CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`204063Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`

`

`ACTION PACKAGE CHECKLIST
`
`APPLICATION INFORMATION1
`
`NDA # 204063
`BLA #
`
`NDA Supplement #
`BLA Supplement #
`
`Proprietary Name: Tecfidera
`Established/Proper Name: dimethyl fumarate
`Dosage Form:
`delayed-release capsules
`
`
`
`
`
`_
`IfNDA, Efficacy Supplement Type.
`
`Applicant: Biogen Idec
`Agent for Applicant (if applicable):
`
`
`
`RPM: Nicole L. Bradley
`
`Division: Division of Neurology Products
`
`
`
`
`ND s and NDA Efficac S
`
`l
`
`ents:
`
`5051b)!” Original NDAs and 505(b)(2) NDA supplements:
`
`
`
`
`
`
`NDA Application Type: 8 _505(b)(l) C] 505(b)(2) Listed drug(s) relied upon for approval (include NDA #(s) and drug
`Efficacy Supplement:
`[:3 505(b)(1) C] 505(b)(2)
`name(s)):
` (A supplement can be either a (b)(1) or a (b)(2)
`
` Provide a brief explanation of how this product is different from the listed
`
`
`drug.
`
`
`
` E], This application does not reply upon a listed drug.
`
`This application relies on literature.
`
`
`[:1 This application relies on a final OTC monograph.
`
`E] This application relies on (explain)
`
`
`rior to EVERY action,
`lications two months
`For ALL
`2 a
`revi w th i ormat'on in the 50
`2 Ass s me tand s bmi
`the
`
`
`
`
`
`
`(1;ng th2(ER 0N2 IO f9: clegrggge. Finalize the 505(b)(2)
`
`
`Assessment at the time of the approval action.
`
`
`
`
`On the. day.of approyal, check the Orange Book again for any new
`patents or pediatric exclusivity.
`
`
`
`regardless of whether the original NDA was a (b)(1)
`or a (b)(2). Consult page 1 of the 505(b)(2)
`Assessment or the Appendix to this Action Package
`Checklist.)
`
`
`
`D No changes E] Updated Date of check:
`
` 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.
`
`
`
` Proposed action
`
`
`0 User Fee Goal Date is March 27 2013
`
`
`
`
`~
`Previous actions (specifi/ type and datefor each action taken)
`
`1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 5) lists
`the documents to be included in the Action Package.
`«' For resubmissions, (b)(2) applications must be cleared before the action, but it is not necessary to resubmit the drafi 505(b)(2)
`Assessment to CDER 0ND 10 unless the Assessment has been substantively revised (e. g., nrew listed drug, patent certification
`revised).
`
`Version: 1/27/12
`
`

`

`
`
`
`
`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
`hgprl/www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatogInfounation/Guida
`nce_cm0699
`odf). If not submitted, exlain
`
`'3' Application Characteristics 3
`
`
`
`I] Priority
`Standard
`Review priority:
`
`Chemical classification (new NDAs only):
`
`
`
`
`
`CI Received
`
`
`
`
`
`
`
`I: Fast Track
`Rolling Review
`Orphan drug designation
`
`I] Rx-to-OTC full switch
`D Rx—to-OTC partial switch
`E] Direct-to-OTC
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`REMS not required
`
`
` Comments:
`
`
`
`.;.
`’ BLAs only: Ensure RMS—VBLA' Productvln‘fonnatiion Sheetfor' TBP and RMS—BLA Facility
`
`
`
`Information Sheetfor TBP have been Completed and forwarded to OPI/OBI/DRM (Vicky D Yes, dates
`Carter)
`,V
`..
`p,
`_.
`__
`i
`._
`.-
`,
`
`
`BLAs only: Is the product subject to official FDA lot release per 21 CFR 610.2
`(approvals only)
`
`NDAs: Subpart H
`D Accelerated approval (21 CFR 314.510)
`[:1 Restricted distribution (21 CFR 314.520)
`Subpart I
`E] Approval based on animal studies
`
`BLAs: Subpart E
`[:1 Accelerated approval (21 CFR 601 ,41)
`Ij Restricted distribution (21 CFR 601.42)
`Subpart H
`[3 Approval based on animal studies
`
`D Submitted in response to a PMR
`[:1 Submitted in response to a PMC
`[:1 Submitted in response to a Pediatric Written Request
`
`REMS:
`
`A MedGuide
`DE] Communication Plan
`EDD
`
`ETASU
`MedGuide w/o REMS
`
`
`
`
`
`
`
`Office of Executive Programs (OEP) liaison has been notified of action
`
`Press Office notified of action (by OEP)
`
`
`
`
` 0 Indicate what types (if any) of information dissemination are anticipated
`I FDA Talk Paper
`Elf CDER Q&As
`
`Other
`
`
`
`
`I ‘None
`33 HHS Press Release
`
`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. For
`example, if the application is a pending BLA supplement, then a new RMS—BLA Product Information Sheetfor TBP must be
`completed.
`
`Version: 1/27/ 12
`
`

