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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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` Silver Spring MD 20993
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` SUPPLEMENT APPROVAL
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` FULFILLMENT OF POSTMARKETING
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`REQUIREMENT(S)
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` NDA 203341/S-003
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` PF PRISM C.V.
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` c/o Pfizer Inc.
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` Attention: Brian Caselli, MSc
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` Senior Manager, Worldwide Safety and Regulatory
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` 445 Eastern Point Road
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` MS-8260-1118
` Groton, CT 06340
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` Dear Mr. Caselli:
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` Please refer to your Supplemental New Drug Application (sNDA) dated March 23, 2015,
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` received March 23, 2015, submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act (FDCA) for BOSULIF® (bosutinib) tablets, 100 and 500 mg.
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`This “Prior Approval” supplemental new drug application provides the final study report for the
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`study entitled “An Open-Label, Randomized, 2-Period Crossover Study to Evaluate the Effect of
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`a Single Oral Dose of Aprepitant, a Moderate CYP3A Inhibitor on Bosutinib Administered
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`Orally to Healthy Subjects.” Also, this supplemental new drug application provides for updates
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`to the Dose and Administration, Drug Interactions, and Clinical Pharmacology sections of the
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`United States Prescribing Information (USPI) based upon data from the study referenced above.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling (text for the package insert and text for the
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`patient package insert), with the addition of any labeling changes in pending “Changes Being
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`Reference ID: 3823172
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` NDA 203341/S-003
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` Page 2
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` Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
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`labeling.
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`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
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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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 includes labeling changes
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` for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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` with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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` changes approved in this supplemental application, as well as annual reportable changes and
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` annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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` up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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` should provide appropriate annotations, including supplement number(s) and annual report
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` 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 new
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`FULFILLMENT OF POSTMARKETING REQUIREMENT
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`We have received your submission dated March 23, 2015, containing the final report for the
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`following postmarketing requirement listed in the September 4, 2012, approval letter.
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`PMR 1912-1 Conduct a drug-drug interaction trial to evaluate the effect of a moderate CYP3A4
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`inhibitor (e.g., erythromycin) on the pharmacokinetics of bosutinib. The proposed
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`protocol must be submitted for review and concurrence prior to trial initiation.
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`The timetable you submitted on August 15, 2012, stated that you will conduct this trial according
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`to the following schedule:
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`Final Protocol Submission: March 2013;
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`Trial Completion: September 2014;
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`Final Report Submission: March 2015.
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`We have reviewed your submission and conclude that the above requirement was fulfilled.
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`Reference ID: 3823172
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` NDA 203341/S-003
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` Page 3
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` We remind you that there is a postmarketing commitment listed in the September 4, 2012,
` approval letter that is still open.
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`PROMOTIONAL MATERIALS
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` You may request advisory comments on proposed introductory advertising and promotional
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` labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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` OPDP Regulatory Project Manager
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` Food and Drug Administration
` Center for Drug Evaluation and Research
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` Office of Prescription Drug Promotion (OPDP)
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` 5901-B Ammendale Road
` Beltsville, MD 20705-1266
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` Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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`For more information about submitting promotional materials in eCTD format, see the draft
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` Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf).
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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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`Reference ID: 3823172
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` NDA 203341/S-003
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` Page 4
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` If you have any questions, call Tinya Sensie, Regulatory Project Manager, at (240) 402-4230.
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`Sincerely,
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`{See appended electronic signature page}
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`Ann T. Farrell, MD
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`Director
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`Division of Hematology Products
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`Office of Hematology and Oncology Products
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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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`Reference ID: 3823172
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`ANN T FARRELL
`09/22/2015
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`Reference ID: 3823172
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