CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`202236Orig1s000
`
`
`OTHER REVIEW(S)
`
`
`
`
`

`

`505(b)(2) ASSESSMENT
`
`NDA # 202236
`
`NDA Supplement #2 S-
`
`Efficacy Supplement Type SE-
`
`DYMISTA
`Proprietary Name:
`Established/Proper Name: azelastine hydrochloride and fluticasone propionate
`Dosage Form:
`Nasal Spray
`Stren hs:
`137 mc /50 mc
`
`Proposed Indication(s): Seasonal Allergic Rhinitis in patients 12 years of age and older
`
`Applicant: Meda Pharmaceuticals
`
`Date of Receipt: April 1. 2011
`
`PDUFA Goal Date: May 1. 2012
`
`Action Goal Date (if different):
`
`GENERAL INFORMATION
`
`1)
`
`Is this application for a recombinant or biologically-derived product and/or protein or peptide
`product OR is the applicant relying on a recombinant or biologically-derived product and/or
`protein or peptide product to support approval of the proposed product?
`
`YES
`
`[I
`
`NOIZ]
`
`If “YES ”contact the (b)(2) review staflin the Immediate Oflice, Oflice ofNew Drugs.
`
`INFORMATION PROVIDED VIA RELIANCE
`
`(LISTED DRUG 0R LITERATURE)
`
`2) List the information essential to the approval of the proposed drug that is provided by reliance
`on our previous finding of safety and efficacy for a listed drug or by reliance on published
`literature. (Ifnot clearly identified by the applicant, this information can usually be derived
`from annotated labeling.)
`
`Source of infonnation* (e.g..
`published literature. name of
`referenced roduct
`Flonase
`NDA 20121
`
`Information provided (e. g..
`pharmacokinetic data, or specific
`sections of labelin
`Label Sections: 5.3. 6.2. 7.2. 7.5. 8.1. 8.3.
`
`8.4. 10. 11. 12.1. 12.3. 13.1. 13.2. 17.9
`
`Reference ID: 31 24549
`
`Page 1
`Version: March 2009
`
`

`

`*each source of information should be listed on separate rows
`
`3) Reliance on information regarding another product (whether a previously approved product
`or from published literature) must be scientifically appropriate. An applicant needs to
`provide a scientific “bridge” to demonstrate the relationship of the referenced and proposed
`products. Describe how the applicant bridged the proposed product to the referenced
`product(s). (Example: BA/BE studies)
`
`The Applicant conducted two pharmacokinetic studies bridging the proposed product
`to the reference products. Trial X-03065-3282 evaluated the proposed product, the
`investigational fluticasone propionate monotherapy, and commercially available
`fluticasone propionate. Trial X-03065-3283 evaluated the proposed product, the
`investigational azelastine hydrochloride product, and commercially available azelastine
`hydrochloride.
`
`RELIANCE ON PUBLISHED LITERATURE
`
`4)
`
`(a) Regardless of whether the applicant has explicitly stated a reliance on published literature
`to support their application, is reliance on published literature necessary to support the
`approval of the proposed drug product (i.e., the application cannot be approved without the
`published literature)?
` YES
` NO
`
`If “NO,” proceed to question #5.
`
`(b) Does any of the published literature necessary to support approval identify a specific (e.g.,
`brand name) listed drug product?
` YES
` NO
`
`If “NO”, proceed to question #5.
`If “YES”, list the listed drug(s) identified by name and answer question #4(c).
`
`(c) Are the drug product(s) listed in (b) identified by the applicant as the listed drug(s)?
` YES
`
` NO
`
`RELIANCE ON LISTED DRUG(S)
`
`Reliance on published literature which identifies a specific approved (listed) drug constitutes
`reliance on that listed drug. Please answer questions #5-9 accordingly.
`
`5) Regardless of whether the applicant has explicitly referenced the listed drug(s), does the
`application rely on the finding of safety and effectiveness for one or more listed drugs
`(approved drugs) to support the approval of the proposed drug product (i.e., the application
`cannot be approved without this reliance)?
`
`
`
`
`
`Page 2
`Version: March 2009
`
`Reference ID: 3124549
`
`

