`NDA 203441/S-020
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`SUPPLEMENT APPROVAL
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` Shire-NPS Pharmaceuticals, Inc.
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` Attention: Denzel Ngoma
` Senior Manager, Global Regulatory Strategy, GI
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` 40 Landsdowne Street
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` Cambridge, MA 02139
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`Dear Mr. Ngoma:
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`Please refer to your supplemental new drug application (sNDA) dated and received on
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`December 17, 2020, and your amendments, submitted under section 505(b) of the
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`Federal Food, Drug, and Cosmetic Act (FDCA) for Gattex (teduglutide) for injection, 5
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`mg.
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`This Changes Being Effected sNDA provides for a proposed modification to the
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`approved Gattex risk evaluation and mitigation strategy (REMS). We have completed
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`our review of this supplemental application, and it is approved effective on the date of
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`this letter.
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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, and
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`the most recent REMS modification was approved on July 14, 2020. The REMS
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`consists of elements to assure safe use and a timetable for submission of assessments
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`of the REMS. Your proposed modifications to the REMS consist of a modification to the
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`REMS website to add a link for prescriber re-training.
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`Your proposed modified REMS, submitted and received on December 17, 2020, and
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`appended to this letter, is approved. The timetable for submission of assessments of the
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`REMS remains the same as that approved on December 21, 2012. There are no
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`changes to the REMS assessment plan as described in our October 20, 2020 letter.
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`We remind you that in addition to the REMS assessments submitted according to the
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`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
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`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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`Reference ID: 4745364
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`NDA 203441/S-020
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`Page 2
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`a) An evaluation of how the benefit-risk profile will or will not change with the new
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`indication;
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`b) A determination of the implications of a change in the benefit-risk profile for the
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`current REMS;
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`c) If the new indication for use introduces unexpected risks: A description of those
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`risks and an evaluation of whether those risks can be appropriately managed
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`with the currently approved REMS.
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`d) If a REMS assessment was submitted in the 18 months prior to submission of the
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`supplemental application for a new indication for use: A statement about whether
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`the REMS was meeting its goals at the time of that last assessment and if any
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`modifications of the REMS have been proposed since that assessment.
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`e) If a REMS assessment has not been submitted in the 18 months prior to
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`submission of the supplemental application for a new indication for use: Provision
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`of as many of the currently listed assessment plan items as is feasible.
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`f)
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`If you propose a REMS modification based on a change in the benefit-risk profile
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`or because of the new indication of use, submit an adequate rationale to support
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`the modification, including: Provision of the reason(s) why the proposed REMS
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`modification is necessary, the potential effect on the serious risk(s) for which the
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`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
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`the proposed change. Additionally, include any changes to the assessment plan
`necessary to assess the proposed modified REMS. If you are not proposing
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`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
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`included in the REMS supporting document, or if you propose changes to the submitted
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`assessment instruments or methodology, you should update the REMS supporting
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`document to include specific assessment instrument and methodology information at
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`least 90 days before the assessments will be conducted. Updates to the REMS
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`supporting document may be included in a new document that references previous
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`REMS supporting document submission(s) for unchanged portions. Alternatively,
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`updates may be made by modifying the complete previous REMS supporting document,
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`with all changes marked and highlighted. Prominently identify the submission containing
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`the assessment instruments and methodology with the following wording in bold capital
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`letters at the top of the first page of the submission:
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4745364
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` NDA 203441/S-020
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` Page 3
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`NDA 203441 REMS ASSESSMENT METHODOLOGY
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`(insert concise description of content in bold capital letters, e.g.,
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`ASSESSMENT METHODOLOGY, PROTOCOL, SURVEY METHODOLOGIES,
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`AUDIT PLAN, DRUG USE STUDY)
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`An authorized generic drug under this NDA must have an approved REMS prior to
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`marketing. Should you decide to market, sell, or distribute an authorized generic drug
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`under this NDA, contact us to discuss what will be required in the authorized generic
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`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
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`or delay approval of an application under section 505(b)(2) or (j). A violation of this
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`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
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`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
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`CHANGES BEING EFFECTED IN 30 DAYS
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`PROPOSED MINOR REMS MODIFICATION
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`or
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4745364
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`or
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`NEW SUPPLEMENT FOR NDA 203441/S-XXX
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 203441/S-XXX
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABELING
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`CHANGES SUBMITTED IN SUPPLEMENT YYY
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` NDA 203441/S-020
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` Page 4
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 203441/S-XXX
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`REMS ASSESSMENT
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`PROPOSED REMS MODIFICATION (if included)
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` Should you choose to submit a REMS revision, prominently identify the submission
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`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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`To facilitate review of your submission, we request that you submit your proposed
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`modified REMS and other REMS-related materials in Microsoft Word format. If certain
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`documents, such as enrollment forms, or website screenshots are only in PDF format,
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`they may be submitted as such, but 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 Structured Product Labeling (SPL) format. If
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`you intend to submit the REMS document in SPL format, as soon as possible, but no
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`later than 14 days from the date of this letter, submit the REMS document in SPL format
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`using the FDA automated drug registration and listing system (eLIST).
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`For more information on submitting REMS in SPL format, please email
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`FDAREMSwebsite@fda.hhs.gov.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, contact Anum Shami, PharmD, Regulatory Project Manager,
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`at 301-837-7103 or anum.shami@fda.hhs.gov.
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` REMS REVISIONS FOR NDA 203441
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`Sincerely,
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`{See appended electronic signature page}
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`Joyce Korvick, MD, MPH
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`Deputy Director for Safety
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`Division of Gastroenterology (DG)
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`Office of Immunology and Inflammation (OII)
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`Center for Drug Evaluation and Research
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`Enclosure:
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`REMS
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4745364
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`Signature Page 1 of 1
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`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.
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`/s/
`------------------------------------------------------------
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`JOYCE A KORVICK
`02/11/2021 10:30:57 AM
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`Reference ID: 4745364
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`(
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