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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 203441/S-012
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Shire-NPS Pharmaceuticals, Inc.
`Attention: Kristen McLaren
`Project Manager, Global Regulatory Affairs
`300 Shire Way
`Lexington, MA 02421
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`Dear Ms. McLaren:
`
`Please refer to your supplemental New Drug Application (sNDA), dated and received on
`February 28, 2018 (eCTD SN0210), and your amendments, submitted under section 505(b) of
`the Federal Food, Drug, and Cosmetic Act (FDCA), for GATTEX (teduglutide) for injection, 5
`mg.
`
`This Prior Approval sNDA provides for the following:
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`1. Updated the Adverse Reactions section of the prescribing information (PI) based upon a
`reanalysis of safety data from the original clinical trials that evaluated GATTEX
`(teduglutide);
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`2. Converted the PI to be compliant with the Pregnancy and Lactation Labeling Rule
`(PLLR);
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`3. Removed the text “rDNA origin” from the established name/drug product title within the
`PI;
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`4. Applied the aforementioned changes, accordingly, to the medication guide (MG),
`instructions for use (IFU), and carton and container labeling; and
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`5. Modified the approved GATTEX (teduglutide) Risk Evaluation and Mitigation Strategy
`(REMS).
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
`
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`Reference ID: 4365346
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`

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`NDA 203441/S-012
`Page 2
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in Structured Product Labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the PI, MG, and IFU), with the
`addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as
`well as annual reportable changes not included in the enclosed labeling. Information on
`submitting SPL files using eLIST may be found in the Guidance for Industry titled, SPL
`Standard for Content of Labeling Technical Qs and As, located at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf. The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that include labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft (MS) Word format that
`includes the changes approved in this supplemental application, as well as annual reportable
`changes. To facilitate the review of your submission, provide a highlighted or marked-up copy,
`which shows all changes, as well as a clean MS Word version. The marked-up copy should
`provide appropriate annotations, including supplement number(s) and annual report date(s).
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`We request that the labeling approved today be available on your website within 10 days of
`receipt of this letter.
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`CARTON AND CONTAINER LABELING
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`Submit final printed carton and container labeling that are identical to the enclosed carton and
`container labeling, which was submitted and received on April 20, 2018 (eCTD SN0228), as
`soon as they are available, but no more than 30 days after they are printed. Please submit these
`labeling electronically according to the Guidance for Industry titled, Providing Regulatory
`Submissions in Electronic Format –– Certain Human Pharmaceutical Product Applications and
`Related Submissions Using the eCTD Specifications (April 2018, Revision 5), located at
`https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm
`333969.pdf. For administrative purposes, designate this submission “Final Printed Carton and
`Container Labeling for approved NDA 203441/S-012.” Approval of this submission by FDA
`is not required before the labeling is used.
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients (which includes new salts and new fixed combinations), new indications, new
`dosage forms, new dosing regimens, or new routes of administration are required to contain an
`assessment of the safety and effectiveness of the product for the claimed indication in pediatric
`patients unless this requirement is waived, deferred, or inapplicable.
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`Reference ID: 4365346
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`

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`NDA 203441/S-012
`Page 3
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
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`The REMS for GATTEX (teduglutide) was originally approved on December 21, 2012
`(Reference ID: 3253828), and the most recent REMS modification was approved on March 21,
`2017 (Reference ID: 4072641). The REMS consists of elements to assure safe use and a
`timetable for submission of assessments of the REMS. Your proposed modifications to the
`REMS consist of modifications to the REMS document and appended materials to align with
`labeling changes related to this efficacy supplement’s approval.
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`In accordance with section 505-1 of the FDCA, we have determined that the following REMS
`modifications are necessary to ensure the benefits of the drug outweigh the risks:
`a. Removal of the text “rDNA origin” from the established name/drug product title in the
`labeling and the REMS;
`b. Requiring that healthcare providers (HCPs) request paper copies of online training
`materials when inquiring about how to become certified; and
`c. Replacing the phone number with a facsimile number for HCPs to report their completion
`of training.
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`Your proposed modified REMS, submitted and received on November 9, 2018 (eCTD SN0277)
`and appended to this letter, is approved. The modified REMS consists of elements to assure safe
`use and a timetable for submission of assessments of the REMS. The timetable for submission
`of assessments of the REMS remains the same as that approved on December 21, 2012, and there
`are no changes to the REMS assessment plan.
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`We remind you that in addition to the REMS assessments submitted according to the timetable in
`the approved REMS, you must include an adequate rationale to support a proposed REMS
`modification for the addition, modification, or removal of any goal or element of the REMS, as
`described in section 505-1(g)(4) of the FDCA.
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`We also remind you that you must submit a REMS assessment when you submit a supplemental
`application for a new indication for use, as described in section 505-1(g)(2)(A) of the FDCA.
`This assessment should include:
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`a. An evaluation of how the benefit-risk profile will or will not change with the new
`indication.
`b. A determination of the implications of a change in the benefit-risk profile for the current
`REMS.
`c. If the new indication for use introduces unexpected risks: A description of those risks
`and an evaluation of whether those risks can be appropriately managed with the currently
`approved REMS.
`d. If a REMS assessment was submitted in the 18 months prior to submission of the
`supplemental application for a new indication for use: A statement about whether the
`REMS was meeting its goals at the time of that last assessment and if any modifications
`of the REMS have been proposed since that assessment.
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`Reference ID: 4365346
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`

