CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`022328Orig1s000
`
`
`OTHER REVIEW(S)
`
`
`
`

`
`505(b)(2) ASSESSMENT
`
`NDA # 22328
`
`NDA Supplement #:S-
`
`Efficacy Supplement Type SE-
`
`Proposed Indication(s): as needed. middle-of-the- night (MOTN) insomnia
`
`Proprietary Name: Intermezzo
`Established/Proper Name: zolpidem taitrate SL
`Dosage Form: SL tablets
`Stren s: 1.75 in
`
`oral SL tablets
`
`Applicant: Transcept Pharma, I11c.
`
`Date of Receipt: original submission 9/30/08: re-sub 1/ 14/ 1 1: re-sub 9/27/ 11
`
`PDUFA Goal Date:
`
`1 1/27/11
`
`Action Goal Date (if different):
`1 1/23/1 1
`
`GENERAL INFORMATION
`
`1.
`
`Is this application for a drug that is an “old” antibiotic as described in the Guidance to
`Industry. Repeal of Section 507 of the Federal Food. Drug and Cosmetic Act? (Certain
`antibiotics are not entitled to Hatch-Waxman patent listing and exclusivity benefits.)
`
`YES
`
`|:|
`
`NO X
`
`If "YES, ” proceed to question #3.
`
`2.
`
`Is this application for a recombinant or biologically-derived product and/or protein or
`peptide product?
`
`YES
`
`I]
`
`NOX
`
`If “YES “contact the (b)(2) review staflin the Immediate Oflice, Oflice ofNew Drugs.
`
`Version 06.30.08
`
`Reference ID: 3049249
`
`page 1
`
`

`
`
`
`INFORMATION PROVIDED VIA RELIANCE
`(LISTED DRUG OR LITERATURE)
`
`3. 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. (If not clearly identified by the applicant, this information can
`usually be derived from annotated labeling.)
`
`
`Source of information (e.g.,
`published literature, name of
`referenced product)
`NDA 19908 Ambien (zolpidem
`tartrate)
`
`
`Information provided (e.g.,
`pharmacokinetic data, or specific
`sections of labeling)
`Three Biopharm studies; specific sections
`PI changed
`Five clinical studies; specific sections PI
`changed
`
`
`
`
`
`
`
`
`4. 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)
`
`This NDA comprises of the following 3 single-dose pharmacokinetic (PK)/ bioequivalence (BE)
`bridging studies in healthy adult and elderly subjects. Study ZI-15, provides comparative
`bioavailability information relative to reference Ambien®. Study ZI-14 includes comparative
`bioavailability of Intermezzo® 1.75 mg and 3.5 mg in elderly and adult cohorts. Study ZI-13
`provides a bridging link between IND formulation and final commercial formulation used in
`different studies. Final commercial formulation was used in most of the studies including pivotal
`BE, pharmacodynamic, and efficacy studies.
`
`RELIANCE ON PUBLISHED LITERATURE
`
`
`
`5. (a) Does the application rely on published literature to support the approval of the
`proposed drug product (i.e., the application cannot be approved without the published
`literature)?
` YES
`
`
`x
`
` NO
`
`If “NO,” proceed to question #6.
`
`
`
`(b) Does any of the published literature necessary to support approval identify a specific
`(e.g., brand name) listed drug product?
` Ambien (zolpidem tartrate)
`YES
`
`If “NO”, proceed to question #6
`If “YES”, list the listed drug(s) identified by name and answer question #5(c)
`
`
`x
`
` NO
`
`Version 06.30.08
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`Reference ID: 3049249
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`

`
`
`.
`
`
`
`
`
`(c) Are the drug product(s) listed in (b) identified by the applicant as the listed drug(s)?
` YES X
` NO
`
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`
`page 3
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`

