`NDA 208700/S-10
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`SUPPLEMENT APPROVAL
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` Advanced Accelerator Applications USA, Inc.
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` Attention: Christopher Jordan, MSHS, RAC
` Americas Head, Regulatory Affairs
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` 57 East Willow Street
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` Millburn, NJ 07041
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`Dear Mr. Jordan:1
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`Please refer to your supplemental new drug application (sNDA) dated and received
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`August 2, 2019, and your amendments, submitted under section 505(b) of the Federal
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`Food, Drug, and Cosmetic Act (FDCA) for LUTATHERA (lutetium Lu 177 dotatate), 370
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`MBq/mL solution for infusion.
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`This Prior Approval supplemental new drug application provides for
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`• Revisions to Dosage and Administration section (subsections 2.3, 2.4, 2.5, and
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`2.6) to revise information regarding anti-emetics and provide additional details
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`regarding amino acid solutions; provide additional details regarding LUTATHERA
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`dose modifications; and add the use of infusion pumps as an administration
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`method in case of dose reduction;
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`revisions to Warnings and Precautions section (subsections 5.1-5.3) to add
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`clarification to the risks from radiation exposure; revise incidence rate of
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`secondary myelodysplastic syndrome in the ERASMUS study;
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`revisions to Adverse Reactions section (subsection 6.1) with corrections to the
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`NETTER-1 Adverse Events and laboratory abnormalities tables (Table 4 and 5),
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`to correct for rounding errors identified;
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`revisions to Drug Interactions section (subsection 7.2) to include potential for
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`drug interactions with repeated administration of corticosteroids;
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`revisions to Clinical Studies section (subsections 14.1 and 14.2); make
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`corrections to NETTER-1 efficacy table based on identified inconsistencies; and,
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`add proposed revisions to the description and data summary of the ERASMUS
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`study;
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`revisions to How Supplied/Storage and Handling section to add “do not freeze”
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`and instructions to store Lutathera in original package; and,
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`Reference ID: 4615991
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` NDA 208700/S-10
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` Page 2
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`•
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`revisions to Highlights of Prescribing Information and Patient Counseling
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`Information in accordance with the proposed changes.
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` APPROVAL & LABELING
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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
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` labeling.
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` WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
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`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
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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), with the addition of any labeling changes in pending “Changes
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`Being Effected” (CBE) supplements, as well as annual reportable changes not included
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`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
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`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
`supplement number(s) and annual report date(s).
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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` 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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`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: 4615991
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` NDA 208700/S-10
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` Page 3
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`new active ingredients (which includes new salts and new fixed combinations), new
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`indications, new dosage forms, new dosing regimens, or new routes of administration
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`are required to contain an assessment of the safety and effectiveness of the product for
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`the claimed indication in pediatric patients unless this requirement is waived, deferred,
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`or inapplicable.
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` Because none of these criteria apply to your application, you are exempt from this
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`requirement.
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` PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and
`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
`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
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`All promotional materials that include representations about your drug product must be
`promptly revised to be consistent with the labeling changes approved in this
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`supplement, including any new safety information [21 CFR 314.70(a)(4)]. The revisions
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`in your promotional materials should include prominent disclosure of the important new
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`safety information that appears in the revised labeling. Within 7 days of receipt of this
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`letter, submit your statement of intent to comply with 21 CFR 314.70(a)(4).
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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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` 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
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` 5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`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: 4615991
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`NDA 208700/S-10
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`Page 4
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`If you have any questions, call Nataliya Fesenko, Pharm.D., Regulatory Health Project
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`Manager, at (240) 402-6376.
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`Sincerely,
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`{See appended electronic signature page}
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`Harpreet Singh, M.D.
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`Director
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`Division of Oncology 2
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`Office of Oncologic Diseases
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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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`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: 4615991
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`Signature Page 1 of 1
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`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.
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`/s/
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`B HARPREET SINGH
`05/28/2020 07:32:53 PM
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`Reference ID: 4615991
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`(
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