CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`21—782
`
`ADMINISTRATIVE and CORRESPONDENCE
`
`DOCUMENTS
`
`
`
`

`

`
`
`1.3.5.1 Patent Information
`
`j ‘ (ramelteon) tablets for the
`Reference is made to the subject NDA 21-782 for l:
`treatment of insomnia and the requirements of 505 (b)( l) of the Federal Food, Drug and
`Cosmetic Act as amended and 21 CFR 314.501(c)(2).
`
`Section 505(b)(1) of the Federal Food, Drug and Cosmetic Act requires that "The
`applicant shall file with the (new drug) application the patent number and the expiration
`date of any patent which claims the drug for which the applicant submitted the
`application or which claims a method of using such drug and with respect to which a
`claim of patent infringement could reasonably be asserted if a person not licensed by the
`OWner engaged in the manufacture, use or sale of the drug"
`
`The following patents were issued for TAK-375. The drug product name for this
`chemical entity is C
`’1.
`
`iii,
`ii),
`21 CFR314.53 c (i),
`US Patent
`Expiration Date
`No.
`
`6,034,239
`
`
`
`
`March 7, 2017
`
`
`Type of
`Patent Owner
`Patent
`
`
`Takeda
`
`Pharmaceutical
`substance,
`
`
`Compound
`Company, Ltd.
`
`
`
`
`
`US Representative
`
`
`
`Takeda Global
`Research and
`
`
`Development
`
`Center, Inc.
`
`
`ors This WOY
`.
`
`9
`
`
`
`

`

`1.3.5.2 Patent Certification
`
`j ‘ (ramelteon) tablets for the
`Reference is made to the subject NDA 21-782 for [-
`treatment of insomnia and the requirements of 505 (b)( l) of the Federal Food, Drug and
`Cosmetic Act as amended and 21 CFR 314.501(c)(2).
`
`Declaration under 21 CFR 314.53tc1g21
`
`The applicant declares that Patent No, 6,034,239 covers the drug substance, compound.
`
`This product is the subject of this application for which approval is sought.
`
`As provided for under the Patent Term Restoration Act, Takeda Global Research &
`Development Center, Inc. will be requesting patent term restoration upon receipt of
`approval of C
`3 ‘ (ramelteon).
`
`Appears This wall
`On Original
`
`

`

`
`
`1.3.5.1 Patent Information
`
`J ' (ramelteon) tablets for the
`Reference is made to the subject NDA 21-782 for C
`treatment of insomnia and the requirements of 505 (b)( 1) of the Federal Food, Drug and
`Cosmetic Act as amended and 21 CFR 314.501(c)(2).
`
`Section 505(b)(1) of the Federal Food, Drug and Cosmetic Act requires that ”The
`applicant shall file with the (new drug) application the patent number and the expiration
`date of any patent which claims the drug for which the applicant submitted the
`application or which claims a method of using such drug and with respect to which a
`claim of patent infringement could reasonably be asserted if a person not licensed by the
`owner engaged in the manufacture, use or sale of the drug"
`
`The following patents were issued for TAK-375. The drug product name for this
`chemical entity is L
`j,
`
`No.
`
`-
`
`
`US Representative
`
`Center, Inc.
`
`6,034,239
`
`March 7, 2017
`
`substance,
`Compound
`
`Takeda
`Pharmaceutical
`Company, Ltd.
`
`Takeda Global
`Research and
`Development
`
`
`
`Appears This Way
`On Original
`
`
`
`