`
`
`
`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 #6-10 accordingly.
`
`
`6. 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)?
` YES x
`
`
` NO
`
`If “NO,” proceed to question #11.
`
`7. 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 #
`
`
`19908
`
`
`
`Did applicant
`specify reliance on
`the product? (Y/N)
`yes
`
`
`
`Ambien
`
`
`
`
`
`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.
`
`
`
`8. If this is a supplement, does the supplement rely upon the same listed drug(s) as the
`original (b)(2) application? N/A
` YES
`
` NO
`
`If “NO”, please contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`
`9. Were any of the listed drug(s) relied upon for this application:
`a. Approved in a 505(b)(2) application?
` NO X
`
` YES
`If “YES”, please list which drug(s).
`Name of drug(s) approved in a 505(b)(2) application: none
`
`
`b. Approved by the DESI process?
` YES
` NO x
`
`If “YES”, please list which drug(s).
`Name of drug(s) approved via the DESI process:
`
`c. Described in a monograph?
` YES
` NO x
`
`If “YES”, please list which drug(s).
`Name of drug(s) described in a monograph:
`
`
`
`Version 06.30.08
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`
`page 4
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`Reference ID: 3049249
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`

`
`d. Discontinued from marketing?
` YES
` NO x
`
`If “YES”, please list which drug(s) and answer question d.1.
`If “NO”, proceed to question #10.
`Name of drug(s) discontinued from marketing:
`
`
`
`
`1. 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.)
`
`
`
`10. 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 change in dosage form, from oral tablet to sublingual
`tablet and for a new method of use, middle of the night insomnia (MOTN). This is also a
`new indication – middle of the night insomnia –to be taken prn (as necessary).
`
`
`
`
`
`
`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.
`
`
`11. (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 x
`
` If “NO,” to (a) proceed to question #12.
`
`
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`Reference ID: 3049249
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`

`
`(b) Is the pharmaceutical equivalent approved for the same indication for which the
`505(b)(2) application is seeking approval?
`
`YES
`
` NO
`
`
`
`
`
`
`Version 06.30.08
`
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`page 6
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`

`
`Is the listed drug(s) referenced by the application a pharmaceutical equivalent?
`(c)
`
` YES
` NO
`
`If “YES” and there are no additional pharmaceutical equivalents listed, proceed to question
`#13.
`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 that there are approved generics listed in
`the Orange Book. Please contact the (b)(2) review staff in the Immediate Office, Office of New
`Drugs.
`
`Pharmaceutical equivalent(s):
`
`
`
`12. (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.
`
` Yes
`X
`
` NO
`
`
`
`
`
`
`
`
`
`
`
`If “NO”, proceed to question #13.
`
`(b) Is the pharmaceutical alternative approved for the same indication for which the
`505(b)(2) application is seeking approval?
` YES X NO
`
`
`Is the approved pharmaceutical alternative(s) referenced as the listed drug(s)?
`(c)
` There are approx 20 generic drugs approved for zolpidem tartrate. X
` NO
`
`If “YES” and there are no additional pharmaceutical alternatives listed, proceed to question
`#13.
`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 that there are approved generics listed in
`the Orange Book. Contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`
`Pharmaceutical alternative(s):
`
`
`
`Version 06.30.08
`
`
`
`page 7
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`Reference ID: 3049249
`
`

`
`PATENT CERTIFICATION/STATEMENTS
`
`
`
`
`List the patent numbers of all 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):
`
`X
`
` NO
`
`13. Did the applicant address (with an appropriate certification or statement) all of the patents
`listed in the Orange Book for the listed drug(s)?
` There are no unexpired patents for this product in the Orange Book
`Database.
`
`
`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.)
`
`
`
`
`
`X
`
`
` No patent certifications are required (e.g., because application solely based on
`published literature that does not cite a specific innovator product or for an “old
`antibiotic” (see question 1.))
`
`
`
` 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): US PATENT No. 4,382,938 RDL for Ambien; patent has
`
`expired
`
`
`
`
`
`
`
`
`
` 21 CFR 314.50(i)(1)(i)(A)(3): The date on which the patent will expire.
`(Paragraph III certification)
`
`
`Patent number(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)
`
`
`Patent number(s):
`
`If the application has been filed, did the applicant submit a signed certification
`stating that the NDA holder and patent owner(s) were notified the NDA was filed
`[21 CFR 314.52(b)]?
` N/A
`
` NO
`
`
`
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`
`

