CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`210259Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 210259
`
`SUPPL #
`
`HFD #
`
`Trade Name: Calquence
`
`Generic Name: acalabrutinib
`
`Applicant Name: Acerta Pharma, B.V.
`
`
`
`Approval Date, If Known October 31, 2017
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes"
`to one or more of the following questions about the submission.
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
` YES
`
`NO
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(1)
`
`b) Did it require the review of clinical data other than to support a safety claim or change
`in labeling related to safety?
`(If it required review only of bioavailability or
`bioequivalence data, answer "no.")
`
` YES
`
`NO
`
`If your answer is "no" because you believe the study is a bioavailability study and,
`therefore, not eligible for exclusivity, EXPLAIN why it is a bioavailability study,
`including your reasons for disagreeing with any arguments made by the applicant that the
`study was not simply a bioavailability study.
`
`
`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
`
`
`
`
`
`Reference ID: 4174698
`
`Page 1
`
`

`

`c) Did the applicant request exclusivity?
`
` YES
`
`NO
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`5 years
`
`d) Has pediatric exclusivity been granted for this Active Moiety?
` YES
`
`NO
`
` If the answer to the above question in YES, is this approval a result of the studies submitted
`in response to the Pediatric Written Request?
`
`
`
`
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY
`TO THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`2. Is this drug product or indication a DESI upgrade?
`
`
` YES
`
`NO
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE
`BLOCKS ON PAGE 8 (even if a study was required for the upgrade).
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the
`same active moiety as the drug under consideration? Answer "yes" if the active moiety
`(including other esterified forms, salts, complexes, chelates or clathrates) has been previously
`approved, but this particular form of the active moiety, e.g., this particular ester or salt (including
`salts with hydrogen or coordination bonding) or other non-covalent derivative (such as a
`complex, chelate, or clathrate) has not been approved. Answer "no" if the compound requires
`metabolic conversion (other than deesterification of an esterified form of the drug) to produce an
`already approved active moiety.
`
`
`
`
`
` YES
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`Reference ID: 4174698
`
`Page 2
`
`

`

`
`NDA#
`
`
`
`NDA#
`
`
`
`NDA#
`
`
`
`2. Combination product.
`
`
`
`
`
`
`
`
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA
`previously approved an application under section 505 containing any one of the active moieties
`in the drug product? If, for example, the combination contains one never-before-approved active
`moiety and one previously approved active moiety, answer "yes." (An active moiety that is
`marketed under an OTC monograph, but that was never approved under an NDA, is considered
`not previously approved.)
`
`YES
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`NDA#
`NDA#
`NDA#
`
`
`
`
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO
`THE SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary
`should only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of
`new clinical investigations (other than bioavailability studies) essential to the approval of the
`application and conducted or sponsored by the applicant." This section should be completed only
`if the answer to PART II, Question 1 or 2 was "yes."
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets
`"clinical investigations" to mean investigations conducted on humans other than bioavailability
`studies.) If the application contains clinical investigations only by virtue of a right of reference to
`clinical investigations in another application, answer "yes," then skip to question 3(a). If the
`
`Reference ID: 4174698
`
`Page 3
`
`

`

`answer to 3(a) is "yes" for any investigation referred to in another application, do not complete
`remainder of summary for that investigation.
`
`
`
`YES
`
`NO
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved
`the application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical
`trials, such as bioavailability data, would be sufficient to provide a basis for approval as an
`ANDA or 505(b)(2) application because of what is already known about a previously approved
`product), or 2) there are published reports of studies (other than those conducted or sponsored by
`the applicant) or other publicly available data that independently would have been sufficient to
`support approval of the application, without reference to the clinical investigation submitted in
`the application.
`
`(a) In light of previously approved applications, is a clinical investigation (either
`conducted by the applicant or available from some other source, including the published
`literature) necessary to support approval of the application or supplement?
` YES
`
`NO
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`
`
`(b) Did the applicant submit a list of published studies relevant to the safety and
`effectiveness of this drug product and a statement that the publicly available data would
`not independently support approval of the application?
`
` YES
`
`NO
`
`
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to
`disagree with the applicant's conclusion? If not applicable, answer NO.
`
`
`
` YES
`
`NO
`
` If yes, explain:
`
`
`
`
`
`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted
`or sponsored by the applicant or other publicly available data that could
`independently demonstrate the safety and effectiveness of this drug product?
`
`Reference ID: 4174698
`
`Page 4
`
`

