CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`206439Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`505(b)(2) ASSESSMENT
`
`NDA # 206439
`
`NDA Supplement #: 8-
`
`Efficacy Supplement Type SE-
`
`Proprietary Name: Namzaric (proposed IIadename)
`Established/Proper Name: memantine HCL extended release & donepezil
`Dosage Form: Capsule
`Stren S: 14/10 m and 28/10 n1
`
`Applicant: Forest Laboratories Inc.
`
`Date of Receipt: February 26. 2014
`
`Proposed Indication(s): Alzheimer’s Disease
`
`PDUFA Goal Date: December 26. 2014
`
`Action Goal Date (if different):
`December 10. 2014
`
`RPM: Teresa Wheelous
`
`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
`
`|:|
`
`NOX
`
`If “YES “contact the (b) (2) review staflin the Immediate Oflice, Ofiice ofNew Drugs.
`
`Reference ID: 3677964
`
`Page 1
`Version: April 2014
`
`

`

`INFORMATION PROVIDED VIA RELIANCE
`(LISTED DRUG OR 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 by reliance on published
`literature, or by reliance on a final OTC monograph. (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 listed
`drug(s), OTC final drug
`monograph)
`NDA 20-690 Aricept (donepezil)
`
`Information relied-upon (e.g., specific
`sections of the application or labeling)
`
`FDA previous findings of safety and
`effectiveness
`
`*each source of information should be listed on separate rows, however individual
`literature articles should not be listed separately
`
`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)
`
`Bioequivalence of the FDC to the individual components (Namenda XR and Aricept) and serves
`as the bridge between the proposed new drug product and the listed drug, Aricept.
`
`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 as labeled
`without the published literature)?
` NO X
` YES
`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?
` NO
` YES
`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
`
`Page 2
`Version: April 2014
`
`Reference ID: 3677964
`
`

`

`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 cited reliance on 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 #10.
`
`6) Name of listed drug(s) relied upon, and the NDA #(s). Please indicate if the applicant
`explicitly identified the product as being relied upon (see note below):
`
`Name of Listed Drug
`
`NDA #
`
`Aricept
`
`20-690
`
`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?
` NO
` N/A X 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?
` NO X
` YES
`If “YES”, please list which drug(s).
`Name of drug(s) approved in a 505(b)(2) application:
`
`b) Approved by the DESI process?
` NO X
` YES
`If “YES”, please list which drug(s).
`Name of drug(s) approved via the DESI process:
`
`c) Described in a final OTC drug monograph?
`
`Page 3
`Version: April 2014
`
`Reference ID: 3677964
`
`

`

` NO X
` YES
`If “YES”, please list which drug(s).
`
`Name of drug(s) described in a final OTC drug monograph:
`
`d) Discontinued from marketing?
` NO X
` YES
`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 a fixed dose combination formulation.
`
`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 intended for the
`same route of administration 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), FDA’s “Approved Drug
`Products with Therapeutic Equivalence Evaluations” (the Orange Book)).
`
`Note that for proposed combinations of one or more previously approved drugs, a pharmaceutical
`equivalent must also be a combination of the same drugs.
`
`Page 4
`Version: April 2014
`
`Reference ID: 3677964
`
`

`

` YES
`
` NO X
`
`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?
` YES
`
`
`(c) Is the listed drug(s) referenced by the application a pharmaceutical equivalent?
` N/A
` YES
` NO
`
` NO
`
`If this application relies only on non product-specific published literature, answer “N/A”
`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 X
` 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)?
` N/A
` YES
` NO
`
`If this application relies only on non product-specific published literature, answer “N/A”
`If “YES” and there are no additional pharmaceutical alternatives listed, proceed to question
`#12.
`
`Page 5
`Version: April 2014
`
`Reference ID: 3677964
`
`

`

`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):
`
`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):
`There is no unexpired exclusivity for this NDA product.
`
` 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?
` NO
` YES
`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)
`
`X 21 CFR 314.50(i)(1)(i)(A)(1): The patent information has not been submitted to
`FDA. (Paragraph I certification)
`
`In accordance with the Federal Food Drug and Cosmetic Act (FDCA) and 21 C.F.R.
`§314.50 (i)(1)(i), the following "Paragraph I Certification" is hereby provided for our Section
`505(b )(2) New Drug Application for memantine HCI extended release and donepezil HCI fixed
`dose combination
`
`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):
`
`Page 6
`Version: April 2014
`
`Reference ID: 3677964
`
`

`

`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.
`
`
`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):
`
`Note, the date(s) entered should be the date the notification occurred (i.e., delivery
`date(s)), not the date of the submission in which proof of notification was provided
`
`(e) Has the applicant been sued for patent infringement within 45-days of receipt of the
`notification listed above?
`
`Reference ID: 3677964
`
`Page 7
`Version: April 2014
`
`

