CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`203794Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`
`
`PMR/PMC Development Template
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`
`NDA #/Product Name:
`
`PMR Description:
`
`NDA 203794/Nucynta (tapentadol) oral solution, 20 mg/mL
`Deferred pediatric study under PREA: A pharmacokinetic, efficacy, and
`safety study of Nucynta for the management of moderate to severe
`acute pain in pediatric patients ages 6 to less than 17 years.
`
`Final Protocol Submission:
`Study/Trial Completion:
`Final Report Submission:
`Other: N/A
`
` 05/31/2014
` 09/30/2018
` 03/31/2019
`
`
`
`
`PMR Schedule Milestones:
`
`
`
`
`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a
`pre-approval requirement. Check type below and describe.
` Unmet need
` Life-threatening condition
` Long-term data needed
` Only feasible to conduct post-approval
` Prior clinical experience indicates safety
` Small subpopulation affected
` Theoretical concern
` Other
`
`
`
`We are deferring submission of this required pediatric study (to evaluate the
`pharmacokinetics, efficacy, and safety of Nucynta in pediatric patients ages 6 to less than
`17 years) for this application because Nucynta oral solution is ready for approval for use in
`adults and the pediatric study has not been completed.
`
`
`
`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is
`a FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new
`safety information.”
`
`To obtain adequate data to describe the dosing, efficacy, and safety of Nucynta in pediatric patients
`ages 6 to less than 17 years.
`
`PMR/PMC Development Template
`
`Last Updated 10/15/2012
`
`Page 1 of 3
`
`Reference ID: 3203460
`
`

`

`
`3. If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
` Accelerated Approval (subpart H/E)
` Animal Efficacy Rule
` Pediatric Research Equity Act
` FDAAA required safety study/clinical trial
`
`
`
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
` Assess a known serious risk related to the use of the drug?
` Assess signals of serious risk related to the use of the drug?
` Identify an unexpected serious risk when available data indicate the potential for a serious
`risk?
`
`
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
` Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to
`assess or identify a serious risk
`
`
`
` Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the
`FDA is required to establish under section 505(k)(3) has not yet been established and is thus
`not sufficient to assess this known serious risk, or has been established but is nevertheless not
`sufficient to assess or identify a serious risk
`
` Study: all other investigations, such as investigations in humans that are not clinical trials as
`defined below (e.g., observational epidemiologic studies), animal studies, and laboratory
`experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a
`serious risk
`
`
`
`
`
` Clinical trial: any prospective investigation in which the sponsor or investigator determines
`the method of assigning investigational product or other interventions to one or more human
`subjects?
`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the
`study or trial will be performed in a subpopulation, list here.
`The study must evaluate the pharmacokinetics, efficacy, and safety of Nucynta (tapentadol)
`in pediatric patients ages 6 to less than 17 years.
`
`
`Required
` Observational pharmacoepidemiologic study
` Registry studies
` Primary safety study or clinical trial
` Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
` Thorough Q-T clinical trial
` Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`
`PMR/PMC Development Template
`
`Last Updated 10/15/2012
`
`Page 2 of 3
`
`Reference ID: 3203460
`
`