`

` YES
`
`NO
`
` If yes, explain:
`
`
`
`(c)
`
`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical
`investigations submitted in the application that are essential to the approval:
`
`
`
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The
`agency interprets "new clinical investigation" to mean an investigation that 1) has not been relied
`on by the agency to demonstrate the effectiveness of a previously approved drug for any
`indication and 2) does not duplicate the results of another investigation that was relied on by the
`agency to demonstrate the effectiveness of a previously approved drug product, i.e., does not
`redemonstrate something the agency considers to have been demonstrated in an already approved
`application.
`
`a) For each investigation identified as "essential to the approval," has the investigation
`been relied on by the agency to demonstrate the effectiveness of a previously approved
`drug product? (If the investigation was relied on only to support the safety of a
`previously approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`
`
`YES
`
`YES
`
`
`
`NO
`
`NO
`
`If you have answered "yes" for one or more investigations, identify each such
`investigation and the NDA in which each was relied upon:
`
`
`
`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support
`the effectiveness of a previously approved drug product?
`
`Investigation #1
`
`Investigation #2
`
`YES
`
`YES
`
`NO
`
`NO
`
`Reference ID: 4174698
`
`Page 5
`
`

`

`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the
`application or supplement that is essential to the approval (i.e., the investigations listed in
`#2(c), less any that are not "new"):
`
`
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored
`by" the applicant if, before or during the conduct of the investigation, 1) the applicant was the
`sponsor of the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or
`its predecessor in interest) provided substantial support for the study. Ordinarily, substantial
`support will mean providing 50 percent or more of the cost of the study.
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`
`
`!!
`
`! NO
`! Explain:
`
`
`
`!!
`
`
`! NO
`! Explain:
`
`
`
`(b) For each investigation not carried out under an IND or for which the applicant was not
`identified as the sponsor, did the applicant certify that it or the applicant's predecessor in
`interest provided substantial support for the study?
`
`Reference ID: 4174698
`
`Page 6
`
`Investigation #1
`
`IND #
`
`YES
`
`
`
`Investigation #2
`
`IND #
`
`YES
`
`
`
`
`
`
`
`

`

`!!
`
`
`! NO
`! Explain:
`
`
`!!
`
`
`! NO
`! Explain:
`
`
`Investigation #1
`
`
`
`YES
`Explain:
`
`
`
`
`Investigation #2
`
`
`
`YES
`Explain:
`
`
`
`
`(c) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that
`the applicant should not be credited with having "conducted or sponsored" the study?
`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to
`the drug are purchased (not just studies on the drug), the applicant may be considered to
`have sponsored or conducted the studies sponsored or conducted by its predecessor in
`interest.)
`
`YES
`
`NO
`
`If yes, explain:
`
`
`
`=================================================================
`
`Name of person completing form: Ashley Lucci Vaughn, MS
`Title: Regulatory Project Manager
`Date: October 31, 2017
`
`
`Name of Division Director signing form: Albert Deisseroth, MD, PhD
`Title: Supervisory Associate Division Director
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 4174698
`
`Page 7
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ASHLEY S LUCCI VAUGHN
`10/31/2017
`
`ALBERT B DEISSEROTH
`10/31/2017
`
`Reference ID: 4174698
`
`