`

` YES
`
` NO
`If “NO,” proceed to question #10.
`
`6) Name of listed drug(s) relied upon, and the NDA/ANDA #(s). Please indicate if the applicant
`explicitly identified the product as being relied upon (see note below):
`
`Name of Drug
`
`NDA/ANDA #
`
`Flonase
`
`
`
`
`
`NDA 20121
`
`
`
`
`
`Did applicant
`specify reliance on
`the product? (Y/N)
`Y
`
`
`
`
`
`Applicants should specify reliance on the 356h, in the cover letter, and/or with their patent
`certification/statement. If you believe there is reliance on a listed product that has not been
`explicitly identified as such by the applicant, please contact the (b)(2) review staff in the
`Immediate Office, Office of New Drugs.
`
`7)
`
`If this is a (b)(2) supplement to an original (b)(2) application, does the supplement rely upon
`the same listed drug(s) as the original (b)(2) application?
` N/A
` NO
`
` YES
`If this application is a (b)(2) supplement to an original (b)(1) application or not a supplemental
`application, answer “N/A”.
`If “NO”, please contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`8) Were any of the listed drug(s) relied upon for this application:
`a) Approved in a 505(b)(2) application?
` YES
` NO
`
`If “YES”, please list which drug(s).
`Name of drug(s) approved in a 505(b)(2) application:
`
`b) Approved by the DESI process?
` YES
` NO
`
`If “YES”, please list which drug(s).
`Name of drug(s) approved via the DESI process:
`
`c) Described in a monograph?
` YES
` NO
`
`If “YES”, please list which drug(s).
`
`Name of drug(s) described in a monograph:
`
`d) Discontinued from marketing?
` YES
`
`
`
` NO
`
`
`
`
`
`Page 3
`Version: March 2009
`
`Reference ID: 3124549
`
`

`

`If “YES”, please list which drug(s) and answer question d) i. below.
`If “NO”, proceed to question #9.
`Name of drug(s) discontinued from marketing:
`
`i) Were the products discontinued for reasons related to safety or effectiveness?
` YES
`
` NO
`(Information regarding whether a drug has been discontinued from marketing for
`reasons of safety or effectiveness may be available in the Orange Book. Refer to
`section 1.11 for an explanation, and section 6.1 for the list of discontinued drugs. If
`a determination of the reason for discontinuation has not been published in the
`Federal Register (and noted in the Orange Book), you will need to research the
`archive file and/or consult with the review team. Do not rely solely on any
`statements made by the sponsor.)
`
`9) Describe the change from the listed drug(s) relied upon to support this (b)(2) application (for
`example, “This application provides for a new indication, otitis media” or “This application
`provides for a change in dosage form, from capsule to solution”).
`
`This application provides for a new nasal spray combination.
`
`The purpose of the following two questions is to determine if there is an approved drug product
`that is equivalent or very similar to the product proposed for approval that should be referenced
`as a listed drug in the pending application.
`
`The assessment of pharmaceutical equivalence for a recombinant or biologically-derived product
`and/or protein or peptide product is complex. If you answered YES to question #1, proceed to
`question #12; if you answered NO to question #1, proceed to question #10 below.
`
`10) (a) Is there a pharmaceutical equivalent(s) to the product proposed in the 505(b)(2)
`application that is already approved (via an NDA or ANDA)?
`
`(Pharmaceutical equivalents are drug products in identical dosage forms that: (1) contain
`identical amounts of the identical active drug ingredient, i.e., the same salt or ester of the
`same therapeutic moiety, or, in the case of modified release dosage forms that require a
`reservoir or overage or such forms as prefilled syringes where residual volume may vary,
`that deliver identical amounts of the active drug ingredient over the identical dosing period;
`(2) do not necessarily contain the same inactive ingredients; and (3) meet the identical
`compendial or other applicable standard of identity, strength, quality, and purity, including
`potency and, where applicable, content uniformity, disintegration times, and/or dissolution
`rates. (21 CFR 320.1(c)).
`
`Note that for proposed combinations of one or more previously approved drugs, a pharmaceutical
`equivalent must also be a combination of the same drugs.
`
` YES
`
`
`
` NO
`
` If “NO” to (a) proceed to question #11.
`If “YES” to (a), answer (b) and (c) then proceed to question #12.
`
`(b) Is the pharmaceutical equivalent approved for the same indication for which the
`505(b)(2) application is seeking approval?
`
`
`
`
`
`Page 4
`Version: March 2009
`
`Reference ID: 3124549
`
`

