CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`
`NDA 022410/S-011
`
`
`SUBOXONE
`
`Trade Name:
`
`Generic Name:
`
`Sponsor:
`
`Approval Date:
`
`Indications:
`
`
`
`Buprenorphine Hydrochloride; Naloxone
`Hydrochloride
`Reckitt Benckiser Pharmaceuticals, Inc.
`
`08/08/2013
`
`SUBOXONE sublingual film is indicated for maintenance
`treatment of opioid dependence and should be used as
`part of a complete treatment plan to include counseling and
`psychosocial support.
`
`
`
`
`
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`NDA 022410/S-011
`
`CONTENTS
`
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`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)
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Other Review(s)
`Administrative/Correspondence Document(s)
`
`
`
`X
`
`
`
`
`
`
`
`X
`
`
`
`
`
`
`
`
`X
`
`

`

`CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`NDA 022410/S-011
`NDA 022410/S-011
`
`APPLICA TION NUMBER:
`
`APPROVAL LETTER
`
`APPROVAL LETTER
`
`
`
`
`
`

`

`
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`
`
`
`NDAs 18401/ S-019, 20732/S-009, 20733/ S-011 & 22410/ S-011bundle
` APPROVAL LETTER
`
`Reckitt Benckiser Pharmaceuticals, Inc.
`Attention: Vanita Dimri, RAC, ASQ-CQA
`Regulatory Affairs-RegEx NA
`10710 Midlothian Turnpike, Suite 430
`Richmond VA 23235
`
`Dear Ms. Dimri:
`
`Please refer to your Supplemental New Drug Application (sNDA), submitted under section
`505(b) of the Federal Food, Drug, and Cosmetic Act for the following:
`
`
`
`
`NDA
`18401
`
`20732
`
`20733
`
`22410
`
`S-009
`
`S-011
`
`Supplement Drug Product
`S-019
`Buprenex®
`(buprenorphine HCI) Injection
`Subutex®
`(buprenorphine HCI)
`Sublingual Tablet
`Suboxone®
`(buprenorphine HCI/
`naloxone HCI) Sublingual
`Tablet
`Suboxone®
`(buprenorphine HCI/
`naloxone HCI) Sublingual film
`
`S-011
`
`Received
`Dated
`March 15, 2013 March 18, 2013
`
`March 15, 2013 March 18, 2013
`
`March 15, 2013 March 18, 2013
`
`March 15, 2013 March 15, 2013
`
`
`These “Changes Being Effected” supplements provide to register post approval drug substance
`changes made to the manufacture of drug substance Buprenorphine HCl, in DMF 12412.
`
`We have completed our review of these supplemental new drug applications. These supplements
`are 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.
`
`
`Reference ID: 3354373
`
`

`

`NDAs 18401/ S-019, 20732/S-009, 20733/ S-011 & 22410/ S-011bundle
`Page 2
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Ramesh Raghavachari, Ph.D.
` Acting 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: 3354373
`
`

`

`---------------------------------------------------------------------------------------------------------
`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
`08/08/2013
`
`Reference ID: 3354373
`
`

`

`CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`NDA 022410/S-011
`NDA 022410/S-011
`
`APPLICA TION NUMBER:
`
`CHEMISTRY REVIEW(S)
`CHEMISTRY REVIEW! S}
`
`
`
`
`
`
`

