CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`203341Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`
`NDA # 203341
`
`
`
`
`
`SUPPL #
`
`
`
`
`
`HFD # 160
`
`Trade Name BOSULIF® Tablets, 100 mg and 500 mg.
`
`Generic Name bosutinib
`
`
`
`
`
`Applicant Name Wyeth Pharmaceuticals, Inc.
`
`Approval Date, If Known
`
`
`
`
`
`PART I
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to
`one or more of the following questions about the submission.
`
`
`
`
`
`
`
`
`
`
`
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
`
`
`
`
` YES
`
`
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`
`
`
`
`NO
`
`
`
`505(b)(1)
`
`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
`
`
`
`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:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3180133
`
`Page 1
`
`

`

`d) Did the applicant request exclusivity?
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`
`5
`
`
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`
` 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?
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`
`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 EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the same
`active moiety as the drug under consideration? Answer "yes" if the active moiety (including other
`esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this
`particular form of the active moiety, e.g., this particular ester or salt (including salts with hydrogen
`or coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate)
`has not been approved. Answer "no" if the compound requires metabolic conversion (other than
`deesterification of an esterified form of the drug) to produce an already approved active moiety.
`
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` YES
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`
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`NO
`
`
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`
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`Reference ID: 3180133
`
`Page 2
`
`

`

`NDA#
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`NDA#
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`NDA#
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`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`NDA#
`NDA#
`NDA#
`
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO THE
`SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary should
`only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`
`PART III
`
`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
`
`
`
`
`
`2. Combination product.
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`approved an application under section 505 containing any one of the active moieties in the drug
`product? If, for example, the combination contains one never-before-approved active moiety and
`one previously approved active moiety, answer "yes." (An active moiety that is marketed under an
`OTC monograph, but that was never approved under an NDA, is considered not previously
`approved.)
`
`YES
`
`
`
`NO
`
`
`
`
`
`
`
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`
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`
`
`Reference ID: 3180133
`
`Page 3
`
`

`

`summary for that investigation.
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`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 of what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been sufficient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`by the applicant or available from some other source, including the published literature)
`necessary to support approval of the application or supplement?
`
`
` YES
`
`
`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:
`
`
`
`NO
`
`
`
`
`
`
`
`
`
`(b) Did the applicant submit a list of published studies relevant to the safety and
`effectiveness of this drug product and a statement that the publicly available data would not
`independently support approval of the application?
`
`
` YES
`
`
`
`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.
`
`
`
`
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`
`
`
`
` YES
`
`
`
`NO
`
`
`
` If yes, explain:
`
`
`
`
`
`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
`
`
`
`
`
`
`
` If yes, explain:
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`Reference ID: 3180133
`
`Page 4
`
`

`

`
`
`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.
`
`
`
`
`(c)
`
`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical
`investigations submitted in the application that are essential to the approval:
`
`
`
`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
`
`YES
`
`
`
`
`
`NO
`
`NO
`
`
`
`
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA in which each was relied upon:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Investigation #1
`
`Investigation #2
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`YES
`
`YES
`
`
`
`
`
`NO
`
`NO
`
`
`
`
`
`
`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?
`
`
`
`
`
`
`
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`
`
`
`Reference ID: 3180133
`
`Page 5
`
`

`

`
`
`
`
`
`
`similar investigation was relied on:
`
`
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
`or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any
`that are not "new"):
`
`
`
`
`
`
`
`4. To be eligible for exclusivity, a new investigation that is essential to 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.
`
`
`Investigation #1
`
`
`
`IND #
`
`
`
`
`
`
`
`
`
`YES
`
`
`Investigation #2
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`IND #
`
`
`
`
`
`
`
`
`
`
`
`
`
`(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?
`
`
`YES
`
`
`
`
`
`
`
`
`
`
`Investigation #1
`
`YES
`
`
`
`
`
`
`
`
`
`
`
`
`
`!
`!
`! NO
`
`
`
`
`
`Reference ID: 3180133
`
`Page 6
`
`

`

`
`
`Explain:
`
`
`
`Investigation #2
`
`
`YES
`Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`! Explain:
`
`
`
`!
`!
`
`! NO
`! 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.)
`
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`If yes, explain:
`
`
`
`
`
`
`
`
`=================================================================
`
`Name of person completing form: CDR Diane Hanner
`Title: Regulatory Project Manger
`Date: August 24, 2012
`
`
`Name of Office/Division Director signing form: Ann T. Farrell, M.D.,
`Title: Director, Division of Hematology Products
`
`
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05
`
`
`
`
`Reference ID: 3180133
`
`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/
`----------------------------------------------------
`
`DIANE C HANNER
`08/24/2012
`
`ANN T FARRELL
`09/04/2012
`
`Reference ID: 3180133
`
`