`

` YES
`
`
` NO
`
`(c) Is the listed drug(s) referenced by the application a pharmaceutical equivalent?
` YES
` NO
`
`
`
`If “YES” to (c) and there are no additional pharmaceutical equivalents listed, proceed to
`question #12.
`If “NO” or if there are additional pharmaceutical equivalents that are not referenced by the
`application, list the NDA pharmaceutical equivalent(s); you do not have to individually list all
`of the products approved as ANDAs, but please note below if approved approved generics are
`listed in the Orange Book. Please also contact the (b)(2) review staff in the Immediate Office,
`Office of New Drugs.
`
`Pharmaceutical equivalent(s):
`
`11) (a) Is there a pharmaceutical alternative(s) already approved (via an NDA or ANDA)?
`
`(Pharmaceutical alternatives are drug products that contain the identical therapeutic moiety, or its
`precursor, but not necessarily in the same amount or dosage form or as the same salt or ester. Each
`such drug product individually meets either the identical or its own respective compendial or other
`applicable standard of identity, strength, quality, and purity, including potency and, where applicable,
`content uniformity, disintegration times and/or dissolution rates. (21 CFR 320.1(d)) Different dosage
`forms and strengths within a product line by a single manufacturer are thus pharmaceutical
`alternatives, as are extended-release products when compared with immediate- or standard-release
`formulations of the same active ingredient.)
`
`Note that for proposed combinations of one or more previously approved drugs, a pharmaceutical
`alternative must also be a combination of the same drugs.
`
` NO
`
` YES
`If “NO”, proceed to question #12.
`
`(b) Is the pharmaceutical alternative approved for the same indication for which the
`505(b)(2) application is seeking approval?
` YES
`
` NO
`
`(c) Is the approved pharmaceutical alternative(s) referenced as the listed drug(s)?
` YES
`
` NO
`
`If “YES” and there are no additional pharmaceutical alternatives listed, proceed to question
`#12.
`If “NO” or if there are additional pharmaceutical alternatives that are not referenced by the
`application, list the NDA pharmaceutical alternative(s); you do not have to individually list all
`of the products approved as ANDAs, but please note below if approved generics are listed in
`the Orange Book. Please also contact the (b)(2) review staff in the Immediate Office, Office of
`New Drugs.
`
`Pharmaceutical alternative(s):
`
`
`
`
`
`Page 5
`Version: March 2009
`
`Reference ID: 3124549
`
`

`

`PATENT CERTIFICATION/STATEMENTS
`
`12) List the patent numbers of all unexpired patents listed in the Orange Book for the listed
`drug(s) for which our finding of safety and effectiveness is relied upon to support approval of
`the (b)(2) product.
`
`Listed drug/Patent number(s):
`
` No patents listed
`
`proceed to question #14
`
`13) Did the applicant address (with an appropriate certification or statement) all of the unexpired
`patents listed in the Orange Book for the listed drug(s) relied upon to support approval of the
`(b)(2) product?
` YES
` NO
`
`If “NO”, list which patents (and which listed drugs) were not addressed by the applicant.
`
`Listed drug/Patent number(s):
`
`14) Which of the following patent certifications does the application contain? (Check all that
`apply and identify the patents to which each type of certification was made, as appropriate.)
`
` No patent certifications are required (e.g., because application is based solely on
`published literature that does not cite a specific innovator product)
`
` 21 CFR 314.50(i)(1)(i)(A)(1): The patent information has not been submitted to
`FDA. (Paragraph I certification)
`
` 21 CFR 314.50(i)(1)(i)(A)(2): The patent has expired. (Paragraph II certification)
`
`Patent number(s):
`
` 21 CFR 314.50(i)(1)(i)(A)(3): The date on which the patent will expire. (Paragraph
`III certification)
`
`Patent number(s):
`
`
`
`
`
`Expiry date(s):
`
` 21 CFR 314.50(i)(1)(i)(A)(4): The patent is invalid, unenforceable, or will not be
`infringed by the manufacture, use, or sale of the drug product for which the
`application is submitted. (Paragraph IV certification). If Paragraph IV certification
`was submitted, proceed to question #15.
`
` 21 CFR 314.50(i)(3): Statement that applicant has a licensing agreement with the
`NDA holder/patent owner (must also submit certification under 21 CFR
`314.50(i)(1)(i)(A)(4) above). If the applicant has a licensing agreement with the
`NDA holder/patent owner, proceed to question #15.
`
` 21 CFR 314.50(i)(1)(ii): No relevant patents.
`
`
`
`
`
`Page 6
`Version: March 2009
`
`Reference ID: 3124549
`
`

