CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`208411Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`The below REV-SUMMARY-03 (Exclusivity Summary) contains an error. Refer to the corrected review
`signed on November 30, 2015.
`
`December 1, 2015
`
`Reference ID: 3848899
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 208411
`
`SUPPL #
`
`HFD #
`
`Trade Name Narcan Nasal Spray
`
`Generic Name Naloxone hydrochloride, 40 mg/mL
`
`Applicant Name Adapt Pharma Operations Limited
`
`
`
`Approval Date, If Known November 18, 2015
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes"
`to one or more of the following questions about the submission.
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
` YES
`
`NO
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(2)
`
`b) Did it require the review of clinical data other than to support a safety claim or change
`in labeling related to safety?
`(If it required review only of bioavailability or
`bioequivalence data, answer "no.")
`
` YES
`
`NO
`
`If your answer is "no" because you believe the study is a bioavailability study and,
`therefore, not eligible for exclusivity, EXPLAIN why it is a bioavailability study,
`including your reasons for disagreeing with any arguments made by the applicant that the
`study was not simply a bioavailability study.
`
`The study was a bioavailability study:
`The clinical/clinical pharmacology data for this NDA consists of one pivotal
`comparative bioavailability study (Naloxone-Ph1a-002) conducted in 29 healthy
`volunteers. In this study, the relative bioavailability from one spray in one nostril (4
`mg, 0.1 mL of 40 mg/mL) and one spray in each nostril (8 mg, 0.1 mL of 40 mg/mL
`in each nostril) was compared to the reference (NDA 16636, Narcan) 0.4 mg of
`naloxone intramuscular injection.
`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`
`Reference ID: 3848899
`
`Page 1
`
`

`

`
`
`supplement, describe the change or claim that is supported by the clinical data:
`
`N/A
`
`c) Did the applicant request exclusivity?
`
` YES
`
`NO
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`
`
`d) Has pediatric exclusivity been granted for this Active Moiety?
` YES
`
`NO
`
` If the answer to the above question in YES, is this approval a result of the studies submitted
`in response to the Pediatric Written Request?
`
`
`
`
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY
`TO THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`2. Is this drug product or indication a DESI upgrade?
`
`
` YES
`
`NO
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE
`BLOCKS ON PAGE 8 (even if a study was required for the upgrade).
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the
`same active moiety as the drug under consideration? Answer "yes" if the active moiety
`(including other esterified forms, salts, complexes, chelates or clathrates) has been previously
`approved, but this particular form of the active moiety, e.g., this particular ester or salt (including
`salts with hydrogen or coordination bonding) or other non-covalent derivative (such as a
`complex, chelate, or clathrate) has not been approved. Answer "no" if the compound requires
`metabolic conversion (other than deesterification of an esterified form of the drug) to produce an
`already approved active moiety.
`
`Reference ID: 3848899
`
`Page 2
`
`

`

`
`
`
`
` YES
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`
`NDA#
`
`16636
`
`NDA#
`
`
`
`NDA#
`
`
`
`2. Combination product.
`
`Narcan
`
`
`
`
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA
`previously approved an application under section 505 containing any one of the active moieties
`in the drug product? If, for example, the combination contains one never-before-approved active
`moiety and one previously approved active moiety, answer "yes." (An active moiety that is
`marketed under an OTC monograph, but that was never approved under an NDA, is considered
`not previously approved.)
`
`
`
`YES
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`NDA#
`NDA#
`NDA#
`
`
`
`
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO
`THE SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary
`should only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of
`new clinical investigations (other than bioavailability studies) essential to the approval of the
`application and conducted or sponsored by the applicant." This section should be completed
`only if the answer to PART II, Question 1 or 2 was "yes."
`
`Reference ID: 3848899
`
`Page 3
`
`