`

`
`
`
`
`Continuation of Question 4
`
`
` Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
` Pharmacokinetic studies or clinical trials
` Drug interaction or bioavailability studies or clinical trials
` Dosing trials
` Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
` Meta-analysis or pooled analysis of previous studies/clinical trials
` Immunogenicity as a marker of safety
` Other (provide explanation)
`Pharmacokinetic, efficacy, and safety study or clinical trial
`
`Agreed upon:
` Quality study without a safety endpoint (e.g., manufacturing, stability)
` Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
`background rates of adverse events)
` Clinical trials primarily designed to further define efficacy (e.g., in another condition,
`different disease severity, or subgroup) that are NOT required under Subpart H/E
` Dose-response study or clinical trial performed for effectiveness
` Nonclinical study, not safety-related (specify)
`
` Other
`
`
`
`5. Is the PMR/PMC clear, feasible, and appropriate?
` Does the study/clinical trial meet criteria for PMRs or PMCs?
` Are the objectives clear from the description of the PMR/PMC?
` Has the applicant adequately justified the choice of schedule milestone dates?
` Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine
`feasibility, and contribute to the development process?
`
`
`PMR/PMC Development Coordinator:
` This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine
`the safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug
`quality.
`
`PMR/PMC Development Template
`
`Last Updated 10/15/2012
`
`Page 3 of 3
`
`Reference ID: 3203460
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DOMINIC CHIAPPERINO
`10/15/2012
`
`JUDITH A RACOOSIN
`10/15/2012
`
`Reference ID: 3203460
`
`

`

`
`
`PMR/PMC Development Template
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`
`NDA #/Product Name:
`
`PMR Description:
`
`NDA 203794/Nucynta (tapentadol) oral solution, 20 mg/mL
`Deferred pediatric study under PREA: A pharmacokinetic, efficacy, and
`safety study of Nucynta for the management of moderate to severe
`acute pain in pediatric patients ages birth to 5 years.
`
`Final Protocol Submission:
`Study/Trial Completion:
`Final Report Submission:
`Other: N/A
`
` 03/31/2017
` 07/31/2021
` 12/31/2021
`
`
`
`
`PMR Schedule Milestones:
`
`
`
`
`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a
`pre-approval requirement. Check type below and describe.
` Unmet need
` Life-threatening condition
` Long-term data needed
` Only feasible to conduct post-approval
` Prior clinical experience indicates safety
` Small subpopulation affected
` Theoretical concern
` Other
`
`
`
`We are deferring submission of this required pediatric study (to evaluate the
`pharmacokinetics, efficacy, and safety of Nucynta in pediatric patients ages birth to 5 years)
`for this application because Nucynta oral solution is ready for approval for use in adults and
`the pediatric study has not been completed.
`
`
`
`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is
`a FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new
`safety information.”
`
`To obtain adequate data to describe the dosing, efficacy, and safety of Nucynta in pediatric patients
`ages birth to 5 years.
`
`PMR/PMC Development Template
`
`Last Updated 10/15/2012
`
`Page 1 of 3
`
`Reference ID: 3203486
`
`

`

`
`3. If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
` Accelerated Approval (subpart H/E)
` Animal Efficacy Rule
` Pediatric Research Equity Act
` FDAAA required safety study/clinical trial
`
`
`
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
` Assess a known serious risk related to the use of the drug?
` Assess signals of serious risk related to the use of the drug?
` Identify an unexpected serious risk when available data indicate the potential for a serious
`risk?
`
`
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
` Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to
`assess or identify a serious risk
`
`
`
` Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the
`FDA is required to establish under section 505(k)(3) has not yet been established and is thus
`not sufficient to assess this known serious risk, or has been established but is nevertheless not
`sufficient to assess or identify a serious risk
`
` Study: all other investigations, such as investigations in humans that are not clinical trials as
`defined below (e.g., observational epidemiologic studies), animal studies, and laboratory
`experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a
`serious risk
`
`
`
`
`
` Clinical trial: any prospective investigation in which the sponsor or investigator determines
`the method of assigning investigational product or other interventions to one or more human
`subjects?
`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the
`study or trial will be performed in a subpopulation, list here.
`The study must evaluate the pharmacokinetics, efficacy, and safety of Nucynta (tapentadol)
`in pediatric patients ages birth to 5 years.
`
`
`Required
` Observational pharmacoepidemiologic study
` Registry studies
` Primary safety study or clinical trial
` Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
` Thorough Q-T clinical trial
` Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`
`PMR/PMC Development Template
`
`Last Updated 10/15/2012
`
`Page 2 of 3
`
`Reference ID: 3203486
`
`