`

`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
`
`Reference ID: 3677964
`
`Page 8
`Version: April 2014
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`TERESA A WHEELOUS
`12/23/2014
`
`Reference ID: 3677964
`
`

`

`REGULATORY PROJECT MANAGER
`PHYSICIAN’S LABELING RULE (PLR) FORMAT REVIEW
`OF THE PRESCRIBING INFORMATION
`
`Complete for all new NDAs, BLAs, Efficacy Supplements, and PLR Conversion Labeling Supplements
`
`Application: 206439
`
`Application Type: New NDA
`
`Name of Drug/Dosage Form: TRADENAME (memantine hydrochloride extended release and donepezil
`hydrochloride) capsules 14mg /10 mg and 28 mg/10 mg
`
`Applicant: Forest Laboratories, Inc.
`
`Receipt Date: February 26, 2014
`
`Goal Date: December 26, 2014
`
`1. Regulatory History and Applicant’s Main Proposals
`The sponsor of this new fixed dose combination product, is also the originator for one of the two
`approved product components, memantine HCl extended release, NDA 22525. The other ingredient,
`donepezil HCl, is referenced making this a 505b2 application. The memantine HCl extended release
`product labeling received a SEALD review, and is the basis of the sponsor’s fixed dose product
`labeling.
`
`2. Review of the Prescribing Information
`This review is based on the applicant’s submitted Word format of the prescribing information (PI).
`The applicant’s proposed PI was reviewed in accordance with the labeling format requirements listed
`in the “Selected Requirements for Prescribing Information (SRPI)” checklist (see the Appendix).
`
`3. Conclusions/Recommendations
`SRPI format deficiencies were identified in the review of this PI. For a list of these deficiencies see
`the Appendix.
`
`All SRPI format deficiencies of the PI will be conveyed to the applicant in the 74-day letter. The
`applicant will be asked to correct these deficiencies and resubmit the PI in Word format by May 30,
`2014. The resubmitted PI will be used for further labeling review.
`
`RPM PLR Format Review of the PI: October 2013 Page 1 of 10
`
`Reference ID: 3677979
`
`

`

`Selected Requirements of Prescribing Information
`
`Appendix
`
`The Selected Requirement of Prescribing Information (SRPI) is a 42-item, drop-down checklist of
`important format elements of the prescribing information (PI) based on labeling regulations (21 CFR
`201.56 and 201.57) and guidances.
`
`Highlights
`
`See Appendix A for a sample tool illustrating the format for the Highlights.
`
`HIGHLIGHTS GENERAL FORMAT and HORIZONTAL LINES IN THE PI
`
`YES
`
`NO
`
`YES
`
`NO
`
`YES
`
`1. Highlights (HL) must be in a minimum of 8-point font and should be in two-column format, with
`½ inch margins on all sides and between columns.
`Comment:
`2. The length of HL must be one-half page or less (the HL Boxed Warning does not count against
`the one-half page requirement) unless a waiver has been granted in a previous submission (e.g.,
`the application being reviewed is an efficacy supplement).
`Instructions to complete this item: If the length of the HL is one-half page or less, then select
`“YES” in the drop-down menu because this item meets the requirement. However, if HL is
`longer than one-half page:
` For the Filing Period:
` For efficacy supplements: If a waiver was previously granted, select “YES” in the drop-
`down menu because this item meets the requirement.
` For NDAs/BLAs and PLR conversions: Select “NO” because this item does not meet the
`requirement (deficiency). The RPM notifies the Cross-Discipline Team Leader (CDTL) of
`the excessive HL length and the CDTL determines if this deficiency is included in the 74-
`day or advice letter to the applicant.
` For the End-of-Cycle Period:
` Select “YES” in the drop down menu if a waiver has been previously (or will be) granted
`by the review division in the approval letter and document that waiver was (or will be)
`granted.
`Comment:
`3. A horizontal line must separate HL from the Table of Contents (TOC). A horizontal line must
`separate the TOC from the FPI.
`Comment:
`4. All headings in HL must be bolded and presented in the center of a horizontal line (each
`horizontal line should extend over the entire width of the column as shown in Appendix A). The
`headings should be in UPPER CASE letters.
`Comment: aligned left
`5. White space should be present before each major heading in HL. There must be no white space
`between the HL Heading and HL Limitation Statement. There must be no white space between
`
`SRPI version 3: October 2013
`
`Reference ID: 3677979
`
`Page 2 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`the product title and Initial U.S. Approval. See Appendix A for a sample tool illustrating white
`space in HL.
`
`Comment:
`
`- 6. Each summarized statement or topic in HL must reference the section(s) or subsection(s) of the
`Full Prescribing Information (FPI) that contain more detailed information. The preferred format
`is the numerical identifier in parenthesis [e.g., (1.1)] at the end of each summarized statement or
`topic.
`
`Comment: **DBL check to see ifcorrect“
`- 7. Section headings must be presented in the following order in HL:
`“_—
`- Hihnms Heaain
`
`
`
`* RMC only applies to the BOXED WARNING. INDICATIONS AND USAGE. DOSAGE AND
`ADMINISTRATION. CONTRAINDICATIONS. and WARNINGS AND PRECAUTIONS sections.
`
`Comment:
`
`HIGHLIGHTS DETAILS
`
`Highlights Heading
`
`- 8. At the beginning of HL, the following heading must be bolded and should appear in all UPPER
`CASE letters: “HIGHLIGHTS OF PRESCRIBING INFORMATION”.
`Comment:
`
`Highlights Limitation Statement
`
`- 9. The bolded HL Limitation Statement must include the following verbatim statement: “These
`highlights do not include all the information needed to use (insert name of drug product)
`safely and effectively. See full prescribing information for (insert name of drug product).”
`The name of drug product should appear in UPPER CASE letters.
`
`Comment:
`
`Product Title in Highlights
`- 10. Product title must be bolded.
`
`SRPI version 3: October 2013
`
`Reference ID: 3677979
`
`Page 3 0f 10
`
`