`

`NDA/BLA #
`
`Page 3
`
`'3' Exclusivity
`
`0
`
`Is approval of this application blocked by any type of exclusivity?
`
`0 NDAs and BLAs: Is there existing orphan drug exclusivity for the “same”
`drug or biologic for the proposed indication(s)? Refer to 21 CFR
`31 6.3(b)(13) for the definition of “same drug"for an orphan drug (i. e.,
`active moiety). This definition is NOT the same as that usedfor NDA
`chemical classification.
`
`0
`
`0
`
`0
`
`(b)(2) NDAs only: Is there remaining 5-year exclusivity that would bar
`effective approval of a 505(b)(2) application)? (Note that, even ifexclusivity
`remains, the application may be tentatively approved ifit is otherwise ready
`for approval.)
`
`(b)(2) NDAs only: Is there remaining 3-year exclusivity that would bar
`effective approval of a 505(b)(2) application? (Note that, even ifexclusivity
`remains, the application may be tentatively approved ifit is otherwise ready
`for approval.)
`
`(b)(2) NDAs only: Is there remaining 6-month pediatric exclusivity that
`would bar effective approval of a 505(b)(2) application? (Note that, even if
`exclusivity remains, the application may be tentatively approved ifit is
`otherwise readyfor approval.)
`
`0 NDAs only: Is this a single enantiomer that falls under the 10—year approval
`limitation of 505(u)? (Note that, even ifthe 10-year approval limitation
`period has not expired, the application may be tentatively approved ifit is
`otherwise readyfor approval.)
`
`'3 ' Patent Information (NDAs only)
`
`0
`
`Patent Information:
`
`0
`
`0
`
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`which approval is sought.
`If the drug is an old antibiotic, skip the Patent
`Certification questions.
`
`Patent Certification [505(b)(2) applications]:
`Verify that a certification was submitted for each patent for the listed drug(s) in
`the Orange Book and identify the type of certification submitted for each patent.
`
`it cannot be approved until the date that the patent to which the certification
`pertains expires (but may be tentatively approved if it is otherwise ready for
`approval).
`
`[505(b)(2) applications] For each paragraph IV certification, verify that the
`applicant notified the NDA holder and patent owner(s) of its certification that the
`patent(s) is invalid, unenforceable, or will not be infiinged (review
`documentation ofnotification by applicant and documentation of receipt of
`notice by patent owner and NDA holder). (Ifthe application does not include
`any paragraph IV certifications, mark “N/A ” and skip to the next section below
`(Summary Reviews)).
`
`X No
`
`I] Yes
`
`I] Yes
`8 ,No
`If, yes, NDA/BLA #
`date exclusivity expires:
`
`and
`
`[:1 No
`If yes, NDA #
`exclusivity expires:
`
`I] Yes
`and date
`
`[:1 No
`If yes, NDA #
`exclusivity expires:
`
`C] Yes
`and date
`
`D No
`If yes, NDA #
`exclusivity expires:
`
`I] Yes
`and date
`
`No
`If yes, NDA #
`
`I] Yes
`and date 10-
`
`year limitation expires:
`El Verified
`
`IHVerified
`E] Not applicable because drug is
`an old antibiotic.
`
`21 CFR 314.50(i)(1)(i)(A)
`E] Verified
`
`21 CFR 314.50(i)(1)
`
`E! (ii) I (iii)
`
`D No paragraph III certification
`Date patent will expire
`
`D} N/A (no paragraph IV certification)
`
`‘ Version: ‘1'/27/12
`
`

