, CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICA TION NUMBER:
`
`2 1 -8 9 7
`
`ADMINISTRATIVE and CORRESPONDENCE
`
`DOCUMENTS
`
`

`

`Alkermes, Inc.
`Vivitrex® (naltrexone long-acting inflection)
`
`CTD Module 1
`
`1.0 MODULE 1: ADMINISTRATIVE INFORMATION AND PRESCRIBING
`
`INFORMATION
`
`1.3.5.2 PATENT CERTIFICATION WITH RESPECT TO ANY PATENT WHICH
`
`CLAIMS THE DRUG
`
`Paragraph ll Certification
`
`Alkermes, Inc. is filing the NDA for Vivitrex® (naltrexone long-acting injection) under
`section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C 355
`
`(b)(2)], becausethe NDA relies in part for approval upon investigations that were not
`conducted by or for Alkermes and for which Alkermes has not obtained a right of
`reference or use from the person by or for whom the investigations were conducted.
`
`Specifically, the NDA for Vivitrex references and relies in part on the NDA for ReVia
`
`(naltrexone hydrochloride) (NDA 18—932).
`
`Alkermes hereby certifies that, in our opinion and to the~best~of~our knowledge,
`
`(a) the only patent that claims the drug that is the subject of NDA 18—932 for ReVia --
`
`and on which investigations that are relied upon by Alkermes for approval of the
`
`NDA for Vivitrex were conducted or that claims an approved use for such drug and
`
`for which information is required to be filed under section 505(b) and (c) of the
`
`’
`
`*fl—‘HIH
`
`Federal Food, Drug, and Cosmetic Act and 21 C.F.R. § 314.53 -- is United States
`Patent No. 3,332,950 (the “’950 Patent"), and (b) the ‘950 has'expired.
`
`We note that the NDA for ReViapreviously listed in the Orange Book United States
`
`Patent No. 3,957,982 (the “’982 Patent") with an expiration date of May 18, 1993.
`
`However, Alkermes believes this listing was incorrect, because the ‘982 Patent is
`
`directed to a “method for contraception by the application of combination-type
`
`sequential preparations” and does not claim naltrexone or a use of naltrexone that is
`
`or was the subject of NDA 18-932 for ReVia. Alkermes believes that the patent
`number that should have been listed for NDA 18—932 for ReVia is the ‘950 patent, .
`
`which dOes claim naltrexone and also has expired. Alkermes thus makes this
`
`Paragraph ll certification to the ‘950 patent.
`
`
`CONFlDENTlAL
`
`Page 1
`
`

`

`Alkermes, Inc.
`\fivitrex® gnaltrexone long-acting in'lectionz
`
`CTD Module 1
`
`The NBA for Vivitrex does not seek to rely on data from any other reference listed
`
`drugs, and thus we believe that no additional patent certifications are required. See
`
`21 C.F.R. 314.500); 54 Fed. Reg. 28872, 28875 (July 10, 1989).
`
`.qu
`
`CONFIDENTIAL
`
`Page 2
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 21-897'
`
`SUPPL # N/A
`
`I-[FD # 170
`
`Trade Name Vivitrol
`
`Generic Name naltrexone for extended—release injectable suspension
`
`Applicant Name Alkermes
`
`Approval Date, If Known April 13, 2006
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements CompletePARTS II and III of this Exclusivity Summary only 1f 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?
`
`~- YESE-
`
`NO |:I
`
`Ifyes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(2)
`
`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.")
`
`*4
`
`YES E
`
`NO [I
`
`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.
`
`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:
`
`Page 1
`
`

`

`(1) Did the applicant request exclusivity?
`
`YESIX]
`
`NOE]
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`3 Years
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`YEslj
`
`NOIZ
`
`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?
`
`_
`
`,_ .yEsEM NOIXI
`
`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 EXCLUSIVIT-Y 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 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.
`
`-
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
`#(s). ,
`‘
`
`YES El
`
`NO 1:]
`
`
`
`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 m 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.)
`
`YES
`
`E]
`
`El
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
`#(s).
`
`NDA#
`
`NDA#
`
`NDA#
`
`,
`
`_
`
`. gm”...
`
`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.
`
`.4“!
`
`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."
`
`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
`
`Page 3
`
`

