CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`APPLICATION NUMBER:
`
`212535Orig1s000
`
` NOURESS™ USP, 50 mg/mL.
`
`cysteine hydrochloride injection
`
`
`
`
`
`Trade Name:
`
`Generic or Proper
`Name:
`
`Sponsor:
`
`
`
`
`Approval Date:
`
`
`Indication:
`
`
`Avadel Legacy Pharmaceuticals, LLC
`
`December 13, 2019
`
`Provides for the use of NOURESS™ (cysteine
`hydrochloride injection) as an additive to amino acid
`solutions to meet nutritional requirements of neonates
`(preterm and term infants less than one month of age)
`requiring total parenteral nutrition (TPN).
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`212535Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Officer/Employee List
`Multidiscipline Review(s)
` Summary Review
` Office Director
` Cross Discipline Team Leader
` Clinical
` Non-Clinical
` Statistical
` Clinical Pharmacology
`Product Quality Review(s)
`Clinical Microbiology / Virology Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`
`X
`
`X
`X
`
`X
`
`X
`
`X
`
`

`

`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`
`
`
`
`
`APPLICATION NUMBER:
`
`212535Orig1s000
`
`
`APPROVAL LETTER
`
`

`

`NDA 212535
`
`
`
`NDA APPROVAL
`
`
`Avadel Legacy Pharmaceuticals, LLC
`c/o The Weinberg Group LLC
`Attention: Marla Scarola (US Authorized Agent)
`Vice President, Regulatory Program Management
`1129 Twentieth Street NW, Suite 600
`Washington, DC 20036
`
`Dear Ms. Scarola,
`
`Please refer to your new drug application (NDA) dated and received on March 15, 2019,
`submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`for NOURESS™ (cysteine hydrochloride injection) USP, 50 mg/mL.
`
`We acknowledge receipt of your major amendment dated July 15, 2019, which
`extended the goal date by three months.
`
`This new drug application provides for the use of NOURESS™ (cysteine hydrochloride
`injection) as an additive to amino acid solutions to meet nutritional requirements of
`neonates (preterm and term infants less than one month of age) requiring total
`parenteral nutrition (TPN).
`
`APPROVAL & LABELING
`
`We have completed our review of this application. It is approved, effective on the date of
`this letter, for use as recommended in the enclosed agreed-upon labeling text.
`
`We note that your December 10, 2019, submission includes final printed labeling (FPL)
`for your Prescribing Information. We have not reviewed this FPL. You are responsible
`for assuring that the wording in this printed labeling is identical to that of the approved
`content of labeling in the structured product labeling (SPL) format.
`
`CONTENT OF LABELING
`
`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
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling Prescribing
`Information as well as annual reportable changes not included in the enclosed labeling.
`
`
`1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`
`Reference ID: 4533723
`
`

`

`NDA 212535
`Page 2
`
`
`Information on submitting SPL files using eLIST may be found in the guidance for
`industry SPL Standard for Content of Labeling Technical Qs and As.2
`
`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND CONTAINER LABELING
`
`Submit final printed carton and container labeling that are identical to the enclosed
`carton and container labeling and carton and container labeling submitted on December
`10, 2019, 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 Providing Regulatory Submissions in Electronic Format — Certain Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD
`Specifications. For administrative purposes, designate this submission “Final Printed
`Carton and Container Labeling for approved NDA 212535.” Approval of this submission
`by FDA is not required before the labeling is used.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`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.
`
`Because none of these criteria apply to your application, you are exempt from this
`requirement.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. To do so, submit, in triplicate, a cover letter requesting advisory
`comments, the proposed materials in draft or mock-up form with annotated references,
`and the Prescribing Information, Medication Guide, and Patient Package Insert (as
`applicable) to:
`
`
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4533723
`
`

`

`NDA 212535
`Page 3
`
`
`
`
`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`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 Providing Regulatory Submissions in Electronic and
`Non-Electronic Format—Promotional Labeling and Advertising Materials for Human
`Prescription Drugs.3
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials,
`and the Prescribing Information, at the time of initial dissemination or publication,
`accompanied by a Form FDA 2253. Form FDA 2253 is available at FDA.gov.4
`Information and Instructions for completing the form can be found at FDA.gov.5 For
`more information about submission of promotional materials to the Office of Prescription
`Drug Promotion (OPDP), see FDA.gov.6
`
`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, call Thao Vu, Regulatory Project Manager, at (240) 402-
`2690.
`
`
`
`
`Sincerely,
`{See appended electronic signature page}
`
`Lisa M. Soule, M.D
`Associate Director
`Division of Gastroenterology and Inborn Errors
`Products
`Office of Drug Evaluation III
`
`
`3 When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent
`version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm
`
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4533723
`
`

`

`NDA 212535
`Page 4
`
`
`
`Center for Drug Evaluation and Research
`
`
`
`ENCLOSURE(S):
`• Content of Labeling
`o Prescribing Information
`o Carton and Container Labeling
`
`
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4533723
`
`

`

`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/
`------------------------------------------------------------
`
`LISA M SOULE
`12/13/2019 04:31:19 PM
`
`Reference ID: 4533723
`
`(
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`
`
`