`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`NDA 22410/S016
`
`
`
`Suboxone® sublingual film
`Trade Name:
`
`
`buprenorphine HCl & naloxone HCl dihydrate
`Generic Name:
`
`Sponsor:
`
`Approval Date:
`
`Changes:
`
`Reckitt Benckiser Pharmaceuticals Inc.
`
`06/05/2014
`
`addition of a new testing laboratory
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`NDA 22410/S016
`
`
`
`
`CONTENTS
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`
`
`
`
`
`
`
`
`X
`
`
`
`
`
`
`
`
`X
`
`

`

`CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`APPLICATION NUMBER:
`NDA 22410/S016
`NDA 22410/5016
`
`
`APPLICA TION NUMBER:
`
`APPROVAL LETTER
`APPROVAL LETTER
`
`
`
`
`
`
`
`
`
`

`

`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`NDA 22410/S-016
`
`Reckitt Benckiser Pharmaceuticals Inc.
`Attention: Bruce Paolella
`Director Regulatory Strategy Category
`10710 Midlothian Turnpike
`Richmond VA 23235
`
`Dear Mr. Paolella:
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`APPROVAL LETTER
`
`Please refer to your Supplemental New Drug Application (sNDA) dated and received December
`6, 2013, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`for Suboxone (Buprenorphine HC1/ Naloxone HC1 Dihydrate) Sublingual Film.
`
`This “Changes Being Effected in 30 Days” supplemental new drug application provides for
`addition of
` as an additional microbiological testing
`laboratory for the testing of raw material components and finished product
`
`We have completed our review of this supplemental new drug application. This supplement is
`approved.
`
`We remind you that you must comply with the requirements for an approved NDA set forth
`under 21 CFR 314.80 and 314.81.
`
`If you have any questions, call LCDR Luz E Rivera, Regulatory Project Manager, at (301) 796
`4013.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Ramesh Raghavachari, Ph.D.
` Branch Chief, Branch IX,
` Division of New Drug Quality Assessment III
` Office of New Drug Quality Assessment
` Center for Drug Evaluation and Research
`
`Reference ID: 3519146
`
`(b) (4)
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAMESH RAGHAVACHARI
`06/05/2014
`
`Reference ID: 3519146
`
`

`

`
`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`APPLICATION NUMBER:
`NDA 22410/S016
`NDA 22410/5016
`
`
`APPLICA TION NUMBER:
`
`CHEMISTRY REVIEW(S)
`CHEMISTRY REVIEW! S!
`
`
`
`
`
`

`

`Chemistry Review # l
`
`1. Division
`HFD-820
`
`2. NDA Number
`22-410
`A raved 8/30/2010
`
`3. Name and Address of Applicant
`Reckitt Benckiser Pharmaceuticals Inc., I 0701 0 Midlothian
`
`Turn ike, Richmond, VA 23235
`
`4. Supplement
`Number
`
`Date
`
`S-I6
`
`[2/6/2013
`
`6. Nonproprietary Name
`5. Name of Drug
`BupreiIorphine/Naloxone (Schedule III)
`Suboxone (m4)
`om), as
`8. Amendment(s)
`7. CBE30 Supplement Provides for: CTL,
`an additional microbiological testing laboratoryfor testing raw
`material com onents and nished the dru_ Il'OdIlCl
`
`9. Pharmacological Category
`
`10. How Dispensed
`Rx
`
`11. Related Documents
`
`12. Dosage Form
`Film, Sub/in lal
`14. Chemical Name and Structure
`_\‘:llo.\'one hydrochlorlde (“hydrate
`
`C',.H;,x04-HC‘1-2Hzo
`XIVV: 399,9
`
`13. Strength
`2m /0.5m,
`
`C‘AS RN:
`
`465-65-6 Naloxmle.
`357-08»! Naloxune hydiucliluiidc unllyrh nus
`S 1481-60-8 Saloxone hydrochloride (lihydiale
`
`4.50—Epoxy-3. ]>1-dihyclroxy-17—(prop-2—enylmmi‘phinan-G-one hydrochloride dihyclmte
`
`Bupreuorphme hydrochloride
`
`Laboratory Code: R_X(3029l\/1.HC1
`
`ngl-IHNOyl-ICI
`
`.\'1VV: 46".6 (base) 504.] (5:11!)
`
`C'AS Registry nmnber: 53152-21-9
`
`
`
`(2.S")-2-[ l 7-C‘ycloplopyhnelliyl—J. 5(I-¢])OX_V-3-ll_\’(llO‘éy-(J-lllélllOXy-GU. IJ-elliano-l40-1non)liinan-'.u-y1]-.‘~.3-
`rliniethylbutnn—Z—nl hydrochloride
`
`15. Comments: EES is acceptablefor CTL to recommend an approval actionfor NDA 22410/S-
`I 7. Enclosed is EES report. Ihe sponsor certifies that
`«no is capable ofperforming
`microbiological testing in accordance with USP 61 and 62, and module 3.2.P.3.1 was updated.
`ox claims in a letter dated 10/15/2013 that cGMP quality systems are in place.
`one claims in a letter dated 9/30/20] 3 that the site is a registeredfacility with DEA and
`FDA to provide microbiological testing services.
`one
`one)
`Monosol Kr is a contractor to the sponsor to manufacture the drugproduct at 8facilities in
`one
`
`16. Conclusions and Recommendations
`
`NDA 22-410/S—I4 is recommendedfor an approval action.
`
`Signature
`17. Name
`Dr. Pramoda Maturu, PhD, Senior Regulatory Review Chemist
`
`Dr. Ramesh Raghavachali, PhD, Branch Chief
`
`File: NDA 22410816
`
`Page I
`
`Reference ID: 351871 1
`
`