`

`summary for that investigation.
`
`YES
`
`IE
`
`NO I]
`
`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 ofpreviously 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?
`YESIX]
`
`NOI:I
`
`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 ofpublished studies relevantto the safety and effectiveness
`ofthis drug product and a statement that the publicly available data would not independently
`support approval of the application?
`
`YES [:1
`
`NO X
`
`(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 [I
`
`NO IE
`
`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?
`
`YESD
`
`NOIE
`
`Page 4
`
`

`

`If yes, explain:
`
`(0)
`
`Ifthe answers to (b)(l) and (b)(2) were both “no," identify the clinical investigations
`submitted in the application that are essential to the approval:
`
`ALK2 1-003
`
`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 apniovai‘,“’fiast“he investigation been
`relied on by theagency 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.")
`'
`
`I Investigation #1
`
`investigation #2
`
`YES [:1 _
`
`NO IXI
`
`YES [1
`
`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?
`
`Investigation #1
`
`Investigation #2
`
`_
`
`YES [I
`
`NO X]
`
`YES [:1
`
`No [I
`
`Page 5
`
`

`

`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 thatis essential to the approval (i. e., the investigations listedin #2(c), less any
`that are not''"new
`
`ALKZ 1-003
`
`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 identified1n 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?
`
`is
`"k
`
`'!
`
`1 NO I]
`! Explain:
`
`Investigation #1
`
`IND#61,138
`
`YES E
`
`'
`I
`
`I NO [I
`Explain:
`
`l.
`
`'
`
`.
`
`YES I]
`.
`’
`
`Investigation #2
`
`1ND #
`
`(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?
`
`Page 6
`
`

`

`InvestigatiOn #1
`
`YESE]
`
`Explain:
`
`_
`
`Investigation???
`.
`
`YES lj
`Explain:
`
`!
`
`!N0|:l
`
`! Explain:
`
`!
`1
`
`! NO El
`!
`Explain:
`
`(0) 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 byits predecessor in interest.)
`
`_.
`
`-_ .YEsEl ' N0 ®
`
`If yes, explain:
`
`Name of person completing form: Lisa Basham-Cruz
`Title: Regulatory Project Manager
`Date: April 10, 2006
`
`Name of Office/Division Director signing form: BobRappaport, MD
`Title: Director, DAARP
`
`Form OGD—Ol 1347; Revised 05/10/2004; formatted 2/15/05
`
`Page 7
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Bob Rappaport
`4/13/2006 03:12:19 PM
`
`

`

`PEDIATRIC PAGE
`giiemgaieie {or as {fled esiginaé appéieatimsa em ‘aau $§§§§3§§3§§§€§§§§§
`
`NDA :
`
`21—897
`
`Supplement Type (e.g. SE5):
`
`Supplement Number:
`
`Stamp Date:
`
`March 31, 2005
`
`Action Date: 2“d cycle: April 13, 2006
`
`HFD 170
`
`Trade and generic names/dosage form: Vivitrol gnaltrexone for extended-release injectable suspension)
`
`Applicant:
`
`Alkermes, Inc.
`
`Therapeutic Class: alcoholism
`
`Indication(s) previously approved:
`
`Each approved indication must have pediatric studies: Completed, Deferred, and/or Waived.
`
`Number of indications for this application(s):
`
`1
`
`the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting
`Indication #1:
`prior to initiation of treatment with Vivitrol.
`
`Is there a full waiver for this indication (check one)?
`
`Cl Yes: Please proceed to Section A.
`
`El No: Please check all that apply: X Partial Waiver
`NOTE: More than one may apply
`Please proceed to Section B, Section C, and/or Section D and complete as necessary.
`
`X Deferred
`
`Completed
`
`I Section A: Fully Waived Studies
`
`Reason(s) for full waiver:
`
`I
`
`Products in this class for this indication have been studied/labeled for pediatric population
`Disease/condition does not exist in children
`
`DECIDE]
`
`Too few children with disease to study
`There are safety concerns
`Other:
`'
`
`Ifstudies arefully waived, then pediatric information is completefor this indication. Ifthere is another indication, please see
`Attachment A. Otherwise, this Pediatric Page is complete and should be entered into DFS.
`
`Section B: Partially Waived Studies
`
`Age/weight range being partially waived:
`
`
`Min
`
`Max
`
`kg
`kg
`
`Reason(s) for partial waiver:
`
`mo.
`mo.
`
`yr.
`yr.
`
`0
`
`11
`
`Tanner Stage
`Tanner Stage
`
`Cl Products in this class for this indication have been studied/labeled for pediatric population
`D Disease/condition does not exist in children
`X Too few children with disease to study
`Cl There are safety concerns
`X Adult studies ready for approval
`El Formulation needed
`
`