`

`PEDIATRIC PAGE
`(Complete for all filed original applications and efficacy supplements)
`Supplement Number: NDA Supplement Type (e.g. SE5):
`NDA/BLA#: 203341
`
`Stamp Date: Nov. 17,2011
`
`Division Name:DHP
`
`PDUFA Goal Date:
`Sept 19, 2012
`
`Proprietary Name: BOSULIF®
`Established/Generic Name: bosutinib
`Tablets, 100 mg and 500 mg.
`Dosage Form:
`Applicant/Sponsor: Wyeth Pharmaceuticals, Inc.
`Indication(s) previously approved (please complete this question for supplements and Type 6 NDAs only):
`(1) For the treatment of adult patients with chronic, accelerated, or blast phase Ph+ chronic myelogenous
`leukemia (CML) with resistance, or intolerance to prior therapy.
`(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 application.)
`Indication: For the treatment of adult patients with chronic, accelerated, or blast phase Ph+
`chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.
`Q1: Is this application in response to a PREA PMR?
`Yes
` Continue
` Please proceed to Question 2.
`
`
`
`
`
`
`
`
`No
`
`If Yes, NDA/BLA#:
`Supplement #:
`PMR #:
`
`Does the division agree that this is a complete response to the PMR?
` Yes. Please proceed to Section 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):
` active ingredient(s) (includes new combination);
`(a) NEW
`regimen; or
` route of administration?*
` No. PREA does not apply. Skip to signature block.
`(b)
`* Note for CDER: SE5, SE6, and SE7 submissions may also trigger PREA.
`Q3: Does this indication have orphan designation?
` Yes. PREA does not apply. Skip to signature block.
`
` No. Please proceed to the next question.
`
`
` indication(s);
`
` dosage form;
`
` dosing
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda hhs.gov) OR AT 301-796-0700.
`Reference ID: 3179432
`
`
`

`

`
`
`Page 2
`
`
`
`NDA/BLA# 203341203341203341203341203341
`Q4: Is there a full waiver for all pediatric age groups for this indication (check one)?
` Yes: (Complete Section A.)
`
` No: Please check all that apply:
`
` Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`
` Deferred for some or all pediatric subpopulations (Complete Sections C)
`
` Completed for some or all pediatric subpopulations (Complete Sections D)
`
` Appropriately Labeled for some or all pediatric subpopulations (Complete Sections E)
`
` 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 brief justification for the reason(s) selected)
` Necessary studies would be impossible or highly impracticable because:
`
` Disease/condition does not exist in children
` Too few children with disease/condition to study
` Other (e.g., patients geographically dispersed):
` 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.
` 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.)
` 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.)
` 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.)
` 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 (cderpmhs@fda hhs.gov) OR AT 301-796-0700.
`Reference ID: 3179432
`
`
`
`

`

`NDA/BLA# 203341203341203341203341203341
`
`
`
`
`
`Page 3
`
`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*
`
`Not
`feasible#
`
`Ineffective or
`unsafe†
`
`Formulation
`failed∆
`
`
`
`minimum
`
`maximum
`
` Neonate
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` wk.
` wk.
`mo.
`mo.
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
` Yes.
` No;
`Are the indicated age ranges (above) based on weight (kg)?
` Yes.
` No;
`Are the indicated age ranges (above) based on Tanner Stage?
`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:
`
`Disease/condition does not exist in children
`
`Too few children with disease/condition to study
`
`Other (e.g., patients geographically dispersed):
`* Not meaningful therapeutic benefit:
` 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).
`† Ineffective or unsafe:
` 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.)
` 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.)
` 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.)
`∆ Formulation failed:
` 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 only 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.)
` 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)
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda hhs.gov) OR AT 301-796-0700.
`Reference ID: 3179432
`
`
`
`

`

`Page 4
`
`
`NDA/BLA# 203341203341203341203341203341
`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 subpopulations.
`
`Section 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):
`
`Population
`
`minimum
`
`maximum
`
` Neonate
`
` wk.
`mo.
` yr. mo.
` yr. mo.
` yr. mo.
` yr. mo.
`
` wk.
`mo.
` yr. mo.
` yr. mo.
` yr. mo.
` yr. mo.
`
` Other
` Other
` Other
` Other
` All Pediatric
`Populations
`Date studies are due (mm/dd/yy):
`
`0 yr. 0 mo.
`
`16 yr. 11 mo.
`
`
`
`Reason for Deferral
`
`Ready
`for
`Approva
`l in
`Adults
`
`Need
`Additional
`Adult Safety or
`Efficacy Data
`
`Other
`Appropriate
`Reason
`(specify
`below)*
`
`Applicant
`Certification
`†
`
`Received
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
`
`
` No;
` No;
`
` Yes.
` Yes.
`
`Are the indicated age ranges (above) based on weight (kg)?
`Are the indicated age ranges (above) based on Tanner Stage?
`* Other Reason:
`† 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 (cderpmhs@fda hhs.gov) OR AT 301-796-0700.
`Reference ID: 3179432
`
`
`
`