`

`ACTION PACKAGE CHECKLIST
`
`APPLICATION INFORMATION1
`NDA Supplement # N/A
`If NDA, Efficacy Supplement Type:
`NDA # 210259
`(an action package is not required for SE8 or SE9 supplements)
`BLA Supplement #
`BLA #
`Proprietary Name: Calquence
`Established/Proper Name: acalabrutinib
`Dosage Form: capsule
`RPM: Ashley Lucci Vaughn, MSc.
`
`Applicant: Acerta Pharma B.V.
`Agent for Applicant (if applicable):
`
`NDA Application Type:
`Efficacy Supplement:
`
` 55(b)(1)
` 55(b)(1)
`
` 55(b)(2)
` 55(b)(2)
`
`BLA Application Type:
`Efficacy Supplement:
`
` 351(k)
` 351(k)
`
` 351(a)
` 351(a)
`
`Division: Division of Hematology Products
`For ALL 55(b)(2) applications, two months prior to EVERY action:
`
` Review the information in the 55(b)(2) Assessment and submit the
`draft2 to CDER OND IO for clearance.
` Check Orange Book for newly listed patents and/or
`exclusivity (including pediatric exclusivity)
`
` No changes
` New patent/exclusivity (notify CDER OND IO)
`Date of check:
`
`Note: If pediatric exclusivity has been granted or the pediatric
`information in the labeling of the listed drug changed, determine whether
`pediatric information needs to be added to or deleted from the labeling of
`this drug.
`
` Actions
`Proposed action is October 31, 2017
`
` User Fee Goal Date is February 13, 2018
`Previous actions (specify type and date for each action taken)
`
` If accelerated approval or approval based on efficacy studies in animals, were promotional
`materials received?
`Note: Promotional materials to be used within 120 days after approval must have been
`submitted (for exceptions, see
`http://www fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida
`nces/ucm69965.pdf). If not submitted, explain
` Application Characteristics 3
`
` AP
`
` TA CR
`
` None
`
` Received
`
`1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 2) lists
`the documents to be included in the Action Package.
`2 For resubmissions, 505(b)(2) applications must be cleared before the action, but it is not necessary to resubmit the draft 505(b)(2)
`Assessment to CDER OND IO unless the Assessment has been substantively revised (e.g., new listed drug, patent certification
`revised).
`3 Answer all questions in all sections in relation to the pending application, i.e., if the pending application is an NDA or BLA
`supplement, then the questions should be answered in relation to that supplement, not in relation to the original NDA or BLA.
`
`Version: 05/09/17
`
`Reference ID: 4174711
`
`

`

`NDA 210259
`
`Page 2
`
`[XI Priority
`El Standard
`Review priority:
`Chemical classification (new NDAs only): Type 1 New Molecular Entity
`(confirm chemical classification at time ofapproval)
`
`E Fast Track
`[I Rolling Review
`IXI Orphan drug designation
`IXI Breakthrough Therapy designation
`(NOIE: Set the submission property in DARRTS and notify the CDER Breakthrough Therapy Program Manager;
`Refer to the “RPM B1' Checklistfor Considerations after Designation Granted”for other required actions: CST SharePoint)
`
`E] Rx-to-OTC full switch
`E] Rx-to-OTC partial switch
`E] Direct-to-OTC
`
`NDAs: Subpart H
`E Accelerated approval (21 CFR 314.510)
`B Restricted distribution (2 1 CFR 3 14.520)
`Subpart I
`El Approval based on animal studies
`
`BLAs: Subpart E
`[:I Accelerated approval (21 CFR 601.41)
`|:] Restricted distribution (21 CFR 601.42)
`Subpart H
`D Approval based on animal studies
`
`I:| Submitted in response to a PMR
`I:| Submitted in response to a PMC
`D Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: El MedGuide
`I: Communication Plan
`|:] ETASU
`[j MedGuide w/o REMS
`IE REMS not required
`
`03° BLAs only: Is the product subject to ofiicial FDA lot release per 21 CFR 610.2
`(approvals only)
`
`I: Yes
`
`El No
`
`{0 Public communications (approvals only)
`
`0 Office of Executive Programs (OEP) liaison has been notified of action
`
`IX Yes El No
`
`0
`
`Indicate what types (if any) of information were issued
`
`{0 Exclusivity
`
`0
`
`0
`
`Is approval of this application blocked by any type of exclusivity (orphan, 5-year
`NCE, 3-year, pedia'tric exclusivity)?
`Ifso,s i
`the p-
`
`0? Patent Information (NDAs only)
`
`0
`
`Patent Information:
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`.
`.
`which approval 15 sought.
`
`I:] None
`[X] FDA Press Release
`E] FDA Talk Paper
`E] CDER Q&As
`[Z Oflier Burst
`
`X No
`
`[:I Yes
`
`
`
`‘2 Verified
`.
`.
`|:] Not apphcable because drug is
`an old antibiotic.
`
`
`
`
`
`
`
`
`O
`
`
`
`°.° List of officers/employees who participated in the decision to approve this application and
`consented to be identified on this list (approvals only) tlink)
`
`
`Documentation of consent/non-consent by officers/employees tlink)
`
`IX Included
`
`IX Included
`
`Reference ID: 4174711
`
`