`

`1. Does the application contain reports of clinical investigations? (The Agency interprets
`"clinical investigations" to mean investigations conducted on humans other than bioavailability
`studies.) If the application contains clinical investigations only by virtue of a right of reference
`to clinical investigations in another application, answer "yes," then skip to question 3(a). If the
`answer to 3(a) is "yes" for any investigation referred to in another application, do not complete
`remainder of summary for that investigation.
`
`
`
`YES
`
`NO
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved
`the application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical
`trials, such as bioavailability data, would be sufficient to provide a basis for approval as an
`ANDA or 505(b)(2) application because of what is already known about a previously approved
`product), or 2) there are published reports of studies (other than those conducted or sponsored by
`the applicant) or other publicly available data that independently would have been sufficient to
`support approval of the application, without reference to the clinical investigation submitted in
`the application.
`
`(a) In light of previously approved applications, is a clinical investigation (either
`conducted by the applicant or available from some other source, including the published
`literature) necessary to support approval of the application or supplement?
` YES
`
`NO
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for
`approval AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`
`
`(b) Did the applicant submit a list of published studies relevant to the safety and
`effectiveness of this drug product and a statement that the publicly available data would
`not independently support approval of the application?
`
` YES
`
`NO
`
`
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to
`disagree with the applicant's conclusion? If not applicable, answer NO.
`
`
`
` YES
`
`NO
`
` If yes, explain:
`
`
`
`
`
`Reference ID: 3848899
`
`Page 4
`
`

`

`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted
`or sponsored by the applicant or other publicly available data that could
`independently demonstrate the safety and effectiveness of this drug product?
`
` YES
`
`NO
`
` If yes, explain:
`
`
`
`(c)
`
`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical
`investigations submitted in the application that are essential to the approval:
`
`
`
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The
`agency interprets "new clinical investigation" to mean an investigation that 1) has not been relied
`on by the agency to demonstrate the effectiveness of a previously approved drug for any
`indication and 2) does not duplicate the results of another investigation that was relied on by the
`agency to demonstrate the effectiveness of a previously approved drug product, i.e., does not
`redemonstrate something the agency considers to have been demonstrated in an already approved
`application.
`
`a) For each investigation identified as "essential to the approval," has the investigation
`been relied on by the agency to demonstrate the effectiveness of a previously approved
`drug product? (If the investigation was relied on only to support the safety of a
`previously approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`
`
`YES
`
`YES
`
`
`
`NO
`
`NO
`
`If you have answered "yes" for one or more investigations, identify each such
`investigation and the NDA in which each was relied upon:
`
`
`
`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support
`the effectiveness of a previously approved drug product?
`
`Reference ID: 3848899
`
`Page 5
`
`

`

`Investigation #1
`
`Investigation #2
`
`YES
`
`YES
`
`NO
`
`NO
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the
`application or supplement that is essential to the approval (i.e., the investigations listed in
`#2(c), less any that are not "new"):
`
`
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored
`by" the applicant if, before or during the conduct of the investigation, 1) the applicant was the
`sponsor of the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or
`its predecessor in interest) provided substantial support for the study. Ordinarily, substantial
`support will mean providing 50 percent or more of the cost of the study.
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`
`
`!!
`
`! NO
`! Explain:
`
`
`
`!!
`
`
`! NO
`! Explain:
`
`
`
`(b) For each investigation not carried out under an IND or for which the applicant was
`not identified as the sponsor, did the applicant certify that it or the applicant's predecessor
`in interest provided substantial support for the study?
`
`Reference ID: 3848899
`
`Page 6
`
`Investigation #1
`
`IND #
`
`YES
`
`
`
`Investigation #2
`
`IND #
`
`YES
`
`
`
`
`
`
`
`

`

`!!
`
`
`! NO
`! Explain:
`
`
`!!
`
`
`! NO
`! Explain:
`
`
`Investigation #1
`
`
`
`YES
`Explain:
`
`
`
`
`Investigation #2
`
`
`
`YES
`Explain:
`
`
`
`
`(c) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe
`that the applicant should not be credited with having "conducted or sponsored" the study?
`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to
`the drug are purchased (not just studies on the drug), the applicant may be considered to
`have sponsored or conducted the studies sponsored or conducted by its predecessor in
`interest.)
`
`YES
`
`NO
`
`If yes, explain:
`
`
`
`=================================================================
`Name of person completing form: Diana L. Walker, Ph.D.
`Title: Senior Regulatory Health Project Manager
`Date: November 13, 2015
`
`
`Name of Office/Division Director signing form: Sharon Hertz, M.D.
`Title: Director, Division of Anesthesia, Analgesia, and Addiction Products
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 3848899
`
`Page 7
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DIANA L WALKER
`11/18/2015
`
`SHARON H HERTZ
`11/18/2015
`
`Reference ID: 3848899
`
`

