CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`210563Orig1s000
`210563Orig2s000
`
`PROPRIETARY NAME REVIEW(S)
`
`
`
`
`
`

`

`PROPRIETARY NAME REVIEW
`Division of Medication Error Prevention and Analysis (DMEPA)
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`Office of Surveillance and Epidemiology (OSE)
`Center for Drug Evaluation and Research (CDER)
`
`*** This document contains proprietary information that cannot be released to the
`public***
`
`Date of This Review:
`12/19/2017
`Application Type and Number: NDA 210563
`Product Name and Strength:
`Imbruvica (ibrutinib) Tablets
`Total Product Strength:
`140 mg, 280 mg, 420 mg, and 560 mg
`Product Type:
`Single Ingredient
`Rx or OTC:
`Rx
`Applicant/Sponsor Name:
`Pharmacyclics, Inc.
`Panorama #:
`2017-17832328
`DMEPA Safety Evaluator:
`Casmir Ogbonna, PharmD, MBA, BCPS, BCGP
`DMEPA Team Leader:
`Hina Mehta, PharmD
`DMEPA Associate Director
`Mishale Mistry, PharmD, MPH
`(Acting):
`
`Reference ID: 4197850
`
`

`

`1
`
`Contents
`INTRODUCTION....................................................................................................................1
`1.1
`Regulatory History............................................................................................................1
`1.2
`Product Information ..........................................................................................................1
`2 RESULTS.................................................................................................................................2
`2.1 Misbranding Assessment ..................................................................................................2
`2.2
`Safety Assessment.............................................................................................................2
`3 CONCLUSIONS......................................................................................................................5
`3.1
`Comments to the Applicant...............................................................................................5
`4 REFERENCES.........................................................................................................................6
`APPENDICES .................................................................................................................................7
`
`
`
`Reference ID: 4197850
`
`