`

`
`
`
`
`Continuation of Question 4
`
`
` Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
` Pharmacokinetic studies or clinical trials
` Drug interaction or bioavailability studies or clinical trials
` Dosing trials
` Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
` Meta-analysis or pooled analysis of previous studies/clinical trials
` Immunogenicity as a marker of safety
` Other (provide explanation)
`Pharmacokinetic, efficacy, and safety study or clinical trial
`
`Agreed upon:
` Quality study without a safety endpoint (e.g., manufacturing, stability)
` Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
`background rates of adverse events)
` Clinical trials primarily designed to further define efficacy (e.g., in another condition,
`different disease severity, or subgroup) that are NOT required under Subpart H/E
` Dose-response study or clinical trial performed for effectiveness
` Nonclinical study, not safety-related (specify)
`
` Other
`
`
`
`5. Is the PMR/PMC clear, feasible, and appropriate?
` Does the study/clinical trial meet criteria for PMRs or PMCs?
` Are the objectives clear from the description of the PMR/PMC?
` Has the applicant adequately justified the choice of schedule milestone dates?
` Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine
`feasibility, and contribute to the development process?
`
`
`PMR/PMC Development Coordinator:
` This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine
`the safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug
`quality.
`
`PMR/PMC Development Template
`
`Last Updated 10/15/2012
`
`Page 3 of 3
`
`Reference ID: 3203486
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DOMINIC CHIAPPERINO
`10/15/2012
`
`JUDITH A RACOOSIN
`10/15/2012
`
`Reference ID: 3203486
`
`

`

`Division of Anesthesia, Analgesia, and Addiction Products
`
`REGULATORY PROJECT MANAGER LABELING REVIEW
`
`
`
`Application: NDA 203794
`
`Name of Drug: Nucynta (tapentadol) oral solution, 20 mg/mL, for proposed indication,
`management of moderate to severe acute pain in adults
`
`Applicant: Janssen Pharmaceuticals, Inc.
`
`
`Labeling Reviewed
`
`
`Submission Date: Orig. December 15, 2011; revised labeling in July 12, 2012 amendment;
`revised Carton & Container labels in August 3, 2012 amendment; and final revised labeling in
`October 15, 2012 amendment.
`
`
`Receipt Date: Submissions received December 15, 2011, and July 12, August 3, and October
`15, 2012
`
`
`
`Background and Summary Description:
`NDA 203794 for Nucynta oral solution represents a new dosage form from the already-approved
`NDA 022304 for Nucynta (tapentadol) immediate-release tablets. The Sponsor’s original NDA
`submission on December 15, 2011, contained their proposed package insert and Medication
`Guide intended to be common labeling with already-approved Nucynta immediate-release
`tablets. The patient labeling for the oral solution also includes Instructions for Use to provide
`detailed instructions for patients to describe how to accurately administer their dose of Nucynta
`oral solution. DMEPA, the Patient Labeling Team in DMPP, and both professional and
`consumer reviewers in OPDP all filed separate reviews in DARRTS for Nucynta oral solution
`labeling.
`
`
`Review
`
`
`The FDA sent a broad set of comments to the Sponsor on June 13, 2012, concerning the package
`insert and Medication Guide, instructing the Sponsor to submit revised labeling for Nucynta oral
`solution that is not based on common labeling with Nucynta IR tablets. The Sponsor was also
`directed to make Nucynta oral solution labeling more consistent where possible with updated
`labeling recently negotiated for Nucynta ER (NDA 200533). The Sponsor resubmitted the
`package insert, Medication Guide, and Instructions for Use on July 12, 2012.
`
`The core review team members incorporated their recommended labeling changes to the group-
`edited package insert and the resulting substantially complete package insert was provided to the
`consulted groups, OPDP and PLT, on September 6, 2012.
`
`
`1
`
`Reference ID: 3203583
`
`