`

`ACTION PACKAGE CHECKLIST
`
`
`
`APPLICATION INFORMATION1
`NDA Supplement #
`If NDA, Efficacy Supplement Type:
`NDA # 208411
`(an action package is not required for SE8 or SE9 supplements)
`BLA Supplement #
`BLA #
`Proprietary Name: Narcan Nasal Spray
`Applicant: Adapt Pharma Operations Limited
`Established/Proper Name: naloxone hydrochloride
`Dosage Form: liquid spray, 4 mg
`RPM: Diana Walker
`
`NDA Application Type:
`Efficacy Supplement:
`
` 505(b)(1)
` 505(b)(1)
`
` 505(b)(2)
` 505(b)(2)
`
`BLA Application Type:
`Efficacy Supplement:
`
` 351(k)
` 351(k)
`
` 351(a)
` 351(a)
`
`Agent for Applicant (if applicable): Pacific-Link Consulting
`Division: DAAAP
`For ALL 505(b)(2) applications, two months prior to EVERY action:
`
` Review the information in the 505(b)(2) Assessment and submit
`the draft2 to CDER OND IO for clearance.
` Check Orange Book for newly listed patents and/or
`exclusivity (including pediatric exclusivity)
`
` No changes
` New patent/exclusivity (notify CDER OND IO)
`Date of check: 11/18/2015
`
`Note: If pediatric exclusivity has been granted or the pediatric
`information in the labeling of the listed drug changed, determine whether
`pediatric information needs to be added to or deleted from the labeling of
`this drug.
`
` Actions
`Proposed action
`
` User Fee Goal Date is January 20, 2016
`Previous actions (specify type and date for each action taken)
`
` If accelerated approval or approval based on efficacy studies in animals, were promotional
`materials received?
`Note: Promotional materials to be used within 120 days after approval must have been
`submitted (for exceptions, see
`http://www fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida
`nces/ucm069965.pdf). If not submitted, explain
` Application Characteristics 3
`
` TA CR
` AP
`November 18, 2015
` None
`
` Received
`
`1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 2) lists
`the documents to be included in the Action Package.
`2 For resubmissions, 505(b)(2) applications must be cleared before the action, but it is not necessary to resubmit the draft 505(b)(2)
`Assessment to CDER OND IO unless the Assessment has been substantively revised (e.g., new listed drug, patent certification
`revised).
`3 Answer all questions in all sections in relation to the pending application, i.e., if the pending application is an NDA or BLA
`supplement, then the questions should be answered in relation to that supplement, not in relation to the original NDA or BLA.
`Version: 8/13/15
`
`Reference ID: 3850556
`
`

`

`NDA 20841 1
`
`Page 2
`
`[XI Priority
`El Standard
`Review priority:
`Type 3, New Dosage Form
`Chemical classification (new NDAs only):
`(confirm chemical classification at time ofapproval)
`
`E Fast Track
`IXI Rolling Review
`El Orphan drug designation
`El Breakthrough Therapy designation
`(NOIE: Set the submission property in DARRTS and notify the CDER Breakthrough Therapy Program Manager;
`Refer to the “RPM B1' Checklistfor Considerations afier Designation Granted”for other require actions: CST SharePoint )
`
`E] Rx-to-OTC full switch
`E] Rx-to-OTC partial switch
`E] Direct-to-OTC
`
`NDAs: Subpart H
`[:I Accelerated approval (21 CFR 314.510)
`B Restricted distribution (21 CFR 3 14.520)
`Subpart I
`El Approval based on animal studies
`
`BLAs: Subpart E
`[:I Accelerated approval (21 CFR 601.41)
`|:] Restricted distribution (21 CFR 601.42)
`Subpart H
`D Approval based on animal studies
`
`D Submitted in response to a PMR
`I:| Submitted in response to a PMC
`D Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: D MedGuide
`I: Communication Plan
`|:] ETASU
`[j MedGuide w/o REMS
`D REMS not required
`
`03° BLAs only: Is the product subject to oflicial FDA lot release per 21 CFR 610.2
`(approvals only)
`
`I: Yes
`
`El No
`
`{0 Public communications (approvals only)
`
`0 Office of Executive Programs (OEP) liaison has been notified of action
`
`0
`
`Indicate what types (if any) of information were issued
`
`IX Yes El No
`[INoue'''''''''''''''''''''''''''''''''''''''''''
`X FDA Press Release
`I:] FDA Talk Paper
`IX] CDER Q&As
`IE Other Blog or CDER
`t rs -
`.
`tive
`
`
`
`
`
`‘3' Exclusivity
`
`0
`
`0
`
`Is approval of this application blocked by any type of exclusivity (orphan, 5-year
`NCE, 3-year, pediatric exclusivity)?
`Ifso,s'
`the p'
`
`[Z No
`
`D Yes
`
`6° Patent Information (NDAs only)
`
`0
`
`Patent Information:
`Verify that form FDA—3542a was submitted for patents that claim the drug for
`which approval is sought.
`
`[Z Verified
`El Not a
`licable because dru is
`pp
`g
`an old antibiotic.
`
`Documentation of consent/non—consent by officers/employees
`
`List of officers/employees who participated in the decision to approve this application and
`consented to be identified on this list (approvals only)
`
`Reference ID: 3850556
`
`