`

`1.3.5.2 Patent Certification
`
`J (ramelteon) tablets for the
`Reference is made to the subject NDA 21-782 for L
`treatment of insomnia and the requirements of 505 (b)(1) of the Federal Food,'Drug and
`Cosmetic Act as amended and 2] CFR 314.501(c)(2).
`
`Declaration under 21 CFR 314.53lcu21
`
`The applicant declares that Patent No, 6,034,239 covers the drug substance, compound.
`
`This product is the subject of this application for which approval is sought.
`
`AS provided for under the Patent Term Restoration Act, Takeda Global Research &
`Development Center. Inc. will be requesting patent term restoration upon receipt of
`approval of t
`3 (ramelteon).
`
`Appears This Way
`On Original
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 21-782
`
`SUPPL # ---
`
`HFD # 170
`
`Trade Name: Rozerem Tablets 8 mg
`
`Generic Name:
`
`ramelteon
`
`Applicant Name: Takeda Global Research & Development Center, Inc
`
`Approval Date, If KnOWn:
`
`July 22, 2005
`
`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 II I of this Exclusivity Summary only ifyou answer "yes" to
`one or more of the following questions about the submission.
`
`2:) Is it a 505(b)(l), 505(b)(2) or efficacy supplement?
`
`YES [XI
`
`NO El
`
`Ifyes, what type? Specify 505(b)(1), 505(b)(2), SEi, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(1)
`
`c) Did it require the review ofcl inical 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 IX]
`
`ND C]
`
`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.
`
`n/a
`
`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:
`
`nfa
`
`Page 1
`
`
`
`

`

`d) Did the applicant request exclusivity?
`
`YES E1
`
`NO [I
`
`If the answer to (d) is ”yes," how many years of exclusivity did the applicant request?
`
`Requested Market Exclusivity determination. Did not specify a timeframe.
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`YES [I
`
`NO [2]
`
`i Y
`t'
`v
`th a
`w
`th
`response to the Pediatric Written Request?
`
`is this approval a result of the studies submitted in
`
`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 [I
`
`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).
`
`PART II
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`
`(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 ciathrates) has been previously approved, but this
`particular form ofthe 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.
`
`YESD
`
`NOE
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
`#(s).
`
`Page 2
`
`

`

`NDA#
`
`NDA#
`
`NDA#
`
`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 as: w 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.)
`
`[:1
`
`YES
`
`D
`
`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 ofnew
`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). Ifthe answer to 3(a)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`
`Page 3
`
`

`

`
`
`summary for that investigation.
`
`YES
`
`1:]
`
`NO [:1
`
`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 ofwhat 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 [I
`
`NO E]
`
`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:
`
`to the safety and
`(b) Did the applicant submit a list of published studies reievant
`effectiveness ofthis drug product and a statement that the publicly available data would not
`independently support approval of the application?
`'
`
`YES {:1
`
`NO [3
`
`(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.
`
`YESEI
`
`NOE]
`
`If yes, explain:
`
`(2) If the answer to 2(b) is "no," are you aware ofpublished 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 [I
`
`NO [:1
`
`If yes, explain:
`
`Page 4
`
`

`

`
`
`(c)
`
`identify the clinical
`if the answers to (b)(l) and (b)(2) were both "no,"
`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 beingessential, 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 ofa 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 I:I
`
`N0 El
`
`YES I:
`
`NO E]
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NBA 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?
`
`Investigation #1
`
`Investigation #2
`
`YES [:1
`
`N0 El
`
`YES E]
`
`NO CI
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`
`Page 5
`
`

`

`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 approvai 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 [ND named in the form FDA 157I 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(0): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`il
`
`! NO [I
`! Explain:
`
`Investigation #1
`
`IND#
`
`YES 1:}
`
`Investigation #2
`
`!
`
`IND#
`
`YES 13
`
`! NO I:
`
`(b) For each investigation not carried out under an [ND 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?
`
`Investigation #1
`
`!
`
`YESE]
`
`INOD
`
`Page 6
`
`

`

`Explain:
`
`1 Explain:
`
`i!
`
`! NO [1
`! Explain:
`
`Investigation #2
`
`YES 1:}
`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 (notjust studies on the drug), the applicant may be considered to have
`sponsored or couducted the studies sponsored or conducted by its predecessor in interest.)
`
`YES 1:]
`
`NO I]
`
`Ifyes, explain:
`
`Name of person completing form: Sara Stradley
`Title: Regulatory Project Manager
`Date: July 18, 2005
`Concurred:
`Parinda Jani 7-18-05
`
`Bob Rappaport 7-20-05
`Copy sent to Lee Ripper 7-18-05
`
`Name of Office/Division Director signing form: Robert J. Meyer
`Title: Office Director, ODEII
`
`Form OGD-Oi 1347; Revised 05/ 10/2004; formatted 2/15/05
`
`Page 7
`
`