`

`
`
`Application:
`Stirrup Dam:
`
`Ragulatory:
`
`Applicant:
`
`FDA CDER EES
`ESTABLISHMENT EVALUATION REQUEST
`DEI'AIL REPORT
`
`Action Goal:
`District Goal:
`
`D2MAY—2014
`
`NBA 224in5
`{IE—DEGZCIB
`
`mun-201.1
`
`RECKHT BENCKISER
`10111} MIDLOTHIAN TPKE STE 430
`
`RICHNDND,VA 23235
`
`Brand Name:
`Estab. m;
`
`Generic Nam:
`
`SUBOXONE {BUFRENORPHII'IE'NALOXONE}
`SUBLIN
`
`Priority:
`Org. Code:
`
`AIS
`1TB
`
`Product Number; Dosage Form; Ingredient: Strengths
`0111: FILM; NALOXONE HYDROCHLORIDE; E0 .EMG BASE
`Dill; FILM; BUPRENORPHINE l-I'YDROCHLORIDE; E0 2MB
`BASE
`0112; FILM; BUPRENORPHINE HYDROCHLORIDE; E08“;
`BASE
`1102; FILM; NALOXC‘NE HYDROCHLORIDE; E0 2MB BASE
`0113; FILM; NALOXONE HYDROCHLORIDE; E0 1MG BASE
`BIB; FILM; BUPRENORP‘HINE l-IYDROCHLORIDE; EQAIN'K}
`BASE
`1104; FILM; NALOXCINE HYDROCHLORIDE; E0 3M8 BASE
`0114; FILM; BUPRENORPHINE HYDROCHLORIDE; E0 12MB
`BASE
`
`Applicatim Garment:
`
`FDA Contacts:
`
`P. MATURU
`
`Prod Clual Reviewer
`
`L. RIVERA
`
`M. SULLIVAN
`
`Product Oualty PM
`
`Regimory Project My
`
`M. GAUTAM BASAK
`
`Team Leader
`
`{HFD—1TU}
`
`{HFD-51D}
`
`3D11"961'."IJ?r
`
`30139641113
`
`31311961245
`
`31317960112
`
`Oven" Remunemiation:
`
`ACCEPTABLE
`
`on 25—APR—2014
`
`by T. SHARP
`
`{3
`
`31117963206
`
`PENDING
`
`on WAN-2614
`
`by EES_PROD
`
`
`
`
`
`
`
`
`
`
` Page 2
`
`Page 2
`
`
`
`Reference ID: 3518711
`Reference ID: 3518711
`
`

