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` NDA 018936/S-112
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` NDA 021520/S-55
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`SUPPLEMENT APPROVAL
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` Eli Lilly and Company
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` Attention: Jennifer Riddle Camp
` Sr. Manager, Global Regulatory Affairs – North America
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` Lilly Corporate Center
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` Indianapolis, IN 46285
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`Dear Ms. Camp:
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`Please refer to your supplemental new drug applications (sNDA) dated and received
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`July 13, 2023, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic
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`Act (FDCA) for Prozac (fluoxetine) capsules and Symbyax (olanzapine and fluoxetine)
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`capsules.
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`We also refer to our letters dated June 15-16, 2023, notifying you, under Section
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`505(o)(4) of the FDCA, of new safety information pertaining to the association between
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`the use of selective serotonin reuptake inhibitors (SSRI)/serotonin and norepinephrine
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`reuptake inhibitors (SNRI) and the occurrence of Postpartum Hemorrhage,
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`Anosmia/Hyposmia, Drug Reaction with Eosinophilia and Systemic Symptoms
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`(DRESS). Additionally, we also identified the association between the concomitant use
`of selective serotonin reuptake inhibitors (SSRI)/serotonin and norepinephrine reuptake
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`inhibitors (SNRI) and opioids and the occurrence of serotonin syndrome.
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`Our June 15-16, 2023, letters also requested revisions, unrelated to the new
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`safety information, to include language that aligns with more recent class language.
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`These supplemental new drug applications provide for revisions to the labeling for
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`Prozac and Symbyax consistent with our June 15-16, 2023, safety labeling change
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`notification letters.
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`APPROVAL & LABELING
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`We have completed our review of this application. It is approved, effective on the date of
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`this letter, for use as recommended in the enclosed agreed-upon labeling.
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`Reference ID: 5229460
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` NDA 018936/S-112
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` NDA 021520/S-55
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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
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`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
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`the FDA automated drug registration and listing system (eLIST), as described at
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`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information and Medication Guide), with the addition of any labeling
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`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
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`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
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`industry SPL Standard for Content of Labeling Technical Qs and As.2
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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 include labeling
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`changes for this NDA, including CBE supplements for which FDA has not yet issued an
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`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
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`format, that includes the changes approved in this supplemental application, as well as
`annual reportable changes. To facilitate review of your submission(s), provide a
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`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
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`Word version. The marked-up copy should provide appropriate annotations, including
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`supplement number(s) and annual report date(s).
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and
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`promotional labeling. For information about submitting promotional materials, see the
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`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
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`Electronic Format-Promotional Labeling and Advertising Materials for Human
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`Prescription Drugs.3
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`You must submit final promotional materials and Prescribing Information, accompanied
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`by a Form FDA 2253, at the time of initial dissemination or publication
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`[21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
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`Instructions for completing the form can be found at FDA.gov.5 All promotional materials
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`that include representations about your drug product must be promptly revised to be
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
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`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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`3 For the most recent version of a guidance, check the FDA guidance web page at
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`https://www.fda.gov/media/128163/download.
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`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5229460
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` NDA 018936/S-112
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` NDA 021520/S-55
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` Page 3
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`consistent with the labeling changes approved in this supplement, including any new
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`safety-related information [21 CFR 314.70(a)(4)]. The revisions in your promotional
`materials should include prominent disclosure of the important new safety-related
` information that appears in the revised labeling. Within 7 days of receipt of this letter,
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` submit your statement of intent to comply with 21 CFR 314.70(a)(4).
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`PATENT LISTING REQUIREMENTS
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`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
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`submitted in a supplement require you to submit patent information for listing in the
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`Orange Book upon approval of the supplement. You must submit the patent information
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`required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
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`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
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`supplement for the patent information to be timely filed (see 21 CFR
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`314.53(c)(2)(ii)). You also must ensure that any changes to your approved NDA that
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`require the submission of a request to remove patent information from the Orange Book
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`are submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
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`314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
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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, call Ermias Zerislassie, Safety Regulatory Project Manager,
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`at 301-796-2770.
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`Sincerely,
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`{See appended electronic signature page}
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`Bernard A. Fischer, M.D.
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`Deputy Director
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`Division of Psychiatry
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`Office of Neuroscience
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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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`o Prescribing Information
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`o Medication Guide
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5229460
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`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/
`------------------------------------------------------------
`
`BERNARD A FISCHER
`08/18/2023 04:32:34 PM
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`Reference ID: 5229460
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