`

`NDA/BLA #
`
`Page 4
`
`0
`
`[505(b)(2) applications] For each paragraph IV certification, based on the
`questions below, determine whether a 30-month stay of approval is in effect due
`to patent infringement litigation.
`
`Answer the following questions for each paragraph IV certification:
`
`(1) Have 45 days passed since the patent owner’s receipt of the applicant’s
`notice of certification?
`
`E] .Yes
`
`D No
`
`(Note: The date that the patent owner received the applicant’s notice of
`certification can be determined by checking the application. The applicant
`is required to amend its 505(b)(2) application to include documentation of
`this date (e. g., copy of return receipt or letter from recipient
`acknowledging its receipt of the notice) (see 21 CFR 314.52(e))).
`
`If “Yes, ” skip to question (4) below. If “No, ” continue with question (2).
`
`(2) Has the patent owner (or NDA holder, if it is an exclusive patent licensee) D Yes
`submitted a written waiver of its right to file a legal action for patent
`infi‘ingement after receiving the applicant’s notice of certification, as
`provided for by 21 CFR 314.107(f)(3)‘?
`
`I] No
`
`If “Yes, ” there is no stay ofapproval based on this certification. Analyze the next
`paragraph IVcertification in the application, ifany. Ifthere are no other
`paragraph IV certifications, skip the rest ofthe patent questions.
`
`If “No, ” continue with question (3).
`
`(3) Has the patent owner, its representative, or the exclusive patent licensee
`filed a lawsuit for patent infringement against the applicant?
`
`D Yes
`
`[:1 No
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice from the (b)(2) applicant (or the patent owner or
`its representative) stating that a legal action was filed within 45 days of
`receipt of its notice of certification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period (see 21 CFR 314.107(f)(2))).
`
`If “No, " the patent owner (or NDA holder, ifit is an exclusive patent licensee)
`has until the expiration ofthe 45-day period described in question (I) to waive
`its right to bring a patent infringement action or to bring such an action. After
`the 45-day period expires, continue with question (4) below.
`
`(4) Did the patent owner (or NDA holder, if it is an exclusive patent licensee)
`submit a written waiver of its right to file a legal action for patent
`infringement within the 45-day period described in question (1), as
`provided for by 21 CFR 314.107(f)(3)?
`
`[:I Yes
`
`[:1 NO
`
`If “Yes, ” there is no stay ofapproval based on this certification. Analyze the next
`paragraph IV certification in the application, ifany. Ifthere are no other
`paragraph IV certifications, skip to the next section below (Summary Reviews).
`
`If “No, ” continue with question (5).
`
`Version: 1/27/12
`
`

