CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`22-334
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`

`

`EXCLUSIVITY SUMMY
`
`NDA# 22-334
`
`SUPPL#
`
`HFD # 150
`
`Trade Name Afinitor tablets
`
`Generic Name everolimus
`
`Applicant Name Novaris Pharmaceuticals Corporation
`
`Approval Date, If
`
`Known March 30, 2009
`
`PART
`
`i
`
`is AN EXCLUSIVITY DETERMATION NEEDED?
`
`1. An exclusivity determination wil be made for all original applications, and all efficacy
`you answer "yes" to
`
`supplements. Complete PARTS II and II of
`
`this Exclusivity Summar only if
`
`one or more of
`
`the following questions about the submission.
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
`YES rz
`
`NoD
`
`If yes, what type? Specify 505(b)(l), 505(b)(2), SEl, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(I)
`
`c) Did it require the review of clinical data other than to support a safety claim or change in
`it required review only ofbioavailabilty or bioequivalence
`NoD
`
`labeling related to safety? (If
`
`data, answer "no.")
`
`YES rz
`
`If your answer is "no" because you believe the study is a bioavailabilty study and, therefore,
`not eligible for exclusivity, EXPLAIN why it is a bioavailabilty study, including your
`reasons for disagreeing with any arguments made by. the applicant that the study was not
`simply a bioavailabilty 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:
`
`d) Did the applicant request exclusivity?
`
`Page 1
`
`

`

`YES i:
`
`NoD
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`5 years
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`YESD
`
`NO i:
`
`Ifthe answer to the above guestion in YES. is this approval a result of
`
`response to the Pediatric Written Request?
`
`the studies submitted in
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRCTLY
`
`THE SIGNATUR BLOCKS AT THE END OF TilS DOCUMNT.
`
`TO
`
`2. Is this drug product or indication a DESI upgrade?
`
`YES 0
`
`NO i:
`
`IF THE ANSWER TO QUESTION
`
`2 is "YES," GO DIRECTLY TO TH SIGNATUR BLOCKS
`ON PAGE 8 (even if a study was required for the upgrade).
`
`PART II FIV-YEAR EXCLUSIVTY FOR NEW CHEMICAL ENTITIES
`(Answer either # 1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of
`
`active moiety as the drug under consideration? Answer "yes" if
`
`the Act any drug product containing the same
`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)
`the compound requires metabolic conversion (other than
`the drug) to produce an already approved active moiety.
`
`has not been approved. Answer "no" if
`
`deesterification of an esterified form of
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if
`
`known, the NDA
`
`YES 0
`
`NO i:
`
`#(s).
`
`NDA#
`
`Page 2
`
`

`

`NDA#
`
`NDA#
`
`2. Combination product.
`
`approved an application under section 505 containing anyone of
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`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.)
`NoD
`
`YEsD
`
`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
`the summar should
`
`SIGNATU BLOCKS ON PAGE 8. (Caution: The questions in part II of
`
`only be answered "NO" for original approvals of
`
`IF "YES," GO TO PART II.
`
`new molecular entities.)
`
`PART
`
`III
`
`THRE-YEAR EXCLUSIVTY FOR NDAs AN SUPPLEMENTS
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`clinical investigations (other than bioavailabilty studies) essential to the approval ofthe application
`the answer
`
`and conducted or sponsored by the applicant." . This section should be completed only if
`
`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 bioavailabilty studies.) If
`the application contains clinical investigations only by virtue of a right of reference to clinical
`the answer to 3(a)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`summary for that investigation.
`NoD
`YES D
`
`investigations in another application, answer "yes," then skip to question 3(a). If
`
`Page 3
`
`

`

`IF "NO," GO DIRECTLY TO THE SIGNATUR 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
`previously approved applications (i.e., information other than clinical trials,
`such as bioavailabilty data, would be sufficient to provide a basis for approval as an ANDA or
`what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been suffcient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`application in light of
`
`505(b )(2) application because of
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`source, including the published literature)
`
`by the applicant or available from some other.
`
`necessary to support approval of
`
`the application or supplement?YESD NoD
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATUR BLOCK ON PAGE 8:
`
`(b) Did the applicant submit a list of published studies relevant to the safety and
`effectiveness ofthis drug product and a statement that the publicly available data would not
`the application?
`
`independently support approval of
`
`YES D NoD
`
`(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.
`
`YEsD
`
`NoD
`
`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?
`
`YEsD
`
`NoD
`
`If yes, explain:
`
`Page 4
`
`