`

`INTRODUCTION
`1
`This review evaluates the proposed proprietary name, Imbruvica, from a safety and misbranding
`perspective. The sources and methods used to evaluate the proposed name are outlined in the
`reference section and Appendix A respectively. The Applicant did not submit an external name
`study for this proposed proprietary name.
`
`REGULATORY HISTORY
`1.1
`Imbruvica (ibrutinib) was approved under NDA 205552 on November 13, 2013 as 140 mg
`capsules and is indicated for the treatment of mantle cell lymphoma (MCL) in patients who have
`received at least one prior therapy, chronic lymphocytic leukemia (CLL)/small lymphocytic
`lymphoma (SLL), CLL/SLL with 17p deletion, Waldenstrom’s macroglobuminemia, marginal
`zone lymphoma who require systemic therapy and have received at least one prior anti-CD20-
`based therapy, and chronic graft versus host disease (cGVHD) after failure of one or more lines
`of systemic therapy. The Applicant proposes a tablet dosage form in strengths of 140 mg, 280
`mg, 420 mg, and 560 mg, intended to be marketed for the treatment of the same approved
`indications as the currently approved capsule formulation. Thus, the Applicant submitted the
`name, Imbruvica, for the new dosage form under review for NDA 210563 on September 28,
`2017.
`
`PRODUCT INFORMATION
`1.2
`The following product information is provided in the September 28, 2017, proprietary name
`submission.
`Table 1. Relevant Product Information for Imbruvica
`Product
`Imbruvica (NDA 210563)
`Initial Approval
`Currently under review.
`Date
`Active Ingredient
`Indication
`
`Imbruvica (NDA 205552)
`November 13, 2013
`
`Ibrutinib
`Imbruvica is a Bruton’s Tyrosine Kinase Inhibitor indicated for:
` treatment of mantle cell lymphoma (MCL) in patients who have
`received at least one prior therapy
` chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma
`(SLL)
` CLL/SLL with 17p deletion
` Waldenstrom’s macroglobuminemia (WM)
` Marginal zone lymphoma (MZL) who require systemic therapy and
`have received at least one prior anti-CD20-based therapy
` chronic graft versus host disease (cGVHD) after failure of one or more
`lines of systemic therapy
`Oral
`
`Route of
`Administration
`Dosage Form:
`Strength:
`
`Tablets
`140 mg, 280 mg, 420 mg, 560
`mg
`
`Capsules
`140 mg
`
`Reference ID: 4197850
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`Dose and
`Frequency
`How Supplied:
`
`Storage:
`
`
`
`MCL and MZL: 560 mg taken orally once daily
`CLL/SLL, WM, and cGVHD: 420 mg taken orally once daily
`140 mg tablet: yellow green to
`The white opaque 140 mg capsules
`green round tablets debossed
`marked with “ibr 140 mg” in black
`with “ibr” on one side and “140”
`ink are available in white HDPE
`on the other side. 2 blisters of 14
`bottles with a child-resistant closure:
`count NDC 57962-014-28
`90 capsules per bottle: NDC
`
`280 mg tablet: purple oblong
`57962-140-09
`tablets debossed with “ibr” on
`120 capsules per bottle: NDC
`one side and “280” on the other
`57962-140-12
`side. 2 blisters of 14 count NDC
`57962-280-28
`420 mg tablet: yellow green to
`green oblong tablets debossed
`with “ibr” on one side and “420”
`on the other side. 2 blisters of 14
`count NDC 57962-420-28
`560 mg tablet: yellow to orange
`oblong tablets debossed with
`“ibr” on one side and “560” on
`the other side. 2 blisters of 14
`count NDC 57962-560-28
`Store bottles at room temperature 20°C to 25°C (68°F to 77°F).
`Excursions are permitted between 15°C and 30°C (59°F to 86°F). Retain
`in original package.
`
`2 RESULTS
`The following sections provide information obtained and considered in the overall evaluation of
`the proposed proprietary name.
`
`2.1 MISBRANDING ASSESSMENT
`The Office of Prescription Drug Promotion (OPDP) determined that the proposed name would
`not misbrand the proposed product. The Division of Medication Error Prevention and Analysis
`(DMEPA) and the Division of Division of Hematology Products (DHP) concurred with the
`findings of OPDP’s assessment of the proposed name.
`
`2.2 SAFETY ASSESSMENT
`The following aspects were considered in the safety evaluation of the name.
`
`Reference ID: 4197850
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`2.2.1 United States Adopted Names (USAN) Search
`There is no USAN stem present in the proprietary namea.
`
`2.2.2 Components of the Proposed Proprietary Name
`The Applicant did not provide a derivation or intended meaning for the proposed name,
`Imbruvica in their submission. This proprietary name is comprised of a single word that does not
`contain any components (i.e. a modifier, route of administration, dosage form, etc.) that are
`misleading or can contribute to medication error.
`
`2.2.3 Comments from Other Review Disciplines at Initial Review
`In response to the OSE, October 19, 2017 e-mail, the Division of Hematology Products (DHP)
`did not forward any comments or concerns relating to the proposed proprietary name at the
`initial phase of the review.
`
`2.2.4 Medication Error Data Selection of Cases
`We searched the FDA Adverse Event Reporting System (FAERS) database using the strategy
`listed in Table 2 (see Appendix A1 for a description of FAERS database) for name confusion
`errors involving Imbruvica that would be relevant for this review.
`
`Table 2. FAERS Search Strategy
`Search Date
`November 14, 2017
`Drug Name
`Imbruvica [ibrutinib]
`Event (MedDRA
`DMEPA Official PNR Name Confusion Search
`Terms)
`Terms Event List:
`Preferred Terms:
`CIRCUMSTANCE OR INFORMATION CAPABLE OF
`LEADING TO MEDICATION ERROR
`DRUG ADMINISTRATION ERROR
`DRUG DISPENSING ERROR
`DRUG PRESCRIBING ERROR
`INTERCEPTED DRUG DISPENSING ERROR
`INTERCEPTED DRUG PRESCRIBING ERROR
`INTERCEPTED MEDICATION ERROR
`MEDICATION ERROR
`PRODUCT NAME CONFUSION
`TRANSCRIPTION MEDICATION ERROR
`
`Lower Level Terms:
`INTERCEPTED PRODUCT SELECTION ERROR
`INTERCEPTED WRONG DRUG PRODUCT SELECTED
`
`a USAN stem search conducted on November 15, 2017.
`
`Reference ID: 4197850
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`Table 2. FAERS Search Strategy
`INTERCEPTED WRONG DRUG SELECTED
`PRODUCT SELECTION ERROR
`WRONG DEVICE DISPENSED
`WRONG DRUG ADMINISTERED
`WRONG DRUG DISPENSED
`WRONG DRUG PRESCRIBED
`WRONG DRUG PRODUCT SELECTED
`WRONG DRUG SELECTED
`WRONG PRODUCT SELECTED
`Date Limits
`11/13/2013 to 11/14/2017 (FDA Receive Dates)
`Each report was reviewed for relevancy and duplication. Duplicates were merged into a single
`case. The NCC MERP Taxonomy of Medication Errors was used to code the case outcome and
`error root causes when provided by the reporter.
`The search yielded 12 cases for review. After individual review, all 12 reports were not included
`in the final analysis for the following reasons: Inappropriate schedule (n = 6), drug dispensing
`error unrelated to Imbruvica (n = 1), drug dispensing error not related to Imbruvica (n = 1), drug
`dose omission (n = 2), drug administration error (n = 1), product storage error (n = 1).
`Following exclusions, the search yielded no relevant cases related to name confusion with
`Imbruvica.
`
`2.2.5 Multiple Dosage Forms under a Single Proprietary Name
`Under NDA 210563, the Applicant proposes a tablet dosage form of Imbruvica, in strengths of
`140 mg, 280 mg, 420 mg, and 560 mg to decrease patient pill burden. The Applicant proposes to
`market the new oral dosage form of tablets under the same proprietary name as the currently
`approved product, Imbruvica 140 mg capsules.
`We note that the currently approved Imbruvica capsule dosage form shares the same active
`ingredient, indication, route of administration, dose, and frequency as the proposed tablet
`formulation. Additionally, we note that the two dosage forms will share a strength of 140 mg.
`Given the overlapping strength and the potential for the oral tablet and oral capsule to substituted
`for one another in practice, we consulted the DHP review team with regard to whether the
`dosage forms are equivalent on a mg per mg basis. Per the Office of Pharmaceutical Quality
`(OPQ) reviewer, the 140 mg tablets and 140 mg capsules differ solely on the inclusion of
`excipients, which are required for
` the tablets. The Applicant conducted
`dissolution tests, which demonstrate that the tablets and capsules are functionally equivalent. Per
`the clinical reviewer, the tablets and capsules can be substituted for one another with no clinical
`significance. Therefore, the risk of dosing errors due to converting between dosage forms is
`mitigated.
`It is a common and accepted practice to have a product line with multiple dosage forms managed
`under one proprietary name within a single package insert. In this case, the residual risk of
`confusion between the capsule and tablet formulations of the product may be mitigated through
`labels and labeling intervention.
`
`Reference ID: 4197850
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`(b) (4)
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`