`
`YES
`
`
`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.
` N/A
`
`
`
` NO
`
`
`Date Received:
`
`Has the applicant been sued for patent infringement (within 45-days of receipt of
`the notification listed above)? Note: you may need to call the applicant to verify
`this information.
`
`YES
`
`
`
` NO X;
`N/A
`
`
`
` 21 CFR 314.50(i)(3): Statement that applicant has a licensing agreement with the
`patent owner (must also submit certification under 21 CFR 314.50(i)(1)(i)(A)(4)
`above).
` There are no agreements betw Trancept and any US partner.
`Patent number(s):
`If the application has been filed, did the applicant submit a signed certification
`stating that the NDA holder and patent owner(s) were notified the NDA was filed
`[21 CFR 314.52(b)]?
` N/A YES
`
`
`
` NO
`
`
`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.
`N/A YES
`
`
`
` NO
`
`
`Date Received:
`
`Has the applicant been sued for patent infringement (within 45-days of receipt of
`the notification listed above)? Note: you may need to call the applicant to verify
`this information.
` N/A
`
`
`
`
`
` NO
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Written statement from patent owner that it consents to an immediate effective
`date of approval (applicant must also submit paragraph IV certification under 21
`CFR 314.50(i)(1)(i)(A)(4) above). N/A
`
`
`Patent number(s):
`
` 21 CFR 314.50(i)(1)(ii): No relevant patents. N/A
`
` 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
`
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`

`
`statement that the method of use patent does not claim any of the proposed
`indications. (Section viii statement) N/A
`Patent number(s):
`
`
`
`
`
`Revised 10.16.09 per B.D. Miller; updated 10.24.11
`
`Version 06.30.08
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`
`page 10
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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.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`CATHLEEN B MICHALOSKI
`11/23/2011
`
`Reference ID: 3049249
`
`

`
`SEALD LABELING REVIEW
`
`This SEALD Labeling Review identifies major aspects of the draft labeling that do not meet the
`requirements of 21 CFR 201.56 and 201.57 and related CDER labeling policies.
`
`I APPLICATION NUMBER
`APPLICANT
`
`| PRODUCTNAME
`SUBMISSIONDATE
`
`
`PDUFA DATE
`SEALD REVIEW DATE
`
`SEALDLABELING
`
`REVIEWER
`
`I NDA 22328
`Transcept Pharmaceuticals, Inc.
`
`Zolpidem Tanrate (Intermezzo)
`
`September 27, 2011
`
`November 25, 201 1
`November 22, 201 1
`
`
`‘ AnnMarie Trentacosti
`
`I
`
`‘
`
`I
`
`I
`
`The following checked Selected Requirements for Prescribing Information items are outstanding
`labeling issues that must be corrected before the final draft labeling is approved.
`
`Reference ID: 3048657
`
`