`

`NDA 210259
`
`Page 3
`
`O
`0.. Copies of all action letters (including approval letter withfinal labeling)
`
`
`
`Approval 10/31/2017
`
`
`
`O
`0.. Package Insert (write submission/communication date at upper right offirstpage ofPI)
`
`
`[I Included
`
`g Included
`
`
`0 Most recent drafi labeling (ifit is division-proposed labeling, it should be in
`track—clian_ es ormat)
`
`0 Original applicant-proposed labeling
`
`D Medication Guide
`IX Patient Package Insert
`{0 Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`E] Instructions for Use
`submission/communication date at upper right offirstpage ofeach piece)
`El Device Labeling
`I:I None
`
`
`
`0 Most-recent draft labeling (ifit is division—proposed labeling, it should be in
`track-changesformat)
`
`0 Original applicant—proposed labeling
`
`O
`0.. Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper light offirstpage ofeach submission)
`
`E] Included
`
`IX Included
`
`0 Most-recent draft labeling
`
`02° Proprietary Name
`Acceptability/non-acceptability letter(s) (indicate date(s))
`Review(s) (indicate date(s)
`
`0
`
`9
`0.. Labeling reviews (indicate dates ofreviews)
`
`[2 Included 09/27/2017
`
`Letter: 8/25/2017
`Review: 8/24/2017
`
`RPM: 10/10/2017
`
`DNIEPA: 10/10/2017; 9/13/2017
`DNlPP/PLT: 10/20/2017
`OPDPI 10/11/2017
`
`SEALD: [2 None
`CSS: E] None
`Product Quality: 9/19/2017
`Other: I:| None DRISK:
`9/30/201 7
`
`0O0..0..
`
`RPM Filing Review/Memo of Filing Meeting (indicate date ofeach review)
`All NDA 55(b)(2) Actions: Date each action cleared by 55(b)(2) Clearance Committee
`
`O
`0.9 NDAs/NDA supplements only: Exclusivity Summary (signed by Division Director)
`9
`9.. Application Integrity Policy (AIP) Status and Related Documents
`hfipflwww fda.govflCECI/EnforcementActions/ApplicationIntegg‘gPolicy/defaulthml
`
`8/01/2017
`
`g Not a (b)(2)
`
`IX Completed
`
`0 Applicant is on the AIP
`
`DYes
`
`[XINO
`
`
`
`
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`Reference ID: 4174711
`
`