`

`NDA 208411
`
`Page 3
`
`.
`‘ .
`.
`‘
`_
`_
`,
`.
`.
`.s
`0 Copies of all action letters (Including app) ma] lettei Withfinal labeling)
`
`
`
`Action(s) and date(s)
`Approval: November 18, 201 5
`
`
`
`02° Package Insert (write submission/communication date at upper right offirstpage ofPI)
`
`""""""""""":"“"‘M;;;;};:;;{aafi‘i;i;;fi.2;WE;2;;;;;;;t;:a;;;;;i‘izz;i;;g';—;‘;i;;;;;‘ia'z;';;;""“"““" E] Included
`______________________________”acts/Iangwfomaf)
`0 Original applicant-proposed labeling
`
`D Included
`
`
`
`
`
`
`'3 Medication Guide/Patient Package Insert/Instructions for Use/Device labeling (write
`submission/communication date at upper right offirstpage ofeach piece)
`
`
`
`D Medication Guide
`IX Patient Package Insert
`IX Instructions for Use and Quick
`Start Guide
`CI Device Labeling
`
`____________________________________________________________________________________________________________________________________________________________________________________________________ El None
`0 Most-recent draft labeling (ifit is division—proposed labeling, it should be in
`IE Included
`track—changesformat)
`
`0 Original applicant-proposed labeling
`
`{0 Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper right offirstpage ofeach submission)
`
`0 Most-recent draft labeling
`
`
`
`03° Proprietary Name
`Acceptability/non-acceptability lette1(s) (indicate date(s))
`.
`_
`,
`Revrew(s) (Indicate date(s)
`
`0
`
`.
`Letter. 108/2015
`Revrew: 9/25/2015
`
`°:° Labeling reviews (indicate dates ofreviews)
`
`RPM: D None 9/10/2015
`DMEPA: D None
`1 0/1 3/201 5
`9/25/201 5
`9/3/20 1 5
`
`DMPP/PLT (DRISK):
`lj None 11/12/2015
`8/25/2015
`OPDP: D None 11/6/2015
`SEALD: E None
`CSS: E] None
`Product Quality |:] None See
`CMC review dated 1 1/18/2015
`
`Other: [:l None
`MHT: 10/26/20 1 5
`
`'3' RPM Filing Review‘lMemo of Filing Meeting (indicate date ofeach review
`'2' All NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`
`Filing Memo: 9/10/2015
`
`I: Not a (b)(2)
`B2 assessment: 11/18/2015
`
`
`
`6° NDAs only: Exclusivity Summary (signed by Division Director)
`
`[Z Included 11/18/2015
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`Reference ID: 3850556
`
`
`
`
`
`