`

`NDA 21—897
`
`Page 2
`
`El Other:
`
`17studies are deferred, proceed to Section C. [fstudies are completed, proceed to Section D. Otherwise, this Pediatric Page is
`complete and should be entered into DFS.
`
`Section C: Deferred Studies
`
`.
`
`Age/weight range being deferred:
`
`Min
`Max
`
`kg
`kg
`
`mo.
`mo.
`
`yr.
`yr.
`
`12
`16
`
`
`Tanner Stage
`
`Tanner Stage
`
`Reason(s) for deferral:
`
`Cl Products in this class for this indication have been studied/labeled for pediatric population
`El Disease/condition does not exist in children
`
`El Too few children with disease to study
`El There are safety concerns
`X Adult studies ready for approval
`El Formulation needed
`Other:
`
`Date studies are due (mm/dd/yy):
`
`Final Report: October, 2010
`
`Ifstudies 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:
`
`I
`
`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 appemz’ed eimrarom’e sigszatme paged
`
`Regulatory Project Manager
`
`cc: NDA 21—897
`HFD-960/ Grace Carmouze
`
`FOR QUESTIONS ON COMPLETING THIS FORM CONTACT THE DIVISION OF PEDIATRIC DRUG
`DEVELOPMENT, HFD-960, 301-594-7337.
`
`(revised 12-22-03)
`
`

`

`NDA 21—897
`
`Page 3
`
`(This attachment is to be completed for those applications with multiple indications only.)
`
`Attachment A
`
`Indication #2:
`
`Is there a full waiver for this indication (check one)?
`
`D Yes: Please proceed to Section A.
`
`Partial Waiver
`D 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.
`
`Deferred
`
`Completed
`
`Section A: Fully Waived Studies
`
`.
`
`Reason(s) for full waiver:
`
`UDDUE}
`
`Products in this class for this indication have been studied/labeled for pediatric population
`Disease/condition does not exist in children
`
`Too few children with disease to study
`There are safety concerns
`Other:
`
`Ifstudies arefully waived, then pediatric information is complete for 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
`
`Age/weight range being partially waived:
`
`Min
`
`Max
`
`kg
`kg
`
`mo.
`mo.
`
`yr.
`yr.
`
`Tanner Stage
`Tanner Stage
`
`Reason(s) for partial waiver:
`
`UUDDUUD
`
`Products in this class for this indication have been studied/labeled for pediatric population
`Disease/condition does not exist in children
`
`Too few children with disease to study
`There are safety concerns
`Adult studies ready for approval
`Formulation needed
`Other:
`
`Ifstudies are deferred, proceed to Section C. Ifstudies are completed, proceed to Section D. Otherwise, this Pediatric Page is
`complete and should be entered into DFS.
`
`

`

`NDA 21-897
`
`Page 4
`
`Section C: Deferred Studies
`
`Age/weight range being deferred:
`
`Min
`Max
`
`kg
`kg
`
`mo.
`mo.
`
`yr.
`yr.
`
`
`
`Tanner Stage
`Tanner Stage
`
`Reason(s) for deferral:
`
`Products in this class for this indication have been studied/labeled for pediatric population
`Disease/condition does not exist in children
`
`Too few children with disease to study
`There are safety concerns
`Adult studies ready for approval
`Formulation needed
`Other:
`
`DUDUUDD
`
`Date studies are due (mm/dd/yy):
`
`Ifstudies 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
`
`kg
`kg
`
`mo.
`mo.
`
`yr.
`yr.
`
`Tanner Stage
`Tanner Stage
`
`Comments:
`
`If there are additional indications, please copy the fields above and complete pediatric information as directed. If there are no
`other indications, this Pediatric Page is complete and should be entered into DFS.
`
`This page was completed by:
`
`{.‘a‘ce appended etectrmzic signatory page}
`
`Regulatory Project Manager
`
`cc: NDA 21-897
`HFD-960/ Grace Carmouze
`
`FOR QUESTIONS ON COMPLETING THIS FORM CONTACT THE DIVISION OF PEDIATRIC DRUG
`DEVELOPMENT, HFD-960, 301-594-7337.
`
`'
`
`(revised 10-14-03)
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Lisa Basham—Cruz
`
`4/13/2006 03:01:11 PM
`
`

