`RESEARCH
`
`
`
`APPLICATION NUMBER:
`202231Orig1s000
`
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`EXCLUSIVITY SUMMARY
`
`
`NDA # 202231
`
`
`
`
`
`SUPPL # N/A
`
`
`
`HFD # N/A
`
`Trade Name None
`
`Generic Name Levothyroxine Sodium for Injection
`
`
`
`
`
`Applicant Name APP Pharmaceuticals, LLC
`
`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
`
`
`
`NO
`
`
`
`
`
`If yes, 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
`
`
`
`If your answer is "no" because you believe the study is a bioavailability study and, therefore,
`not eligible for exclusivity, EXPLAIN why it is a bioavailability study, including your
`reasons for disagreeing with any arguments made by the applicant that the study was not
`simply a bioavailability study.
`
`
`N/A
`
`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
`
`N/A
`
`
`
`d) Did the applicant request exclusivity?
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 2964389
`
`Page 1
`
`
`
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`N/A
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`N/A
`
`
` 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 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.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`
`NDA# 21342
`
`
`
`Levo-T
`
`
`
`Reference ID: 2964389
`
`Page 2
`
`
`
`NDA# 21210
`
`NDA# 21301
`
`Unithroid
`
`Levoxyl
`
`
`
`
`
`
`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
`summary for that investigation.
`
`
`
`
`
`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
`
`
`
`
`
`
`
`
`
`
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`
`Reference ID: 2964389
`
`Page 3
`
`
`
`(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
`
`
`
`
`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.
`
`
`
`
`
`
`
`
`(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.
`
`
`
`
`
`
`
`
`
`
` 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: 2964389
`
`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
`similar investigation was relied on:
`
`
`
`Reference ID: 2964389
`
`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 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
`Explain:
`
`
`
`
`
`
`
`
`
`Reference ID: 2964389
`
`
`
`
`
`
`
`
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`Page 6
`
`
`
`
`
`Investigation #2
`
`
`YES
`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: Linda V. Galgay
`Title: Regulatory Project Manager
`Date: May 25, 2011
`
`
`Name of Office/Division Director signing form: Mary H. Parks, MD
`Title: Director, Division of Metabolism and Endocrinology Products
`
`
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05
`
`
`
`
`Reference ID: 2964389
`
`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/
`----------------------------------------------------
`
`LINDA V GALGAY
`06/22/2011
`
`DRAGOS G ROMAN
`06/23/2011
`
`Reference ID: 2964389
`
`
`
`
`
`
`
`
`
`
`From:
`Sent:
`To:
`Cc:
`
`Subject:
`
`
`Greeley, George
`
`
`
`
`
`Thursday, June 02, 2011 2:21 PM
`Galgay, Linda
`
`
`
`
`
`
`
`
`
`Addy, Rosemary; Mathis, Lisa; Suggs, Courtney; Lee, Catherine 8.;
`
`
`
`
`Elekwachi, Oluchi; Parks, Mary H
`
`
`
`
`NDA 202-231 Levothyroxine Sodium - (Update)
`
`Importance:
`
`High
`
`Attachments:
`Hi Linda,
`
`
`1_Pediatric_Record.pdf
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`The email serves as confirmation of the review for levothyroxine sodium conducted by the
`
`
`
`
`
`
`PeRC PREA Subcommittee on April 13, 2011.
`
`
`
`
`
`
`
`
`
`
`
`
`
`The Division presented a full waiver for all pediatric patients ‘for the indication of
`
`myxedcma coma.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`The PeRC agreed with the Division to grant a full waiver for the indication of myxedcma
`
`
`
`
`
`
`
`
`coma. The pediatric record is attached for Levothyroxine Sodium.
`
`1_Pediatric_Record
`.pdf (62 KB)...
`
`
`
`
`Thank you.
`
`
`George Greeley
`
`
`
`Regulatory Health Project Manager
`
`
`
`
`Pediatric and Maternal Health Stall
`FDA/CDER/ON D
`
`
`
`10903 New Hampshire Avenue
`
`
`
`Bldg. 22, Room 6/167
`
`
`
`Silver Spring, MD 20998—0002
`Phone: 301.796.4025
`
`Email: george.greeley@lda.hhs.gov
`
`® Please consider the environment before printing this e-mail.