`

`
`The information request (email) to Sponsor dated October 10, 2012, concerning the package
`insert, Medication Guide, and Instructions for Use, incorporated the labeling recommendations
`of the core review team and of PLT and OPDP, based on their reviews in DARRTS. After an
`additional exchange of comments, the Sponsor submitted their final amendment on October 15,
`2012, accepting all FDA revisions.
`
`DMEPA comments about Carton & Container labeling were communicated to the Sponsor in an
`Information Request email on July 12, 2012. Carton & Container labeling was resubmitted on
`August 3, 2012, incorporating all of the changes FDA had requested.
`
`All final labeling is appended to this labeling review.
`
`Recommendations
`
`
`
`
`
`
`
`
`10-15-12
`Date
`
`
`The Nucynta oral solution package insert, Medication Guide, and Instructions for Use submitted
`on October 15, 2012, and the Carton & Container labeling submitted on August 3, 2012,
`represents agreed-upon labeling and can be approved.
`
`
`
`
`
`
`
`
`
`
`Dominic Chiapperino, Ph.D.
`Regulatory Project Manager
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3203583
`
`2
`
`42 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DOMINIC CHIAPPERINO
`10/15/2012
`
`Reference ID: 3203583
`
`

`

`RPM FILING REVIEW
`
`(Including Memo of Filing Meeting)
`To be completed for all new NDAs, BLAs, and Efficacy Supplements [except SE8 (labeling
`change with clinical data) and SE9 (manufacturing change with clinical data]
`
`NDA # 203 794 (original NDA)
`
`A lication Information
`
`Proprietary Name: Nucynta
`Established/Proper Name:
`tapentadol
`Dosage Form: oral solution
`Stren ths: 20 111 mL
`
`Applicant: Janssen Pharmaceuticals, Inc.
`A cut for A .licant (if a 0 licable): Janssen Research & Develo .ment, LLC
`Date of Application: December 15, 2011
`Date of Receipt: December 15. 2011
`Date clock started afier UN: not a licable n/a
`
`PDUFA Goal Date: October 15 2012
`Filim Date: Feb .
`13, 2012
`
`Action Goal Date (if different):
`Date ofFilin Meetin: Janua
`
`same
`31, 2012
`
`
`
`Type of Original NDA:
`AND (if applicable)
`Type of NDA Supplement: n/a
`
`If505(b)(2): Drafl the “505(b)(2) Assessment”form found at:
`h
`://inside. do. ov:9003/CDER/0 ceo 'ewDru s/ImmediateO ce/UCM027499
`and re er to A endirA or urther in ormation.
`
`Review Classification:
`
`Ifthe application includes a complete response to pediatric WR, review
`classification is Priority.
`
`K4 505(b)(l)
`I 505 u 2
`I] 505(b)(1)
`E] 505(b)(2)
`
`D Priority
`
`E] Tropical Disease Priority
`Review Voucher submitted
`Ifa tropical diseasepriority review voucher was submitted, review
`classification is Priority.
`
`
`Resubmission afier withdrawal? E]
`Part 3 Combination Product? No
`
`Resubmission after refuse to file? El
`I Convenience kit/Co-package
`E] Pre-filled drug delivery device/system
`E] Pre-filled biologic delivery device/system
`Ifyt’s, can!!!“ the 0177“ 0fCombination
`Products (OCP) and copy them on all Inter- E] Device coated/impregnated/combined with drug
`Center “"3",“
`[I Device coated/unpregnated/combined with biologic
`E] Drug/Biologic
`E] Separate products requiring cross-labeling
`El Possible combination based on cross-labeling of separate
`products
`C] Other (dru . device/biolo 'cal roduct)
`
`Version: 1/2411 2
`
`Reference ID: 32021 93
`
`1
`
`