`

`
`
` ‘ éfigscmame
`' "if: ADMINISTRATIVE INFRMATIGN A
`1120: M131?!
`ENFRMATIN
`
`133 vfiggflmggxzsciggnsgcmieN:‘(Séfcn;orst;3fii§(ig(1)::fiF-itiéisg.t=fi€§;fie%§33
`
`.
`
` inherebycemfié thanfdldnetandwmno use in anycapam h
`servmesofanypersndebarredunderSecimnSflS that—“ede .. .\
`
`
`,.
`
`Signédby
`
`"fiuéi Eater
`
`
`
`

`

`NDA/EFFICACY SUPPLEMENT ACTION PACKAGE CHECKLIST
`
`- A»M
`
`NDA 21—897
`
`Efficac Su plement Type SE-
`
`
`Supplement Number
`
`Drug: VIVITROL (naltrexone for extended-release injectable
`susension)
`
`Applicant: Alkermes, Inc.
`
`RPM: Lisa Basham-Cruz
`
`HFD-l70
`
`'
`
`Phone # 301-796-1 175
`
`Application Type: () 505(b)(l) (X) 505(b)(2)
`(This can be determined by consulting page 1 of the NDA
`Regulatory Filing Review for this application or Appendix
`A to this Action Package Checklist.)
`
`Listed drug(s) referred to in 505(b)(2) application (NDA #(s), Drug
`name(s)):
`
`.
`NDA 18‘9323 Rev1a (oral naltrexone)
`
`If this is a 505(b)(2) application, please review and
`confirm the information previously provided in
`Appendix B to the NDA Regulatory Filing Review. _
`Please update any information (including patent
`certification information) that is no longer correct.
`
`() Confirmed and/or corrected
`
`'3' Application Classifications:
`0
`Review priority _
`.
`Chem_c1_ass (NDAs only) '
`0 Other (e.g., orphan, OTC)
`
`'3' Special programs (indicate all that apply)
`
`_
`
`_
`
`_,
`
`__
`
`‘
`
`_l
`
`.
`
`.
`_
`....,.
`,1
`___()Standard (X) Priority
`Type 3
`
`.
`(X) None
`'7‘"
`Subpart H -
`() 21 CFR 314.510 (accelerated
`approval)
`( ) 21 CFR 314.520
`(restricted distribution)
`() Fast Track
`( ) Rolling Review
`( ) CMA Pilot 1
`() CMA Pilot 2
`
`( ) Other (specify)
`
`
`
`(X) Paid UF ID number
`
`300603214928)
`() Small business
`User Fee waiver
`V
`I
`I
`( ) Public health
`() Barrier-to-Innovation
`( ) Other (specify)
`
`User Fee exception
`
`'1' Application Integrity Policy (AIP)
`Version: 6/16/2004
`
`( ) Orphan designation
`() No-fee 505(b)(2) (see NDA
`Regulatory Filing Review for
`instructions)
`
`