`
`
`
`
`
`
`
`
`
`Reference ID: 2970731
`Reference ID: 2970731
`
`
`
`(i/Lt/H'
`
`
`
`PEDIATRIC PAGE
`
`
`
`
`
`
`
`
`(Complete for all filed original applications and efficacy supplements)
`
`
`.JA 202231
`
`
`Division Name: DMEP
`
`Proprietary Name:
`
`
`
`none
`
`
`
`Supplement Number: LILA
`
`
`
`PDUFA Goal Date: 6/30/11
`
`
`
`
`
`
`NDA Supplement Type (e.g. SE5): MA
`
`
`Stamp Date: 8/30/10
`
`
`
`
`
`
`Established/Generic Name: Levothyroxine Sodium for Injection
`
`
`
`
`
`Dosage Form: Lyophilized powder for Injection
`
`
`
`Applicant/Sponsor: APP Pharmaceuticals
`
`
`
`
`
`
`
`
`
`
`
`
`lndic_ation(s) previously approved (please complete this question for supplements and Type 6 NDAs only):
`(drug is a marketed, unapproved product)
`(1)
`
`
`
`
`
`(2) _.__.__
`(3) __
`
`(4)
`
`
`
`
`Yes D Continue
`No IX Please proceed to Question 2.
`
`
`
`
`
`
`
`
`
`
`PMR #:—
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`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): 2
`
`
`
`
`
`
`
`
`
`
`(Attach a completed Pediatric Page for each indication in current application.)
`
`
`Indication: Myxedema Coma
`
`
`
`
`
`
`
`
`Q1: Is this application in response to a PREA PMR?
`
`
`Supplement #:
`If Yes, NDA/BLA#:
`
`
`
`
`
`
`
`
`
`
`
`
`Does the division agree that this is a complete response to the PMR?
`I] Yes. Please proceed to Section D.
`
`
`
`
`
`[I 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 C] active ingredient(s) (includes new combination); E indication(s); E dosage form; IX] dosing
`regimen; or E route of administration?*
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(b) I] 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?
`
`
`
`
`
`
`
`
`I] 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)?
`IE Yes: (Complete Section A.)
`
`
`
`
`E] No: Please check all that apply:
`
`
`
`
`
`
`[:1 Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`
`
`
`
`
`
`
`
`
`E] Deferred for some or all pediatric subpopulations (Complete Sections C)
`
`
`
`
`
`
`
`
`
`
`[3 Completed for some or all pediatric subpopulations (Complete Sections D)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`E] Appropriately Labeled for some or all pediatric subpopulations (Complete Sections E)
`El 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.)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) 0R AT 301-796-0700.
`Reference ID: 2970731
`-
`Reference ID: 2970731
`
`
`
`A
`
`|
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`NDA/BLA# Error! Reference source not found.Error! Reference source not found.Error! Reference
`
`
`
`
`
`source not found.
`Error! Reference source not found.
`Pa e 2
`I Section A: Fully Waived Studies (for all pediatric age groups)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`ason(s) for full waiver: (check, and attach a brief justification for the reason(s) selected)
`8 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
`
`
`
`
`
`
`
`
`
`
`
`
`B Other (e.g., patients geographically dispersed): __
`E] 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.)
`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 includedIn the labeling.)
`El Evidence strongly suggests that product would be ineffective and unsafeIn all pediatric
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`subpopulations (Note: if studies are fully waived on this ground, this information must be included in
`
`the labeling.)
`XI 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. OthenII/ise, 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).
`
`failedA
`
`
`
`
`
`
`Reason (see below for fIIrther detail):
`
`Not meaningful
`therapeutic
`benefit*
`
`
`ineffective or
`unsafe't
`
`Formulation
`
`
`
`
`
`
`
`
`
`
`
`
`[I No; [I Yes.
`Are the indicated age ranges (above) based on weight (kg)?
`
`
`
`
`
`
`
`
`
`
`
`[3 No; I] Yes.
`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:
`
`
`
`
`
`
`
`
`
`E] Necessary studies would be impossible or highly impracticable because:
`Disease/condition does not exist in children
`I]
`
`
`
`
`
`Too few children with disease/condition to study
`[J
`
`
`
`
`
`Other (e.g., patients geographically dispersed): _
`C]
`
`
`
`
`
`
`
`
`Not meaningful therapeutic benefit:
`[I 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).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL tcderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`
`
`Reference ID: 2970731
`Reference ID: 2970731
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`NDA/BLA# Error! Reference source not found.Error! Reference source not found.Error! Reference
`source not found.
`Error! Reference source not found.
`Page 3
`1' Ineffective or unsafe:
`
`
`El 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.)
`El 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.)
`[:1 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 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 '3 website if waiver is granted.)
`E] 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 all of the
`
`pediatric subpopulations.