`

`NDA 210259
`Page 4
`
`
`
`This application is on the AIP
`o If yes, Center Director’s Exception for Review memo (indicate date)
`o If yes, OC clearance for approval (indicate date of clearance
`communication)
` Pediatrics (approvals only)
` Date reviewed by PeRC
`If PeRC review not necessary, explain: Orphan drug designation
`
` Yes
`
`
`
`N/A
`
` No
`
` Not an AP action
`
` Breakthrough Therapy Designation
`
`
`
`
`
`
`Breakthrough Therapy Designation Letter(s) (granted, denied, an/or rescinded)
`CDER Medical Policy Council Breakthrough Therapy Designation
`Determination Review Template(s) (include only the completed template(s) and
`not the meeting minutes)
`CDER Medical Policy Council Brief – Evaluating a Breakthrough Therapy
`Designation for Rescission Template(s) (include only the completed template(s)
`and not the meeting minutes)
`
`(completed CDER MPC templates can be found in DARRTS as clinical reviews or on
`the MPC SharePoint Site)
`
` Outgoing communications: letters, emails, and faxes considered important to include in
`the action package by the reviewing office/division (e.g., clinical SPA letters, RTF letter,
`Formal Dispute Resolution Request decisional letters, etc.) (do not include OPDP letters
`regarding pre-launch promotional materials as these are non-disclosable; do not include
`Master File letters; do not include previous action letters, as these are located elsewhere
`in package)
`
` Internal documents: memoranda, telecons, emails, and other documents considered
`important to include in the action package by the reviewing office/division (e.g.,
`Regulatory Briefing minutes, Medical Policy Council meeting minutes)
` Minutes of Meetings
`If not the first review cycle, any end-of-review meeting (indicate date of mtg)
`
`
`
`
`Pre-NDA/BLA meeting (indicate date of mtg)
`
`EOP2 meeting (indicate date of mtg)
`
` Mid-cycle Communication (indicate date of mtg)
`Late-cycle Meeting (indicate date of mtg)
`
`
` Other milestone meetings (e.g., EOP2a, CMC focused milestone meetings)
`(indicate dates of mtgs)
`
` N/A
`
`Granted 7/31/2017
`
`7/28/2017
`
`N/A
`
`10/30/2017; 10/29/2017;
`10/25/2017; 10/18/2017 (2);
`10/11/2017; 10/10/2017;
`10/6/2017 (2); 9/28/2017;
`9/27/2017 (3); 9/25/2017 (2);
`9/22/2017 (2); 9/21/2017;
`9/20/2017; 9/19/2017; 9/15/2017;
`9/13/2017; 9/7/2017; 8/28/2017;
`8/25/2017; 8/22/2017; 8/18/2017
`(2); 8/17/2017; 8/16/2017;
`8/11/2017; 8/10/2017; 8/7/2017;
`8/04/2017; 8/3/2017; 8/01/2017
`(3); 7/31/2017; 7/27/2017;
`7/24/2017; 7/21/2017; 7/18/2017;
`6/22/2017; 6/21/2017; 6/20/2017
`
`7/24/2017
`
` N/A or no mtg
` No mtg
`Preliminary meeting comments
`issued 5/26/2017; cancelled
`6/2/2017 pre-NDA meeting
`3/21/2016
`9/01/2017
`9/29/2017
`CMC: 8/17/2017
`EOP1: 10/10/2014
`
`Reference ID: 4174711
`
`