`

`Moreover, we have not identified any relevant medication errors involving name confusion with
`the proprietary name Imbruvica. Therefore, we find the Applicant’s proposal to market the
`proposed product with the proprietary name Imbruvica acceptable.
`
`2.2.6 Communication of DMEPA’s Analysis at Midpoint of Review
`DMEPA communicated our findings to the Division of Hematology Products (DHP) via e-mail
`on December 18, 2017. At that time we also requested additional information or concerns that
`could inform our review. Per e-mail correspondence from the DHP on December 19, 2017, they
`stated no additional concerns with the proposed proprietary name, Imbruvica.
`
`3 CONCLUSIONS
`The proposed proprietary name is acceptable.
`If you have any questions or need clarifications, please contact Neil Vora, OSE project manager,
`at 240-402-4845.
`
`COMMENTS TO THE APPLICANT
`3.1
`We have completed our review of the proposed proprietary name, Imbruvica, and have
`concluded that this name is acceptable.
`If any of the proposed product characteristics as stated in your September 28, 2017 submission
`are altered prior to approval of the marketing application, the name must be resubmitted for
`review.
`
`Reference ID: 4197850
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`

`

`4
`
`REFERENCES
`
`1. USAN Stems (http://www.ama-assn.org/ama/pub/physician-resources/medical-science/united-
`states-adopted-names-council/naming-guidelines/approved-stems.page)
`USAN Stems List contains all the recognized USAN stems.
`
`2. Electronic Drug Registration and Listing System (eDRLS) database
`The electronic Drug Registration and Listing System (eDRLS) was established to supports the FDA’s
`Center for Drug Evaluation and Research (CDER) goal to establish a common Structured Product
`Labeling (SPL) repository for all facilities that manufacture regulated drugs. The system is a reliable, up-
`to-date inventory of FDA-regulated, drugs and establishments that produce drugs and their associated
`information.
`
`Reference ID: 4197850
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`