`

`
`
`E] Fast Track
`E] Rolling Review
`E] Orphan Designation
`
`E] Rx-to-OTC switch Full
`E] Rx-to-OTC switch, Partial
`[:1 Direct-to—OTC
`
`Other:
`
`E] PMC response
`E] PMR response:
`El FDAAA [505(0)]
`El PREA deferred pediatric studies [21 CFR
`314.55(b)/21 CFR 601.27(b)]
`El Accelerated approval confirmatory studies (21 CFR
`314.510/21 CFR 601.41)
`El Animal rule postmarketing studies to verify clinical
`benefit and safe
`21 CFR 314.610/21 CFR 601.42
`
`Collaborative Review Division (if OTC product): n/a
`
`List referenced IND Number(s): INDs 061345. 105766. and 108134
`
`Goal Dates/Product Names/Classification Pro - rties
`
`PDUFA and Action Goal dates correct in tracking system?
`
`Ifno, ask the document room staff'to correct them immediately.
`These are the dates used or calculating ins
`
`Are the proprietary. established/proper. and applith names
`correct in tracking system?
`
`Ifno, ask the document room staffto make the corrections. Also,
`ask the document room stafl'to add the establishedélroper name
`to the supporting IND(s) ifnot already entered into tracking
`5 stem.
`
`Is the review priority (S or P) and all appropriate
`classifications/properties entered into tracking system (e.g.,
`chemical classification. combination product classification,
`505(b)(2), orphan drug)? For NDAsflVDA supplements, check
`the Application and Supplement Notification Checklistsfor a list
`ofall classifications/properties at:
`h
`://inside. do. ov:9003/CDER/0 ceo usinessProcessSu
`m
`
`orI/ucm163970Jlt
`
`Ifno, ask the document room staffto make the appropriate
`entries.
`
`
`
`Is the application affected by the Application Integrity Policy
`(AIP)? Check the AIP list at:
`
`W“"”‘“‘“°mm“”°‘“m"
`
`II.—
`
`If affected by AIP. has OC/DMPQ been notified of the
`submission? If yes, date notified:
`—mm
`Is Form 3397 (User Fee Cover Sheet) included with
`X
`authorized signature?
`
`n/a
`
`Version: 1/24/12
`
`Reference ID: 3202193
`
`2
`
`

`

`
`
`User Fee Status
`
`Payment for this application:
`
`Ifa userfee is required and it has not been paid (and it E Paid
`is not exempted or waived), the application is
`E] Exempt (orphan. government)
`unacceptableforfilingfollowing a 5-day graceperiod.
`'3 Waived (e.g.. small business‘ public health)
`Review stops. Send Unacceptablefor Filing (07V) letter B Not required
`and contact userfee stafl.‘
`
`Payment of other user fees:
`
`E Not in arrears
`Ifthefirm is in arrearsfor otherfees (regardless of
`whether a userfee has been paidfor this application), D In arrears
`the application is unacceptableforfiling (5-day grace
`period does not apply). Review stops. Send UN letter
`and contact the user ee stai .
`
`IAs/NDA Effica Su lements o
`
`mill—
`Istheapplicationforaduplicateofa listeddrugandeligible --X-_
`
`for a. roval under section 505 ') as an ANDA?
`Is the application for a duplicate of a listed drug whose only
`difference is that the extent to which the active ingredient(s)
`is absorbed or otherwise made available to the site of action
`
`
`
`is less than that of the reference listed drug (RLD)? [see 21
`CFR 314.54 u
`
`Is the application for a duplicate of a listed drug whose only
`difi‘erence is that the rate at which the proposed product’s
`active ingredient(s) is absorbed or made available to the site
`of action is unintentionally less than that of the listed drug
`[see 21 CFR 314.54(b)(2)]?
`
`Ifyou answered yes to any ofthe above questions, the application
`may be refusedforfiling under 21 CFR 314.101(d)(9). Contact
`the (b)(2) review stafl'in the Immediate omce ofNew Drugs
`Is there unexpired exclusivity on the active moiety (e.g., 5-
`year, 3-year, orphan or pediauic exclusivity)?
`Check the Electronic Orange Book at:
`h@://www.accessdata.(do.gov/scriets/cder/ob/detault.ctm
`
`If es, lease list below:
`
`Ifthere is unexpired, 5—year exclusivitv remaining on the active moietyfor the proposed drugproduct, a 505(b)(2)
`application cannot be submitted until the period ofexclusivity expires (unless the applicantprovides paragraph IV
`patent certification; then an application can be submittedfour years afier the date ofapproval.) Pediatric
`exclusivitv will attend both ofthe timefi'ames in this provision by 6 months. 21 CFR 108(b)(2). Unerpired, 3-year
`
`Does another product (same active moiety) have orphan
`exclusivity for the same indication? Check the Orphan Drug
`Designations and Approvals list at:
`
`Version: 1/2411 2
`
`Reference ID: 32021 93
`
`3
`
`