`
`
`
`Selected Requirements for Prescribing Information
`(SRPI)
`
`This document is meant to be used as a checklist in order to identify critical issues during
`labeling development and review. For additional information concerning the content and
`format of the prescribing information, see regulatory requirements (21 CFR 201.56 and
`201.57) and labeling guidances. When used in reviewing the PI, only identified
`deficiencies should be checked.
`
`Highlights (HL)
` General comments
` HL must be in two-column format, with ½ inch margins on all sides and
`between columns, and in a minimum of 8-point font.
` HL is limited in length to one-half page. If it is longer than one-half page, a
`waiver has been granted or requested by the applicant in this submission.
` There is no redundancy of information.
`
`If a Boxed Warning is present, it must be limited to 20 lines. (Boxed Warning
`lines do not count against the one-half page requirement.)
` A horizontal line must separate the HL and Table of Contents (TOC).
` All headings must be presented in the center of a horizontal line, in UPPER-
`CASE letters and bold type.
` Each summarized statement must reference the section(s) or subsection(s) of the
`Full Prescribing Information (FPI) that contains more detailed information.
` Section headings are presented in the following order:
` Highlights Limitation Statement (required statement)
` Drug names, dosage form, route of administration, and
`controlled substance symbol, if applicable (required
`information)
`Initial U.S. Approval (required information)
`
` Boxed Warning (if applicable)
` Recent Major Changes (for a supplement)
`Indications and Usage (required information)
`
` Dosage and Administration (required information)
` Dosage Forms and Strengths (required information)
` Contraindications (required heading – if no contraindications are
`known, it must state “None”)
` Warnings and Precautions (required information)
` Adverse Reactions (required AR contact reporting statement)
` Drug Interactions (optional heading)
` Use in Specific Populations (optional heading)
` Patient Counseling Information Statement (required statement)
` Revision Date (required information)
`
`SRPI version March 2, 2011
`
`
`
`Page 1 of 6
`
`Reference ID: 3048657
`
`

`
`
`
` Highlights Limitation Statement
` Must be placed at the beginning of HL, bolded, and read as follows: “These
`highlights do not include all the information needed to use (insert name of
`drug product in UPPER CASE) safely and effectively. See full prescribing
`information for (insert name of drug product in UPPER CASE).”
` Add space between Highlights Limitation Statement and Product Title Line.
`
` Product Title
` Must be bolded and note the proprietary and established drug names, followed
`by the dosage form, route of administration (ROA), and, if applicable,
`controlled substance symbol.
`
`
`
`Initial U.S. Approval
` The verbatim statement “Initial U.S. Approval” followed by the 4-digit year in
`which the FDA initially approved of the new molecular entity (NME), new
`biological product, or new combination of active ingredients, must be placed
`immediately beneath the product title line. If this is an NME, the year must
`correspond to the current approval action.
`
` Boxed Warning
` All text in the boxed warning is bolded.
` Summary of the warning must not exceed a length of 20 lines.
` Requires a heading in UPPER-CASE, bolded letters containing the word
`“WARNING” and other words to identify the subject of the warning
`(e.g.,“WARNING: LIFE-THREATENING ADVERSE REACTIONS”).
` Must have the verbatim statement “See full prescribing information for
`complete boxed warning.” If the boxed warning in HL is identical to boxed
`warning in FPI, this statement is not necessary.
`
` Recent Major Changes (RMC)
` Applies only to supplements and is limited to substantive changes in five
`sections: Boxed Warning, Indications and Usage, Dosage and Administration,
`Contraindications, and Warnings and Precautions.
` The heading and, if appropriate, subheading of each section affected by the
`recent change must be listed with the date (MM/YYYY) of supplement
`approval. For example, “Dosage and Administration, Coronary Stenting (2.2) ---
`2/2010.”
` For each RMC listed, the corresponding new or modified text in the FPI must be
`marked with a vertical line (“margin mark”) on the left edge.
` A changed section must be listed for at least one year after the supplement is
`approved and must be removed at the first printing subsequent to one year.
`
`SRPI version March 2, 2011
`
`
`
`Page 2 of 6
`
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`
`

