharmaceutics
`
`Reference ID: 3633270
`
`12
`
`

`

`
`
`Chemistry Review Section
`
`B. Description of How the Drug Product is Intended to be Used
`
`The drug (memantine HCl extended—release and donepezil HCl) capsules 28/10 mg is for use in patients
`currently stabilized on memantine HCl (10 mg twice daily or 28 mg extended-release once daily) and
`donepczil HCl 10 mg. The drug (mcmantine HCl extended-release and doncpezil HCl) capsules 14/10
`mg is for use in patients with severe renal impairment currently stabilized on memantine HC1(5 mg
`twice daily or 14 mg extended-release once daily) and donepezil HCl 10 mg.
`
`C. Basis for Approvability or Not—Approval Recommendation
`
`From the perspective of chemistry. manufacturing and controls. this application is recommended for
`approval pending the recommendation of the biopharmaceutics reviewer. The applicant has addressed all
`issues raised through information requests and the Office of Compliance has rendered an acceptable
`recommendation.
`
`II.
`
`Administrative
`
`A. Reviewer’s Signature
`
`Pei-I Chu, Ph.D.
`
`B. Endorsement Block
`
`Chemist Name:
`
`Pei-I Chu, Ph.D.
`
`Chemistry CMC Lead:
`Chemistry Branch Chief:
`Chemistry Project Manager :
`
`Martha Heimann. Ph.D.
`Olen Stephens. PhD.
`Teshara Bouie
`
`C. CC Block
`
`Orig. NDA 206439
`
`62 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`Reference ID: 3633270
`
`13
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`PEI-I CHU
`09/24/2014
`
`OLEN M STEPHENS
`09/24/2014
`
`Reference ID: 3633270
`
`

`

`FDA CDER EES
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`
`Ar
`
`won:
`
`Org; .0110:
`
`Priority:
`
`Stamp Date:
`PDUFA Date:
`
`NDA 206439l000
`
`120
`
`4
`
`26-FEB-2014
`26-DEC-2014
`
`Acflon Goal:
`District Goal:
`
`,
`
`_
`.
`“ 27-OCT-2014
`
`.
`
`‘
`‘ "-
`
`.
`
`g
`
`'
`
`Sponson
`
`FOREST LABS INC
`
`PLAZA V STE 1900
`
`JERSEY crI'Y. NJ 07311
`
`Bland Namo:
`Estab. Name:
`
`MEMANTINE HC1 EXTENDED RELEASE AND
`DONEP
`
`6011qu Nam:
`- MEMANTINE HC1 EXTENDED RELEASE AND
`Product Numb"; 0.32:1gm, Inst-4km; smug
`001: CAPSULE: DONEPEZIL HYDROCHLORIDE; 10MG
`001‘ CAPSULE; MEMANTINE HYDROCHLORIDE; 14MG
`002: CAPSULE: DONEPEZIL HYDROCHLORIDE 10MG
`002; CAPSULE; MEMANTINE HYDROCHLORIDE; 23MB
`
`FDA Contacts:
`
`'P.CHU '
`T. EOU'IE
`
`-
`
`Prod Oname'viawer
`Product 06':me PM
`
`-
`j
`
`.~
`1'
`
`T. WHEELOUS
`
`ReguIanry Ptoject Mgr
`
`(HFD-120)
`
`3017963687
`3017961649
`
`3017961161
`
`M. HEIMANN
`Team Leader
`3017961676
`
`
`Overall mm»:
`
`ACCEPTABLE
`
`on 30-MAY-2014
`
`by T. SHARP
`
`0
`
`3017963208
`
`PENDING
`
`on 14-MAR-2014
`
`by EES_PROD
`
`PENDING
`on 14-MAR-2014
`by EES_PROD
`
`
`Establishment:
`
`CFN:
`
`(m4)
`
`FEI:
`
`(1614)
`
`DMF No:
`
`(um)
`
`AADA:
`
`Ruponslbumos:
`
`FlNlSHED DOSAGE PACKAGER
`
`Profile:
`
`CAPSULES. MODIFIED RELEASE
`
`0A1 sums:
`
`NONE
`
`um "um“
`
`unmom Data:
`
`Dodslon:
`
`0C RECOMMENDATiON
`
`18-MAR-2014
`
`ACCEPTABLE
`
`BASED ON PROFILE
`Ruson:
`
`
`July 22, 2014 4:04 PM
`
`FDA Confidential - Morn-I Distribution Only
`
`Page 1 015
`
`