`

`(c) If the answers to (b)(l) and (b)(2) were both "no," identify the clinical
`investigations submitted in the application that are essential to the approval:
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailabilty
`this section.
`
`studies for the purpose of
`
`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 drg 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 #J
`
`Investigation #2
`
`YEsD
`
`YESD
`
`NoD
`NoD
`
`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
`
`YEsD
`
`YESD
`
`NoD
`NoD
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`Page 5
`
`

`

`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
`or supplement that is essential to the approval (i.e., the investigations listed in #2( c), less any
`that are not "new"):
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by"
`the applicant if, before or during the conduct ofthe investigation, 1) the applicant was the sponsor of
`(or its predecessor
`in interest) provided substantial support for the study. Ordinarily, substantial support wil mean
`the study.
`
`the IN named in the form FDA 1571 fied with the
`
`Agency, or 2) the applicant
`
`providing 50 percent or more of
`
`the cost of
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an IN, was the applicant identified on the FDA 1571 as the sponsor?
`
`! !!
`
`NOD
`
`! Explain:
`
`Investigation # i
`IN#
`
`YES D
`
`Investigation #2
`IN#
`
`YES 0
`
`! NO 0
`! Explain:
`
`(b) For each investigation not caried 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?
`
`! !!
`
` NO 0
`
`! Explain:
`
`Page 6
`
`Investigation # 1
`
`YES 0
`Explain:
`
`

`

`Investigation #2
`
`YES D
`Explain:
`
`NO (j
`Explain:
`
`(c) Notwithstanding an answer of
`
`"yes" to (a) or (b), are there other reasons to believe that
`the applicant should not be credited with having "conducted or sponsored" the study?
`(purchased studies may not be used as the basis for exclusivity. However, if all rights to the
`drug are purchased (not just studies on the drug), the applicant may be considered to have
`sponsored or conducted the studies sponsored or conducted by its predecessor in interest.)
`NoD
`
`YEsD
`
`If yes, explain:
`
`Name of
`
`person completing form: Christy Cottrell
`Title: Consumer Safety Offcer
`Date: 4-1-09
`
`Name of OfficelDivision Director signing form: Robert Justice, MD
`Title: Division Director, DDOP
`
`Form OGD-:Ol 1347; Revised 05/1012004; 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.
`/s/
`Christy Cottrell
`4/1/2009 02: 00: 45 PM
`
`Robert Justice
`4/1/2009 06: 35: 17 PM
`
`

`

`PEDIATRIC PAGE
`(Complete for all filed original applications and effcacy supplements)
`Supplement Number: n/a
`NDNBLA#: NDA 22-334
`NDA Supplement Type (e.g. SE5): n/a
`PDUFA Goal Date: 3-30-09
`Division Name:DDOP
`Stamp Date: 6/30/2008
`Proprietary Name: Afinitor
`Established/Generic Name: everolimus
`Dosage Form: Tablets
`Appl icanUSponsor: Novartis
`Indication(s) previously approved (please complete this question for supplements and Type 6 NDAs only):
`
`(1)_(2)_(3)_
`
`Q1: Is this application
`
`(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 applicati on(s):l
`(Attach a completed Pediatric Page for each indication in current app!ication.)
`Indication: Advanced renal cell carcinoma
`in response to a PREA PMR? Yes D Continue
`No i: Please proceed to Question 2.
`If Yes, NDNBLA#: _ Supplement #:_ PMR #::.
`Does the division agree that this is a complete respo"nse to the PM R?
`D Yes. Please proceed to Section D.
`D No. Please proceed to Question 2 and complete the Pediatric Page, as applicable.
`Q2: Does this application provide for (If yes, please check all categories that apply and proceed to the next
`question):
`(a) NEW ~ active ingredient(s) (includes new combination); D indication(s); D dosage form; D dosing
`regimen; or D route of administration?*
`(b) D No. PREA does not apply. Skip to signature block. "
`also trigger PREA.
`
`* Note for CDER: SE5, SE6, and SE7 submissions may
`
`Q3: Does this indication have orpha n designation?
`DYes. PREA does not apply. Skip to signature block.
`i: No. Please proceed to the next question.
`Q4: Is there a full waiver for all pediatric age groups for this indication (check one)?
`
`i: Yes: (Complete Section A.)
`D No: Please check all that apply:
`D Partial Waiver for selected pediatric subpopulations (Com plete Sections B)
`D Deferred for some or all pediatric subpopulations (Com plete Sections C)
`D Completed for some or all pediatric subpopulations (Com plete Sections D)
`D Appropriately Labeled for some or all pediatric subpopulations (Com plete Sections E)
`D Extrapolation in One or More Pediatric Age Groups (Com plete Section F)
`(Please note that Section F may be used alone or in addition to Sections C, D, and/or E.)
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (ederpmhs(tÌifd:i.hhs.g(l\') OR AT 301-796-0700.
`
`