`

`-----n------------------—--———---u-q-qu.nn..¢nnnu-—u_____-_--—---------___------—uq--.-----n--_-—-——---—-—--—
`
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`Odo-C..-.0-.--u.u-u-..—-ut-d-n--------------------------.------—--------—-n------q-In90-h-----------—----—------
`
`/5/
`
`Robert Meyer
`7/22/05 03:29:59 PM
`
`

`

`(Complete for all filed original applications and efficacy supplements)
`
`PEDIATRIC PAGE
`
`NDA/BLA it:
`
`21-782
`
`Supplement Type {e.g. SE5):
`
`N
`
`Supplement Number:
`
`000
`
`Stamp Date:
`
`22 Sept 2004
`
`Action Date:
`
`22 July 2005
`
`llFD 170
`
`Trade and generic names/dosage form: ROZEREM tramelteonl Tablets 8mg
`
`Applicant: Takeda Global Research & Development Center
`lndication(s) previously approved: None
`
`Therapeutic Class: 2020400
`
`Each approved indication must have pediatric studies: Completed, Deferred, andtor Waived.
`
`Number of indications for this application(s):
`
`I
`
`indication #1:
`
`treatment ofinsomnia
`
`Is there a full waiver for this indication (check one)?
`
`D Yes: Please proceed to Section A.
`
`Partial Waiver
`X No: Please check all that apply:
`NOTE: More than one may apply
`Please proceed to Section B, Section C, and/or Section D and complete as necessary.
`
`X Deferred
`
`Completed
`
`Section A: Fully Waived Studies
`
`Reasonts) for full waiver:
`
`Products in this class for this indication have been studiedflabeled for pediatric population
`Diseasefcondition does not exist in children
`
`UUDDU
`
`Too few children with disease to study
`There are safety concerns
`Other:
`
`Ifstudies arefully waived, then pediatric information is completefor this indication. if there is another indication, please see
`Attachment A. Otherwise, this Pediatric Page is complete and should be entered into DFS.
`
`Section B: Partially Waived Studies
`
`Agelweight range being partially waived:
`
`Min
`Max
`
`kg
`kg
`
`mo.
`mo.
`
`yr.
`yr.
`
`Tanner Stage
`Tanner Stage
`
`Reason(s) for partial waiver:
`
`Cl Products in this class for this indication have been studiedtlabeled for pediatric population
`Cl Disease/condition does not exist in children
`
`Cl Too few children with disease to study
`Cl There are safety concerns
`Cl
`Adult studies ready for approval
`Formulation needed
`Cl
`Other:
`Cl
`
`

`

`I
`
`1
`
`NDA 21-782
`
`Page 2
`
`If studies are deferred, proceed to Section C Ifstudies are completed, proceed to Section D. Otherwise, this Pediatric Page is complete
`and should be entered into DFSI
`
`Section C: Deferred Studies
`
`Ageiweight range being deferred: ALL
`
`yr.
`0
`
`mo.
`
`mo.
`
`Tanner Stage
`Tanner Stage
`
`16
`
`yr.
`
`Min
`Max
`
`kg
`kg
`
`
`
`Reason(s) for deferral:
`
`D Products in this class for this indication have been studied/labeled for pediatric population
`1:] Disease/condition does not exist in children
`El Too few children with disease to study
`X There are safety concerns with the use of this drug with known endocrine effects. More data needs to be accumulated in
`the adult population before its use in children.
`CI Adult studies ready for apprOVal
`D Formulation needed
`Other:
`
`.._._______..._.__.___—_-_——-—
`
`Date studies are due (mm/ddtyy}:
`
`Jul); 22, 2012
`
`Ustiidies are completed proceed to Section D. Otherwise, this Pediatric Page is complete and should be entered into DFS.
`
`| Section D: Completed Studies
`
`Age/weight range of completed studies:
`
`Min
`Max
`
`Comments:
`
`kg
`kg
`
`mo.
`mo.
`
`yr.
`yr.
`
`Tanner Stage
`Tanner Stage
`
`Ifthere are additional indications, please proceed to Attachment A. Otherwise, this Pediatric Page is complete and should be entered
`into DFS.
`
`This page was completed by:
`
`{See appended electronic signature page}
`
`
`Regulatory Project Manager
`
`CC:
`
`NDA 21-782
`HFD-960i Grace Carmouze
`
`FOR QUESTIONS ON COMPLETING THIS FORM CONTACT THE DIVISION OF PEDIATRIC DRUG
`DEVELOPMENT, HFD-960, 301-594-7337.
`
`(revised 12-22-03)
`
`
`
`