`

`(5) Did the patent owner, its representative, or the exclusive patent licensee
`bring suit against the (b)(2) applicant for patent infiingement within 45
`days of the patent owner’s receipt of the applicant’s notice of
`certification?
`
`D Yes
`
`D No
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice from the (b)(2) applicant (or the patent owner or
`its representative) stating that a legal action was filed within 45 days of
`receipt of its notice of certification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period (see 21 CFR 314.107(f)(2)). If no written notice appears in the
`NDA file, confirm with the applicant whether a lawsuit was commenced
`within the 45-day period).
`
`If "No, ”there is no stay ofapproval based on this certification. Analyze the
`next paragraph IV certification in the application, ifany. Ifthere are no other
`paragraph IV certifications, skip to the next section below (Summary
`Reviews).
`
`If “Yes, ” a stay ofapproval may be in effect. To determine ifa 30-month stay
`is in eflect, consult with the 0ND ADRA and attach a summary ofthe
`response.
`
`‘3‘ Copy of this Action Package Checklist4
`
`V
`
`CONTENTS OF ACTION PACKAGE
`
`Officer/Employee List
`
`
`» List ofofficers/employees who participated in'the decision to approve this application and X Included
`
`consented to be identified on this list (approvals only)
`'
`
`
`
`Copies of all action letters (including approval letter with final labeling)
`
`Documentation of consent/non—consent by officers/employees
`
`
`
`
`Included
`
`Action Letters
`
`Labeling
`
`‘ Package Insert (write submission/communication date at upper right offirst page ofPI)
`
`
`
`
`
`
`
`02/27/20
`N/A
`
`
`Example of class labeling, if applicable
`
`Original applicant-proposed labeling
`
`4 Fill in blanks with dates ofreviews, letters, etc.
`
`Version: 1/27/12
`
`

`

`NDA/BLA #
`
`Page 6
`
`
`
`D Medication Guide
`
`Patient Package Insert
`
`
`
`' Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`[:1 Instructions for Use
`
`submission/communication date at upper right offirst page ofeach piece)
`
`
`E] Device Labeling
`
`[:1 None
`
`
`
`o Most-recent drafi labeling. If it is division-proposed labeling, it should be in
`
`track—changes format.
`
`
`Original applicant-proposed labeling
`
`
`Example of class labeling, if applicable
`
` " Labels (full color carton and immediate-container labels) (write
`
`submission/communication date on upper right offirst page ofeach submission)
`
`
`
`Most-recent draft labeling
`
`Proprietary Name
`
`Acceptability/non—acceptability letter(s) (indicate date(s))
`0
`
`0
`Review(s) (indicate date(s)
`
`
`0
`Ensure that both the proprietary name(s), ifany, and the generic name(s) are
`
`
`listed in the Application Product Names section ofDARR TS, and that the
`
`I r01rieta /trade name is checked as the ‘re erred’ name.
`
`
`
`
`
`
`
`DMPP/PLT(DRISK)
`
`
`Labeling reviews (indicate dates ofreviews and meetings)
`I4 ODPD (DDMAC)
`’ SEALD
`[:1 css
`
`'Other reviews
`
`
`Administrative Reviews (e.g., RPM Filing Review /Memo ofFiling Meeting) (indicate
`date ofeach review)
`
`All NDA (b)(2) Actions: Date each action cleared by (b)(2) Clearance Cmte
`
`
`NDAs only. Exclusivity Summary (signed byDivision Director)
`2‘ Application Integrity Policy (AIP) Status and Related Documents
`http://www. fda. gov/ICECI/EnforcementActions/ApplicationIntegggPolicy/defaulthtm
`
`DMEPA
`
`[21 Not a (b)(2)
`V
`81Included
`
`9 v
`
`
`
`
`
`
`
`Applicant is on the AIP
`[:1 Yes E No
`
`
`
`
`0
`This applicationis on the AIP
`D Yes X No
`
`
`
`
` o
`If yes, Center Director’s Exception for Review memo (indicate date)
`
`
`
`
`
`
`Pediatrics (approvals only)
`
`
`0 Date reviewed by PeRC November 28 2012
`
`
`
`If PeRC review not necessary, explain:
`
`
`
`Pediatric Page/Record (approvals only, must be reviewed by PERC before
`0‘
`, Included
`
`
`
`
`
`
`i Debarment certification (original applications only): verified that qualifying language was
` [X : Ven'fied, statement is
`not used in certification and that certifications from foreign applicants are cosigned by
`
`
`
`acceptable
`
`
`US. agent (include certification)
`
`o
`
`If yes, OC clearance for approval (indicate date ofclearance
`.
`.
`communication)
`
`E] Not an AP action
`
`5 Filing reviews for scientific disciplines should be filed behind the respective discipline tab.
`
`Version: 1/27/12
`
`