`-
`
`
`
`
`
`
`Section C: Deferred Studies (for selected pediatric subpopulations).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`‘eck pediatric subpopulation(s) for which pediatric studies are being deferred (and fill in applicable reason
`.ow):
`
`
`
`Applicant
`
`
`
`
`
`Reason for Deferral
`Certification
`
`
`
`
`
`
`
`Deferrals (for each or all age groups):
`
`
`
`
`Ready
`Need
`Other
`
`
`
`Additional
`for
`Afigggite
`
`
`
`
`
`
`Approval Adult Safety or
`(SPeCifY
`
`
`
`
`
`Efficacy Data
`in Adults
`beIOW)*
`_
`
`__El_-E--i-
`__ mo.
`
`
`._mo. IEl-i-m-
`_,. _
`
`
`
`
`._ lain-:-
`—__IEI-i--E-
`_ mo.
`
`——-l:l-:--:-
`_ mo.
`All Pediatric
`
`
`
`
`Populations
`16 yr. 11 mo.
`
`
`
`
`
`
`Date studies are due (mm/dd/yy):
`
`Population
`
`minimum
`
`maXImum
`
`
`
`
`
`
`yr.
`
`
`
`
`
`
`
`
`
`Received
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`a the indicated age ranges (above) based on weight (kg)?
`
`
`
`
`
`
`
`
`
`Are the indicated age ranges (above) based on Tanner Stage?
`
`
`
`* Other Reason:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`[3 No; I] Yes.
`
`
`I] No; I] Yes.
`
`
`
`Reference ID: 2970731
`Reference ID: 2970731
`
`
`
`
`saaaaaE:E":ElE1ElE1
`
`
`
`
`
`
`minimum
`
`maximum
`
`
`
`
`PeRC Pediatric Assessment form
`attached?.
`
`mo.
`wk.
`_ yr. _ mo.
`
`l
`
`mo.
`wk.
`___'yr. _ mo.
`
`' w
`No I]
`
`
`
`
`
`
`
`
`
`_ yr. _ mo. _ yr. _ mo.
`
`_ yr. __ mo.
`
`__ yr. __ mo.
`
`__ yr. _ mo. _ yr. _ mo.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`w
`
`No C]
`
`
`
`
`
`
`
`
`
`
`
`
`NDA/BLA# Error! Reference source not found.Error! Reference source not found.Error! Reference
`
`
`
`
`
`
`
`
`
`
`
`Error! Reference source not found.
`source not found.
`Page 4
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`7‘ Note: Studies may only be deferred if an applicant submits a certification of grounds for deferring the studies,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`'escription of the planned or ongoing studies, evidence that the studies are being conducted or will be
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`iducted 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 theearliest 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):
`
`Population
`
`Neonate
`Other
`
`Other
`Other
`
`iiiiiil l
`
`
`
`
`
`
`
`
`All Pediatric Subpopulations
`
`16 yr. 11 mo.
`0 yr. 0 mo.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`E] No; I] Yes.
`2 the indicated age ranges (above) based on weight (kg)?
`
`
`
`
`
`
`
`
`
`
`
`E] No; [I] Yes.
`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:
`
`
`
`
`
`
`
`
`
`
`
` All Pediatric Subpopulations
`
`
`
`
`
`
`
`
`
`
`
`[:1 No; I] Yes.
`3 the indicated age ranges (above) based on weight (kg)?
`
`
`
`
`
`
`
`
`
`
`
`El No; [:1 Yes.
`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
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`
`
`
`
`
`
`__m0.
`
`_m0.
`
`0 yr. 0 mo.
`
`
`
`
`
`
`
`
`
`
`16 yr. 11 mo.
`
`
`
`
`
`
`Reference ID: 2970731
`Reference ID: 2970731
`
`
`
`
`
`
`
`
`
`
`
`
`
`NDA/BLA# Error! Reference source not found.Error! Reference source not found.Error! Reference
`
`
`
`
`.
`source not found.
`Error! Reference source not found.
`Page 5
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`existing appropriate labeling, this Pediatric Page is complete and should be signed.
`If not, complete the rest of
`
`
`
`
`‘ 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 it) (1) the course of the disease/condition Mg (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:
`
`
`Population
`
`minimum
`
`maXImum
`
`E_——
`
`
`
`
`
`
`
`
`mo.
`
`_ mo.
`
`mo.
`
`_ mo.
`
`
`
`
`Extrapolated from:
`
`Other Pediatric
`
`Studies?
`
`'2
`'
`
`Adult Studies.
`
`
`
`
`All Pediatric
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Are the indicated age ranges (above) based on weight (kg)?
`E] No; I] Yes.
`
`
`
`
`
`
`
`
`
`
`
`I
`Are the indicated age ranges (above) based on Tanner Stage?
`[:1 No; [I 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 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 (cdergmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 2970731
`Reference ID: 2970731
`
`
`
`NDA/BLA# Error! Reference source not found.Error! Reference source not found.Errng Reference
`source not found.
`Error! Reference source not foun