CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`22-301
`
`ADMINISTRATIVE and CORRESPONDENCE
`
`DOCUMENTS
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 22-301
`
`SUPPL #
`
`HFD #
`
`Trade Name Apriso
`
`Generic Name Mesalamine
`
`Applicant Name Salix Pharmaceuticals, Inc.
`
`.
`
`Approval Date, If Known 10/31/08
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to
`one or more of the following questions about the submission.
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`-
`
`YES IE
`
`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.")
`
`YES
`
`NO 13
`
`Ifyour 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?
`.
`
`YES
`
`NO 1:]
`
`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?
`YES E]
`
`NO X
`
`Ifthe answer to the above question in YES, is this approval a result of the studies submitted in
`response to the Pediatric Written Request?
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`2. Is this drug product or indication a DESI upgrade?
`,
`-
`
`YES E]
`
`NO
`
`IF THE ANSWER TO QUESTION 2 IS "YES," G0 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" ifthe 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 E
`
`No D
`
`Page 2
`
`

`

`NDA#
`
`19-651, 21-830
`
`Asacol, Mesalamine
`
`NDA#
`
`21-252, 20-049
`
`Canasa, Pentasa
`
`NDA#
`
`22—000, 19—618
`
`Lialda, Rowasa/SFRowasa
`
`2. Combination product.
`
`If the product contains more than one active moiety(as defined in Part H, #1), has FDA previously
`approved an application under section 505 containing fly 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.)
`. E]
`[Z
`
`YES
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
`#(s).
`
`NDA#
`
`NDA#
`
`NDA#
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART 11 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 HI
`
`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 ofthe application
`and conducted or sponsored by the applicant." This section should be completed only ifthe answer
`to PART 11, 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
`
`NO D
`
`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
`essentialto 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?
`.YES-
`
`Nolj
`
`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 relevant to the safety and effectiveness
`ofthis drug product and a statement that the publicly available data would not independently
`support approval of the application?
`
`YES I: _ NO-
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree
`with the applicant's conclusion? If not applicable, answer NO.
`
`YES D
`
`NO lj
`
`If yes, explain:
`
`(2) Ifthe answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
`
`YEs 1:]
`
`NO
`
`Page 4
`
`

`

`If yes, explain:
`
`(c)
`
`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:
`
`Two pivotal, Phase 3 studies, MPUC3003 and MPUC3004. to evaluate the
`clinical efficacy and safety of eMG (encapsulated mesalamine granules) for the
`maintenance of remission of ulcerative colitis (UC) in patients 18 years and over for
`consecutive therapyup to six months.
`In addition, a single open-label long-term
`extension study, MPUCSOOS, was submitted. '
`'
`
`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 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‘approvcd 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 [:1
`
`NO
`
`YES I:
`
`NO X]
`
`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
`
`YES [3
`
`NO
`
`Page 5
`
`

`

`Investigation #2
`
`YES [1
`
`NO K4
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`c) Ifthe 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" :
`
`Study MPUC3003 and Study MPUC3004
`
`' 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 ofthe investigation, 1) the applicant was the sponsor of
`the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor
`in interest) provided substantial support for the study. Ordinarily, substantial support will mean
`providing 50 percent or more of the cost of the study.
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an 1ND, was the applicant identified on the FDA 1571 as the sponsor?
`
`l1
`
`! NO [I
`! Explain:
`
`!
`!
`
`1 NO [:1
`! Explain:
`
`Investigation #1
`
`IND#62,113
`
`YES
`
`Investigation #2
`-
`
`IND#62,113
`
`YES
`
`(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
`
`I
`
`YESEI
`Explain:
`
`!N0l:]
`! Explain:
`
`Investigation #2
`
`!
`
`YESI:I
`Explain:
`
`!NOI:]
`! 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 usedas the basis for exclusivity. However, ifall rights to the
`drug are purchased (not just studies on the drug), the applicant may be considered to have
`sponsored or conducted the studies sponsored or conducted by its predecessor in interest.)
`
`YES [:|’ ' NO-
`
`If yes, explain:
`
`Name of person completing form: Cristi Stark
`Title: Regulatory Health Project Manager
`Date: 10/30/08 .
`
`Name of Office/Division Director signing form: Donna Griebel, MD
`Title: Director, Division of Gastroenterology Products
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05
`
`Page 7
`
`