`

`
`
`If another product has orphan exclusivity, is the product
`considered to be the same product according to the orphan
`drug definition of sameness [see 21 CFR 316.3(b)(13)]?
`
`X
`
`Ifyes, consult the Director, Division ofRegulatory Policy II,
`0] Ice 0 Re nlato Poli
`v
`
`Has the applicant requested 5-year or 3-year Waxman-Hatch
`exclusivity? (NDAsAVDA eflicaqi supplements only)
`
`X
`
`If yes. # years requested:
`
`Note: An applicant can receive exclasivitv without requesting it;
`there are, re nestin exclusivitv is not re aired.
`
`Is the proposed product a single enantiomer of a racemic drug
`previously approved for a different therapeutic use (NDAs
`on] )?
`
`If yes, did the applicant: (a) elect to have the single
`enantiomer (contained as an active ingredient) not be
`considered the same active ingredient as that contained in an
`already approved racemic drug, and/or (b): request
`exclusivity pursuant to section 505(u) of the Act (per
`
`OGD/DLPS/LRB.
`
`X
`
`X
`
`Format and Content
`
`I All paper (except for COL)
`IE All electronic
`Do not check mixed submission ifthe only electronic component B IVIiXCd (paper/electronic)
`is the content oflabeling (COL).
`
`I] CTD
`El Non-CTD
`
`If mixed (paper/electronic) submission, which parts of the
`a lication are submitted in electronic format?
`
`FDAAA Section 1 1 l3)? Ifyes, contact Mary Ann Holovac, Director ofDrug Information,
`
`Overall Format/Content
`
`Ifelectronicsubmission,doesitfollowtheeCTD IIIC-
`
`mm-_
`
`Index. Does the submission contain an accurate
`com .rehensive index?
`
`Is the submission complete as required under 21 CFR 314. 50
`(NDAs/NDA efi‘icacy supplements) or under 21 CFR 601.2
`
`
`
`://www fda. ov/downloads/Dru s/GuidanceCon lianceReh lato Information/Guidances/ucn1072349.
`
`
`
`Version: 1/2411 2
`
`Reference ID: 32021 93
`
`4
`
`