`

`APPENDICES
`Appendix A
`FDA’s Proprietary Name Risk Assessment evaluates proposed proprietary names for
`misbranding and safety concerns.
`1. Misbranding Assessment: For prescription drug products, OPDP assesses the name for
`misbranding concerns. . For over-the-counter (OTC) drug products, the misbranding
`assessment of the proposed name is conducted by DNDP. OPDP or DNDP evaluates
`proposed proprietary names to determine if the name is false or misleading, such as by
`making misrepresentations with respect to safety or efficacy. For example, a fanciful
`proprietary name may misbrand a product by suggesting that it has some unique
`effectiveness or composition when it does not (21 CFR 201.10(c)(3)). OPDP or DNDP
`provides their opinion to DMEPA for consideration in the overall acceptability of the
`proposed proprietary name.
`2. Safety Assessment: The safety assessment is conducted by DMEPA, and includes the
`following:
`a. Preliminary Assessment: We consider inclusion of USAN stems or other characteristics
`that when incorporated into a proprietary name may cause or contribute to medication
`errors (i.e., dosing interval, dosage form/route of administration, medical or product name
`abbreviations, names that include or suggest the composition of the drug product, etc.)
`See prescreening checklist below in Table 2*. DMEPA defines a medication error as any
`preventable event that may cause or lead to inappropriate medication use or patient harm
`while the medication is in the control of the health care professional, patient, or
`consumer. b
`
`b National Coordinating Council for Medication Error Reporting and Prevention.
`http://www nccmerp.org/aboutMedErrors html. Last accessed 10/11/2007.
`
`Reference ID: 4197850
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`*Table 2- Prescreening Checklist for Proposed Proprietary Name
`
`Answer the questions in the checklist below. Affirmative answers
`to any of these questions indicate a potential area of concern that
`should be carefully evaluated as described in this guidance.
`Y/N Is the proposed name obviously similar in spelling and pronunciation to other
`names?
`Proprietary names should not be similar in spelling or pronunciation to proprietary
`names, established names, or ingredients of other products.
`Y/N Are there inert or inactive ingredients referenced in the proprietary name?
`Proprietary names should not incorporate any reference to an inert or inactive
`ingredient in a way that might create an impression that the ingredient’s value is
`greater than its true functional role in the formulation (21 CFR 201.10(c)(4)).
`Y/N Does the proprietary name include combinations of active ingredients?
`Proprietary names of fixed combination drug products should not include or
`suggest the name of one or more, but not all, of its active ingredients (see 21 CFR
`201.6(b)).
`Y/N Is there a United States Adopted Name (USAN) stem in the proprietary name?
`Proprietary names should not incorporate a USAN stem in the position that USAN
`designates for the stem.
`Y/N Is this proprietary name used for another product that does not share at least
`one common active ingredient?
`Drug products that do not contain at least one common active ingredient should not
`use the same (root) proprietary name.
`Y/N Is this a proprietary name of a discontinued product?
`Proprietary names should not use the proprietary name of a discontinued product if
`that discontinued drug product does not contain the same active ingredients.
`
`Reference ID: 4197850
`
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`

`

`Appendix A1: Description of FAERS
`The FDA Adverse Event Reporting System (FAERS) is a database that contains information on
`adverse event and medication error reports submitted to FDA. The database is designed to
`support the FDA's postmarket safety surveillance program for drug and therapeutic biologic
`products. The informatic structure of the FAERS database adheres to the international safety
`reporting guidance issued by the International Conference on Harmonisation. FDA’s Office of
`Surveillance and Epidemiology codes adverse events and medication errors to terms in the
`Medical Dictionary for Regulatory Activities (MedDRA) terminology. Product names are coded
`using the FAERS Product Dictionary. More information about FAERS can be found at:
`http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDr
`ugEffects/default.htm.
`
`Reference ID: 4197850
`
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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/
`----------------------------------------------------
`
`CASMIR I OGBONNA
`12/19/2017
`
`MISHALE P MISTRY on behalf of HINA S MEHTA
`12/19/2017
`
`MISHALE P MISTRY
`12/19/2017
`
`Reference ID: 4197850
`
`