`

` 21 CFR 314.50(i)(1)(iii): The patent on the listed drug is a method of use patent
`and the labeling for the drug product for which the applicant is seeking approval
`does not include any indications that are covered by the use patent as described in
`the corresponding use code in the Orange Book. Applicant must provide a
`statement that the method of use patent does not claim any of the proposed
`indications. (Section viii statement)
`
`
`
`
`Patent number(s):
`Method(s) of Use/Code(s):
`
`15) Complete the following checklist ONLY for applications containing Paragraph IV
`certification and/or applications in which the applicant and patent holder have a licensing
`agreement:
`
`(a) Patent number(s):
`(b) Did the applicant submit a signed certification stating that the NDA holder and patent
`owner(s) were notified that this b(2) application was filed [21 CFR 314.52(b)]?
` YES
`
` NO
`If “NO”, please contact the applicant and request the signed certification.
`
`(c) Did the applicant submit documentation showing that the NDA holder and patent
`owner(s) received the notification [21 CFR 314.52(e)]? This is generally provided in the
`form of a registered mail receipt.
` NO
`
` YES
`If “NO”, please contact the applicant and request the documentation.
`
`(d) What is/are the date(s) on the registered mail receipt(s) (i.e., the date(s) the NDA holder
`and patent owner(s) received notification):
`
`Date(s):
`
`(e) Has the applicant been sued for patent infringement within 45-days of receipt of the
`notification listed above?
`
`Note that you may need to call the applicant (after 45 days of receipt of the notification)
`to verify this information UNLESS the applicant provided a written statement from the
`notified patent owner(s) that it consents to an immediate effective date of approval.
`
`YES
`
`NO
`
` Patent owner(s) consent(s) to an immediate effective date of
`approval
`
`
`
`
`
`Page 7
`Version: March 2009
`
`Reference ID: 3124549
`
`

`

`Drafted by:
`
` Bowen/11-21-11
`
`505b2 Clearance: Bertha/3-30-12
` Duvall/3-30-12
` Ripper/3-30-12
`
`Finalized:
`
` Jackson/5-1-12
`
`
`
`
`
`Page 8
`Version: March 2009
`
`Reference ID: 3124549
`
`

`

`
`
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`
`
`
`
`
`
`This is a representation of an electronic record that was signed
`
`
`
`
`
`
`
`
`
`electronically and this page is the manifestation of the electronic
`
`signature. ,
`
`
`
`
`
`
`
`COLETTE C JACKSON
`
`05/01/2012
`
`
`
`Reference ID: 3124549
`
`
`
`
`
`Reference ID: 3127881
`Reference ID: 3127881
`
`

`

`
`
`PMR/PMC Development Template
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`
`
`
`
`
`PMR/PMC1n the Action Package.
`
`
`
`NDA/BLA #
`
`
`
`Product Name:
`
`
`
`202-236
`
`
`
`
`
`
`
`
`
`
`Dymista (azelastine hydrochloride and fluticasone propionate) Nasal Spray,
`137 mcg / 50 mcg
`
`
`
`
`
`
`PMIUPMC Description:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Long-term safety trial in children 4 to 11 years of age with seasonal allergic
`rhinitis or perenniallallergic rhinitis.
`
`
`
`
`
`
`
`
`PMR/PMC Schedule Milestones:
`
`
`
`
`
`Final Protocol Submission:
`
`
`Study/Trial Completion:
`
`
`Final Report Submission:
`
`
`
`
`
`.
`
`10/2012
`02/2014
`06/2014
`
`
`
`
`
`
`
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`
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`
`
`
`
`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.
`
`
`
`
`D Unmet need
`
`
`El Life-threatening condition
`
`
`
`
`[I Long-term data needed
`
`
`
`
`
`
`I] Only feasible to conduct post-approval
`
`
`
`
`
`[Z Prior clinical experience indicates safety
`
`
`
`
`[:1 Small subpopulation affected
`
`
`
`[:1 Theoretical concern
`
`[:1 Other
`
`
`
`
`Safety and efficacy in patients 12 years and older have; been established.
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`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is
`
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`
`
`
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`
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`a FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new
`
`
`safety information.”
`
`Evaluate long-term safety in children 4 to 11 years of age.
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`PMR/PMC Development Template
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`
`
`
`
`Last Updated 4/30/2012
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`Page 1 of 3
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`Reference ID: 3123684
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`Reference ID: 3127881
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`

