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` NDA 205103-S06
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`SUPPLEMENT APPROVAL
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` Genus Lifesciences, Inc.
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` Attn: William Reightler
` Vice President of Regulatory Affairs
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`
` 514 North 12th Street
` Allentown, PA 18102
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` Dear Mr. Reightler:
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` Please refer to your supplemental new drug application (sNDA) dated and received July
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` 17, 2020, and your amendments, submitted pursuant to section 505(b)(2) of the Federal
` Food, Drug, and Cosmetic Act (FDCA) for YOSPRALA (aspirin and omeprazole)
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` delayed-release tablets.
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` We also refer to our letter dated June 18, 2020, 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
` labeling for proton pump inhibitors (PPIs). This information pertains to the risk of
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` subclinical acute or chronic interstitial nephritis associated with PPIs leading to chronic
` renal inflammation and reduced renal function reported in published literature.
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` This supplemental new drug application provides for revisions to the labeling for
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` YOSPRALA. The agreed upon changes to the language included in our June 18, 2020,
` letter are as follows (additions are noted by underline and deletion are noted by
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` strikethrough).
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` 5.8 Acute Tubulointerstitial Nephritis
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` Acute
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` tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and
` may occur at any point during PPI therapy. Patients may present with varying signs and
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`from symptomatic
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` symptoms
` hypersensitivity reactions to
` non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia)
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` In reported case series,
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` some patients were diagnosed on biopsy and in the absence of extra-renal
` manifestations (e.g., fever, rash or arthralgia).
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` Discontinue YOSPRALA and evaluate patients with suspected acute
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`TIN
` [see Contraindications (4)].
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`Reference ID: 4707980
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`(b
`)
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`(b) (4)
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`(b) (4)
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`

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` NDA 205103-S06
` Page 2
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` APPROVAL & LABELING
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` We have completed our review of this application, as amended. It is approved, effective
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` on the date of this letter, for use as recommended in the enclosed agreed-upon
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` labeling.
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` We note that your November 19, 2020, submission includes final printed labeling (FPL)
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` for your Prescribing Information and Medication Guide. We have not reviewed this FPL.
` You are responsible for assuring that the wording in this FPL is identical to that of the
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` approved content of labeling in the structured product labeling (SPL) format.
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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
` 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
` 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
` 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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` 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: 4707980
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`

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` NDA 205103-S06
` Page 3
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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
` 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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` If you have any questions, call Andrew Kelleher, Regulatory Project Manager, at (240)
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` 402-0075.
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` Sincerely,
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` {See appended electronic signature page}
`
`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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` ENCLOSURES:
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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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`
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`Reference ID: 4707980
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`

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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/
`------------------------------------------------------------
`
`JOYCE A KORVICK
`11/27/2020 08:36:14 AM
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`Reference ID: 4707980
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`