Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`NDA 21-196/S-005
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`Orphan Medical, Inc.
`(A Subsidiary of Jazz Pharmaceuticals)
`13911 Ridgedale Drive, Suite 250,
`Minnetonka, MN 55305
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`Dear Dr. Reardan:
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`Please refer to your supplemental new drug application dated January 14, 2005, received January 18,
`2005, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Xyrem ®
`(sodium oxybate) oral solution.
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`We also refer to your new drug application for this drug product, which was reviewed and approved
`under the restricted distribution regulations contained in 21 CFR 314.500 (Subpart H) to assure safe
`use of the product.
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`We acknowledge receipt of your additional submissions to this supplemental application dated March
`15, 2005, April 4, 2005, and November 7, 2005.
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`This supplemental new drug application provides for the use of Xyrem ® (sodium oxybate) oral
`solution for the treatment of excessive daytime sleepiness in patients with narcolepsy.
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`We have completed our review of this application, as amended, and have concluded that adequate
`information has been presented to demonstrate that the drug product is safe and effective for use as
`recommended in the enclosed, agreed-upon labeling text. Accordingly, this application is approved,
`effective on the date of this letter.
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`Final Printed Labeling
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`The final printed labeling (FPL) must be identical to the enclosed agreed upon labeling text for the
`Product Package Insert, Medication Guide, Xyrem® Success Program For Physicians (Book, Letter
`and Registration Form), and Xyrem® Success Program For Physicians (Book, Letter, and Patient
`Prescription & Enrollment Form).
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`Please submit an electronic version of the FPL according to the guidance for industry titled Providing
`Regulatory Submissions in Electronic Format - NDA. Alternatively, you may submit 20 paper copies
`of the FPL as soon as it is available but no more than 30 days after it is printed. Individually mount 15
`of the copies on heavy-weight paper or similar material. For administrative purposes, designate this
`submission "FPL for approved supplement NDA 21-196/S-005.” Approval of this submission by
`FDA is not required before the labeling is used.
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`Page 1 of 4
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`JAZZ EXHIBIT 2002
`Amneal Pharms. et al. (Petitioners) v. Jazz Pharms., Inc. (Patent Owner)
`Case IPR2015-01903
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`NDA 21-196/S-005
`Page 2
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`Request for Removal of the Pre-submission Requirement for Promotional Materials
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`We note that in your January 14, 2005 submission, you request FDA to withdraw the 30-day
`promotional pre-submission requirement (21 CFR Part 314.550) as allowed under 21 CFR 314.560 for
`Xyrem (sodium oxybate) oral solution, NDA 21-196. We are denying your request. We believe that it
`is important for the Division of Drug Marketing, Advertising, and Communications (DDMAC) to
`review the proposed materials before their dissemination to ensure the continued appropriateness of the
`advertising campaign.
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`Accordingly, as required by 21 CFR 314.550, please continue to submit three copies of all promotional
`materials including promotional labeling and advertisements at least 30 days before the intended time
`of initial distribution of labeling or initial publication of the advertisement with a cover letter
`requesting advisory comment. Send one copy to this Division and two copies of both the promotional
`materials and the package insert directly to:
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`Fulfillment of Postmarketing Commitment
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`We note that, in the supplemental application, you propose to discontinue the Xyrem® Post-Marketing
`Evaluation Program, which was intended to collect solicited safety data on an additional 1000 patients
`following the approval of Xyrem® and was specified as Postmarketing Study Commitment #3 in the
`original Xyrem® approval letter dated July 17, 2002.
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`We have reviewed your arguments regarding the discontinuation of this program and agree that it may
`be stopped. Therefore, we also conclude that Postmarketing Study Commitment #3 has been fulfilled.
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`Please note, however, that Postmarketing Study Commitment #2 (Conduct a clinical study in subjects
`with respiratory compromise), acknowledged in our July 17, 2002 letter, is still open.
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`Dear Health Care Professional Letter
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`If you issue a letter communicating important information about this drug product (i.e., a “Dear Health
`Care Professional” letter), we request that you submit a copy of the letter to this NDA and a copy to
`the following address:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`MEDWATCH
`Food and Drug Administration
`Building 22 Mail Stop 4447
`10903 New Hampshire Avenue
`Silver Spring, MD 20993-0002
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`Page 2 of 4
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`NDA 21-196/S-005
`Page 3
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`We remind you that you must comply with the requirements for an approved NDA set forth under 21
`CFR 314.80, 314.81, 314.520, 314.550 and 314.560.
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`If you have any questions, call Jacqueline H. Ware, Pharm.D., Senior Regulatory Project Manager, at
`(301) 796-2050.
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`Sincerely,
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`{See appended electronic signature page}
`
`Russell Katz, M.D.
`Director
`Division of Neurology Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`Enclosures:
`Package Insert
`Patient MedGuide
`Risk Management Plan
`Xyrem® Success Program For Physicians (Book, Letter and Registration Form)
`Xyrem® Success Program For Physicians (Book, Letter, and Patient Prescription & Enrollment Form)
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`Page 3 of 4
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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/
`---------------------
`Russell Katz
`11/18/2005 04:09:04 PM
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`Page 4 of 4