`

`
`
`E legible
`E English (or translated into English)
`X] pagination
`X] navigable hyperlinks (electronic submissions only)
`
`If no. exlain.
`
`BLAs only: Companion application received if a shared or
`divided manufacturing arrangement?
`
`If es. BLA #
`Forms and Certifications
`
`Electronicforms and certifications with electronic signatures (scanned, digital, or electronic — similar to BARTS,
`e.g., /s/) are acceptable. Otherwise,paperforms and certifications with hand—written signatures must be included.
`Farms include: userfee cover sheet (3397), application form (356h), patent infonnation (3542a), financial
`disclosure (3454/3455), and clinical trials (3674); Certifications include: debannent certification, patent
`certi cation(s), eld co Icerti cation, and ediatric certi cation.
`
`_Xizmm
`
`Is form FDA 356h included with authorized signature per 21
`CFR 314.50(a)?
`
`Ifforeign applicant, a US. agent must sign theform [see 21 CFR
`
`on the form/attached to the form?
`
`—-II_
`mull—IAs/NDA eflicac sn lements o
`XIII-
`
`Is patent information submitted on form FDA 35423 per 21
`
`5
`
`—EE-—IEI
`Are financial disclosure fomis FDA 3454 and/or 3455
`X
`Due to granted
`included with authorized signature per 21 CFR 54.4(a)(1) and
`“OWN"?T- no [311111031
`(3)?
`studies. including
`bioequivalence
`studies were
`necessary to support
`approval.
`
`Forms must be signed by the APPLICANT, not an Agent [see 21
`CFR 542%”.
`
`Note: Financial disclosure is requiredfor bioequiralence studies
`that are the basis or a I n'oval.
`
`Clinical Trials Database
`Is form FDA 3674 included with authorized signature?
`
`BEE-—
`X
`
`Ifyes, ensure that the application is also coded with the
`supporting document category, “Form 36 74. ”
`
`Ifno, ensure that language requesting submission oftheform is
`included in the acknowledgement letter sent to the a licant
`Debarment Certification
`Is a correctly worded Debarment Certification included with
`authorized si 1 ature?
`
`Emil-—
`X
`
`Version: 1/2411 2
`
`Reference ID: 3202193
`
`

`

`
`
`Certification is not requiredfor supplements ifsubmitted in the
`original application; Ifforeign applicant, m the applicant and
`the US. Agent must sign the certification filer Guidancefor
`Industry: Submitting Debarment Certifications].
`
`Note: Debamlent Certification should use wording in FDCA
`Section 306(k)(1) i.e., “[Name ofapplicant] hereby certifies that it
`did not and will not use in any capacity the services ofany person
`debarred under section 306 ofthe Federal Food, Drug, and
`Cosmetic Act in connection with this application. " Applicant may
`not use wordin . such as, "To the best 0 mv knowled_ e... "
`
`Field Copy Certification
`IAs/NDA effica
`sn. lements on]
`
`NA Comment
`
`For paper submissions only: Is a Field Copy Certification
`(that it is a true copy of the CMC technical section) included?
`
`Field Copy Certification is not needed ifthere is no CMC
`technical section or ifthis is an electronic submission (the Field
`Office has access to the EDR)
`
`Ifmaroon field copyjacketsfrom foreign applicants are received,
`'
`to the a ro riate teId oj ice.
`
`Controlled Substance/Product with Abuse Potential WEI-—
`
`Is an Abuse Liability Assessment, including a proposal for
`scheduling. submitted per 21 CFR 314.50(d)(5)(vii)?
`
`Ifyes, date consult sent to the Controlled Substance Stafi?
`
`For non-NMEs:
`
`Date ofconsult sent to Controlled Substance Stafl: 12/27/11 X
`
`
`
`—EE-—IEI
`PREA
`
`PeRC notified
`
`Does the application nigger PREA?
`
`X
`
`Ifyes, notify PeRC RPM (PeRC meeting is requiredf
`
`Note: NDAs/BLAs/eflicaqr supplementsfor new active ingredients,
`new indications, new dosageforms, new dosing regimens, or new
`routes ofadministration trigger PREIL All waiver & defeITal
`requests, pediatric plans, andpediatric assessment studies must be
`reviewed bv PeRC Irior to a: roval o the m Ivlication/su I lement.
`
`If the application triggers PREA. are the required pediatric
`assessment studies or a full waiver of pediatric studies
`included?
`
`X
`
`://inside fda. ovz9003/CDER/OfficeofNeme s/Pediatn'candMatemalHealthStaff/ucmOZ7829.htm
`2h
`
`
`Version: 1/24/12
`
`Reference ID: 32021 93
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`6
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`