`

`Selected Requirements of Prescribing Information
`
`Comment:
`
`YES
`
`Initial U.S. Approval in Highlights
`11. Initial U.S. Approval in HL must be bolded, and include the verbatim statement “Initial U.S.
`Approval:” followed by the 4-digit year.
`Comment:
`
`Boxed Warning (BW) in Highlights
`12. All text in the BW must be bolded.
`Comment:
`13. The BW must have a heading in UPPER CASE, containing the word “WARNING” (even if
`more than one warning, the term, “WARNING” and not “WARNINGS” should be used) and
`other words to identify the subject of the warning (e.g., “WARNING: SERIOUS
`INFECTIONS and ACUTE HEPATIC FAILURE”). The BW heading should be centered.
`Comment:
`14. The BW must always have the verbatim statement “See full prescribing information for
`complete boxed warning.” This statement should be centered immediately beneath the heading
`and appear in italics.
`Comment:
`15. The BW must be limited in length to 20 lines (this includes white space but does not include the
`BW heading and the statement “See full prescribing information for complete boxed
`warning.”).
`Comment:
`
`Recent Major Changes (RMC) in Highlights
`16. RMC pertains to only the following five sections of the FPI: BOXED WARNING,
`INDICATIONS AND USAGE, DOSAGE AND ADMINISTRATION,
`CONTRAINDICATIONS, and WARNINGS AND PRECAUTIONS. RMC must be listed in
`the same order in HL as the modified text appears in FPI.
`Comment:
`17. The RMC must include the section heading(s) and, if appropriate, subsection heading(s) affected
`by the recent major change, together with each section’s identifying number and date
`(month/year format) on which the change was incorporated in the PI (supplement approval date).
`For example, “Warnings and Precautions, Acute Liver Failure (5.1) --- 9/2013”.
`Comment:
`18. The RMC must list changes for at least one year after the supplement is approved and must be
`removed at the first printing subsequent to one year (e.g., no listing should be one year older than
`revision date).
`Comment:
`
`Indications and Usage in Highlights
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`YES
`
`SRPI version 3: October 2013
`
`Reference ID: 3677979
`
`Page 4 of 10
`
`