`
` Removal of a section or subsection should be noted. For example, “Dosage and
`Administration, Coronary Stenting (2.2) --- removal 2/2010.”
`
`Indications and Usage
`
`If a product belongs to an established pharmacologic class, the following
`statement is required in HL: [Drug/Biologic Product) is a (name of class)
`indicated for (indication(s)].” Identify the established pharmacologic class for
`the drug at:
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm
`162549.htm.
`
`
`
`
`
` Contraindications
` This section must be included in HL and cannot be omitted. If there are no
`contraindications, state “None.”
` All contraindications listed in the FPI must also be listed in HL.
` List known hazards and not theoretical possibilities (i.e., hypersensitivity to the
`drug or any inactive ingredient). If the contraindication is not theoretical,
`describe the type and nature of the adverse reaction.
` For drugs with a pregnancy Category X, state “Pregnancy” and reference
`Contraindications section (4) in the FPI.
`
` Adverse Reactions
` Only “adverse reactions” as defined in 21 CFR 201.57(a)(11) are included in
`HL. Other terms, such as “adverse events” or “treatment-emergent adverse
`events,” should be avoided. Note the criteria used to determine their inclusion
`(e.g., incidence rate greater than X%).
` For drug products other than vaccines, the verbatim bolded statement, “To
`report SUSPECTED ADVERSE REACTIONS, contact (insert name of
`manufacturer) at (insert manufacturer’s phone number) or FDA at 1-800-
`FDA-1088 or www.fda.gov/medwatch” must be present. Only include toll-free
`numbers.
`
` Patient Counseling Information Statement
` Must include the verbatim statement: “See 17 for Patient Counseling
`Information” or if the product has FDA-approved patient labeling: “See 17 for
`Patient Counseling Information and (insert either “FDA-approved patient
`labeling” or “Medication Guide”).
`
` Revision Date
` A placeholder for the revision date, presented as “Revised: MM/YYYY or
`Month Year,” must appear at the end of HL. The revision date is the
`month/year of application or supplement approval.
`Revision date is missing.
`
`
`
`SRPI version March 2, 2011
`
`
`
`Page 3 of 6
`
`Reference ID: 3048657
`
`

`
`
`
`
`
`Contents: Table of Contents (TOC)
`
`
`
`
` The heading FULL PRESCRIBING INFORMATION: CONTENTS must
`appear at the beginning in UPPER CASE and bold type.
` The section headings and subheadings (including the title of boxed warning) in
`the TOC must match the headings and subheadings in the FPI.
`Section 17 should be listed as “PATIENT COUNSELING INFORMATION”
`and not “PATIENT COUNSELING INFORMATION and Medication Guide.”
` All section headings must be in bold type, and subsection headings must be
`indented and not bolded.
` When a section or subsection is omitted, the numbering does not change. For
`example, under Use in Specific Populations, if the subsection 8.2 (Labor and
`Delivery) is omitted, it must read:
`8.1 Pregnancy
`8.3 Nursing Mothers (not 8.2)
`8.4 Pediatric Use (not 8.3)
`8.5 Geriatric Use (not 8.4)
`If a section or subsection is omitted from the FPI and TOC, the heading “Full
`Prescribing Information: Contents” must be followed by an asterisk and the
`following statement must appear at the end of TOC: “*Sections or subsections
`omitted from the Full Prescribing Information are not listed.”
`
`
`
`
`Full Prescribing Information (FPI)
` General Format
` A horizontal line must separate the TOC and FPI.
` The heading – FULL PRESCRIBING INFORMATION – must appear at the
`beginning in UPPER CASE and bold type.
` The section and subsection headings must be named and numbered in
`accordance with 21 CFR 201.56(d)(1).
`There are no periods after the numbers for the section or subsection headings.
`For example, the numbers 2. and 2.1. should be replaced with 2 and 2.1 without
`periods. The numbering needs to be corrected throughout the FPI.
` Boxed Warning
`
`
`
`SRPI version March 2, 2011
`
`
`
`Page 4 of 6
`
`Reference ID: 3048657
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`