`

`Appears This Way
`On Original
`
`Appears This Way
`On Original
`
`Page 8
`
`

`

`(Complete for all filed original applications and efficacy supplements)
`
`PEDIATRIC PAGE
`
`NDA/BLA#: 22-301
`
`Supplement Number:
`
`NDA Supplement Type (e.g. SE5):
`
`-
`
`Division Name:Gastroenterology
`Products
`
`PDUFA Goal Date: 10/31/08
`
`Stamp Date: 12/31/2007
`
`Proprietary Name:
`
`Apriso
`
`Established/Generic Name: Mesaiamine
`
`Dosage Form:
`
`Applicant/Sponsor:
`
`Extended-release Capsules
`
`Salix Pharmaceuticals Inc.
`
`Indication(s) previously approved (please complete this question for supplements and Type 6 NDAs only): .
`
`(1)
`(2) __
`(3) ____.
`
`
`(4)
`.
`
`Pediatric use for each pediatric subpopulation must be addressed for each indication covered by current
`application under review. A Pediatric Page must be completed for each indication.
`
`.
`Number of indications for this pending application(s):1
`(Attach a completed Pediatric Page for each indication in current appiication.)
`
`Indication: maintenance of remission of ulcerative colitis in adults
`
`Q1: is this application in response to a PREA PMR?
`
`Yes [I Continue
`
`If Yes, NDA/BLA#: __
`
`Supplement #:__
`
`'
`
`PMR #:___
`
`Does the division agree that this is a complete response to the PMR?
`
`(:1 Yes. Please proceed to Section D.
`
`[:1 No. Please proceed to Question 2 and complete the Pediatric Page, as applicable.
`
`No E Please proceed to Question 2.
`
`02: Does this application provide for (If yes, please check all categories that apply and proceed to the next
`question):
`_
`
`(a) NEW E active ingredient(s) (includes new combination); E indication(s); E dosage form; E dosing
`regimen; or E route of administration?*
`'
`(b) E No. PREA does not apply. Skip to signature block.
`* Note for CDER: SE5, SE6, and SE7 submissions may also trigger PREA.
`
`Q3: Does this indication have orphan designation?
`
`D Yes. PREA does not apply. Skip to signature block.
`E No. Please proceed to the next question.
`
`Q4: Is there a full waiver for all pediatric age groups for this indication (check one)?
`D Yes: (Complete Section A.)
`
`E No: Please check all that apply:
`E Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`E Deferred for some or all pediatric subpopulations (Complete Sections C)
`I] Completed for some or all pediatric subpopulations (Complete Sections D)
`E Appropriately Labeled for some or all pediatric subpopulations (Complete Sections E)
`[:1 Extrapolation in One or More Pediatric Age Groups (Complete Section F)
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdcrpmhsfil‘dahhsgov) 0R AT 301—796-0700.
`
`