`

`YES
`
`YES
`
`YES
`
`YES
`
`Selected Requirements of Prescribing Information
`
`19. If a product belongs to an established pharmacologic class, the following statement is required
`under the Indications and Usage heading in HL: “(Product) is a (name of established
`pharmacologic class) indicated for (indication)”.
`Comment:
`
`Dosage Forms and Strengths in Highlights
`20. For a product that has several dosage forms (e.g., capsules, tablets, and injection), bulleted
`subheadings or tabular presentations of information should be used under the Dosage Forms and
`Strengths heading.
`Comment:
`
`Contraindications in Highlights
`21. All contraindications listed in the FPI must also be listed in HL or must include the statement
`“None” if no contraindications are known. Each contraindication should be bulleted when there
`is more than one contraindication.
`Comment:
`
`Adverse Reactions in Highlights
`22. For drug products other than vaccines, the verbatim bolded statement must be present: “To
`report SUSPECTED ADVERSE REACTIONS, contact (insert name of manufacturer) at
`(insert manufacturer’s U.S. phone number) or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch”.
`Comment:
`
`Patient Counseling Information Statement in Highlights
`23. The Patient Counseling Information statement must include one of the following three bolded
`verbatim statements that is most applicable:
`If a product does not have FDA-approved patient labeling:
` “See 17 for PATIENT COUNSELING INFORMATION”
`If a product has FDA-approved patient labeling:
` “See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling”
` “See 17 for PATIENT COUNSELING INFORMATION and Medication Guide”
`Comment:
`
`YES
`
`Revision Date in Highlights
`24. The revision date must be at the end of HL, and should be bolded and right justified (e.g.,
`“Revised: 9/2013”).
`Comment:
`
`SRPI version 3: October 2013
`
`Reference ID: 3677979
`
`Page 5 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`Contents: Table of Contents (TOC)
`
`See Appendix A for a sample tool illustrating the format for the Table of Contents.
`
`YES
`
`YES
`
`N/A
`
`YES
`
`NO
`
`YES
`
`YES
`
`25. The TOC should be in a two-column format.
`Comment:
`26. The following heading must appear at the beginning of the TOC: “FULL PRESCRIBING
`INFORMATION: CONTENTS”. This heading should be in all UPPER CASE letters and
`bolded.
`Comment:
`27. The same heading for the BW that appears in HL and the FPI must also appear at the beginning
`of the TOC in UPPER CASE letters and bolded.
`Comment:
`28. In the TOC, all section headings must be bolded and should be in UPPER CASE.
`Comment:
`29. In the TOC, all subsection headings must be indented and not bolded. The headings should be in
`title case [first letter of all words are capitalized except first letter of prepositions (through),
`articles (a, an, and the), or conjunctions (for, and)].
`Comment: 2.1 "G" (Guidelines) needs capitalized; 7.2 "O" (Other) needs capitalized
`30. The section and subsection headings in the TOC must match the section and subsection headings
`in the FPI.
`Comment: **Need to check**
`31. In the TOC, when a section or subsection is omitted, the numbering must not change. If a section
`or subsection from 201.56(d)(1) 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.”
`Comment: TOC reflects omission as instructed, 8.2 is omitted
`
`SRPI version 3: October 2013
`
`Reference ID: 3677979
`
`Page 6 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`Full Prescribing Information (FPI)
`
`FULL PRESCRIBING INFORMATION: GENERAL FORMAT
`
`YES
`
`32. The bolded section and subsection headings in the FPI must be named and numbered in
`accordance with 21 CFR 201.56(d)(1) as noted below (section and subsection headings should
`be in UPPER CASE and title case, respectively). If a section/subsection required by regulation
`is omitted, the numbering must not change. Additional subsection headings (i.e., those not
`named by regulation) must also be bolded and numbered.
`
`BOXED WARNING
`1 INDICATIONS AND USAGE
`2 DOSAGE AND ADMINISTRATION
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`6 ADVERSE REACTIONS
`7 DRUG INTERACTIONS
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Labor and Delivery
`8.3 Nursing Mothers
`8.4 Pediatric Use
`8.5 Geriatric Use
`9 DRUG ABUSE AND DEPENDENCE
`9.1 Controlled Substance
`9.2 Abuse
`9.3 Dependence
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`12.4 Microbiology (by guidance)
`12.5 Pharmacogenomics (by guidance)
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`13.2 Animal Toxicology and/or Pharmacology
`14 CLINICAL STUDIES
`15 REFERENCES
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`Comment:
`33. The preferred presentation for cross-references in the FPI is the section (not subsection)
`heading followed by the numerical identifier. The entire cross-reference should be in italics and
`enclosed within brackets. For example, “[see Warnings and Precautions (5.2)]” or “[see
`Warnings and Precautions (5.2)]”.
`
`NO
`
`SRPI version 3: October 2013
`
`Reference ID: 3677979
`
`Page 7 of 10
`
`

`

`Selected Requirements of Prescribing Information
`
`N/A
`
`YES
`
`N/A
`
`N/A
`
`N/A
`
`YES
`
`YES
`
`Comment: In 8.6, 8.7 and 12.3, cross reference for Dosage and Administration should state 2.2,
`not 2.
`34. If RMCs are listed in HL, the corresponding new or modified text in the FPI sections or
`subsections must be marked with a vertical line on the left edge.
`Comment:
`
`FULL PRESCRIBING INFORMATION DETAILS
`
`FPI Heading
`35. The following heading must be bolded and appear at the beginning of the FPI: “FULL
`PRESCRIBING INFORMATION”. This heading should be in UPPER CASE.
`Comment:
`BOXED WARNING Section in the FPI
`36. In the BW, all text should be bolded.
`Comment:
`37. The BW must have a heading in UPPER CASE, containing the word “WARNING” (even if
`more than one Warning, the term, “WARNING” and not “WARNINGS” sh