`

`NDA 20841 1
`
`Page 4
`
`o
`0.0
`
`Application Integrity Policy (AIP) Status and Related Documents
`lmp‘flwww fda.gov/ICECI/EnforcementActions/ApplicationInteQ'gPolicy/defaulthtm
`
`
`
`This application is on the ATP
`
`0
`
`0
`
`Ifyes. Center Director‘s Exception for Review memo (indicate date)
`
`Ifyes. 0C clearance for approval (indicate date ofclearance
`communication)
`
`[:I Not an AP action
`
`Pediatrics (approvals only)
`Date reviewed by PeRC 1 1/4/2015
`IfPeRC review not necessary. explain:
`
`O
`0.0
`
`O
`0.0
`
`Breakthrough Therapy Designation
`
`IX] N/A
`
`Breakthrough Therapy Designation Letter(s) (granted. denied. an/or rescinded)
`
`CDER Medical Policy Council Breakthrough Therapy Designation
`Determination Review Tomplate(s) (include only the completed template(s) and
`not the meetin minutes)
`
`CDER Medical Policy Council Brief — Evaluating a Breakthrough Therapy
`Designation for Rescission Template(s) (include only the completed template(s)
`and not the meeting minutes)
`
`(completed CDER Ilfl’C templates can befound in DARRTS as clinical reviews or on
`the MPC SharePoint Site
`
`Outgoing communications: letters. emails. and faxes considered important to include in
`the action package by the reviewing office/division (e.g.. clinical SPA letters. RTF letter,
`Formal Dispute Resolution Request decisional letters. etc.) (do not include previous
`action letters, as these are located elsewhere in acka e)
`Internal documents: memoranda, telecons, emails, and other documents considered
`important to include in the action package by the reviewing oflice/division (e.g..
`Re-
`.to Briefin- minutes. Medical Poli Council meetin minutes
`
`included
`
`included
`
`Minutes of Meetings
`
`IX N/A or no mtg
`
`
`
`
`Mid-cycle Communication (indicate date ofmtg)
`
`Late-cycle Meeting (indicate date ofmtg)
`Other milestone meetings (e.g.. EOP2a. CMC focused milestone meetings)
`(indicate dates 0 mt s)
`Advisory Committee Meeting(s)
`
`6/18/2012
`
`IE No AC meeting
`
`Date(s) of Meeting(s)
`
`Oflice Director Decisional Memo (indicate datefor each review)
`
`IX] None
`
`PMR/PMC Development Templates (indicate total number)
`
`|:] None 4 templates. dated
`1 1/18/2015
`
`Reference ID: 3850556
`
`I] None
`
`11/18/2015
`
`G None
`
`11/18/2015
`
`

`

`NDA 20841 1
`
`Page 5
`
`4° Clinical Reviews
`
`
`
`0
`
`0
`
`0
`
`Clinical Team Leader Review(s) (indicate datefir each review)
`
`IX No separate review
`
`Clinical review(s) (indicate datefor each review)
`
`Filing: 9/3/2015
`
`Social scientist review(s) (if OTC drug) (indicate datefor each review)
`
`X None
`
`°.° Fmanc1al Disclosure rev1ews(s) (animation/date 1faddressed in another rev1ew
`Ifno financial disclosure information was required, check here E] and include a
`review/memo explaining why not (indicate date ofreview/memo)
`
`See CDTL memo
`
`4° Clinical reviews-from immunology and other clinical areas/divisions/Centers (indicate
`date ofeach review)
`
`D None Pediatrics: 11/10/2015
`
`4° Controlled Substance Staflreview(s) and Scheduling Recommendation (indicate date of
`each review)
`
`'2 N/A
`
`4° Risk Management
`0
`REMS Documents and REMS Supporting Document (indicate date(s) of
`submission(s))
`REMS Memo(s) and letter(s) (indicate date(s))
`Risk manage-ant review(s) and recommendations (including fliose by OSE and
`CSS) (indicate date ofeach review and indicate location/date ifincorporated
`into another review)
`
`N/A
`
`N/A
`
`[Z None
`
`4° 081 Clinical Inspection Review Summary(ies) (include copies of081 letters to
`im'estigators)
`
`‘3 None re
`
`ted
`
`4° Clinical Microbiology Team Leader Review(s) (indicate datefor each review)
`
`El No separate review
`
`Clinical Microbiology Review(s) (indicate datefor each review)
`
`I: None
`
`4° Statistical Division Director Review(s) (indicate datefor each review)
`
`Statistical Team Leader Review(s) (indicate datefor each review)
`
`Statistical Review(s) (indicate datefor each revien)
`
`I: No separate review
`
`I: No separate review
`
`El None
`
`4° Clinical Pharmacology Division Director Review(s) (indicate datefor each revieu)
`
`IX No separate review
`
`Clinical Pharmacology Team Leader Review(s) (indicate datefor each review)
`
`[X] No separate review
`
`Clinical Pharmacology review(s) (indicate datefor each review)
`
`4° 081 Clinical Pharmacology Inspection Review Summary (include copies of 081 letters)
`
`E] None
`Filing: 9,11/201 5
`Primary review: 10/22/2015
`Addendum review: 1 1/2/2015
`
`D None requested
`Mono: 9/17/2015
`Final: 10/30/2015
`
`
`
`Reference ID: 3850556
`
`

