( .I# I U.S. FOOD & DRUG
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`,.,. .........
`•-..:::::i~
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`ADMINISTRATION
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` NDA 22301-S18
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`SUPPLEMENT APPROVAL
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` Salix Pharmaceuticals, Inc
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` Attention: Libette Luce, MA
` Senior Director, Global Regulatory Affairs
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` 400 Somerset Corporate Blvd
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` Bridgewater, NJ 08807
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`Dear Ms. Luce:
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`Please refer to your supplemental new drug application (sNDA) dated August 31, 2021,
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`received and submitted under section 505(b) of the Federal Food, Drug, and Cosmetic
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`Act (FDCA) for Apriso (mesalamine) extended-release capsules.
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`We also refer to our letter dated August 3, 2021 notifying you, under Section 505(o)(4)
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`of the FDCA, of new safety information that we believe should be included in the
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`labeling for aminosalicylic acid and similar agents. This information pertains to the risk
`of severe cutaneous adverse reactions (SCARs), which includes Stevens-Johnson
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`syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia
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`and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis
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`(AGEP), reported in FAERS.
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`This supplemental new drug application provides for revisions to the labeling for Apriso,
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`consistent with our August 3, 2021 letter.
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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 with minor editorial revisions listed below and reflected in the enclosed
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`labeling:
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`• Highlights of the Prescribing Information: removed a line of white space from
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`Recent Major Changes.
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`• Section 6 Adverse Reactions in the Full Prescribing Information: italicized the
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`brackets for “[see Warnings and Precautions (5.5)]”
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`We note that your August 31, 2021, submission includes final printed labeling (FPL) for
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`your Prescribing Informations. We have not reviewed these FPL. You are responsible
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`for assuring that the wording in these FPL is identical to that of the approved content of
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`labeling in the structured product labeling (SPL) format.
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`Reference ID: 4881178
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` NDA 22301-S18
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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 (Prescribing
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`Information), with the addition of any labeling changes in pending “Changes Being
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`Effected” (CBE) supplements, as well as annual reportable changes not included in the
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`enclosed labeling. If the content of labeling in SPL format initially submitted with this
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`CBE-0 labeling supplement is identical to the attached approved labeling, an additional
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`submission of content of labeling in SPL format is not required.
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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
`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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`All promotional materials that include representations about your drug product must be
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`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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` 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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`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: 4881178
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`NDA 22301-S18
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`Page 3
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`If you have any questions, call Kelly Richards, Regulatory Project Manager, at (240)
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`402-4276.
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`Sincerely,
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`{See appended electronic signature page}
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`Joyce Korvick, M.D., M.P.H.
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`Deputy Director for Safety
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`Division of Gastroenterology (DG)
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`Office of Immunology and Inflammation (OII)
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`Center for Drug Evaluation and Research
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`ENCLOSURE:
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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: 4881178
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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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`JOYCE A KORVICK
`11/01/2021 09:58:07 AM
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`■
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`Reference ID: 4881178
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