`

`NDA/BLA #
`
`Page 7
`
`‘t‘ Outgoing communications (letters, including response to FDRR (do not include previous '
`action letters in this tab , emails, axes, telecons
`
`Regulatory Briefing (indicate date ofmtg)
`
`E ”No mtg
`
`0
`
`0
`
`Pre—NDA/BLA meeting (indicate date ofmtg)
`
`EOP2 meeting (indicate date ofmtg)
`
`[:1 No mtg
`
`1/25/2012
`
`D No mtg
`
`08/30/2006
`
`
`
`1 Minutes of Meetings
`
`
`
`
`If not the first review cycle, any end-of—review meeting (indicate date ofmtg)
`8 N/A or no mtg
`
`
`
`
`
`0
`
`
`
`
`
`CMC — 07/21/2011
`Other milestone meetings (e.g., EOP2_a, CMC pilots) (indicate dates ofmtgs)
`
`No AC meeting
`V
`'
`l
`i
`V
`
`
`
`Office Director Decisional Memo (indicate datefor each review)
`
`[3 None
`
`3/27/2013
`
`Division Director Summary Review (indicate datefor each review)
`
`I: None
`
`3/27/2013
`
`Cross-Discipline Team Leader Review (indicate datefor each review)
`
`D 'None
`
`3/25/2013
`
`PMR/PMC Development Templates (indicate total number)
`
`E] None
`
`‘3‘ Clinical Reviews
`
`Clinical Information6
`
`6
`0 1 Social scientist review(s) (if OTCdrug) (indicatedatefor each review)
`
`0
`0
`
`Clinical Team Leader Review(s) (indicate datefor each review)
`Clinical review(s) (indicate datefor each review)
`
`Safety TL — 02/07/2013
`Efficacyglegggglgn
`
`Financial Disclosure reviews(s) or location/date if addressedIn another review
`OR
`If no financial disclosure information was required, check here [:I and include a
`review/memoexplaining why notv(tindicavte date ofreview/memo)
`
`Addressed in Primary Clinical
`Efficacy Review
`
`
`
`-. 3:23;:2‘23351-3311 immunology and other clinical areas/divisions/Centers (indicate
`Pediatrics, DPV
`Controlled Substance Staffreview(s) and Scheduling Recommendation (indicate date of D Not a
`licable
`12/20/2012
`
`reach'review) ,
`,
`,
`..
`.
`,
`..
`,
`.
`V
`_
`.
`_
`1
`V
`.
`pp
`.,
`1
`
`Risk Management
`0
`REMS Documents and Supporting Statement (indicate date(s) ofsubmissi0n(s))
`0
`REMS Memo(s) and letter(s) (indicate date(s))
`
`
`E] ' None
`0
`Risk management review(s) and recommendations (including those by OSE and
`
`
`
`02/06/2013
`
`
`CSS) (indicate date ofeach review and indicate location/date if incorporated
`
`into another review)
`
`OSI Clinical Inspection Review summary(ies) (inclade copies ofOS] letters to
`
`
`investigators)
`
`
`QT/IRT, Maternal Health,
`
`,
`
`[:1 None requested
`
`11/16/2012
`
`6 Filing reviews should be filed with the discipline reviews.
`
`Version: 1/27/12
`
`

