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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 202231/S-003
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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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`Fresenius Kabi USA, LLC
`Attention: Aditi Dron
`Regulatory Affairs Manager
`1501 East Woodfield Road, Suite 300 East
`Schaumburg, IL 60173
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`Dear Ms. Dron:
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`Please refer to your Supplemental New Drug Application (sNDA) dated June 26, 2012, received June
`26, 2012, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Levothyroxine Sodium for Injection, 100 mcg/vial, 200 mcg/vial (discontinued), and 500/mcg/vial.
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`This “Changes Being Effected” supplemental new drug application provides for the following changes
`in response to our supplement request letter dated March 29, 2012:
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`1. Deleted in the HIGHLIGHTS section, boxed warning,
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`“See full prescribing information for complete boxed warning.”
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`2. Added directly under the heading FULL PRESCRIBING INFORMATION: CONTENTS*:
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` “WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT
`LOSS”
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`3. Under the heading FULL PRESCRIBING INFORMATION, the boxed warning is added
`exactly as we asked that it appear in the HIGHLIGHTS section (i.e., without “See full
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`prescribing information for complete boxed warning.”).
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`4. The FULL PRESCRIBING INFORMATION section, DOSAGE AND
`ADMINISTRATION subsection, 2.3 Reconstitution Directions, is revised as follows:
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` “… Reconstituted drug product is preservative free and is stable for 4 hours. Use
` immediately after reconstitution. Discard any unused portion…”
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`Reference ID: 3234589
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` NDA 202231/S-003
`Page 2
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`The following additional changes were made to the PI.
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`1. Deletion of the 200 mcg dosage strength effected changes to DOSAGE AND
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`ADMINISTRATION, DOSAGE FORMS AND STRENGTHS, and HOW
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`SUPPLIED/STORAGE AND HANDLING sections.
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`2. The revised part number and container closure statement were added to the HOW
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`SUPPLIED/STORAGE AND HANDLING section (“This container closure is not made of
`natural rubber latex”).
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`3. The following sections were omitted as not being applicable: DRUG ABUSE AND
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`DEPENDENCE, REFERENCES, and PATIENT COUNSELING INFORMATION.
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`4. Minor editorial changes (i.e., capitalization, punctuation, and spacing).
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`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 and with the minor
`editorial revision changing the version revision year to 12/2012 from 6/2011 in the labeling.
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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
`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, with the addition of any
`labeling changes in pending “Changes Being Effected” (CBE) supplements, as 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
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/UCM07
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`2392.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 for this NDA, including CBE
`supplements for which FDA has not yet issued an action letter, with the content of labeling
`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this supplemental
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` application, as well as annual reportable changes and annotate each change. To facilitate review of
`your submission, provide a highlighted or marked-up copy that shows all changes, as well as a clean
`Microsoft Word version. The marked-up copy should provide appropriate annotations, including
`supplement number(s) and annual report date(s).
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`We request that the labeling approved today be available on your website within 10 days of receipt of
`this letter.
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`Reference ID: 3234589
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` NDA 202231/S-003
`Page 3
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` REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
`314.80 and 314.81).
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`If you have any questions, call Linda Galgay, Regulatory Project Manager, at (301) 796-5383.
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`Sincerely,
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` {See appended electronic signature page}
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`Mary H. Parks, MD
`Director
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`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`Reference ID: 3234589
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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 H PARKS
`12/20/2012
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`Reference ID: 3234589
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