`

`3.
`
`
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`
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`If the study/clinical trial is a PMR, check the applicable regulation.
`
`
`
`
`
`
`Ifnot a PMR, skip to 4.
`
`
`
`
`
`- Which regulation?
`
`
`
`
`[:1 Accelerated Approval (subpart H/E)
`
`
`
`
`E] Animal Efficacy Rule
`
`
`
`
`
`Pediatric Research Equity Act
`
`
`
`
`
`D FDAAA required safety study/clinical trial
`
`
`
`
`
`—
`
`—
`
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`If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
`
`
`
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`
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`
`
`
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`
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`E] Assess a known serious risk related to the use of the drug?
`
`
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`
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`7!: Assess signals of serious risk related to the use of the drug?
`
`[:1 Identify an unexpected serious risk when available data indicate the potential for a serious
`
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`risk?
`
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`If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
`
`D Analysis of spontaneous postmarketing adverse events?
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`Do not select the above study/clinical trial type if. such an analysis will not be sufficient to
`
`
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`assess or identify a serious risk
`
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`D Analysis using pharmacovigilance system?
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`Do not select the above study/clinical trial type if. the new pharmacovigilance system that the
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`FDA is required to establish under section 505(k)(3) has not yet been established and is thus
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`not sufficient to assess this known serious risk, or has been established but is nevertheless not
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`sufficient to assess or identify a serious risk
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`E] Study: all other investigations, such as investigations in humans that are not clinical trials as
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`defined below (e.g., observational epidemiologic studies), animal studies, and laboratory
`
`experiments?
`.
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`Do not select the above study type if. a study will not be sufficient to identify or assess a
`serious risk
`
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`E] Clinical trial: any prospective investigation in which the sponsor or investigator determines
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`the method of assigning investigational product or other interventions to one or more human
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`subjects?
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`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the
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`
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`study or trial will be performed in a subpopulation, list here.
`A randomized, parallel—group, placebo— or activercontrolled, 3-month safety trial evaluating
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`Dymista Nasal Spray in approximately 400 children 4-ll years of age.
`
`
`Reguired .
`
`[:I Observational pharrnacoepidemiologic study
`
`
`
`[:I Registry studies
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`Primary safety study or clinical trial
`
`[I Pharmacogenetic or pharrnacogenomic study or clinical trial if required to further assess safety
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`El Thorough Q-T clinical trial
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`D Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
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`PMR/PMC Development Template
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`Continuation a
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`uestion 4
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`I] Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
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`1:] Pharmacokinetic studies or clinical trials
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`D Drug interaction or bioavailability studies or clinical trials
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`El Dosing trials
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`El Additional data or analysis required for a previously submitted or expected study/clinical trial
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`(provide explanation)
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`El Meta-analysis or pooled analysis of previous studies/clinical trials
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`Immunogenicity as a marker of safety
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`C] Other (provide explanation)
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`Agreed upon:
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`[I Quality study without a safety endpoint (e.g., manufacturing, stability)
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`CI Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
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`background rates of adverse events)
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`I] Clinical trials primarily designed to further define efficacy (e.g., in another condition,
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`different disease severity, or subgroup) that are NOT required under Subpart H/E
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`E] Dose-response study or clinical trial performed for effectiveness
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`E] Nonclinical study, not safety—related (specify)
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`D Other
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`Primam safety trial
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`5.
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`Is the PMR/PMC clear, feasible, and appropriate?
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`Does the study/clinical trial meet criteria for PMRs or PMCs?
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`Are the objectives clear from the description of the PMR/PMC?
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`Has the applicant adequately justified the choice of schedule milestone dates?
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`E Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine
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`feasibility, and contribute to the development process?
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`PMR/PMC Development Coordinator:
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`X This PMR/PMC has been reviewedfor clarity and consistency, and is necessary to further refine
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`the safety, ejficacy, 0r optimal use ofa drug, or to ensure consistency and reliability ofdrug
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`quality.
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`(signature line for BLAs)
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`PMR/PMC Development Template
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`Last Updated 4/30/2012
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`Reference ID: 3123684
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`Reference ID: 3127881
`Reference ID: 3127881
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`This is a representation of an electronic record that was signed
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`electronically and this page is the manifestation of the electronic
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`signature.
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`SALLY M SEYMOUR
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`04/30/2012
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`Reference ID: 3123684
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`Reference ID: 3127881
`Reference ID: 3127881
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`PMR/PMC Development Template
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`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
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`NDA/BLA #
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`Product Name:
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`202-236
