NDA 212690 / S009
`NDA 21196 / S039
`
`
`
`SUPPLEMENT APPROVAL
`
`
`Jazz Pharmaceuticals Ireland Limited
`Attention: Arthur Merlin d’Estreux
`Sr. Director, Regulatory Affairs Neurosciences
`Jazz Pharmaceuticals
`2005 Market Street, 21st Floor, Philadelphia, PA 19103
`
`
`Dear Mr. d’Estreux:
`
`Please refer to your supplemental new drug application (sNDA) dated December 14,
`2021, received December 14, 2021, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for XYWAV (calcium, magnesium, potassium,
`and sodium oxybates), oral solution 0.5 g/mL and XYREM (sodium oxybate) oral
`solution 0.5g/ml.
`
`These “Changes Being Effected” sNDAs provide for revisions to the approved XYWAV
`and XYREM risk evaluation and mitigation strategy (REMS) prescription forms.
`
`APPROVAL & LABELING
`
`We have completed our review of these supplements, as amended. They are approved,
`effective on the date of this letter, for use as recommended in the enclosed agreed-
`upon labeling.
`
`We request that the labeling approved today be available on your website within 10
`days of receipt of this letter.
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
`The REMS for XYREM was originally approved on February 27, 2015, and the REMS
`for XYWAV was approved on July 21, 2020. The two drugs are subject to the same
`REMS, known as the XYWAV and XYREM REMS. The most recent REMS
`modification was approved on December 9, 2021. The REMS consists of elements to
`assure safe use, an implementation system, and a timetable for submission of
`assessments of the REMS.
`
`Your proposed modifications to the REMS consist of changes to the XYWAV and
`XYREM Prescription Forms to decrease prescriber confusion when documenting the
`indication for use and signing the form.
`
`
`Reference ID: 4935525
`
`

`

`NDA 212690 / S009
`NDA 21196 / S039
`Page 2
`
`
`Your proposed modified REMS, submitted on December 14, 2021, amended and
`appended to this letter, is approved.
`
`The timetable for submission of assessments of the REMS remains the same as that
`approved on August 12, 2021.
`
`There are no changes to the REMS assessment plan described in our August 12, 2021,
`letter.
`
`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.
`
`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:
`
`
`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.
`
`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
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4935525
`
`

`

`NDA 212690 / S009
`NDA 21196 / S039
`Page 3
`
`
`
`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.
`
`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:
`
`
`NDA ###### REMS ASSESSMENT METHODOLOGY
`(insert concise description of content in bold capital letters, e.g.,
`ASSESSMENT METHODOLOGY, PROTOCOL, SURVEY METHODOLOGIES,
`AUDIT PLAN, DRUG USE STUDY)
`
`
`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.
`
`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.
`
`
`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:
`
`
`NDA ###### REMS ASSESSMENT
`
`
`or
`
`
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4935525
`
`

`

`NDA 212690 / S009
`NDA 21196 / S039
`Page 4
`
`
`
`NEW SUPPLEMENT FOR NDA ######/S-000
`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
`
`
`or
`
`
`NEW SUPPLEMENT FOR NDA ######/S-000
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED MAJOR REMS MODIFICATION
`
`or
`
`
`NEW SUPPLEMENT FOR NDA ######/S-000
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABELING
`CHANGES SUBMITTED IN SUPPLEMENT XXX
`
`
`
`or
`
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA ######/S-000
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
`
`REMS REVISIONS FOR NDA ######
`
`
`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:
`
`
`
`To facilitate review of your submission, we request that you submit your proposed
`modified REMS and other REMS-related materials in Microsoft Word format. If certain
`documents, such as enrollment forms, or website screenshots are only in PDF format,
`they may be submitted as such, but Word format is preferred.
`
`SUBMISSION OF REMS DOCUMENT IN SPL FORMAT
`
`FDA can accept the REMS document in Structured Product Labeling (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 drug registration and listing system (eLIST).
`
`For more information on submitting REMS in SPL format, please email
`FDAREMSwebsite@fda.hhs.gov.
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4935525
`
`

`

`NDA 212690 / S009
`NDA 21196 / S039
`Page 5
`
`
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`If you have any questions, contact, Teresa Wheelous, Regulatory Project Manager, at
`teresa.wheelous@fda.hhs.gov.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Teresa Buracchio, MD
`Director
`Division of Neurology 1
`Office of Neuroscience
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
`• REMS
`
`
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4935525
`
`

`

`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.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`TERESA J BURACCHIO
`02/09/2022 03:41:40 PM
`
`Reference ID: 4935525
`
`