`

`NDA/BLA# 22—30122-30122—30122—30122-301
`
`g
`
`
`Section A: Fully Waived Studies (for all pediatric age groups)
`
`Please note that Section F ma be used alone or in addition to Sections C, D, and/or E.
`
`
`
`
`
`
`Reason(s) for full waiver: (check, and attach a brief justification for the reason(s) selected)
`I:] Necessary studies would be impossible or highly impracticable because:
`[:1 Disease/condition does not exist in children
`
`Page 2
`
`
`
`
`[:I Too few children with disease/condition to study
`[:1 Other (e.g., patients geographically dispersed): __
`[J Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients AND is not likely to be used in a substantial number of pediatric patients.
`I] Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, ' this information must be included in the labeling.)
`I] Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`[:1 Evidence strongly suggests that product would be ineffective and unsafe in all pediatric
`subpopulations (Note: if studies are fully waived on this ground, this information must be included in
`the labeling.)
`D Justification attached.
`If there is another
`If studies are fully waived, then pediatric information is complete for this indication.
`indication, please complete another Pediatric Page for each indication. Otherwise, this Pediatric Page is
`complete and should 'be signed.
`Section B: Partially Waived Studies (for selected pediatric subpopulations)
`Check subpopulation(s) and reason for which studies are being partially waived (fill in applicable criteria below):
`
`Note: If Neonate includes premature infants, list minimum and maximum age in “gestational age” (in weeks).
`
`Reason (see below for further detail):
`
`-
`
`Not meaningful
`therapeutic
`benefit*
`
`Ineffective or
`unsafeT
`
`Formulation
`
`gyr._mo. El
`
`-_
`
`El
`IEI
`
`Are the indicated age ranges (above) based on weight (kg)?
`
`El No; [:1 Yes.
`
`Are the indicated age ranges (above) based on Tanner Stage?
`
`No; [:1 Yes.
`
`Reason(s) for partial waiver (check reason corresponding to the category checked above, and attach a brief
`justification):
`# Not feasible:
`
`Necessary studies would be impossible or highly impracticable because:
`I]
`Disease/condition does not exist in children
`X)
`Too few children with disease/condition to study
`I:I
`Other (e.g., patients geographically dispersed): __
`* Not meaningful therapeutic benefit:
`E] Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients in this/these pediatric subpopulation(s) AND is not likely to be used in a substantial number of
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdcrgmhsfiflfdamhsgov) 0R AT 301-796—0700.
`
`

`

`NDA/BLA# 22-30122-30122—30122—301 22—301
`
`'
`
`Page 3
`
`pediatric patients in this/these pediatric subpopulation(s).
`1' Ineffective or unsafe:
`
`I:| Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if studies
`are partially waived on this ground, this information must be included in the labeling.)
`E] Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are partially waived on this ground, this information must be included in the labeling.)
`I:l Evidence strongly suggests that product would be ineffective and unsafe in all pediatric subpopulations
`(Note: if studies are partially waived on this ground, this information must be included in the labeling.)
`A Formulation failed:
`
`I] Applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for
`this/these pediatric subpopulation(s) have failed. (Note: A partial waiver on this ground may gn_ly cover
`the pediatric subpopulation(s) requiring that formulation. An applicant seeking a partial waiver on this
`ground must submit documentation detailing why a pediatric formulation cannot be developed. This
`submission will be posted on FDA ’8 website if waiver is granted.)
`El Justification attached.
`
`For those pediatric subpopulations for which studies have not been waived, there must be (1) corresponding
`study plans that have been deferred (if so, proceed to Sections C and complete the PeRC Pediatric Plan
`Template); (2) submitted studies that have been completed (if so, proceed to Section D and complete the
`PeRC Pediatric Assessment form); (3) additional studies in other age groups that are not needed because the
`drug is appropriately labeled in one or more pediatric subpopulations (if so, proceed to Section E); and/or (4)
`additional studies in other age groups that are not needed because efficacy is being extrapolated (if so,
`proceed to Section F). Note that more than‘ one of these options may apply for this indication to cover a_ll of the
`pediatric subpopulations.
`
`‘ S
`
`ection C: Deferred Studies (for selected pediatric subpopulations).
`
`Check pediatric subpopulation(s) for which pediatric studies are being deferred (and fill in applicable reason
`below):
`
`Deferrals (for each or all age groups):
`
`Reason for Deferral
`
`Applicant
`Certification
`1
`
`Additional
`Approval Adult Safety or
`in Adults
`Efficacy Data
`
`Other
`
`Appmpriate
`
`
`
`Date studies are due (mm/dd/yy): 06/01/13
`
`Population
`
`lil
`Neonate
`_ wk. _ mo.
`. _;yr...
`Iil
`Iil
`
`E
`
`. Are the indicated age ranges (above) based on weight (kg)?
`
`No; I] Yes.
`
`Are the indicated age ranges (above) based on Tanner Stage? E No; C] Yes.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL lcdergmhs-fit‘da.hhsyov) 0R AT 301-796—0700.
`
`