`

`Chemistry Review:# 1
`
`1. Division:
`ONDQA-DAAAP
`
`2. NDA Number: (a) 20-733 S011,
`(b) 20-732 S009, (c) 18-401 S019
`(d) 22-410 S011
`4. Supplement(s): CBE-0
` Number: Refer to NDA number
` Date(s): 02/25/2013
` PDUFA Date: 09/18/2013
`6. Nonproprietary name:
`Buprenorphine HCl
`
`3. Name and Address of Applicant:
`RECKITT BENCKISER
`10710 Midlothian Turnpike
`Richmond VA 23235
`5. Name of Drug:
`(a) Suboxone® (buprenorphine HCl/Naloxone HCl),
`sublingual tablets
`(b) Subutex® (buprenorphine HCl), sublingual tablets,
`(c) Buprenex® injection (buprenorphine HCl)
`(d) Suboxone® (buprenorphine HCl/Naloxone HCl)
`Sublingual Film
`7. Supplement Provides for: incorporation of CMC changes made to
`manufacture of drug substance Buprenorphine HCl, in DMF 12412.
`9. Pharmacological Category:
`10. How
`Dispensed:
`mu-opioid receptor partial agonist and a kappa-opioid
` Rx
`receptor antagonist
`12. Dosage Form: Refer to Name of Drug
`13. Potency: 2 mg and 8 mg
`14. Chemical Name and Structure:
`Buprenorphine HCl: 6 (2S)-2-[17-Cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6-methoxy-6α,14-ethano-
`14α-morphinan-7α-yl]-3,3dimethylbutan-2-ol hydrochloride; CAS: [53152-21-9]; C29H41NO4·HCl;
`MW = 504.10
`
`8. Amendment(s):
`
`11. Related Documents:
`DMF12412
`
`
`Nalonxone HCl: 17-Allyl-4, 5 α -epoxy-3, 14-dihydroxymorphinan-6-one hydrochloride dihydrate;
`CAS: [357-08-4]; C19H21NO4 • HCl • 2H2O; MW = 399.87
`
`(cid:131)
`
`
`
`
`
`15. Comments:
`Incorporation of CMC changes made to drug substance, buprenorphine HCl in DMF 12412 to
`NDA
`(cid:131) LOA provided 3/10/2013
`16. Conclusion: This supplement is recommended for approval from CMC perspective
`17. Name: Signature: Date:
`Erika E. Englund, Ph.D., Chemist
`18. Concurrence: Signature: Date:
`Ramesh Raghavachari, Ph.D., Acting Branch Chief, Br., IX, ONDQA
`
`5 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ERIKA E ENGLUND
`08/07/2013
`
`RAMESH RAGHAVACHARI
`08/07/2013
`
`Reference ID: 3353834
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`NDA 022410/S-011
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`
`
`
`
`

`

`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`
`
`NDAs 18401/ S-019, 20732/S-009, 20733/ S-011 & 22410/ S-011 bundle
`
`
`GENERAL CORRESPONDENCE
`
`
`Reckitt Benckiser Pharmaceuticals, Inc.
`Attention: Vanity Dimri, RAC, ASQ, CQA
`Regulatory Affairs
`10710 Midlothian Turnpike
`Richmond VA 23235
`
`Dear Ms. Dimri:
`
`Please refer to your supplemental new drug applications submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act for the following:
`
`
`
`
`The March 22, 2013 Acknowledgement letter did not include sNDA 22410/ S-011, dated and
`received March 15, 2013. These “Changes Being Effected” supplements propose to register post
`approval drug substance changes.
`
`Unless we notify you within 60 days of the receipt date that the applications are not sufficiently
`complete to permit a substantive review, we will file the applications on the new date of May 15,
`2013 not May 27, 2013, in accordance with 21 CFR 314.101(a). If the applications are filed, the
`user fee goal date will be September 15, 2013 not September 18, 2013 as was indicated on the
`March 22, 2013 acknowledgement letter.
`
`Reference ID: 3286388
`
`NDA
`18401
`
`20732
`
`20733
`
`22410
`
`Supplement Drug Product
`S-019
`Buprenex Injectable
`(buprenorphine HCI)
`Subutex Sublingual Tablet
`(buprenorphine HCI)
`Suboxone Sublingual Tablet
`(buprenorphine HCI/
`naloxone HCI dihydrate)
`Suboxone Sublingual film
`(buprenorphine HCI/
`naloxone HCI dihydrate
`
`S-009
`
`S-011
`
`S-011
`
`Received
`Dated
`March 15, 2013 March 18, 2013
`
`March 15, 2013 March 18, 2013
`
`March 15, 2013 March 18, 2013
`
`March 15, 2013 March 15, 2013
`
`

`

`NDA 18401/ S-019, 20732/S-009, 20733/ S-011 & 22410/ S-011 bundle
`Page 2
`
`
`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.
`Acting 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: 3286388
`
`

`

`---------------------------------------------------------------------------------------------------------
`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
`04/02/2013
`
`Reference ID: 3286388
`
`