`

`NDA 210259
`
`Page 5
`
`0
`
`v Advisory Committee Meeting(s)
`
`IX No AC meeting
`
`0 Date(s) of Meeting(s)
`
`9
`0,9 Ofiice Director Decisional Memo (indicate datefor each review)
`
`Division Director Summary Review (indicate datefor each review)
`
`Cross-Discipline Team Leader Review (indicate datefor each review)
`
`|:| None See Multidisciplinary
`10/27/2017 see u . e175
`
`|:| None See Multidisciplinary
`10/27/2017 see 0 . e 174
`
`E] None See Multidisciplinary
`10/27/2017 see 0 . e 20/21
`
`PMR/PMC Development Templates (indicate total number)
`
`D None
`
`3 PMR's; 10/30/2017
`
`
`
`
`
`
`
`
`°§° Clinical Reviews
`
`[0/27/2017
`
`0
`
`Clinical Team Leader Review(s) (indicate datefor each revieu)
`
`IX No separate review
`See Multidiscin 'I .
`
`0
`
`0
`
`Clinical review(s) (indicate datefor each review)
`
`
`
`See Multidiscipljm 10/27/2017
`
`
`
`Social scientist review(s) (if OTC drug) (indicate datefor each review)
`
`g None
`
`03° Financial Disclosure reviews(s) or location/date if addressed in another review
`OR
`Ifno financial disclosure information was required, check here El and include a
`review/memo explaining why not (indicate date ofrevierMnemo)
`O
`0.. Clinical reviews from immunology and other clinical areas/divisions/C-ters (indicate
`date ofeach review)5
`
`Controlled Substance Staff review(s) and Scheduling Recommendation (indicate date of
`each review)
`
`0
`0..
`
`See Multidisciplinary review
`10/27/2017 page 161
`
`IE None
`
`IX] N/A
`
`‘30 Risk Management
`0
`REMS Documents and REMS Supporting Document (indicate date(s) of
`submission(s))
`REMS Memo(s) and letter(s) (indicate date(;s'))
`Risk management review(s) and recommendations (including those by OSE and
`CSS) (indicate date ofeach review and indicate location/date ifincmporated
`into another review)
`
`REMS review 9/30/2017
`
`{0 081 Clinical Inspection Review Summary(ies) (include copies of081 letters to
`im'estigators)
`
`8/18/2017
`
` O
`0.9 Clinical Microbiology Team Leader Review(s) (indicate datefor each review)
`
`I: No separate review
`
`Clinical Microbiology Review(s) (indicate datefor each review)
`
`4° Statistical Division Director Review(s) (indicate datefor each review)
`
`Statistical Team Leader Review(s) (indicate datefor each review)
`
`Statistical Revrew(s) (Indicate datefor each review)
`
`|:] None
`
`
`E No separate review
`See Multidiscipljm 10/27/2017
`
`Cosi u: ed 10/4/2017 review
`
`IE No separate review
`
`See Multidisciplm‘ 10/27/2017
`Cosigned 10/4/2017 review
`S374Il\;13111;disc1
`1007/2017
`
`5 For Part 3 combination products, all reviews from the reviewing Center(s) should be entered into the official archive (for further
`instructions, see “Section 508 Compliant Documents: Process for Regulatory Project Managers” located in the CST electronic
`repository).
`
`Reference ID: 4174711
`
`

`

`NDA 210259
`
`Page 6
`
`O
`0.9
`
`,
`_
`_
`,
`_
`.
`.
`...
`..
`Chmcal Pharmacology Divisron Director Rev1ew(s) (Indicate datefor each 1 e1 zen)
`.
`.
`.
`_
`.
`_
`_
`.
`Clinical Pharmacology Team Leader Revrew(s) (Indicate datefor each let zen)
`
`Clinical Pharmacology review(s) (indicate datefor each review)
`
`
`
`IX] Noseparatereview
`See Multidisci !'
`10/27/2017
`IX] No separate review
`See M111tidisci !.
`10/27/2017
`See Multidiscim' 10/27/2017
`0 T-IRT review 1 0/ 1 2/201 7
`
`IX None requested
`
`O
`
`0.0 Pharmacology/Toxicology Discipline Reviews
`
`0 ADP/T Review(s) (indicate datefor each review)
`
`IX No separate review
`
`See Multidiscin 'I .
`10/27/2017
`
`IX No separate review
`See Multidisciu .l .
`10/27/2017
`
`
`
`
`
`
`
`
`9
`9.. 081 Clinical Pharmacology Inspection Review Summary (include copies of081 letters)
`
`
`
`
`
`Supervisory Review(s) (indicate datefor each review)
`
`0
`
`0
`
`Pharm/tox review(s), including referenced IND reviews (indicate datefor each
`review)
`
`See Multidisciflary’ 10/27/2017
`
`4° Review(s) by other disciplines/divisions/Centeis requested by P/T reviewer (indicate date
`.
`for each review)
`
`IX]
`
`None
`
`{0 Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`
`IX] No care
`
`-
`.
`0 ECAC/CAC report/memo ofmeeting
`
`[X] None
`Included in PIT review, . a . e
`
`°:' OSI Nonclinical Inspection Review Summary (include copies of081 letters)
`
`IX None requested
`
`Reference ID: 4174711
`
`