`

`
`
`If studies or full waiver not included, is a request for full
`waiver of pediatric studies OR a request for partial waiver
`and/or deferral with a pediatric plan included?
`
`I no, reuest in 74-d
`
`letter
`
`If a request for full waiver/partial waiver/deferral is
`included, does the application contain the certification(s)
`required by FDCA Section 505B(a)(3) and (4)?
`
`X
`
`X
`
`I no, reuest in 74-da * letter
`
`BPCA (NDAs/NDA eflicacy supplements only):
`
`Is this submission a complete response to a pediatric Written
`Request?
`
`X
`
`Ifyes, notify Pediatric Exclusivity Board RPM (pediatric
`exclusivi determination is re r uired)3
`_EE-—IID
`Is a proposed proprietary name submitted?
`X
`Same name as
`approved immediate-
`
`Ifyes, ensure that the application is also coded with the
`supporting document category, “Proprietary Name/Requestfor
`Review. ”
`
`“516356 tablet
`
`_EEII'L§I-—
`Is a REMS submitted?
`X
`
`Ifyes, send consult to OSE/DRISK and notify OC/
`OSI/DSC/PMSB via the DCRMSRMP mailbox
`
`Prescri ntion Labelin_
`Check all types of labeling submitted.
`
`D Not applicable
`Kt Package Insert (PI)
`D Patient Package Insert (PPI)
`Instructions for Use (IFU)
`Medication Guide (MedGuide)
`Carton labels
`Immediate container labels
`
`
`
`Is Electronic Content of Labeling (COL) submitted in SPL
`format?
`
`I no, re I uest a Iicant to submit SPL be ore the Ilin date.
`Is the PI submitted in PLR format?
`
`3h
`://inside fda. ov:9003/CDER/OfficeofNeme s/PediatricandMatemalHealthStaff/ucmOZ7837.htm
`
`
`://inside fda. ovz9003/CDER/OfficeoiNeme s/Stud End
`intsandLabelin
`evelo mentTeam/ucmO
`
`25576.htm
`
`4 h
`
`Version: 1/24/12
`
`Reference ID: 3202193
`
`7
`
`

`

`
`
`If PI not submitted in PLR format. was a waiver or
`
`X
`
`deferral requested before the application was received or in
`the submission? If requested before application was
`submitted. what is the status of the request?
`
`Ifno waiver or deferral, request applicant to submit labeling in
`PLR armat be are the tliu; date.
`
`container labels) consulted to OPDP?
`
`MedGuide. PPI. IFU (plus PI) consulted to DMPP/PLT?
`(send WORD version ifavailable)
`
`Carton and immediate container labels. PI. PPI sent to
`
`OSE/DMEPA and appropriate CMC review office (OBP or
`ONDQA)?
`
`OTC Labelin_
`Check all types of labeling submitted.
`
`Is electronic content of labeling (COL) submitted?
`
`I no, reuest in 74-dv * letter.
`
`Are annotated specifications submitted for all stock keeping
`units (SKUs)?
`
`If representative labeling is submitted, are all represented
`SKUs defined?
`
`I no, reuest in 74-da letter.
`
`Kt Not Applicable
`I Outer carton label
`I] Immediate container label
`I] Blister card
`I] Blister backing label
`El Consumer Information Leaflet (CIL)
`I] Physician sample
`[I Consumer sample
`
`
`
`Other Consults
`Are additional consults needed? (e. g.. IFU to CDRH; QT
`study report to QT Interdisciplinary Review Team)
`
`mama-—
`X
`
`eei‘ consult s and date 3 sent:
`_EE-—IID
`End-of Phase 2 meeting(s)?
`X
`Date(s): n/a
`
`I yes, distribute minutes be are tlin meetin
`
`Version: 1/2411 2
`
`Reference ID: 3202193
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`8
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`

`

`
`Pre-NDA/Pre-BLA/Pre—Supplemcnt meeting(s)?
`X
`Written/emailed
`comm