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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 205552/S-010
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` NDA 205552/S-013
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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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`Pharmacyclics LLC
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`Attention: Jill Herendeen, PharmD, RAC
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`Senior Director, Regulatory Affairs
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`995 East Arques Avenue
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`Sunnyvale, CA 94085-4521
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`Dear Dr. Herendeen:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated November 12, 2015,
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`received November 12, 2015, and your amendments, submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for IMBRUVICA® (ibrutinib) Capsules,
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`140 mg.
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`Prior Approval supplemental new drug application 010 (S-010) provides for a revised indication
`for the use of IMBRUVICA® (ibrutinib) in the treatment of patients with chronic lymphocytic
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`leukemia (CLL)/small lymphocytic lymphoma (SLL), and dosing of IMBRUVICA® (ibrutinib)
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`with bendamustine and rituximab in patients with chronic lymphocytic leukemia/small
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`lymphocytic lymphoma.
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`Prior Approval supplemental new drug application 013 (S-013) provides for a revised indication
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`for the use of IMBRUVICA® (ibrutinib) in the treatment of patients with chronic lymphocytic
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`leukemia (CLL)/small lymphocytic lymphoma (SLL) with 17p deletion.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended. They are
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`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling 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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`Reference ID: 3927922
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` NDA 205552/S-010
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` NDA 205552/S-013
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` Page 2
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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
`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,
` 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 these supplemental applications, 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 this drug product for this indication has an orphan drug designation, you are exempt
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`from this requirement.
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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
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
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`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`Reference ID: 3927922
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` NDA 205552/S-010
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` NDA 205552/S-013
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` Page 3
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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
`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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`If you have any questions, call Elleni Alebachew, Regulatory Project Manager, at
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`(301) 796-5225.
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`Sincerely,
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`{See appended electronic signature page}
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`Edvardas Kaminskas, M.D.
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`Deputy 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: 3927922
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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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`EDVARDAS KAMINSKAS
`05/06/2016
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`Reference ID: 3927922
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