`

`.----_----_-_-au-------——-----.a---—--—----non-u-—--------n--------.-._---_-_-uan...--------——---—---—----—---——---
`
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---_-—nu-——_----_-_--uu__-—-___----_———-----—----—-----___-_--——————--_----_--______-__-_-----———--------—-—_——-—____
`
`Sara Stradley
`7/21/05 08:54:46 AM
`
`
`
`
`
`

`

`Certification Statement
`
`as requested by the
`Generic Drug Enforcement Act of 1992
`
`This certification statement is provided for New Drug Application (NDA) 21-782. drug
`code TAK-375 and is provided in compliance with the Generic Drug Enforcement Act
`of 1992.
`
`3 hereby certifies that we did not and will not use
`C-
`in any capacity the services of any person debarred under subsection (a) or (b) of section
`306 of the Federal Food, Drug and Cosmetic Act, (21 U.S.C. 335a (a) and (b)), were not
`used in any capacity in connection with this application.
`_
`[flu/{At*
`
`t
`
`a?
`
`(9
`
`I
`
`' E
`
`Céélfiifie/ 2d”
`
`

`

`
`
`
`
`Certification Statement
`
`as requested by the
`Generic Drug Enforcement Act of 1992
`
`This certification statement is provided for New Drug Application (NDA) 21-782, drug
`code TAR-375 and is provided in compliance with the Generic Drug Enforcement Act
`of 1992. Takeda Global Research & Development Center, Inc. hereby certifies that the
`applicant did not and will not use in any capacity the services of any person debarred
`under subsection (a) or (b) of section 306 of the Federal Food, Drug and Cosmetic Act,
`(21 U.S.C. 3353 (a) and (b)), were not used in any capacity in connection with this
`application.
`
`
`
`. Sainati, M.D., PhD.
`Vice President, Clinical Research
`CNS, MPDRAP IIIb
`
`Takeda Global Research & Development
`
`
`
`TAKEDA GLOBAL RESEARCH 8: DEVELOPMENT CENTER, INC.
`475 Half Day Road
`Lincolnshire, Illinois 60069
`Phone: 84?-383-3000
`
`

`

`
`
`Certification Statement
`
`' as requested by the
`Generic Drug Enforcement Act of 1992
`
`This certification statement is provided for New Drug Application (NBA) 21-782, drug
`code TAK-37S and is provided in compliance with the Generic Drug Enforcement Act
`of 1992.
`
`J . hereby certifies that we did not and will not use in
`L
`any capacity the services of any person debarred under subsection (a) or (b) of section
`306 of the Federal Food, Drug and Cosmetic Act, (21 U.S.C. 335a (a) and (b)), were not
`used in any capacity in connection with this application.
`
`;._,,,[§/____ W
`1.
`Date
`L
`
`

