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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 205552/S-012
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
`FULFILLMENT OF POSTMARKETING
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`REQUIREMENT
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`Pharmacyclics LLC
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`Attention: Annie Dang
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`Associate Director, Regulatory Affairs
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`995 East Arques Avenue
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`Sunnyvale, CA 94085-4521
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` Dear Ms. Dang:
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`Please refer to your Supplemental New Drug Application (sNDA) dated March 25, 2016,
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`received March 25, 2016, and your amendments, submitted under section 505(b) of the Federal
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`Food, Drug, and Cosmetic Act (FDCA) for Imbruvica (ibrutinib), oral capsule 140 mg.
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`This Prior Approval supplemental new drug application provides for updates to the package
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`insert with addition of interstitial lung disease in Section 6.2 Postmarketing Experience and QT
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`information in Section 12.2 Pharmacodynamics.
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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), with the
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`addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as
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`well as annual 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 industry titled
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`“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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`Reference ID: 3952152
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` NDA 205552/S-012
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` Page 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 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
`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 December 11, 2015, containing the final report for the
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`following postmarketing requirement listed in the November 13, 2013 approval letter.
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`PMR 2060-7 Determine the effect of ibrutinib on the QT/QTc interval in healthy subjects on
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`one or more therapeutic dose levels. Conduct and submit results of a thorough
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`QT trial to evaluate the effects of ibrutinib on the QT /QTc interval.
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`The timetable you submitted on November 13, 2013, states that you will conduct this trial
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`according to the following schedule:
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`Draft Protocol Submission: 03/2014
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`Final Protocol Submission: 06/2014
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`06/2015
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`Trial Completion:
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`Final Report Submission:
`12/2015
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`We have reviewed your submission and conclude that the above requirement was fulfilled.
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`We remind you that there are open postmarketing requirements and commitments listed in the
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`approval letters dated November 13, 2013, January 29, 2015, and March 4, 2016.
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`Reference ID: 3952152
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` NDA 205552/S-012
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` Page 3
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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 Kris Kolibab, Senior Regulatory Project Manager, at (240) 402­
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`0277.
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`Sincerely,
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`{See appended electronic signature page}
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`Barry W. Miller
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`Acting Deputy Director for Safety
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`Division of Hematology Products
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`Office of Hematology Oncology Products
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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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`Reference ID: 3952152
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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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`BARRY W MILLER
`06/28/2016
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`Reference ID: 3952152
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`(
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