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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 20845/S-016, S-017
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Mallinckrodt Hospital Products IP Limited
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`c/o: INO Therapeutics
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`Attention: Mary Ellen Anderson
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`Senior Director, Regulatory Affairs
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`Perryville III Corporate Park
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`53 Frontage Road, Third Floor, Box 9001
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`Hampton, NJ 08827
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`Dear Ms. Anderson:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated December 8, 2014 (S­
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`016) and December 11, 2014 (S-017) submitted under section 505(b) of the Federal Food, Drug,
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`and Cosmetic Act (FDCA) for INOmax (nitric oxide) for inhalation.
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`We acknowledge receipt of your amendments dated August 27, 2015 (S-016) and January 30 and
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`February 13, 2015 (S-017).
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`The August 27, 2015 submission constituted a complete response to our June 4, 2015 action
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`letter for S-016.
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`These “Prior Approval” supplemental new drug applications propose the following:
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` S-016
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`The removal of the 100 ppm nitric oxide concentration from the labeling and revisions to the
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`DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS sections of
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`the INOmax package inserts.
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`S-017
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`Revisions to the labeling based on the clinical study entitled “Bronchopulmonary Dysplasia
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`(BPD) in Preterm Infants Requiring Mechanical Ventilation or Positive Pressure Support on
`Days 5 to 14 After birth (IK-3001-BPD-301)”.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended. They are
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`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
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`upon labeling text.
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`Reference ID: 3831195
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` NDA 20845/S-016 & 017
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` 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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert), with the
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`addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as
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`well as annual reportable changes not included in the enclosed labeling.
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` 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 at
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
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`the product misbranded and an unapproved new drug.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
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`Reference ID: 3831195
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` NDA 20845/S-016 & 017
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` Page 3
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
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` CM443702.pdf ).
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` Information and Instructions for completing the form can be found at
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` http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`should include prominent disclosure of the important new safety information that appears in the
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
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`electronically in eCTD format. For more information about submitting promotional materials in
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`eCTD format, see the draft Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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, please call Brian Proctor, Regulatory Project Manager, at (240) 402­
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`3596.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary Ross Southworth, Pharm.D.
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`Deputy Director for Safety
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`Division of Cardiovascular and Renal Products
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`Office of Drug Evaluation I
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`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
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`Content of Labeling
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`Reference ID: 3831195
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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/
`----------------------------------------------------
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`MARY R SOUTHWORTH
`10/09/2015
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`Reference ID: 3831195
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