`

`
`
`NBA/EFFICACY SUPPLEMENT ACTION PACKAGE CHECKLIST
`
`
` 3 MCétion.Information
`
`
`
`_7
`,,
`Supplement Number
`El‘ticagLStipplement Epc- SE— fl
`NDA 21-75?
`Drug: Rozerem (ramelteon)
`_
`_
`7 Applieant: Talfeda Global Research & Developm_ent Center
`
`REM: Sara Stradle‘v
`HFD-l 70 _
`L
`LPhone # 30l-827-7430
`
`
`
`_
`
`_
`
`Application Type: (x ) 505(b)(l) ()505(b)(2)
`(This can be determined b) consulting page I ofthe NDA
`Regulatory Filing Review for this application or Appendix
`A to this Action Package Checklist.)
`
`lfthis is a 505(b)(2) application, please review and
`confirm the information previously provided in
`appendix 8 to the-NBA Regulatory Flllng Revuew.
`ease update any Information (Including patent
`certification information) that is no longer correct.
`
`( ) Confirmed and/'or corrected
`
`Listed drug(sl referred to in 505(b)(2) application (NDA #(s). Drug
`name(s)):
`
`[0m 6 '¢ THU “chm pQquaC
`Lou Randal-mt be (“aw ”Hw-
`Or|6\nd packet? ”.344
`m misplaced I
`0'. my“
`_
`made l+ ‘17 W («DR
`
`'1' Application Classi tieations:
`0
`Review priority
`_
`_
`(x )fitandard 0 Priority ,
`,
`7
`Chem class (NDAS only)
`is
`0
`Other (erg, orphan, OTC)
`
`
`'2' USer Fee Goal Dates
`July 22, 2005
`
`Special programs (indicate all that apply)
`(x ) None
`Subpart H
`
`( ) 2| CFR 314.5l0 (accelerated
`approval}
`
`( ) 2| CFR 314.520
`
`(restricted distribution)
`( ) Fast Track
`( ) Rolling Review
`() CMA Pilot |
`( CMA Pilot 2
`
`'2' User Fee Information
`
`
`
`
`
`
`
`
`(x) Paid UF ID number
`
`
`mfléi.
`_. ,
`-
`User Fee waiver
`
`
`( ) Small business
`
`() Public health
`
`( ) Barrier-to-lnnovation
`
`
`( ) Other (specify)
`
`
` ( ) Orphan designation
`
`()No-l‘ee 505(b)(2) (see NDA
`
`Regulatory Filing Review for
`instructions)
`( ) Other (specify)
`
`
`
`=1, APplisatien{attestitrtolisrWP)...
`_
`,
`,
`.
`.
`,,
`..
`r
`
`()Yes
`0 ApplicantisontheAlP
`(x)No
`Verston 6! “5/2004
`
`0
`
`User Fee
`
`
`
`'
`
`User Fee exception
`
`
`
`
`
`
`
`

`

`
`
`NDA 2l—782
`
`Page 2
`
`-
`-
`
`9
`
`This application is on the AIP
`Exception for review (Center Director‘s memo)
`
`0C clearance for approval
`
`7
`
`_
`(it ) No
`
`(
`
`) Yes
`
`
`
`
`{ x) Verified
`'i' Debarment certification: verified that qualifying language (cg, willingly. l-(nouinglyi \\ as
`not used in certification 8; certifications from forei n a ulicants are cosianed bv US agent.
`
`
`
`
`
`
`information: Verify that form FDA-3542a was submitted for patents that claim
`
`
`the drug for which approval is sought.
`
`2: cradmsonnrimiai
`Patent certification [505(bll2) applications}: Verify that a certification was
`
`
`( ) Verified
`submitted for each patent for the listed drugts} in the Orange Book and identify
`
`
`the type ol'certification submitted for each patent.
`
`
`21(‘1—‘R 3I4_50(i)(1}
`
`
`(Hii)
`(lifii)
`
`
`[505(b){2) applications] lithe application includes a paragraph [I] certification, 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 read} for
`
`
`a roval).
`
` ( ) NJ'A (no paragraph lV certification}
`0
`[505(bli2) applications] For each paragraph IV certification, verify that the
`( ) Verified
`applicant notified the NDA holder and patent owneris] ofits certification that the
`
`patentts) is invalid, unenforceable, or will not be infringed (review
`documentation of notification by applicant and documentation of receipt of
`notice by patent owner and NDA holder). (Hike application does not include
`any paragraph il 'certifications. mark ”N .4 " and skip to the next box below
`
`-
`
`0
`
`I
`
`(it } Verified
`
`
`
`(’Exclusit'ityjl
`
`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.
`
`Ans“ er the following questions for each paragraph lV certification:
`
`(I) Have 45 days passed since the patent owner‘s receipt ofthe applicant‘s
`notice of certification?
`
`(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 (cg, copy of return receipt or letter from recipient
`acknowledging its receipt of the notice) (see 2i CFR 3I4.52(e))).
`
`if “Yes, " skip to question (4) below.
`
`if "No. " continue our}: question (2).
`
`{2) Has the patent owner (or NDA holder. ifit is an exclusive patent licensee)
`submitted a written waiver ofits right to file a legal action for patent
`infringement after receiving the applicant's notice of certification, as
`provided for by 21 CFR 3l4.107(fl(3)?
`
`if ” Yes, " there is no stay ofapproval based on this certification. Analyze the next
`paragraph I V certification in the application, if any. 0" there are no other
`paragraph ll ' certifications. skip to the next box below (Exciusiviggl.
`
`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?
`
`Versron 6116/2004
`
`