`

`NDA 20841 1
`
`Page 6
`
`'2' Pharmacology/1'oxicology Discipline Reviews
`
`0 ADP/T Review(s) (indicate datefor each review)
`
`Supervisory Review(s) (indicate datefor each review)
`
`0
`
`O
`
`Pharm/tox rev1ew(s), including referenced IND revrews (indicate datefor each
`review)
`
`IE No separate review
`
`IE No separate review
`I:]None""""""""""""""""""""""""""""""
`Filing: 8/26/201 5
`Final: 11/2/2015
`
`°3° Review(s) by other disciplines/divisions/Centers requested by P/T reviewer (indicate date
`_
`for each review?
`
`X None
`
`'2' Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`
`E No carc
`
`-
`.
`. ECAC/CAC report/memo ofmeeting
`°§° OSI Nonclinical Inspection Review Summary (include copies of031 letters)
`
`03° Product Quality Discipline Reviews
`
`IE None
`Included in PIT review, page
`IX None requested
`
`Integrated Quality Assessment (contains the Executive Summary and the primary E] None
`reviews from each product quality review discipline) (indicate datefor each
`Filing: 8/18/201 5
`review)
`Final: 1 l/18/2015
`E] None
`Fac1ht1es: 10/14/2015
`CDRH Devices: 1 1/5/2015
`
`°3° Reviews by other disciplines/divisions/Centers requested by product quality review team
`(indicate date ofeach review)
`
`03° Environmental Assessment (check one) (original and suppluntal applications)
`
`IXI Categorical Exclusion (indicate review date)(all original applications and
`all eflicacy supplements that could increase the patientpopulation)
`
`El Review & Environmental Impact Statement (indicate date ofeach review)
`
`'2' Facilities Review/Inspection
`
`X Facilities inspections (action must be taken prior to the re-evaluation date) (only
`original applications and eflicacy supplements that require a manufacturing
`facility inspection(e.g., new strength, manufacturingprocess, or manufacturing
`site change)
`
`IX Acceptable
`Re-evaluation date:
`
`I:] Withhold recommendation
`
`Tertiary review (indicate datefor each review)
`
`Secondary review (e.g., Branch Chief) (indicate datefor each review)
`
`X None
`
`IE None
`
`0
`
`0
`
`0
`
`
`
`
`
`
`
`Reference ID: 3850556
`
`

`

`NDA 208411
`Page 7
`
`Day of Approval Activities
`
` For all 505(b)(2) applications:
` Check Orange Book for newly listed patents and/or exclusivity (including
`pediatric exclusivity)
`
`Finalize 505(b)(2) assessment
`
` For Breakthrough Therapy (BT) Designated drugs:
` Notify the CDER BT Program Manager
` For products that need to be added to the flush list (generally opioids): Flush List
` Notify the Division of Online Communications, Office of Communications
` Send a courtesy copy of approval letter and all attachments to applicant by fax or secure
`email
` If an FDA communication will issue, notify Press Office of approval action after
`confirming that applicant received courtesy copy of approval letter
` Ensure that proprietary name, if any, and established name are listed in the
`Application Product Names section of DARRTS, and that the proprietary name is
`identified as the “preferred” name
`
` Ensure Pediatric Record is accurate
`
` Send approval email within one business day to CDER-APPROVALS
`
` No changes
` New patent/exclusivity (Notify
`CDER OND IO)
`
` Done
`
` Done – N/A
`(Send email to CDER OND IO)
` Done – N/A
`
` Done
`
` Done
`
` Done
`
` Done - N/A – no studies
`required
`
` Done
`
`Reference ID: 3850556
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DIANA L WALKER
`11/23/2015
`
`Reference ID: 3850556
`
`