`

`NDA/BLA #
`
`Page 8
`
`IE None
`Clinical Microbiology
`f: Clinical Microbiology Team Leader Review(s) (indicate datefor each review)
`Clinical Microbiology Review(s) (indicate datefor each review)
`
`'3" Statistical Division Director Review(s) (indicate datefor each review)
`
`Statistical Team Leader Review(s) (indicate datefor each review)
`
`Statistical Review(s) (indicate datefor each review)
`
`Nonclinical
`
`E] None
`
`ADP/T Rev1ew(s) (indicate datefor each review)
`Supervisory Review(s) (indicate datefor each review)
`
`Pharm/tox review(s), including referenced IND reviews (indicate datefor each
`
`0..
`. ' Review(s) by other disciplines/divisions/Centers requested by'P/Treviewer (indicate date
`for each review)»
`
`°§° OSI Nonclinical InspectionReview Summary (include copies ofOS] letters)
`Product Quality
`El None
`
`E] None
`
`09/21/2012
`
`
`
`Ij None
`
`03/20/2013
`
`C] None
`
`01/28/2013
`
`10/24/2012
`
`02/21/2013
`10/01/2012
`i ' None
`Included in P/T review, pa_e
`
`K None requested
`
`
`
`
`
`ONDQA/OBP Division Director Review(s) (indicate datefor each review)
`
`[:1 None
`
`02/13/2013
`
`Branch Chief/Team Leader Review(s) (indicate datefor each review)
`
`Product quallty rev1ew(s) mcluding ONDQA biopharmaceutics reviews (indicate
`.
`datefor each rev1ew)
`
`1 1/19/2012
`
`O a
`
`! Microbiology Reviews
`D NDAs: Microbiology reviews (sterility & pyrogenicity) (OPS/NDMS) (indicate
`date ofeach review)
`[J ’ BLAs: Sterility assurance, microbiology, facilities reviews
`(OMPQ/MAPCB/BMT) (indicate date ofeach review)
`9
`0.01 Reviews by other d1sc1plmes/d1v1510ns/Centers requested by CMC/quality reviewer
`.findieatedateofeachrenew)
`,
`a,
`_
`.
`
`1.
`
`1 Not needed
`
`D .1 None
`BiopharmweutEr11/19/2012.,
`
`Version: 1/27/ 12
`
`

`

`NDA/BLA #
`
`Page 9
`
`CMC primary review —
`1 1/1 9/20 1 2
`
` NDAs: Methods Validation (check box only, do not include documents)
`
`E NDAs: Facilities inspections (include EER printout) (date completed must be
`within 2 years ofaction date) (only original NDAs and supplements that include
`a newfacility or a change that afi’ects the manufacturing sites7)
`
`Date completed: 03/20/2013 '
`f, Acceptable
`E] Withhold recommendation
`
`[:1 BLAs: TB-EER (date ofmost recent TB—EER must be within 30 days ofaction
`date) (original andsupplementalBLAs)
`
`Date completed:
`B \Alifi‘tzlfhbelzlfecommendation
`
`Completed
`E] Requested
`E] Not yet requested
`E] Not needed (per review)
`
`/ Le, a new facility or a change in the facility, or a change in the manufacturing process in a way that impacts the Quality
`Management Systems of the facility.
`
`Version: 1/27/12
`
`