`

`
`
`NDA 2l-782
`
`Page 3
`
`I
`
`(Note: This can be determined by confirming uhettier the l)i\ision has
`received a written notice from the applicant (or the patent owner or its
`representative} stating that a legal action was filed within 45 days of
`receipt ofits notice ofcertilicationt The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45—da}
`period (see 2| ("FR 3 l4. |O7ifii2ili
`
`if "No, ” the patent U‘It‘flt’l’ (or .\'lJ.-l holder. iftt is an exclusive patent licensee)
`has until the expiration of the 45-day period described in question ii) to waive its
`right to lirtng a patent inji‘ingenrent action or to bring such an action trifler the
`45-day period expires, continue with question (4) belon-
`
`(4) Did the patent owner (or NDA holder, ifit 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 (I). as
`provided for by 2| CFR 314. l07ifit3l‘?
`
`U " YES. " there is no stay ofapproval based on this certification ,lnaly:e the next
`paragraph ll/certyication in the application, if any. U'there are no other
`paragraph li'certyicotions. skip to the next box below (Erclitsii‘io').
`
`H "No. " continue with question (5)
`
`(5) Did the patent owner. its representatixe, or the exclusive patent licensee
`bring suit against the applicant for patent infringement within 45 days of
`the patent owner’s receipt ofthe applicant’s notice of certification?
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice From the applicant (or the patent owner or its
`representative) stating that a legal action was filed within 43 days of
`receipt of its notice ofcertification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period {see 2i CFR 3l4.107(i)(2)).
`lino 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 ofapprovai based on this certification .imtly:e the
`next paragraph l V certyication in the application. ifany if there are no other
`
`
`paragraph li'certiflcations. skip to the next box below (lirclnsivity
`
`
`If " Yes, " a stay of approval may be in eflect, To determine {fa 3 0—month stay
`is in eflect. consult with the Director, Division of Regulatory Policy ll, Oflice
`
`
`of Regulatory Policy (HMO—007) and attach a summary of the response,
`
`
`
`'2' Exciusivity {approvals only}
`
`
`
`
`
`
`
`
`‘
`
`
`
`-
`.
`
`Exclusivity summary
`Is there remaining 3-year exclusivity that would bar effeeth e approval ofa
`
`505(b}(2) application? (Note that, even if exclusivity remains‘ the application
`
`ma ' be tentativel ' a nroved it‘it is otherwise read ' for an roval.)
`
`I
`
`
`Administrative Reviews (Project Manager, ADRA) (indicate date ofeach review)
`
` 5 year exclusivity
`
`
`
`
`Is there existing orphan drug exclusivity protection for the "same drug" for the
`
`() Yes, Application ll
`proposed indication(s)? Refer to 21 CFR 3 l6,3(b)(13)for the definition of “same
`(X )No
`drug"for an orphan drug (i_e.. active moiety) This definition is NOT the same
`
`
`as that used or NDA chemical classi tcation.
`
`
`7/21l0:->(ADRA)
`
`Version 6/! 6/2004
`
`
`
`
`
`