`

`FDA CDER EES
`ESTABLISHMENT EVALUATION REQUEST
`DETAIL REPORT
`
`mm cm:
`
`Ffl:-
`
`”No:
`
`AADA:
`
`Mam:
`
`FNIS-EDMSAGEOTHER'IESTER
`
`WNW-Inuit: mmmmwmwmmsammmuemnmmmqumo
`8117964013)
`WESTINGLABGRATWY
`
`DAIStIus: NOIE
`
`Profile:
`
`IlestoneDdo Mm EM Decbion
`
`“Wm
`Con-mm
`OAISIIinI'tToOC
`WmEnendReavdD‘eTo
`WWW
`Reason
`
`
`Cm
`
`StBMTIEDTOOC
`
`alum-2014
`
`MDTODO
`
`(IMAM-2014
`
`1ST FDA EVIA PDIfA 02-MAY-2014
`
`PlomdSpecic
`alii‘lGMa
`km
`
`ASSIGDEDINSPECDONTOIB
`
`inn-2014 WM
`hapedinn
`FRST FDA EVALUMKN - PleA MAY 2014 (MAY 2“»
`
`RIVERAL
`
`WILSON
`
`—
`
`mm — _ —
`‘I'II‘swsaciededMJA
`'
`' da
`’ WMpeIfansbdiigforadelllelewleMJAMflo
`(W16).
`(header
`IIsfadfiy.afliefinn)isisIedasFli§iedDosqeofiierhsht “is
`.Iapecionfouaedon mm
`
`mammmmmm, aidwlfllheya'empdiled
`milieu mumpafimmiaummmmmmnsammmma
`“373464832
`hspeclionslWIS
`
`.Mhnbammiiavmmmimw inliestahof-
`ann-name!
`mumawW”WMW
`mwmmmmmm
`
`m,“mmmu>perhm m
`WWW.Wa1OTDWTmWSflh43.WVA 23235. Nodddendesm
`
`
`WM
`
`Magi-'3
`
`AmiewdlluFAC‘lSCovaormhms
`sfiedlieyhadieoaivedone
`[Idioufliei
`mismwedwasiflliei
`
`"°‘—
`
`._;
`Imebeenfled .~
`
`«mu-um
`
`:wv '
`=
`
`
`AOCE’TABIE —
`214912-2014
`DORECOMENDATION
`mmumimcmmm-mmwmmm FORMAL
`
`OCECGWBJDATIW
`3YRFORC‘II.
`
`25—APR-ZN4
`
`ACCEPTABLE
`
`SHARPT
`
`mumumm
`
`mammal-mmwmomy
`
`Pagozon
`
`Page 3
`
`Reference ID: 3518711
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`PRAMODA K MATURU
`06/04/2014
`
`RAMESH RAGHAVACHARI
`06/04/2014
`
`Reference ID: 3518711
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`NDA 22410/S016
`
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`
`
`
`

`

`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`NDA 22410/S-016
`
`CBE-30 SUPPLEMENT
` ACKNOWLEDGEMENT
`
`Food and Drug Administration
`Silver Spring, MD 20993
`
`Reckitt Benckiser Pharmaceuticals Inc.
`Attention: Bruce Paolella
`Director Regulatory Strategy Category
`10710 Midlothian Turnpike
`Richmond VA 23235
`
`Dear Mr. Paolella:
`
`We have received your Supplemental New Drug Application (sNDA) submitted under section
`505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA or the Act) for the following:
`
`NDA NUMBER:
`
` 22410
`
`SUPPLEMENT NUMBER:
`
`016
`
`PRODUCT NAME:
`
`Suboxone (Buprenorphine HC1/ Naloxone HC1 Dihydrate)
`Sublingual Film
`
`DATE OF SUBMISSION:
`
` December 6, 2013
`
`DATE OF RECEIPT: December 6, 2013
`
`This supplemental application, submitted as a “Changes Being Effected in 30 Days” supplement,
`proposes to add
` as an additional microbiological testing
`laboratory for the testing of raw material components and finished product.
`
`Unless we notify you within 60 days of the receipt date that the application is not sufficiently
`complete to permit a substantive review, we will file the application on February 4, 2014, in
`accordance with 21 CFR 314.101(a). If the application is filed, the user fee goal date will be
`June 6, 2014.
`
`Cite the application number listed above at the top of the first page of all submissions to this
`application. Send all submissions, electronic or paper, including those sent by overnight mail or
`courier, to the following address:
`
`Reference ID: 3433139
`
`(b) (4)
`
`

`

`NDA 22410/S-016
`Page 2
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Anesthesia, Analgesia and Addiction Products
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`All regulatory documents submitted in paper should be three-hole punched on the left side of the
`page and bound. The left margin should be at least three-fourths of an inch to assure text is not
`obscured in the fastened area. Standard paper size (8-1/2 by 11 inches) should be used; however,
`it may occasionally be necessary to use individual pages larger than standard paper size.
`Non-standard, large pages should be folded and mounted to allow the page to be opened for
`review without disassembling the jacket and refolded without damage when the volume is
`shelved. Shipping unbound documents may result in the loss of portions of the submission or an
`unnecessary delay in processing which could have an adverse impact on the review of the
`submission. For additional information, see
`http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Drug
`MasterFilesDMFs/ucm073080.htm.
`
`If you have questions, call me, at (301) 796- 4013
`
`Sincerely,
`
`LCDR Luz E Rivera, Psy.D.
` Regulatory Project Manager
` Division of New Drug Quality Assessment III
` Office of New Drug Quality Assessment
` Center for Drug Evaluation and Research
`
`Reference ID: 3433139
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LUZ E RIVERA
`01/08/2014
`
`Reference ID: 3433139
`
`