`

`NDA/BLA #
`
`Page 10
`
`Appendix to Action Package Checklist
`
`An NDA or NDA supplemental application is likely to be a 505(b)(2) application if:
`(1) It relies on published literature to meet any of the approval requirements, and the applicant does not have a written
`right of reference to the underlying data.
`If published literature is cited in the NDA but is not necessary for
`approval, the inclusion of such literature will not, in itself, make the application a 505(b)(2) application.
`(2) Or it relies for approval on the Agency's previous findings of safety and efficacy for a listed drug product and the
`applicant does not own or have right to reference the data supporting that approval.
`(3) Or it relies on what is "generally known" or "scientifically accepted" about a class of products to support the
`safety or effectiveness of the particular drug for which the applicant is seeking approval. (Note, however, that this
`does not mean any reference to general information or knowledge (e.g., about disease etiology, support for
`particular endpoints, methods of analysis) causes the application to be a 505(b)(2) application.)
`
`Types of products for which 505(b)(2) applications are likely to be submitted include: fixed-dose combination drug
`products (e.g., heart drug and diuretic (hydrochlorothiazide) combinations); OTC monograph deviations(see 21 CFR
`330.11); new dosage forms; new indications; and, new salts.
`
`An efficacy supplement can be either a (b)(l) or a (b)(2) regardless of whether the original NDA was a (b)(l) or a (b)(2).
`
`An efficacy supplement is a 505(b)(l) supplement if the supplement contains all of the information needed to support the
`approval of the change proposed in the supplement. For example, if the supplemental application is for a new indication,
`the supplement is a 505(b)(l) if:
`(1) The applicant has conducted its own studies to support the new indication (or otherwise owns or has right of
`reference to the data/studies).
`(2) And no additional information beyond what is included in the supplement or was embodied in the finding of
`safety and effectiveness for the original application or previously approved supplements is needed to support the
`change. For example, this would likely be the case with respect to safety considerations if the dose(s) was/were
`the same as (or lower than) the original application.
`(3) And all other “criteria” are met (e.g., the applicant owns or has right of reference to the data relied upon for
`approval of the supplement, the application does not rely for approval on published literature based on data to
`which the applicant does not have a right of reference).
`
`An efficacy supplement is a 505(b)(2) supplement if:
`(1) Approval of the change proposed in the supplemental application would require data beyond that needed to
`support our previous finding of safety and efficacy in the approval of the original application (or earlier
`supplement), and the applicant has not conducted all of its own studies for approval of the change, or obtained a
`right to reference studies it does not own. For example, if the change were for a new indication AND a higher
`dose, we would likely require clinical efficacy data and preclinical safety data to approve the higher dose. If the
`applicant provided the effectiveness data, but had to rely on a different listed drug, or a new aspect of a previously
`cited listed drug, to support the safety of the new dose, the supplement would be a 505(b)(2).
`(2) Or the applicant relies for approval of the supplement on published literature that is based on data that the
`applicant does not own or have a right to reference. If published literature is cited in the supplement but is not
`necessary for approval, the inclusion of such literature will not, in itself, make the supplement a 505(b)(2)
`supplement.
`(3) Or the applicant is relying upon any data they do not own or to which they do not have right of reference.
`
`If you have questions about whether an application is a 505(b)(l) or 505(b)(2) application, consult with your ODE’s
`ADRA.
`
`Version: 1/27/12
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`

`

`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
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` YES
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`NO
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`NDA # 204063
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`EXCLUSIVITY SUMMARY
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`SUPPL #
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`HFD # 120
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`Trade Name Tecfidera
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`Generic Name dimethyl fumarate
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`Applicant Name Biogen Idec
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`Approval Date, If Known March 27, 2013
`
`PART I
`
`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.
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`IS AN EXCLUSIVITY DETERMINATION NEEDED?
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`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`
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`505(b)(1)
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`c) 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.")
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` YES
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`NO
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`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.
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`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
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`Reference ID: 3283104
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`Page 1
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`d) Did the applicant request exclusivity?
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` YES
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`NO
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`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
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`e) Has pediatric exclusivity been granted for this Active Moiety?
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` YES
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`NO
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` 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?
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`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
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`2. Is this drug product or indication a DESI upgrade?
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` YES
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`NO
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`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
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` YES
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`NO
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`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).
`
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`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.
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`Reference ID: 3283104
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`Page 2
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`NDA#
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`NDA#
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`NDA#
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`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
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`NDA#
`NDA#
`NDA#
`
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`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.
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`PART III
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`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."
`
`
`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)
`
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`2. Combination product.
`
`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.)
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`YES
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`NO
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`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
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`Reference ID: 3283104
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`Page 3
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`is "yes" for any investigation referred to in another application, do not complete remainder of
`summary for that investigation.
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`YES
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`NO
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`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
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`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
`
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`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:
`
`
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`NO
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`(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
`
`
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`NO
`
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`(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.
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` YES
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`NO
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` If yes, explain:
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`(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?
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` YES
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`NO
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`Reference ID: 3283104
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`Page 4
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` If yes, explain:
`
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`(c)
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`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:
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`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
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`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 be