`

`NDA 21-897
`
`Page 2
`
`(X) No
`() Yes
`Applicant is on the AIP
`
` ( ) Yes (X) No
`
`
`Debaunent certification: verified that qualifying language (e.g., willingly, knowingly) was
`not used in certification & certifications from forei_n a. - licants are cosi_ ed b US a ent.
`
`(X) Verified
`Information. Verify that form FDA-3542a was submitted for patents that claim
`
`the drug for which appproval15 sought
`.
`Patent certification [505(b)(2) applications]: Verify that a certification was
`submitted for each patent for the listed drug(s)1n the Orange Book and identify
`the type of certification submitted for each patent.
`
`21 CFR 314.50(i)(1)(i)(A)
`(X) Verified
`
`[505(b)(2) applications] If the application includes a paragraph III 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 ready for
`an roval).
`
`[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 infringed (review
`documentation of notification by applicant and documentation of receipt of
`notice by patent owner and NDA holder).
`(1]the application does not include
`any paragraph IV certifications, mark "N/A ” and skip to the next box below
`(Exclusivity)).
`_
`-
`“
`
`21 CFR 314.50(i)(1)
`(X) (ii)
`() (iii) _
`
`() N/A (no paragraph IV certification)
`( ) Verified
`
`
`
`0
`
`0
`
`0
`
`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?
`
`(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)
`submitted a written waiver of its right to file a legal action for patent
`'
`infringement afier receiving the applicant’s notice of certification, as
`provided for by 21 CFR 314.107(f)(3)?
`
`If "Yes, " there is no stay ofapproval based on this certification. Analyze the next
`paragraph IV certification in the application, ifany. If there are no other
`paragraph IV certifications, skip to the next box below (Exclusivity).
`
`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?
`
`I Version: 6/16/2004
`
`

`

`NDA 21—897
`
`Page 3
`
`(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 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(1)(2))).
`
`If "No, " the patent owner (or NDA holder, if it is an exclusive patent licensee)
`has until the expiration ofthe 45-day period described in question (1) 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(t)(3)?
`
`() Yes
`
`() No
`
`If "Yes, " there is no stay ofapproval based on this certification. Analyze the next
`paragraph IV certification in the application, ifany. If there are no other
`paragraph IV certifications, skip to the next box below (Exclusivity).
`
`If "No, ” continue with question (5).
`
`(5) Did the patent owner, its representative, or the exclusive patent licensee
`bring suit against the applicant for patent infringement within 45 days of
`the patent owner’s receipt of the applicant’s notice of certification?
`‘”' "" ' "‘ '
`
`() Yes
`
`() No
`
`(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 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(t)(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 box below (Exclusivity).
`
`If "Yes, " a stay ofapproval may be in effect. To determine ifa 3 0—month stay
`is in eflect, consult with the Director, Division ofRegulatory Policy II, Office
`ofRegulatory Policy (HFD-007) and attach a summary ofthe response.
`
`.
`’-
`
`,
`
`’3' Exclusivity (approvals only)
`
`
`
`
`
`0
`
`N0
`
`Exclusivity summary
`Is there remaining 3-year exclusivity that would bar effective approval of a
`505(b)(2) application? (Note that, even if exclusivity remains, the application
`
`
`ma be tentativel a oroved if it is otherwise read for approval.)
`
`
`
`Is there existing orphan drug exclusivity protection for the “same drug” for the
`
`
`() Yes, Application #
`proposed indication(s)? Refer to 21 CFR 316. 3(b)(13) for the definition of “same
`
`' (X) No
`drug'’for an orphan drug (i. 2., active moiety). This definition is NOTthe same
`
`
`as that used or NDA chemical classi tcation.
`4° Administrative Reviews (Project Manager, ADRA) (indicate date ofeach review) —
`
`
`
`
`Version: 6/16/2004
`
`

`

`NDA 21-897
`
`Page 4
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`0'0
`:11
`. Actions
`
`(mm? ()TA_ ()_A_E (ISN'AW J
`Proposed action
`
`hAE; December 23, 2005
`Previous actions (specify type and date for each action taken)
`(X) M_aterials requestedin AP
`letter
`
`Status of advertising (approvals only)
`
`( ) Reviewed for Subpart H
`We
`<
`r
`
`we:
`
`a
`
`Press Office notified of action (approval only)
`
`(X) Yes
`(X) None
`() Press Release
`( ) Talk Paper
`Indicate what types (if any) of information dissemination are anticipated
`( ) Dear Health Care Professional
`Letter
`.w
`4,
`W 2,
`
`() Not applicable
`
`1
`
`
`Labeling (package insert, patient package insert (if applicable), MedGuide (if—applicable))
`Divisionn5 proposed labeling (only ifgenerated afler latest applicant submission
`
`Most recent applicant—proposed labeling
`
`Original applicant-proposed labeling
`
`00
`
`2
`
`Labeling reviews (including DDMAC, DMETS, DSRCS) and minutes of
`
`labeling meeting_s_(indicate dateigfreviews and meLtings)
`
`Other relevant labeling (e.g., most recent 31n class, class labeling)
`
`2
`Labels (immediate container & carton labels)
`
`Division proposed (only ifg_enerated after latest applicant submission)
`
`Applicant proposed_
`Reviews
`
`
`
`1
`
`.
`
`Post-marketing commitments
`Agency request for post—marketing commitments
`Documentation of discussions and/or agreements relating to post—marketing
`commitments
`
`°2° Outgoing correspondence (i.e., letters, E-mails, faxes)
`. Memoranda and Telecoms
`Minutes of Meetings
`
`Type C_meeting (in—dicate date)
`
`Type C meeting
`
`Pre—NDA meeting P/T & Clinical (indicate date)—
`Pre-NDA CMC
`
`Post Action Meeting
`0’0
`0 Advisory Committee Meeting
`
`Date of Meeting
`48-hour alert
`
`'2' Federal Register Notices, DESI documents, NAS/NRC reports (if applicable)
`
`5/4/01
`8/8/02
`
`1 1/2/04
`
`3/4/05
`
`1/24/06
`
`N/A
`
`Version: 6/16/2004
`
`