`

`DEPARTMENT OF HEALTH & HUMAN SERVICES
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`
`DATE:
`
`11/16/2015
`
`TO:
`
`Bunavail (buprenorphine and naloxone) buccal film (new drug application (NDA)
`205637)
`Narcan (naloxone) nasal spray (NDA 208411)
`
`CDER Exclusivity Board
`
`
`FROM:
`
`THROUGH: Sharon Hertz, MD, Director, Division of Anesthesia, Analgesia, and Addiction
`Products (DAAAP)
`
`
`SUBJECT: Whether 3-Year Exclusivity for Bunavail (buprenorphine and naloxone) buccal
`film (NDA 205637) blocks the approval of Narcan (naloxone) nasal spray (NDA
`208411)
`________________________________________________________________________
`
`
`SUMMARY
`
`This memorandum addresses whether the unexpired 3-year exclusivity for NDA 205637 for
`Bunavail buccal film (Bunavail), a fixed-combination drug product that contains two active
`ingredients with the active moieties buprenorphine and naloxone, blocks the initial approval of
`the 505(b)(2) NDA for Narcan nasal spray (NS), a single-entity drug with only naloxone as its
`active moiety (NDA 208411).1
`
`The Exclusivity Board (Board) in the Center for Drug Evaluation and Research (CDER), in
`consultation with CDER’s Division of Anesthesia, Analgesia, and Addiction Products (DAAAP
`or Division) and other components of FDA, concludes that Bunavail’s 3-year exclusivity for the
`conditions of approval of NDA 205637 is tied to the combination of active moieties in Bunavail,
`and thus recommends that 3-year exclusivity for Bunavail should not block the approval of
`Narcan NS.2
`
`1 A drug containing a single active ingredient will be referred to as a single-entity drug and a drug containing two or
`more active ingredients in a single dosage form will be referred to as a fixed-combination in this memorandum.
`2 This memorandum only discusses whether the 3-year exclusivity for Bunavail should block the approval of the
`
`Reference ID: 3848749
`
`

`

`LEGAL BACKGROUND
`
`
`
`
`I.
`
`
`A. Drug Approval Pathways Under the FD&C Act
`
`
`Section 505 of the Federal Food, Drug & Cosmetic (FD&C) Act establishes approval pathways
`for three categories of drug applications: (1) 505(b)(1) NDAs, (2) 505(b)(2) NDAs, and (3)
`505(j) abbreviated new drug applications (ANDAs). Because Bunavail and Narcan NS are
`505(b)(2) NDAs, the remaining discussion will focus primarily on the 505(b)(2) pathway.
`
`
`1.
`
`505(b)(1) NDAs: Stand-Alone Approval Pathway
`
`Section 505(b)(1) of the FD&C Act requires that an application contain, among other things,
`“full reports of investigations” to show that the drug for which the applicant is seeking approval
`is safe and effective.3 NDAs that are supported entirely by investigations either conducted by the
`applicant or to which the applicant has a right of reference are referred to as 505(b)(1) NDAs or
`stand-alone NDAs.
`
`FDA will approve a 505(b)(1) NDA if it finds that the information and data provided by the
`applicant demonstrate that the drug product is safe and effective for the conditions prescribed,
`recommended, or suggested in the proposed labeling.4 One basis for FDA not approving a
`505(b)(1) NDA is that there is a lack of substantial evidence that the drug product is effective
`under the conditions of use prescribed, recommended, or suggested in the proposed labeling.5
`
`
`2.
`
`505(b)(2) NDAs and ANDAs: Abbreviated Pathways
`
`
`The Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman
`Amendments)6 amended the FD&C Act to add section 505(b)(2) and 505(j) as well as other
`conforming amendments. These provisions describe abbreviated pathways for 505(b)(2) NDAs
`and ANDAs, respectively.7 The Hatch-Waxman Amendments reflect Congress’s efforts to
`