`
`in UPPER CASE, bold type, containing the word
`I: Must have a heading,
`“WARNING” and other words to identify the subject of the warning. Use bold
`type and lower-case letters for the text.
`
`information and cross-
`include a brief, concise summary of critical
`[Z Must
`reference to detailed discussion in other sections (e.g., Contraindications,
`Warnings and Precautions).
`
`Incorrect cross-referencing:
`
`(hm)
`
`o Contraindications
`
`E] For Pregnancy Category X drugs, list pregnancy as a contraindication.
`
`0 Adverse Reactions
`
`El Only “adverse reactions” as defined in 21 CFR 201.57(c)(7) should be included
`in labeling. Other terms, such as “adverse events” or “treatment-emergent
`adverse events,” should be avoided.
`
`the following verbatim
`E] For the “Clinical Trials Experience” subsection,
`statement or appropriate modification should precede the presentation of
`adverse reactions:
`
`trials are conducted under widely varying conditions,
`“Because clinical
`adverse reaction rates observed in the clinical trials of a drug cannot be
`directly compared to rates in the clinical trials of another drug and may not
`reflect the rates observed in clinical practice.”
`
`E] For the “Postmarketing Experience” subsection, the listing of post-approval
`adverse reactions must be separate from the listing of adverse reactions
`identified in clinical
`trials.
`Include the following verbatim statement or
`appropriate modification:
`
`“The following adverse reactions have been identified during post-
`approval use of (insert drug name). Because these reactions are reported
`voluntarily from a population of uncertain size, it is not always possible to
`reliably estimate their frequency or establish a causal relationship to drug
`exposure.”
`
`0 Use in Specific Populations
`
`SRPIve|'sionMan:I12, 2011
`
`Reference ID: 3048657
`
`Page5ot6
`
`

`
`
`
` Subsections 8.4 Pediatric Use and 8.5 Geriatric Use are required and cannot be
`omitted.
`
` Patient Counseling Information
` This section is required and cannot be omitted.
` Must reference any FDA-approved patient labeling, including the type of patient
`labeling. The statement “See FDA-approved patient labeling (insert type of
`patient labeling).” should appear at the beginning of Section 17 for prominence.
`For example:
` “See FDA-approved patient labeling (Medication Guide)”
` “See FDA-approved patient labeling (Medication Guide and Instructions for Use)”
` “See FDA-approved patient labeling (Patient Information)"
` “See FDA-approved patient labeling (Instructions for Use)"
` “See FDA-approved patient labeling (Patient Information and Instructions for Use)”
`
`
`
`SRPI version March 2, 2011
`
`
`
`Page 6 of 6
`
`Reference ID: 3048657
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`

`
`
`
`
`
`
`
`Reference ID: 3048657
`
`SEALD LABELING REVIEW
`
`2
`
`
`
`
`
`APPEARS THIS WAY ON ORIGINAL
`
`

`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ANN M TRENTACOSTI
`11/22/2011
`
`Reference ID: 3048657
`
`

`
`SEALD LABELING: PI SIGN—OFF REVIEW
`
`APPLICATION NUMBER
`
`APPLICANT
`
`PRODUCT NAME
`
`STAFF OND I0
`
`DIRECTOR, S'I‘UDY
`ENDPOINTS AND LABELING
`
`Laurie Burke
`
`This memo confirms that all critical prescribing information G’I) deficiencies noted in the
`SEALD Labeling Review filed November 22, 2011, have been addressed in the final agreed-
`upon PI. SEALD has no objection to P1 approval at this time.
`
`Reference ID: 3048816
`
`

`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LAURIE B BURKE
`11/22/2011
`
`Reference ID: 3048816
`
`

`
`NDA 22328
`Intermezzo
`
`
`
`PMR/PMC Development Template for Intermezzo (Zolpidem Tartrate)
`PMR # 1
`
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`PMR/PMC Description: A pharmacokinetic dose-ranging, tolerability, and pharmacodynamic
`study of Intermezzo in pediatric patients with insomnia related to
`attention-deficit/hyperactivity disorder (ADHD) ages 6-17 years.
`
` 11/2012
` 05/2016
` 11/2016
` MM/DD/YYYY
`
`
`PMR/PMC Schedule Milestones: Final protocol Submission Date:
`
`Study/Clinical trial Completion Date:
`
`Final Report Submission Date:
`
`Other:
`
`