`

`NDA/BLA# 22-30122—30122-30122-30122—301
`
`Page 4
`
`* Other Reason:
`
`T Note: Studies may only be deferred if an applicant submits a certification of grounds for deferring the studies,
`a description of the planned or ongoing studies, evidence that the studies are being conducted or will be
`conducted with due diligence and at the earliest possible time, and a time/ine for the completion of the studies.
`If studies are deferred, on an annual basis applicant must submit information detailing the progress made in
`conducting the studies or, if no progress has been made, evidence and documentation that such studies will be
`conducted with due diligence and at the earliest possible time. This requirement should be communicated to
`the applicant in an appropriate manner (e.g., in an approval letter that specifies a required study as a post-
`marketing commitment.)
`‘
`
`If all of the pediatric subpopulations have been covered through partial waivers and deferrals, Pediatric Page is
`complete and should be signed.
`If not, complete the rest of the Pediatric Page as applicable.
`
`
`Section D: Completed Studies (for some or all pediatric subpopulations).
`
`Pediatric subpopulation(s) in which studies have been completed (check below):
`
`16 yr. 11 mo.
`
`Population
`
`Neonate
`
`wk.
`
`mo.
`
`w ._ mo.
`
`.
`
`Other
`Other
`
`Other
`
`Other
`
`_ yr. _ mo. _ yr. _ mo.
`_ yr. _ mo. _ yr. __ mo.
`
`yr.
`
`mo.
`
`__yr._mo.
`
`_ yr. _ mo.
`
`__ yr. _ mo.
`
`All Pediatric Subpopulations
`
`0 yr. 0 mo.
`
`PeRC Pediatric Assessment form
`attached?
`
`Yes I]
`
`No [:1
`No [:|
`
`~
`
`Are the indicated age ranges (above)‘based on weight (kg)?
`
`E] No; I] Yes.-
`
`Are the indicated age ranges (above) based on Tanner Stage?
`
`E] No; D Yes.
`
`Note: If there are no further pediatric subpopulations to cover based on partial waivers, deferrals and/or
`completed studies, Pediatric Page is complete and should be signed.
`If not, complete the rest of the Pediatric
`Page as applicable.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdcrgmhsfa‘tfdamhsgov) OR AT 301-796-0700.
`
`

`

`NDA/BLA# 22-30122-30122—30122-30122-301
`1 Section E: Drug Appropriately Labeled (for some or all pediatric subpopulations):
`I
`
`
`
`
`
`
`Page 5
`
`Additional pediatric studies are not necessary in the following pediatric subpopulation(s) because product is
`appropriately labeled for the indication being reviewed:
`
`_wk. _
`
`
`
`J...
`
`_y._mo.
`
`._ mo.
`
`_y._
`_yr._mo.
`
`
`
`
`
`
`
`Are the indicated age ranges (above) based on weight (kg)?
`
`El No; 1:] Yes.
`
`V
`
`Are the indicated ‘age ranges (above) based on Tanner Stage?
`
`E] No; I] Yes.
`
`If all pediatric subpopulations have been covered based on partial waivers, deferrals, completed studies, and/or
`existing appropriate labeling, this Pediatric Page is complete and should be signed.
`If not, complete the rest of
`the Pediatric Page as applicable.
`
`Section F: Extrapolation from Other Adult and/or Pediatric Studies (for deferred and/or'completed studies)
`Note: Pediatric efficacy can be extrapolated from adequate and well-controlled studies in adults and/or other
`1 pediatric subpopulations if (and only if) (1) the course of the disease/condition M (2) the effects of the
`product are sufficiently similar between the reference population and the pediatric 'subpopulation for which '
`information will be extrapolated. Extrapolation of efficacy from studies in adults and/or other children usually
`requires supplementation with other information obtained from the target pediatric subpopulation, such as
`pharmacokinetic and safety studies. Under the statute, safety cannot be extrapolated.
`
`
`Pediatric studies are not necessary in the following pediatric subpopulation(s) because efficacy can be
`
`extrapolated from adequate and well-controlled studies in adults and/or other pediatric subpopulations:
`
`
`
`
`
`P°P”'afi°”
`
`maXimum
`
`_ wk.
`
`._ mo.
`
`Extrapolated from:
`.
`Other Pediatric
`Adult Studies?
`Studies?
`
`
`
`.
`
`yr. __ mo
`
`_y.
`
`. _ mo.
`
`. _ mo
`
`. _ mo.
`
`All Pediatric
`
`
`
`
`
`
`Are the indicated age ranges (above) based on weight (kg)?
`
`[:I No; 1:] Yes.
`
`Are the indicated age ranges (above) based on Tanner Stage?
`
`E] No; D Yes.
`
`‘ Note: If extrapolating data from either adult or pediatric studies, a description of the scientific data supporting
`the extrapolation must be included in any pertinent reviews for the application.
`-
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdcrgmhsfififdahhsgov) 0R AT 301-796-0700.
`
`

