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`U.S. FOOD & DRUG
`ADMINISTRATION
`
`
` NDA 21083/S-069 and S-070
`
`NDA 21110/S-087 and S-088
`
`
`
`
`
`
`
` PF PRISM C.V.
`
` c/o Pfizer, Inc.
` 500 Arcola Rd.
`
` Collegeville, PA 19426
`
`
`
`Attention: Deneen Stewart,
`
`
`Director, Pfizer Global Regulatory Affairs
`
`SUPPLEMENT APPROVAL
`
`
`
`
` Product Name
`
`
`
`
`
` NDA Number Supplement
`
` Number
`
` 69
`
`
`
` 21083
`
`
`
` 21110
`
`
`
` 87
`
`
`
` and
`
`
`
`
`
` NDA Number Supplement
`
` Number
`
` 70
`
`
`
` 21083
`
`
`
` Date and Receipt
`
` of Submission
`
`
` July 2, 2021
`
`
`
` July 2, 2021
`
`
`
`
`
`
`
` Date and Receipt
`
` of Submission
`
` November 22,
`
` 2021
` November 22,
`
` 2021
`
`
`
`Dear Ms. Stewart:
`
`
`
`Please refer to your supplemental new drug applications (sNDA) and your amendments,
`
`
`
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`
`for the following:
`
`
`
`
` Rapamune (sirolimus) Oral
`
` Solution, 1mg/mL
` Rapamune (sirolimus) Tablet,
`
` 0.5mg, 1mg, 2mg
`
`
`
`
`
` Product Name
`
`
`
`
`
` Rapamune (sirolimus) Oral
`
` Solution, 1mg/mL
` Rapamune (sirolimus) Tablet,
`
` 0.5mg, 1mg, 2mg
`
`
`
` 21110
`
`
`
` 88
`
`
`
`
`
`
`
`
` These Prior Approval supplemental new drug applications provides for:
`
` 1. Revisions to update the DRUG INTERACTIONS and CLINICAL
`
`
`
`
` PHARMACOLOGY sections to add information about letermovir.
`
`
` 2. Revisions to update the WARNINGS AND PRECAUTIONS and DRUG
`
`
`
` INTERACTIONS sections to add a new subsection on cannabidiol drug
`
`
`
`
` interactions.
`
`
`
`
`
`
`Reference ID: 5033875
`
`

`

`
`
`
` NDA 21083/S-069 and S-070
` NDA 21110/S-087 and S-088
`
`
` Page 2
`
`
` APPROVAL & LABELING
`
`
`
`
`
`We have completed our review of these applications, as amended on August 8, 2022.
`
`They are approved, effective on the date of this letter, for use as recommended in the
`
`enclosed agreed-upon labeling.
`
`
`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
`
`
`
`
`the FDA automated drug registration and listing system (eLIST), as described at
`
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`
`Prescribing Information and Medication Guide), with the addition of any labeling
`
`
`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
`
`reportable changes not included in the enclosed labeling.
`
`
`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
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`
`
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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
`
`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
`
`
`
`
`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
`
`
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`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.
`
`
`
`
`
` 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: 5033875
`
`

`

`
`
`
`
`
` NDA 21083/S-069 and S-070
` NDA 21110/S-087 and S-088
`
`
` Page 3
`
`
` Because none of these criteria apply to your application, you are exempt from this
`
` requirement.
`
`
`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
`
`
`
`You must submit final promotional materials and Prescribing Information, accompanied
`
`
`
`by a Form FDA 2253, at the time of initial dissemination or publication
`
`
`
`
`
`
`
`[21 CFR 314.81(b)(3)(i)]. 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 that include representations about your drug product must be
`
`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
`
`
`
`in 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 314.70(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).
`
`
`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
`
`
`
` 3 For the most recent version of a guidance, check the FDA guidance web page at
` https://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: 5033875
`
`

`

`
` NDA 21083/S-069 and S-070
` NDA 21110/S-087 and S-088
`
`
` Page 4
`
`
` 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 these supplemental applications, you are
`
`
`
`exempt from this requirement.
`
`
`REPORTING REQUIREMENTS
`
`
`We remind you that you must comply with reporting requirements for an approved NDA
`
`
`(21 CFR 314.80 and 314.81).
`
`
`
`
`
`
`If you have any questions, call Ms. June Germain, Safety Regulatory Project Manager,
`
`at 301-796-4024.
`
`
`
`
`
`Sincerely,
`
`
`
`{See appended electronic signature page}
`
`
`
`Ozlem Belen, MD, MPH
`
`Deputy Director
`
`Division of Rheumatology and Transplant Medicine
`
`Office of Immunology and Inflammation
`
`Office of New Drugs
`
`Center for Drug Evaluation and Research
`
`
`
`
`ENCLOSURES:
`
`Content of Labeling
`
`
` Prescribing Information
`
`
` Medication Guide
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 5033875
`
`

`

`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/
`------------------------------------------------------------
`
`OZLEM A BELEN
`08/22/2022 02:01:42 PM
`
`Reference ID: 5033875
`
`