`

`NDA/BLA# NDA 22-334NDA 22-334NDA 22-334NDA 22-334NDA 22-334
`
`Page
`
`2
`
`¡ Section A: Fully Waived Studies (for all pediatric age groups)
`
`Reason(s) for full waiver: (check, and attach a brief justification for the reason(s) selected)
`~ Necessary studies would be impossible or highly impracticable because:
`o Disease/condition does not exist in children
`~ Too few children with disease/condition to study
`D Other (e.g., patients geographically dispersed):_
`o Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients AND is not likely to be used in a substantial num ber of pediatric patients.
`o 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 incl uded in the labeling. )
`o Evidence strongly suggests that productwould be ineffective in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be incl uded in the labeling. )
`D 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 stuçlies 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. .
`¡Section B: Partially Waived Studies (for selected pediatric subpopulations)
`
`Check subpopulation(s) and reason for which studies are being partially waived (fil in applicable criteria
`below):
`Note: If Neonate includes premature infants, list minimum and maximum age in "gestational age" (in weeks).
`
`minimum
`
`maximum
`
`Not
`feasible#
`
`Reason (see below for further detail):
`Not meaningful
`therapeutic
`benefit*
`
`i neffective or
`unsafeT
`
`Formulation
`failedd
`
`- wk.-
`0 Neonate - wk. -
`0
`D
`mo.
`mo.
`0
`0 Other
`_yr._mo. _yr._ mo.
`D
`0
`0
`0 Other
`_yr._mo. _yr._ mo.
`0
`0 Other
`_yr._ mo. _yr._mo.
`D
`0
`0 Other
`_yr._mo. _yr._mo.
`D
`Are the indicated age ranges (above) based on weight (kg)? 0 No; DYes.
`Are the indicated age ranges (above) based on Tanner Stage? 0 No; 0 Yes.
`Reason(s) for partial waiver (check reason corresponding to the category checked above, and attach a brief
`justification):
`# Not feasible:
`o Necessary studies would be impossible or highly impracticable because:
`o Disease/condition does not exi st in children
`
`0
`0
`0
`0
`0
`
`0
`0
`0
`0
`0
`
`o Too few children with disease/condition to study
`
`o Other (e.g., patients geographically dispersed):_
`
`* Not meaningful therapeutic benefit:
`o Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VI EMAIL (cderpmhsÛi,fda.hbs.gov) OR AT 301-796-0700.
`
`

`

`NDNBLA# NDA 22-334NDA 22-334NDA 22-334NDA 22-334NDA 22-334
`
`Page
`
`3
`
`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 s ubpopulation(s).
`
`t Ineffective or unsafe:
`D 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 incl uded in the labeling.)
`D 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 incl uded in the labeling.)
`D 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. )
`ß Formulation failed:
`D Applicant can demonstrate that reasonable attem pts to produce a pediatric formulation necessary for
`this/these pediatric subpopulation(s) have failed. (Note: A partial waiver on this ground may only cover
`the pediatric subpopulation(s) requiring that for mulation. 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.)
`
`o 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 ne eded because the
`drug is appropriately labeled in one or more pediatric subpopulations (if so, proceed to Secti on 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 mar e than one of these options may apply for this indication to cover all of the
`pediatric subpopul ations.
`
`Appears This Way
`On Original
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpinhs(æfd:i.hhs.gov) OR AT 301-796-0700.
`
`