`

`NDA/BLA# 22—30122—30122—30122—30122-301
`
`Page 6
`
`If there are additional indications please complete the attachment for each one of those indications.
`Otherwise, this Pediatric Page is complete and should be signed and entered into DFS or DARRTS as
`appropriate after clearance by PeRC.
`
`This page was completed by:
`
`{See appended electronic signature page}
`
`Regulatory Project Manager
`
`(Revised: 6/2008)
`
`If you have no other indications for this application, you may delete the attachments from this
`NOTE:
`document.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdernmhs-‘Efdahhsgow OR AT 301-796-0700.
`
`

`

`NDA/BLA# 22—30122-30122—30122—30122—301
`
`_
`
`Page 7
`
`(This attachment is to be completed for those applications with multiple indications only.)
`Indication #2:
`
`Attachment A
`
`Q1: Does this indication have orphan designation?
`
`[:1 Yes. PREA does not apply. Skip to signature block.
`D No. Please proceed to the next question.
`
`02: is there a full waiver for all pediatric age groups for this indication (check one)?
`I] Yes: (Complete Section A.)
`
`E] No: Please check all that apply:
`I] Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`[Z] Deferred for some or all pediatric subpopulations (Complete Sections C)
`E] Completed for some or all pediatric subpopulations (Complete Sections D)
`E} Appropriately Labeled for some or all pediatric subpopulations (Complete Sections E)
`[:1 Extrapolation in One or More Pediatric Age Groups (Complete Section F)
`
`(Please note that Section F may be used alone or in addition to Sections C, D, and/or E.)
`
`Section A: Fully Waived Studies (for all pediatric age groups)
`
`'
`
`Reason(s) for full waiver: (check, and attach a briefjustification for the reaSon(s) selected) -
`I:l Necessary studies would be impossible or highly impracticable because:
`[I Disease/condition does not exist in children
`
`El Too few children with disease/condition to study
`[:| Other (e.g., patients geographically dispersed): _
`[J Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients AND is not likely to be used in a substantial number of pediatric patients.
`[:1 Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`E] Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`[:1 Evidence strongly suggests that product would be ineffective and unsafe in all pediatric
`subpopulations (Note: if studies are fully waived on this ground, this information must be included in
`the labeling.)
`E] Justification attached.
`
`.
`
`If studies are fully waived, then pediatric information is complete for this indication. If there is another
`indication, please complete another Pediatric Page for each indication. Otherwise, this Pediatric Page is
`complete and should be signed.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdcrpmhsftfifdamhsgov) OR AT 301-796-0700.
`
`

