`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`
`202231Orig1s000
`
`Levothyroxine
`
`Levothyroxine Sodium
`
`APP Pharms
`
`6/24/2011
`
`Indicated for the treatment of myxedema
`coma
`
`Trade Name:
`
`Generic Name:
`
`Sponsor:
`
`Approval Date:
`
`Indications:
`
`
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`202231Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this BLA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
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`X
`
`X
`X
`
`
`X
`X
`
`X
`
`X
`X
`X
`
`
`X
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`202231Orig1s000
`
`APPROVAL LETTER
`
`
`
`
`

`

`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`NDA APPROVAL
`
`
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`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`NDA 202231
`
`APP Pharmaceuticals, LLC
`Attention: Brent Yurschak
`Regulatory Scientist
`1501 East Woodfield Road, Suite 300 East
`Schaumburg, IL 60173
`
`
`Dear Mr. Yurschak:
`
`Please refer to your new drug application (NDA) dated August 30, 2010, received
`August 30, 2010, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and
`Cosmetic Act, for Levothyroxine Sodium for Injection, 100 mcg, 200 mcg, and 500 mcg vials.
`
`We acknowledge receipt of your amendments dated September 2, December 10 and 20, 2010,
`and January 31, February 18, March 25, April 20, May 13, and June 15, and emails dated
`June 22, 23, and 24, 2011.
`
`This new drug application provides for the use of Levothyroxine Sodium for Injection for the
`treatment of myxedema coma.
`
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
`
`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
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling text for the package insert. 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
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`
`
`
`Reference ID: 2965603
`
`

`

`NDA 202231
`Page 2
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`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`Submit final printed carton and container labels that are identical to the enclosed carton and
`immediate container labels as soon as they are available, but no more than 30 days after they are
`printed. Please submit these labels electronically according to the guidance for industry titled
`“Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product
`Applications and Related Submissions Using the eCTD Specifications (June 2008).”
`Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on
`heavy-weight paper or similar material. For administrative purposes, designate this submission
`“Final Printed Carton and Container Labels for approved NDA 202231.” Approval of this
`submission by FDA is not required before the labeling is used.
`
`Marketing the products with FPL that is not identical to the approved labeling text may render
`the product misbranded and an unapproved new drug.
`
`PROPRIETARY NAME
`
`If you intend to have a proprietary name for this product, the name and its use in the labels must
`conform to the specifications under 21 CFR 201.10 and 201.15. We recommend that you submit
`a request for a proposed proprietary name review. (See the guidance for industry titled,
`“Contents of a Complete Submission for the Evaluation of Proprietary Names”, at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/u
`cm075068.pdf and “PDUFA Reauthorization Performance Goals and Procedures Fiscal Years
`2008 through 2012”.)
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, 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.
`
`Given the extreme rarity of myxedema coma in children, we are waiving the pediatric study
`requirement for this application because necessary studies are impossible or highly
`impracticable.
`
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`Reference ID: 2965603
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`

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`NDA 202231
`Page 3
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`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 package insert
`to:
`
`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
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
`information about submission of promotional materials to the Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`ADDITIONAL COMMENTS
`
`Chemistry, Manufacturing, and Controls: Based on the provided stability data, an expiration
`dating period of 12 months at controlled room temperature (20°C – 25°C) is granted for the drug
`product packaged in the container closure system submitted in the NDA.
`
`Clinical: Because your application did not provide enough information to guide conversion from
`an oral to an intravenous (IV) levothyroxine regimen for hypothyroid patients who are controlled
`on oral levothyroxine products but require IV replacement temporarily, as discussed in the May
`11, 2011 teleconference, we encourage you to conduct a bioavailability study addressing the
`issue of oral to IV dose conversion. The results of such a study may be submitted as an efficacy
`supplement.
`
`
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`
`
`
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`Reference ID: 2965603
`
`

`

`Sincerely,
`
`
`{See appended electronic signature page}
`
`Mary H. Parks, MD
`Director
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`NDA 202231
`Page 4
`
`
`If you have any questions, call Linda Galgay, Regulatory Project Manager, at (301) 796-5383.
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`
`
`
`ENCLOSURES:
`Content of Labeling
`Carton and Vial Labels
`
`
`
`
`Reference ID: 2965603
`
`