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`Dymista (azelastine hydrochloride and fluticasone propionate) Nasal Spray,
`137 mcg / 50 mcg
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`PMR/PMC Description:
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`Efficacy and safety trial in children 4 to 11 years of age with seasonal allergic
` rhinitis.
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`PMR/PMC Schedule Milestones:
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`Final Protocol Submission:
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`Study/Trial Completion:
`Final Report Submission:
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`02/2013
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`12/2013
`06/2014
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`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.
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`C] Unmet need
`[I Life-threatening condition
`D Long-term data needed
`D Only feasible to conduct post-approval
`E Prior clinical experience indicates safety
`[I Small subpopulation affected
`[:I Theoretical concern
`C] Other
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`Safety and efficacy have been established in patients 12 years and older.
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`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.”
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`Evaluate efficacy and safety in children 4 to 11 years of age.
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`PMR/PMC Development Template
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`Last Updated 4/30/2012
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`Page 1 of 3
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`Reference ID: 3123680
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`Reference ID: 3127881
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`3.
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`If the study/clinical trial is a PMR. check the applicable regulation.
`Ifnot a PMR, skip to 4.
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`— Which regulation?
`[I Accelerated Approval (subpart H/E)
`El Animal Efficacy Rule
`X Pediatric Research Equity Act
`E] FDAAA required safety study/clinical trial
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`-
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`—
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`If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
`E] Assess a known serious risk related to the use of the drug?
`E] Assess signals of serious risk related to the use of the drug?
`[:1 Identify an unexpected serious risk when available data indicate the potential for a serious
`risk?
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`If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
`E] Analysis of spgntaneous pgstmarketing 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
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`E] Analysis using pharmagovigilance 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
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`[I 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
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`[:1 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?
`‘
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`4. Whattype 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.
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`of age with seasonal allergic rhinitis.
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`”(0 trial in children 4 to 11 years
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`Required
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`D Observational pharmacoepidemiologic study
`[:1 Registry studies
`a
`Primary safety study or clinical trial
`Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
`|‘_'| Thorough Q-T clinical trial
`[:1 Nonclinical (animal) safety study(e.g., carcinogenicity, reproductive toxicology)
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`PMR/PMC Development Template
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`Last Updated 4/30/2012
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`Page 2 of 3
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`Reference ID: 3123680
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`Reference ID: 3127881
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`Continuation at Question 4 _
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`[:1 Nonclinical study(laboratory resistance, receptor affinity, quality study related to safety)
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`D Pharmacokinetic studies or clinical trials
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`[3 Drug interaction or bioavailability studies or clinical trials
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`E] Dosing trials
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`E] Additional data or analysis required for a previously submitted or expected study/clinical trial
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`(provide explanation)
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`[:1 Meta-analysis or pooled analysis ofprevious studies/clinical trials
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`El Immunogenicity as a marker of safety
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`[:1 Other (provide explanation)
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`Agreed upon:
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`[I Quality study without a safety endpoint (e.g., manufacturing, stability)
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`El Pharrnacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
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`background rates of adverse events)
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`I] Clinical trials primarily designed to further define efficacy (e.g., in another condition,
`
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`different disease severity, or subgroup) that are NOT required under Subpart H/E
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`I] Dose-response study or clinical trial performed for effectiveness
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`[:1 Nonclinical study, not safety-related (specify)
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`I] Other-
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`5.
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`Is the PMR/PMC clear, feasible, and appropriate?
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`Does the study/clinical trial meet criteria for PMRs or PMCs?
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`Are the objectives clear from the description of the PMR/PMC?
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`Has the applicant adequately justified the choice of schedule milestone dates?
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`Has the applicant had sufficient time to review the PMRs/PMCS, ask questions, determine
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`feasibility, and contribute to the development process?
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`,
`PMR/PMC Development Coordinator:
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`
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`This PMR/PMC has been reviewedfor clarity and consistency, and is necessary to further refine
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`the safety, efiicacy, or optimal use of a drug, or to ensure consistency and reliability of drug
`
`quality.
`
`
`
`
`
`
`(signature line for BLAs)
`
`
`
`PMR/PMC Development Template
`
`
`
`
`
`Last Updated 4/30/2012
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`
`
`
`
`Page 3 of 3
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`. Reference ID: 3123680
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`Reference ID: 3127881
`Reference ID: 3127881
`
`

`

`
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`This is a representation of an electronic record that was signed
`
`
`
`
`
`
`
`
`
`electronically and this page is the manifestation of the electronic
`
`signature-
`
`
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`
`ls/
`____________________________________________________
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`
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`SALLY M SEYMOUR
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`04/30/2012
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`
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`Reference ID: 3123680
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`
`
`
`
`Reference ID: 3127881
`Reference ID: 3127881
`
`

`

`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`
`****Pre-decisional Agency Information****
`
`Memora