`

`NDAlBLA# NDA 22-334NDA 22-334NDA 22-334NDA 22-334NDA 22-334
`
`Page
`
`4
`
`ISection C: Deferred Studies (for selected pediatric subpopulations).
`which pediatric studies are being deferred (and fil in applicable reason
`
`Check pediatric subpopulation(s) for
`
`below):
`
`Deferrals (for each or all age groups):
`
`Reason for Deferral
`
`Population
`
`minimum
`
`maximum
`
`- wk.-
`- wk.-
`mo.
`mo.
`_yr._mo. _yr._ mo.
`_yr._mo. _yr._ mo.
`_yr._mo. _yr._ mo.
`_yr._mo. _yr._mo.
`
`0 Neonate
`0 Other
`0 Other
`0 Other
`0 Other
`0 All Pediatric
`Populations
`Date studies are due (mm/dd/yy):_
`
`o yr. 0 mo.
`
`16 yr. 11 mo.
`
`Effcacy Data
`
`Ready
`Need
`for
`Additional
`Approva Adult Safety or
`I in
`Adults
`0
`0
`0
`0
`0
`0
`
`0
`0
`0
`0
`0
`0
`
`Other
`Appropriate
`Reason
`(specify
`below)*
`
`0
`0
`0
`0
`0
`0
`
`Applicant
`Certification
`t
`
`Received
`
`0
`0
`0
`0
`0
`0
`
`Are the indicated age ranges (~bove) based on weight (kg)?
`Are the indicated age ranges (above) based on Tanner Stage?
`
`o No; o
`
`o No; o
`
`Yes.
`Yes.
`
`* Other Reason:
`
`t Note: Studies may only be deferre d 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 w ill 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 w ill
`be conducted with due diligence and at the earliest possible time. This requirement should be communicated
`letter that specifi es a required study as a post-
`
`to the applicant in an appropriate manner (e.g., in an approval
`
`marketing commitment.)
`If all of the pediatric subpopulations have been covere d through partial waivers and deferrals, Pediatric Page is
`complete and should be signed. If not, compl ete the rest of the Pediatric Page as applicable.
`
`IF THERE ARE QUESTIONS. PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdemmhs:á1fda.hhs.gov) OR AT 301-796-0700.
`
`

`

`NDA/BLA# NDA 22-334NDA 22-334NDA 22-334NDA 22-334NDA 22-334
`
`Page 5
`
`I Section D: Completed Studies (for some or all pediatric subpopulations).
`
`Pediatric subpopulation(s) in which studies have been completed (check below):
`
`minimum
`
`maximum
`
`- wk.- mo. - wk.- mo.
`
`_yr._mo.
`_yr._mo.
`_yr._mo.
`_yr._mo.
`o yr. 0 mo.
`
`_yr._mo.
`_yr._mo.
`_yr._mo.
`_yr._mo.
`16 yr. 11 mo.
`
`Population
`0 Neonate
`0 Other
`0 Other
`0 Other
`0 Other
`0 All Pediatric Subpopulations
`Are the indicated age ranges (above) based on weight (kg)? 0 No; DYes.
`Are the indicated age ranges (above) based on Tanner Stage? 0 No; 0 Yes.
`Note: If there are no further pediatric subpopulations to cover based on pa rtial waivers, deferrals and/or
`completed studies, Pediatric Page is complete and should be signed. If not, complete the r est of the Pediatric
`Page as applicable.
`
`PeRC Pediatric Assessment form
`attached?
`
`YestJ
`YesD
`YesD
`YesD
`YesD
`
`Yes
`
`0
`
`NoO
`NoO
`NoO
`NoO
`NoO
`NoO
`
`I Section E: Drug Appropriately Labeled (for some or all pediatric subpopulations):
`
`Additional pediatric studies are not necessary in the following pediatric subpopulation(s) because product is
`appropriately labeled for the indication being reviewed:
`Population
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric Subpopulations
`
`maximum
`
`- wk.- mo.
`_yr._ mo.
`_yr._ mo.
`_yr._mo.
`_yr._mo.
`16 yr. 11 mo.
`
`0
`0
`0
`0
`0
`0
`Are the indicated age ranges (above) based on weight (kg)? 0 No; 0 Yes.
`Are the indicated age ranges (above) based on Tanner Stage? 0 No; 0 Yes.
`If all pediatric subpopulations have been covered based on par tial waivers, deferrals, completed studies,
`and/or existing appropriate labeling, thi s Pediatric Page is complete and should be signed. If not, complete the
`rest of the Pediatric Page as applicable. .
`
`minimum
`
`- wk.- mo.
`
`_yr._mo.
`_yr._mo.
`_yr._mo.
`_yr._mo.
`o yr. 0 mo.
`
`,i 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
`pediatric subpopulations if (and only if) (1) the course of the disease/conditi on AND (2) the effects of the
`product are sufficiently similar between the reference population and the pediatric subpopulati on for which
`information wil be extrapolated. Extrapolation of effic acy from studies in adults and/or other children usually
`requires supplementation with other information obtained from the target pediatric subpopulation, such as
`IF THERE ARE QUESTIONS, PLEASE CONTACT TH CDER PMHS VI EMA (cderpmhs(il\fda.hbs.gov) OR AT 301-796-0700.
`
`

