BLA 125469/S-046
`BLA 125469/S-052
`
`
`
`SUPPLEMENT APPROVAL
`
`
`Eli Lilly and Company
`Attention: Jennie L. Walgren, Ph.D.
`Associate VP, Global Regulatory Affairs
`Lilly Corporate Center
`Drop Code 2543
`Indianapolis, IN 46285
`
`Dear Dr. Walgren:
`
`Please refer to the following supplemental biologics license applications (sBLAs) and
`your amendments, submitted under section 351(a) of the Public Health Service Act for
`Trulicity (dulaglutide) injection.
`
`
`Supplement Number
`S-046
`S-052
`
`Dated and Received
`December 7, 2021
`May 20, 2022
`
`
`We also refer to our letter dated March 28, 2022, notifying you, under Section 505(o)(4)
`of the FDCA, of new safety information that we have determined should be included in
`the labeling for glucagon-like peptide-1 receptor agonist (GLP-1 RA) products. This
`information pertains to the risk of acute gallbladder disease.
`
`The sBLA S-052 provides for revisions to the labeling for Trulicity, consistent with our
`March 28, 2022, letter and the comments sent to you in our May 21, 2022,
`correspondence.
`
`The “Changes Being Effected” sBLA S-046 provides for the addition of ‘Elevations of
`liver enzymes, cholestasis, hepatitis’ to section 6.3 Postmarketing Experience of the
`Prescribing Information (PI), per our October 29, 2021, Supplement Request letter.
`
`APPROVAL & LABELING
`
`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
`with minor editorial revisions listed below and reflected in the enclosed labeling.
`
`
`• Updated revision dates in PI and Medication Guide (MG)
`
`WAIVER OF HIGHLIGHTS ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
`
`Reference ID: 4997161
`
`

`

`BLA 125469/S-046
`BLA 125469/S-052
`Page 2
`
`
`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit, via
`the FDA automated drug registration and listing system (eLIST), the content of labeling
`[21 CFR 601.14(b)] in structured product labeling (SPL) format, as described at
`FDA.gov,1 that is identical to the enclosed labeling (text for the Prescribing Information,
`Instructions for Use, and Medication Guide) and include the labeling changes proposed
`in any pending “Changes Being Effected” (CBE) supplements.
`
`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.
`
`Also within 14 days, amend all pending supplemental applications that include labeling
`changes for this BLA, including pending “Changes Being Effected” (CBE) supplements,
`for which FDA has not yet issued an action letter, with the content of labeling [21 CFR
`601.12(f)] in Microsoft Word 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 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).
`
`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.
`
`
`
`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
`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: 4997161
`
`

`

`BLA 125469/S-046
`BLA 125469/S-052
`Page 3
`
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`final 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 601.12(f)(4), 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
`
`All promotional materials for your drug product that include representations about your
`drug product must be promptly revised to make it consistent with the labeling changes
`approved in this supplement, including any new safety information [21 CFR
`601.12(a)(4)]. The revisions to your promotional materials should include prominent
`disclosure of the important new safety information that appears in the revised labeling.
`Within 7 days of receipt of this letter, submit your statement of intent to comply with 21
`CFR 601.12(a)(4).
`
`PATENT LISTING REQUIREMENTS
`
`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
`submitted in a supplement require you to submit patent information for listing in the
`Orange Book upon approval of the supplement. You must submit the patent information
`required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
`supplement for the patent information to be timely filed (see 21 CFR 314.53(c)(2)(ii)).
`You also must ensure that any changes to your approved NDA that require the
`submission of a request to remove patent information from the Orange Book are
`submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
`314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved BLA
`(in 21 CFR 600.80 and in 21 CFR 600.81).
`
`
`3 For the most recent version of a guidance, check the FDA guidance web page
`athttps://www.fda.gov/media/128163/download.
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4997161
`
`

`

`BLA 125469/S-046
`BLA 125469/S-052
`Page 4
`
`
`
`Your product is a Part 3 combination product (21 CFR 3.2(e)); therefore, you must also
`comply with postmarketing safety reporting requirements for an approved combination
`product (21 CFR 4, Subpart B). Additional information on combination product
`postmarketing safety reporting is available at FDA.gov.6
`
`If you have any questions, call Supendeep Dosanjh, Regulatory Project Manager, at
`301-837-7649.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Monika Houstoun, Pharm.D., M.P.H
`Deputy Director for Safety
`Division of Diabetes, Lipid Disorders, and Obesity
`Office of Cardiology, Hematology, Endocrinology,
`and Nephrology
`Office of New Drugs
`Center for Drug Evaluation and Research
`
`
`
`ENCLOSURES:
`• Content of Labeling
`o Prescribing Information
`o Medication Guide
`Instructions for Use (3.0 and 4.5 mg doses; versions approved September
`o
`3, 2020)
`o
`Instruction for Use (0.75 and 1.5 mg doses; versions approved September
`21, 2018)
`
`
`6 https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-
`combination-products
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4997161
`
`

`

`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/
`------------------------------------------------------------
`
`MONIKA A HOUSTOUN
`06/10/2022 11:19:38 AM
`
`Reference ID: 4997161
`
`(
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