`

`
`
`NDA 2l—782
`Pa-c 4
`
`'2' Actions
`
`-
`I
`
`-
`
`-
`
`{-
`
`Proposed action
`Previous actions (specify type and date for each action takeni
`
`Status of advertising (approvals only)
`
`
`
`
`
`
`
`(x ) Materialsreduested in AP
`letter
`
`
`
`Press Office notified ofaction (approval only)
`
`()Not applicable
`
`General Information
`
`
`
`
`U" } AP UTA ()AE UNA
`[10116
`
`
`
`
`( ) Reviewed for Subpart H
`Public communications
`
` ( it) Yes
`
`
`
`( x) None
`
`
`( ) Press Release
`
`
`( ) Talk Paper
`
`
`( ) Dear Health Care Professional
`
`
`Letter
`
`
`no
`' Labeling [package insert. patient package insert {ifapplieable}, .VledGuide (ifapplicablefl
`
`I ' Division's proposed labeling (only if generated after latest applicant submission
`
`oflabeling)”
`
`
`
`
`
`0 Other relevant labeling (e.g., most recent 3 in class, class labeling)
`
`'2' Labels (immediate container & carton labels)
`
`
`
`
`Post-marketing commitments
`
`
`
`
`
`
`
`
`
`X
`l/l7/2003 and l l/8/200l
`____ ___k,a,,,
`
`
`x 12/1512003 and 6/22/2004
`
`
`
`7/11/2005
`Pre-Approval Safety Conference (indicate date; approvals only)
`
`Other
`
`~1~ Advisory Committee Meeting
`
`-
`
`Indicate what types (ifany) of information dissemination are anticipated
`
`- Most recent applicant-proposed labeling
`
`-
`I
`
`Original applicant-proposed labeling
`Labeling reviews (including DDMAC, DMETS, DSRCS) and minutes of
`labeling meetings (indicate dates ofrew'ews and meetings)
`
`Division proposed (only if generated after latest applicant submission)
`I
`- Applicant proposed
`0
`Reviews
`
`'2'
`
`-
`
`-
`
`Agency request for post-marketing commitments
`
`Documentation of discussions andi’or agreements relating to post-marketing
`commitments
`
`'1' Outgoing correspondence (i.e., letters. E-mails. faxes)
`vi. Memoranda and Telecons
`
`'3' Minutes of Meetings
`
`EOP2 meeting. (indicate date)
`Pre-NDA meeting (indicate date}
`
`0
`0
`
`I
`0
`
`__
`
`
`Date of Meeting
`-
`
`
`48-hour alert
`I
`
`
`
`
`Federal Register Notices. DES] documents, NAB/NRC reports (if applicable)
`
`
`
`Version MIG/2004
`
`

`

`
`
`NDA 21—782
`
`Page 5
`
`4-
`
`Clinical Information '-
`
`K s
`
`Demographic Worksheet (NM/i approvals only)
`
`Slimmer}! Application Retiiéw
`
`
`
`722.05 (Office)
`
`
`Summary Reviews tog” Office Director. Division Director. Medical Team Leader)
`7/l8'05 (Director)
`(indicate ciaicfor each review}
`
`
`7/22/01 6030/05 (M0 TL)
`
`
`
`
` '2' Clinical revie\v(s) {indicate da/efor each review)
`7 '22 05, 629/05
`
`“a Microbiology (efficacy) review(s) {indicate dare/or each review n/a
`
`
`
`
`see Clinical review
`
`
`'3'
`Safety Update review(s) (indicate date or location if incorporated in another review)
`
`See CSS review
`'1- Risk Management Plan reviewls) (indicate date location if incorporated in another rev)
`
`
`
`'
`n
`'1' Pediatric Page(separate page for each indication addressing status of all age groups)
`
`
`ee clinical review
`
`6/22/05
`
`Statistical revie\v(s) (indicate darefor each review)
`
`
`
` Biopharmaceutical revie\v(s) (indicate date for each review)
`693 0/05, 6/2 l/OS
`
`6/l 3/05 or each review)
`
`
` Clinical Inspection Review Summary (08!)
`Clinical studies
`
`Bioequivalencestudies
`
`
`
`
`C MC review(s) (indicate darefor each review)
`
`
`
`
`See CMC review
`
`
`
`