`

`NDA/BLA# 22—30122—30122—30122—30122—301
`
`Page 8
`
`
`Check subpopulation(s) and reason for which studies are being partially waived (fill in applicable criteria below):
`
`Note: If Neonate includes premature infants, list minimum and maximum age in "gestational age” (in weeks).
`
`maximum
`
`feahégle"
`
`Not meaningful
`therapeutic
`
`
`
`.
`Ineffective or
`
`.
`Formulation
`
`Are the indicated age ranges (above) based on weight (kg)?
`Are the indicated age ranges (above) based on Tanner Stage?
`
`[:1 No; Cl Yes.
`E} No; 1:! Yes.
`
`Reason(s) for partial waiver (check reason corresponding to the category checked above, and attach a brief
`justification):
`.
`-
`# Not feasible:
`
`E} Necessary studies would be impossible or highly impracticable because:
`[:1
`Disease/condition does not exist in children
`
`Too few children with disease/condition to study
`[:1
`Other (e.g., patients geographically dispersed): __
`1:]
`* Not meaningful therapeutic benefit:
`
`[1 Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients in this/these pediatric subpopulation(s) AND is not likely to be used in a substantial number of
`pediatric patients in this/these pediatric subpopulation(s).
`1' ineffective or unsafe:
`
`E] Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if
`studies are partially waived on this ground, this information mast be included in the labeling.)
`[:1 Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are partially waived on this ground, this information must be included in the labeling.)
`E! Evidence strongly suggests that product would be ineffective and unsafe in all pediatric '
`subpopulations (Note: if studies are partially waived on this ground, this information must be
`included in the labeling.)
`A Formulation failed:
`
`2
`
`|:I Applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for
`this/these pediatric subpopulation(s) have failed. (Note: A partial waiver on this ground may o_nly cover
`the pediatric subpopulation(s) requiring that formulation. An applicant seeking a partial waiver on this
`ground must submit documentation detailing 'why a pediatric formulation cannot be developed. This
`submission will be posted on FDA's website if waiver is granted.)
`[:1 Justification attached.
`
`For those pediatric subpopulations for which studies have not been waived, there must be (1) corresponding
`study plans that have been deferred (if so, proceed to Section C and complete the PeRC Pediatric Plan
`Template); (2) submitted studies that have been completed (if so, proceed to Section D and complete the
`PeRC Pediatric Assessment form); (3) additional studies in other age groups that are not needed because the
`drug is appropriately labeled in one or more pediatric subpopulations (if so, proceed to Section E); and/or (4)
`additional studies in other age groups that are not needed because efficacy is being extrapolated (if so,
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdcrgnlhs@f(la.hhs.gov) 0R AT.301-796-0700.
`
`

`

`NDA/BLA# 22—30122-30122—30122-30122—301
`
`Page 9
`
`proceed to Section F).. Note that more than one of these options may apply for this indication to cover all of the
`pediatric subpopulations.
`
` Section C: Deferred Studies (for some or all pediatric subpopulations).
`
`Check pediatric subpopulation(s) for which pediatric studies are being deferred (and fill in applicable reason
`below):
`'
`'
`
`.Deferrals (for each or all age groups):
`
`Reason for Deferral
`
`Need
`Ready
`Additional
`for
`Approval Adult Safety or
`Efficacy Data
`
`Other
`Appropriate
`Reason
`(s ecify
`p
`
`Date studies are due (mm/dd/yy):
`
`Applicant
`Certififation
`
`Received
`
`I!-
`I:-
`
`_mo.
`
`._ .
`mmo.
`
`All Pediatric
`
`Are the indicated age ranges (above) based on weight (kg)?
`
`E] No; 1:] Yes.
`
`Are the indicated age ranges (above) based on Tanner Stage?
`
`E] No; I:I Yes.
`
`* Other Reason:
`
`1' Note: Studies may only be deferred if an applicant submits a certification of grounds for deferring the studies,
`a description of the planned or ongoing studies, evidence that the studies are being conducted or will be
`conducted with due diligence and at the earliest possible time, and a timeline for the completion of the studies.
`If studies are deferred, on an annual basis applicant must submit information detailing the progress made in
`conducting the studies or, if no progress has been made, evidence and documentation that such studies will be
`conducted with due diligence and at the earliest possible time. This requirement should be communicated to
`the applicant in an appropriate manner (e.g., in an approval letter that specifies a required study as a post-
`marketing commitment.)
`
`If all of the pediatric subpopulations have been covered through partial waivers and deferrals, Pediatric Page is
`complete and should be signed.
`If-not, complete the rest of the Pediatric Page as applicable.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL tcdcrgmhsfififdahhsgov) OR AT 301-796-0700.
`
`

`

`NDA/BLA# 22-30122-30122-30122-30122-301
`10
`‘
`l Section D: Completed Studies (for some or all pediatric subpopulations).
`
`'
`
`Page
`
`I
`
`Pediatric subpopula