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`NDA 203441/S-012
`Page 4
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`e. If a REMS assessment has not been submitted in the 18 months prior to submission of the
`supplemental application for a new indication for use: Provision of as many of the
`currently listed assessment plan items as is feasible.
`f. If you propose a REMS modification based on a change in the benefit-risk profile or
`because of the new indication of use, submit an adequate rationale to support the
`modification, including: Provision of the reason(s) why the proposed REMS
`modification is necessary, the potential effect on the serious risk(s) for which the REMS
`was required, on patient access to the drug, and/or on the burden on the health care
`delivery system; and other appropriate evidence or data to support the proposed change.
`Additionally, include any changes to the assessment plan necessary to assess the
`proposed modified REMS. If you are not proposing REMS modifications, provide a
`rationale for why the REMS does not need to be modified.
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`If the assessment instruments and methodology for your REMS assessments are not included in
`the REMS supporting document, or if you propose changes to the submitted assessment
`instruments or methodology, you should update the REMS supporting document to include
`specific assessment instrument and methodology information at least 90 days before the
`assessments will be conducted. Updates to the REMS supporting document may be included in a
`new document that references previous REMS supporting document submission(s) for
`unchanged portions. Alternatively, updates may be made by modifying the complete previous
`REMS supporting document, with all changes marked and highlighted. Prominently identify the
`submission containing the assessment instruments and methodology with the following wording
`in bold capital letters at the top of the first page of the submission:
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`NDA 203441 REMS ASSESSMENT METHODOLOGY
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`An authorized generic drug under this NDA must have an approved REMS prior to marketing.
`Should you decide to market, sell, or distribute an authorized generic drug under this NDA,
`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
`application with elements to assure safe use from using any element to block or delay approval
`of an application under section 505(b)(2) or (j). A violation of this provision in 505-1(f) could
`result in enforcement action.
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`Prominently identify any submission containing the REMS assessments or proposed
`modifications of the REMS with the following wording in bold capital letters at the top of the
`first page of the submission as appropriate:
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`NDA 203441 REMS ASSESSMENT
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`or
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`NEW SUPPLEMENT FOR NDA 203441/S-XXX
`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
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`Reference ID: 4365346
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`

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`NDA 203441/S-012
`Page 5
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`or
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`NEW SUPPLEMENT FOR NDA 203441/S-XXX
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 203441/S-XXX
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
`SUBMITTED IN SUPPLEMENT YYY
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`or
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 203441/S-XXX
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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`REMS REVISIONS FOR NDA 203441
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`Should you choose to submit a REMS revision, prominently identify the submission containing
`the REMS revisions with the following wording in bold capital letters at the top of the first page
`of the submission:
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`
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`To facilitate review of your submission, we request that you submit your proposed modified
`REMS and other REMS-related materials in MS Word format. If certain documents, such as
`enrollment forms, or website screenshots are only in PDF format, they may be submitted as such,
`but MS Word format is preferred.
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`SUBMISSION OF REMS DOCUMENT IN SPL FORMAT
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`FDA can accept the REMS document in SPL format. If you intend to submit the REMS
`document in SPL format, as soon as possible, but no later than 14 days from the date of this
`letter, submit the REMS document in SPL format using the FDA automated eLIST.
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`For more information on submitting REMS in SPL format, please email
`FDAREMSwebsite@fda.hhs.gov.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the PI to:
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`Reference ID: 4365346
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`

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`NDA 203441/S-012
`Page 6
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry titled, Providing Regulatory Submissions in Electronic and Non-
`Electronic Format –– Promotional Labeling and Advertising Materials for Human Prescription
`Drugs, located at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf.
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`You must submit final promotional materials and the PI, accompanied by a Form FDA 2253, at
`the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is
`available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`Reference ID: 4365346
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`

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`NDA 203441/S-012
`Page 7
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`If you have any questions, contact Benjamin Vali, Regulatory Project Manager, at (301) 796-
`4261 or benjamin.vali@fda.hhs.gov.
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`Sincerely,
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`{See appended electronic signature page}
`
`Jessica J. Lee, M.D., M.M.Sc.
`Associate Director
`Division of Gastroenterology and Inborn Errors
`Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
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`Enclosures:
` Content of Labeling:
` PI
` MG
` IFU
` Carton and Container Labeling
` REMS
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`Reference ID: 4365346
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`

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`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
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`JESSICA J LEE
`12/18/2018
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`Reference ID: 4365346
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`(
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