`

`FDA CDER EES
`
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`
`Establishment:
`
`CFN:
`
`00(4)
`
`FEI:
`(m4)
`
`(6)“)
`
`DMF No:
`
`Reeponeiblllties:
`
`‘
`
`§
`
`Profile:
`
`Last Milestone:
`Milestone om:
`Decision:
`
`,.
`
`’
`
`'
`
`-
`T
`
`MBA:
`
`DRUG SUBSTANCE MANUFACTURER
`DRUG SUBSTANCE RELEASE. TESTER
`
`DRUG SUBSTANCE STABILITY TESTER
`
`.
`
`NON-STERILE API BY CHEMICAL SYNTHESIS
`
`DAI Stains:
`
`NONE
`
`oc RECOMMENDATION
`17-MAR-2014
`‘7
`ACCEPTABLE
`
`M W
`
`Reason:
`_
`’ BASED ON PROFILE
`
`Establishment:
`CFN:
`(I!) (4)
`FE]:
`(5X4)
`(5) (4)
`
`DMF No:
`
`Responsibilities:
`
`Profile:
`
`Last Milestone:
`
`Milestone Date:
`
`Decision:
`
`AADA:
`
`0’) (4)
`
`CAPSULES, MODIFIED RELEASE
`
`0A! Status:
`
`NONE
`
`0C RECOMMENDATION
`
`18-MAR-2014
`
`ACCEPTABLE
`
`Reason:
`BASED ON PROFILE
`
`
`Estdflishment:
`
`CFN:
`
`(b) (4)
`
`FE]:
`
`(5X4)
`
`(5X4)
`
`DllF No:
`
`(5) (4)
`
`MBA:
`
`Responsibilities:
`
`FINISHED DOSAGE OTHER TESTER
`
`Profile:
`
`CONTROL TESTING LABORATORY
`
`OAI Status:
`
`NONE
`
`Last Milestone:
`
`Milestone Date:
`
`Declslon:
`
`OC RECOMMENDATION
`
`17-MAR-2014
`
`ACCEPTABLE
`
`BASED ON PROFILE
`Reason:
`
`
`July 22. 2014 4:04 PM
`
`FDA Confidential - Internal Distribution Only
`
`Page 2 of 5
`
`

`

`FDA CDER EES
`
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`
`E:
`
`Ihmont:
`
`CFN:
`
`(5H4)
`
`FEI:
`
`(0(4)
`00(4)
`
`DMF No:
`
`MDA:
`
`Responsibilities:
`
`FINISHED DOSAGE OTHER TESTER
`
`Profile:
`
`CONTROL TESTING LABORATORY ;
`
`OAI sums: ” - NONE
`
`us, "Heston“
`
`‘ loc RECOMMENDATION
`
`Mllastono Date:
`
`A
`
`TEN-2°14,
`
`.0
`
`‘ Doclslon:
`
`- ACCEPTABLE
`
`-
`
`:
`
`~
`
`_
`
`.>
`
`.
`
`‘
`
`.
`
`.
`
`-
`
`f
`
`.
`
`Rsason:
`: BASED ON PROFILE
`'
`'
`
`
`Establishmeht:
`
`CFN:
`
`2436921
`
`FEI:
`
`1000521503
`
`TFOREST LABORATORIES INC '
`
`~
`
`DMF No:
`
`Responslbllitiu:
`
`FARMINGDALE, , UNITED STATES 117353900
`
`AADA:
`
`FINISHED DOSAGE RELEASE TESTER
`FINISHED DOSAGE STABILITY TESTER
`
`Profile:
`
`CONTROL TESTING LABORATORY
`
`OAI Status:
`
`NONE
`
`Last Milestone:
`
`M.
`
`,no Date:
`
`Decision:
`
`OC RECOMMENDATION
`
`17-MAR-2014
`
`ACCEPTABLE
`
`Reason:
`BASED ON PROFILE
`
`Establishment:
`CFN:
`9616660
`FEI:
`3002806993
`
`DMF No:
`
`Responslhlmles:
`
`FOREST LABORATORIES IRELAND. LTD.
`CLONSHAUGH BUSINESS AND TECHNOLOGY PARK
`
`DUBLIN 17, CLONSHAUGH. IRELAND
`
`AADA:
`
`FINISHED DOSAGE MANUFACTURER
`FINISHED DOSAGE RELEASE TESTER
`
`FINISHED DOSAGE STABILITY TESTER
`
`Profile:
`
`CAPSULES. MODIFIED RELEASE
`
`OAI Status:
`
`NONE
`
`I3“ Huang";
`Mllestone Date:
`
`0C RECOMMENDATION
`25-MAR-2014
`
`Dodslon:
`
`ACCEPTABLE
`
`DISTRICT RECOMMENDATION
`Reason:
`
`
`July 22. 2014 4:04 PM
`
`-
`
`FDA Confidential - lnumal Dlwbutlon OnIy
`
`Page 3 015
`
`