`

`NDA 21—897
`
`Page 5
`
`
`
`
`
`
`
`
`
`
`
`_4,1 . W
`
`If):
`
`Summary Reviews (e.g., Office Director, Division Director, Medical Team Leader)
`(indicate datefor each review)
`
`
`
`
`’ DD 1st cycle: 12/23/05
`DD 2“‘1 cycle: 4/13/06
`Med TL 1“ cycle: 12/22/05
`Med TL 2nd cycle: 4/11/06
`
`Clinical review(s) (indicate datefor each review)
`
`Microbiology (efficacy) review(s) (indicate datefor each review)
`
`1S‘cyc1e: 12/19/05
`2nd cycle: 4/11/06
`NA
`
`Med 1“ cycle review, page 146; 2n
`cycle review, page 9.
`NA
`
`X N
`
`A
`
`
`12/16/05
`
`lSl cycle: 11/21/05
`2nde cle: 4/7/06
`
`Safety Update review(s) (indicate date or location ifincorporated in another review)
`
`Risk Management Plan review(s) (indicate date/location ifincorporated in another rev)
`
`Pediatric Page(separate page for each indication addressing status of all age groups)
`
`Demographic Worksheet (NME approvals only)
`
`Statistical review(s) (indicate date for each review)
`
`Biopharmaceutical review(s) (indicate datefor each review)
`
`90o
`
`o
`
`o
`0.0
`
`o
`
`O
`0.0
`O
`0..
`O
`0.0
`o 0
`
`NA
`
`3
`
`Controlled Substance Staff review(s) and recommendation for scheduling (indicate date
`.
`or each review)
`
`
`'3' Clinical Inspection Review Summary (DSI)
`g
`
`I
`_0
`Clinical stud1e—s_‘
`_
`~
`9/13/05
`_..._
`._
`.
`...__
`_
`.
`.. H...
`.
`......................
`_ _
`_ _
`........:
`_._NA_
`__
`0
`Bioequivalence studies
`1
`.._
`.1.-.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`li‘cycle: 1’2/16/05
`2“cl cycle: 4/7/06
`
`NA
`
`NA
`
`9/23/05 and 10/24/05
`
`Date completed:
`(X) Acceptable
`() Withhold recommendation
`() Completed
`(X) Requested
`( ) Not yet requested
`
`12/16/05 1
`TL memo 181 cycle: 12/21/05
`TL memo 2“d c cle: 4/12/06
`NA
`
`NA
`
`NA
`
`
`
`
`
`
`0 Review& FONSI (indicatedate ofreview)
`0
`Review & Environmental Impact Statement (indicate date ofeach review)
`Microbiology (validation of sterilization & product sterility) review(s) (indicate datefor
`each review)
`Facilities inspection (provide EER report)
`
`Methods validation
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Pham1/tox review(s), including referenced IND reviews (indicate date for each review)
`
`Nonclinical inspection review summary
`
`Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`
`CAC/ECAC report
`
`0
`
`o0
`
`.0
`
`O
`0.0
`0
`0‘0
`
`Version: 6/16/2004
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Lisa Basham—Cruz
`4/20/2006 02:06:01 PM
`
`

`

`Phase 4 COITIIIlllIIlC