`

`NDNBLA# NDA 22-334NDA 22-334NDA 22-334NDA 22-334NDA 22-334
`
`Page 6
`
`pharmacokinetic and safety st udies. Under the statute, safety cannot be extrapo lated.
`
`Pediatric studies are not necessary in the following pediatric subpopulation(s) be cause efficacy can be
`extrapolated from adequate and well-controlled studies in adults and/or other pediatric subpopulations:
`Extrapolated from:
`
`Population
`
`minimum
`
`maximum
`
`Adult Studies?
`
`Other Pediatric
`Studies?
`0
`0
`0
`0
`0
`0
`
`- wk.- mo. - wk.- mo.
`_yr._ mo.
`_yr._mo.
`_yr._mo.
`_yr._mo.
`
`_yr._mo.
`_ yr. _ mo.
`_yr._mo.
`_yr._mo.
`
`o yr. 0 mo.
`
`16 yr. 11 mo.
`
`0
`0 Neonate
`0
`0 Other
`0 Other
`0
`0
`0 Other
`0
`0 Other
`0
`0 All Pediatric
`Subpopulations
`Are the indicated age ranges (above) based on weight (kg)? 0 No; 0 Yes.
`Are the indicated age ranges (above) based on Tanner Stage? 0 No; 0 Yes.
`Note: If extrapolating data from either adult or ped iatric studies, a description of the sc ientific data supporting
`the extrapolation must be included in any pertinent review s for the application.
`If there are additional indications, pI ease complete the attachment for each one of those indications.
`Otherwise, this Pediatric Page is complete and should be signed and entered into DFS or DAR RTS as
`appropriate after clearance by PeRC.
`This page was completed by:
`
`(See êlPfJended electronic: signature page)
`
`Regulatory Project Manager
`
`(Revised: 6/2008)
`
`NOTE: If you have no other indications for this application, you may delete the attachments from this
`document.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL rcdei-pmhS((iifda.hhs.gov) OR AT 301-796-0700.
`
`

`

`NDA/BLA# NDA 22-334NDA 22-334NDA 22-334NDA 22-334NDA 22-334
`
`Page 7
`
`Attachment A
`(This attachment is to be completed for those applications with multiple indications only.)
`
`Indication #2:
`
`Q1: Does this indication have orpha n designation?
`DYes. PREA does not apply. Skip to signature block.
`D No. Please proceed to the next question.
`Q2: Is there a full waiver for all pediatric age groups for this indication (check one)?
`D Yes: (Complete Section A.)
`D No: Please check all that apply:
`D Partial Waiver for selected pediatric subpopulations (Com plete Sections B)
`(Com plete Sections C)
`D Completed for some or all pediatric subpopulations (Com plete Sections D)
`D Appropriately Labeled for some or all pediatric subpopulations (Com plete Sections E)
`D Extrapolation in One or More Pediatric Age Groups (Com plete Section F)
`(Please note that Section F may be used alone or in addition to Sections C, 0, and/or E.)
`
`D Deferred for some or all pediatric subpopulations"
`
`I Section A: Fully Waived Studies (for all pediatric age groups)
`
`Reason(s) for full waiver: (check, and attach a brief justification for the reason(s) selected)
`D Necessary studies would be impossible or highly impracticable because:
`D Disease/condition does not exist in children
`D Too few children with disease/condition to study
`D Other (e.g., patients geographically dispersed):_
`D Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients AND is not likely to be used in a substantial num ber of pediatric patients.
`o 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 incl uded in the labeling. )
`o 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 incl uded in the labeling. )
`o 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 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 signe.d.
`
`IF THRE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmbsÚ'Ndii.bbs.gov) OR AT 301-796-0700.
`
`

