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`BLA 125387/S-061
`
`Regeneron Pharmaceuticals, Inc.
`Attention: Amanda Cook, Bsc. (Hons), Dip.Reg.Aff.
`Associate Director, Regulatory Affairs
`777 Old Saw Mill River Road
`Tarrytown, NY 10591-6707
`
`Dear Ms. Cook:
`
`Food and Drug Administration
`Silver Spring, MD 20993
`
`SUPPLEMENT APPROVAL
`
`Please refer to your Supplemental Biologics License Application (sBLA), dated and received
`July 13, 2018, and your amendments, submitted under section 351(a) of the Public Health
`Service Act for EYLEA (aflibercept) Injection. This supplemental biologics application provides
`for the use of EYLEA (aflibercept) Injection for the treatment of diabetic retinopathy.
`
`APPROVAL & LABELING
`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text which is identical to the labeling submitted on May 3, 2019.
`
`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
`http://www. fda. gov IF or Industry /DataS tandards/StructuredProductLabeling/ default.htm, that is
`identical to the enclosed labeling text for the package insert 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 titled "SPL
`Standard for Content of Labeling Technical Qs and As" at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatorylnformation/Guidances/U
`CM072392.pdf. 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 oflabeling [21 CFR 601.12(f)] in MS Word
`format that includes the changes approved in this supplemental application.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`
`Reference ID: 4432580
`
`Novartis Exhibit 2231.001
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`BLA 125387/S-061
`Page2
`
`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(s) in
`pediatric patients unless this requirement is waived, deferred, or inapplicable. We are waiving
`the pediatric study requirement for this application because diabetic retinopathy rarely occurs in
`the pediatric population and therefore studies are impossible or highly impracticable.
`
`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 prescribing
`information to:
`
`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry ( available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryinformation/Guidances/U
`CM443702.pdf ).
`
`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
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http:/ /www.fda.gov/downloads/ AboutFDA/ReportsManualsForms/Forms/UCM3 75154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), 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 BLA (in
`21 CFR 600.80 and in 21 CFR 600.81).
`
`Reference ID: 4432580
`
`Novartis Exhibit 2231.002
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`BLA 125387/S-061
`Page 3
`
`If you have any questions, call Michael Puglisi, Regulatory Project Manager, at (301) 796-0791.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Wiley A. Chambers, M.D.
`Deputy Director
`Division of Transplant and Ophthalmology Products
`Office of New Drugs
`Center for Drug Evaluation and Research
`
`ENCLOSURE:
`Content of Labeling
`
`Reference ID: 4432580
`
`Novartis Exhibit 2231.003
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`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.
`
`Signature Page 1 of 1
`
`Isl
`
`WILEY A CHAMBERS
`0511312019 12:54:34 PM
`
` ÿ■
`
`Reference ID: 4432580
`
`Novartis Exhibit 2231.004
`Regeneron v. Novartis, IPR2021-00816
`
`