`

`FDA CDER EES
`
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`
`Establishment:
`
`CFN:
`
`1523957
`
`PEI:
`
`1523957
`
`FOREST PHARMACEUTICALS INC
`
`CINCINNATI. . UNITED STATES 45209
`
`DMF No:
`
`Responsibilities:
`Promo:
`
`FINISHED DOSAGE PACKAGER
`j ,j CAPSULES. MODIFIED RELEASE. ‘_
`
`I
`
`Last Milestone:
`
`j i
`
`I
`
`- 0c RECOMMENDATION
`
`I
`
`Milestone Date:
`Decision:
`
`_
`
`>
`
`.
`
`—
`._
`
`l
`i“
`
`30-MAY~2014
`"ACCEPTABLE
`
`MDA:
`
`OA'I Status; I
`
`I ,. NONE
`
`»
`
`Reason:
`7
`:
`DISTRICT RECOMMENDATION 7
`
`Establishment:
`-
`CFN:
`(In) (4)
`ES]:
`(5) (4)
`(mo
`
`DMF No:
`
`AADA:
`
`Responsibilities:
`
`DRUG SUBSTANCE MANUFACTURER
`
`Profile:
`
`NON-STERILE API BY CHEMICAL SYNTHESIS
`
`OAI Status:
`
`NONE
`
`Last unestone;
`
`' 0C RECOMMENDATION
`
`Milestone Date:
`
`Decision:
`
`18-MAR-2014
`
`ACCEPTABLE
`
`Reason:
`BASED ON PROFILE
`
`
`Establishment:
`
`CFN:
`
`(m4)
`
`FEI:
`
`DMF No:
`
`Responsibilities:
`
`DRUG SUBSTANCE MANUFACTURER
`DRUG SUBSTANCE RELEASE TESTER
`
`DRUG SUBSTANCE STABILITY TESTER
`
`(m4)
`(m4)
`
`AADA:
`
`Profile:
`
`NON-STERILE API BY CHEMICAL SYNTHESIS
`
`OAI Status:
`
`NONE
`
`Last MIIestone:
`
`Milestone Date:
`
`Decision:
`
`0C RECOMMENDATION
`
`17-MAR-2014
`
`ACCEPTABLE
`
`BASED ON PROFILE
`Reason:
`
`
`July 22, 2014 4:04 PM
`
`FDA Conflm -lntemel 1')an Only
`
`Page 4 of 5
`
`

`

`FDA CDER EES
`ESTABLISHMENT EVALUATION REQUEST
`SUMMARY REPORT
`
`5
`
`'shmom:
`
`cm:
`
`am
`
`m:
`
`(m4)
`one
`
`MBA:
`
`our No:
`
`Rummnnm:
`male;
`
`Last mm:
`minimum:
`mm:
`Reason:
`‘
`
`FINISHED DOSAGE OTHER TESTER
`CONTROL TEstNGLABORATORY
`
`V
`
`S, .‘,;,_QiAl,Status:
`
`NONE
`
`.
`
`M
`
`,
`.,
`
`_,
`
`00 RECOMMENDATION
`14-MAR-2014 ,1
`.7
`Accemau: ;.
`BASED ON PRO—FiL-E-
`
`I
`
`‘
`
`July 22, 2014 4:04 PM
`
`FDA Confidential - [humal Distribution Only
`
`Page 5 of 5
`
`