`

`NDA/BLA# NDA 22-334NDA 22-334NDA 22-334NDA 22-334NDA 22-334
`
`Page 8
`
`ISection B: Partially Waived Studies (for selected pediatric subpopulations)
`Check subpopulation(s) and reason for which studies are being partially waived (fil in applicable criteria
`below):
`
`Note: If Neonate includes premature infants, list minimum and maximum age in "gestational
`
`age" (in weeks).
`
`minimum
`
`maximum
`
`- wk.-
`
`Reason (see below for further detail):
`Not meaningful
`therapeutic
`benefit*
`
`Ineffective or
`unsafeT
`
`Formulation
`failedt.
`
`0
`0
`0
`0
`0
`
`0
`0
`0
`0
`0
`
`Not
`feasible#
`0 Neonate - wk.-
`0
`0
`mo.
`mo.
`0 Other
`0
`0
`mo.
`mo.
`yr.
`yr.
`0 Other
`0
`0
`_yr.
`mo.
`mo.
`yr.
`0
`0 Other
`0
`_yr._mo. _yr._ mo.
`0
`0 Other
`0
`mo.
`mo.
`yr.
`yr.
`Are the indicated age ranges (above) based on weight (kg)? 0 No; 0 Yes.
`Are the indicated age ranges (above) based on Tanner Stage? 0 No; 0 Yes.
`Reason(s) for partial waiver (check reason corresponding to the category checked above, and attach a brief
`
`justification): .
`
`# Not feasible:
`o Necessary studies would be impossible or highly impracticable because:
`o Disease/condition does not exi st in children
`
`o Too few children with disease/condition to study
`
`o Other (e.g., patients geographically dispersed):_
`
`* Not meaningful therapeutic benefit:
`o Product does not repr,esent 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). .
`
`t Ineffective or unsafe:
`D 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 incl uded in the labeling.)
`o 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 incl uded in the labeling.)
`D 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.)
`L\ Formulation failed:
`D Applicant can demonstrate that reasonable attem pts to produce a pediatric formulation necessary for
`this/these pediatric subpopulation(s) have failed. (Note: A partial waiver on this ground may only cover
`the pediatric subpopulation(s) requiring that for mulation. An applicant seeking a partial waiver on this
`ground must submit documentation detailng why a pediatric formulation cannot be developed. This
`submission wil be posted on FDA's website if waiver is granted.)
`
`o Justification attached.
`For those pediatric subpopulations for which studies have not been waived, there must be (1) corresponding
`study plans that have been defer red (if so, proceed to Section C and complete the PeRC Pediatric Plan
`Template); (2) submited studies that have been completed (if so, proceed to Section D and complete the
`PeRC Pediatric Assessment form); (3) additonal studies in other age groups that are not ne eded because the
`IF THRE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhS(âlfda.hbs.g(w) OR AT 301-796-0700.
`
`

`

`NDA/BLA# NDA 22-334NDA 22-334NDA 22-334NDA 22-334NDA 22-334
`
`Page 9
`
`drug is appropriately labeled in one or more pediatric subpopulations (if so, proceed to Secti on 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 all of the
`pediatric subpopul ations.
`
`ISection C: Deferred Studies (for some or all pediatric subpopulations).
`Check pediatric subpopulation(s) for which pediatric studies are being deferred (and fil in applicable reason
`below):
`
`Deferrals (for each or all age groups):
`
`Reason for Deferral
`
`Population
`
`minimum
`
`maximum
`
`- wk.-
`
`- wk.-
`
`mo.
`mo.
`_yr._mo. _yr._mo.
`_yr._mo. _yr._ mo.
`_yr._mo. _yr._mo.
`_yr._mo. _yr._mo.
`
`0 Neonate
`0 Other
`0 Other
`0 Other
`0 Other
`D All Pediatric
`Populations
`Date studies .are due (mm/dd/yy): _
`
`Ready
`for
`Approva
`I in
`Adults
`
`Need
`Additional
`Adult Safety or
`Effcacy Data
`
`Other
`Appropriate
`Reason
`(specify
`below)*
`
`0
`0
`0
`0
`0
`0
`
`0
`0
`0
`0
`0
`0
`
`0
`0
`0
`0
`0
`D
`
`Applicant
`Certification
`t
`
`Received
`
`0
`0
`0
`0
`0
`0
`
`o yr. 0 mo.
`
`16 yr. 11 mo.
`
`Are the indicated age ranges (above) based on weight (kg)?
`Are the indicated age ranges (above) based on Tanner Stage?
`
`D No; o
`
`Yes.
`D No; DYes.
`
`* Other Reason:
`
`conducted with due diligence and at the earliest possible time, and a timeline for the completion of
`
`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 w ill be
`the studies.
`If st