`

`NDA/BLA# 203341203341203341203341203341
`
`
`
`
`
`Page 5
`
`Section D: Completed Studies (for some or all pediatric subpopulations).
`
`Pediatric subpopulation(s) in which studies have been completed (check below):
`PeRC Pediatric Assessment form
`attached?.
`No
`No
`No
`No
`No
`No
`
`Population
`
`minimum
`
`maximum
`
` Neonate
` Other
` Other
` Other
` Other
` All Pediatric Subpopulations
`
` wk. mo.
` yr. mo.
` yr. mo.
` yr. mo.
` yr. mo.
`0 yr. 0 mo.
`
` wk. mo.
` yr. mo.
` yr. mo.
` yr. mo.
` yr. mo.
`16 yr. 11 mo.
`
`Yes
`Yes
`Yes
`Yes
`Yes
`Yes
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Yes.
` No;
`Are the indicated age ranges (above) based on weight (kg)?
` Yes.
` No;
`Are the indicated age ranges (above) based on Tanner Stage?
`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.
`
`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.
`
`minimum
` wk. mo.
` yr. mo.
` yr. mo.
` yr. mo.
` yr. mo.
`0 yr. 0 mo.
`
` Yes.
` No;
`Are the indicated age ranges (above) based on weight (kg)?
` Yes.
` No;
`Are the indicated age ranges (above) based on Tanner Stage?
`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
`pediatric subpopulations if (and only if) (1) the course of the disease/condition AND (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
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda hhs.gov) OR AT 301-796-0700.
`Reference ID: 3179432
`
`
`
`

`

`NDA/BLA# 203341203341203341203341203341
`pharmacokinetic and safety studies. Under the statute, safety cannot be extrapolated.
`
`
`
`
`
`Page 6
`
`Population
`
`minimum
`
`maximum
`
`Adult Studies?
`
`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:
`Extrapolated from:
`Other Pediatric
`Studies?
`
`
`
`
`
`
` Neonate
` Other
` Other
` Other
` Other
` All Pediatric
`Subpopulations
`
` wk. mo.
` yr. mo.
` yr. mo.
` yr. mo.
` yr. mo.
`
` wk. mo.
` yr. mo.
` yr. mo.
` yr. mo.
` yr. mo.
`
`
`
`
`
`
`
`0 yr. 0 mo.
`
`16 yr. 11 mo.
`
`
`
`
`
` Yes.
` No;
`Are the indicated age ranges (above) based on weight (kg)?
` Yes.
` No;
`Are the indicated age ranges (above) based on Tanner Stage?
`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 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)
`
`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 (cderpmhs@fda hhs.gov) OR AT 301-796-0700.
`Reference ID: 3179432
`
`
`
`

`

`NDA/BLA# 203341203341203341203341203341
`Attachment A
`(This attachment is to be completed for those applications with multiple indications only.)
`
`
`
`
`
`Page 7
`
`
`Indication #2:
`Q1: Does this indication have orphan designation?
` Yes. PREA does not apply. Skip to signature block.
`
` No. Please proceed to the next question.
`
`Q2: Is there a full waiver for all pediatric age groups for this indication (check one)?
`
` Yes: (Complete Section A.)
` No: Please check all that apply:
`
` Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`
` Deferred for some or all pediatric subpopulations (Complete Sections C)
`
` Completed for some or all pediatric subpopulations (Complete Sections D)
`
` Appropriately Labeled for some or all pediatric subpopulations (Complete Sections E)
`
` 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 brief justification for the reason(s) selected)
` Necessary studies would be impossible or highly impracticable because:
`
` Disease/condition does not exist in children
` Too few children with disease/condition to study
` Other (e.g., patients geographically dispersed):
` 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.
` 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.)
` 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.)
` 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.)
` 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 (cderpmhs@fda hhs.gov) OR AT 301-796-0700.
`Reference ID: 3179432
`
`
`
`

`

`NDA/BLA# 203341203341203341203341203341
`
`
`
`
`
`Page 8
`
`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*
`
`Not
`feasible#
`
`Ineffective or
`unsafe†
`
`Formulation
`failed∆
`
`
`
`minimum
`
`maximum
`
` Neonate
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` wk.
` wk.
`mo.
`mo.
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
` Yes.
` No;
`Are the indicated age ranges (above) based on weight (kg)?
` Yes.
` No;
`Are the indicated age ranges (above) based on Tanner Stage?
`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:
`
`Disease/condition does not exist in children
`
`Too few children with disease/condition to study
`
`Other (e.g., patients geographically dispersed):
`* Not meaningful therapeutic benefit:
` Product does not represent a meaningful therapeutic bene