`

`NDA 210259
`
`Page 7
`
`'2' Product Quath Discipline Reviews6
`
`Tertiary review (indicate datefor each review)
`
`Secondary review (e.g., Branch Chief) (indicate datefor each review)
`
`Integrated Quality Assessment (contains the Executive Summary and the primary
`reviews from each product quality review discipline) (indicate datefor each
`review)
`
`
`
`O
`0.0
`
`O
`0.0
`
`O
`0.9
`
`IX None
`
`IX None
`
`Executive Summary 10/17/2017
`
`Drug Product 10/5/2017;
`9/14/2017
`
`Drug Substance 10/10/2017:
`9/22/2017
`
`Process 10/1 1/2017; 9/27/2017
`
`Biopharmaceutics 10/16/2017;
`10/04/201 7
`
`Facilities 9/27/201 7
`
`Risk Assessment 9/19/2017
`
`Labeling 9/19/2017
`
`Review S II n.
`
`8/02/2017
`
`
`
`Reviews by other disciphnes/div'isionleenters requested by product quality review team
`(indicate date ofeach review)
`
`IE None
`
`Environmental Assessment (check one) (original and supplemental applications)
`
`IX Categorical Exclusion (indicate review date) (all original applications and
`all eflicacv supplements that could increase the patientpopulation)
`
`See Executive Summary review
`10/17/2017 page 06
`
`I:I Review & FONSI (indicate date ofreview)
`
`El Review & Environmental Impact Statement (indicate date ofeach review)
`
`Facilities Review/Inspection
`
`IX Facilities inspections (indicate date of recommendation: within one week of
`taking an approval action, confirm that there is an acceptable recommendation
`before issuing approval letter) (only original applications and efi‘icacy
`supplements that require a manufacturingfacility inspection(e.g., new strength,
`manufacturing process, or mamdacturing site change)
`
`X Acceptable
`I:] Withhold recommendation
`E] Not applicable
`
`6 Do not include Master File (IMF) reviews or communications to MF holders. However, these documents should be made available
`upon signatory request.
`
`Reference ID: 4174711
`
`

`

`NDA 210259
`Page 8
`
`Day of Approval Activities
`
` For all 55(b)(2) applications:
` Check Orange Book for newly listed patents and/or exclusivity (including
`pediatric exclusivity)
`
`Finalize 55(b)(2) assessment
`
` For Breakthrough Therapy (BT) Designated drugs:
` Notify the CDER BT Program Manager
` For products that need to be added to the flush list (generally opioids): Flush List
` Notify the Division of Online Communications, Office of Communications
` Send a courtesy copy of approval letter and all attachments to applicant by fax or
`secure email
` If an FDA communication will issue, notify Press Office of approval action after
`confirming that applicant received courtesy copy of approval letter
` Ensure that proprietary name, if any, and established name are listed in the
`Application Product Names section of DARRTS, and that the proprietary name is
`identified as the “preferred” name
` Ensure Pediatric Record is accurate
`
` Send approval email within one business day to CDER-APPROVALS
` Take Action Package (if in paper) down to Document Room for scanning within
`two business days
`
` No changes
` New patent/exclusivity
`(Notify CDER OND IO)
`
` Done
`
` Done
`(Send email to CDER OND IO)
` Done
`
` Done
`
` Done
`
` Done
`
` Done
`
` Done
`
` Done
`
`Reference ID: 4174711
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ASHLEY S LUCCI VAUGHN
`10/31/2017
`
`Reference ID: 4174711
`
`

`

`From:
`To:
`Cc:
`Bcc:
`Subject:
`Date:
`Attachments:
`Importance:
`
`Carioti, Theresa
`Yasameen Qazen
`Carioti, Theresa; LucciVaughn, Ashley
`Wroblewski, Tanya
`Additional FDA edits to label: NDA 210259 Acalabrutinib - please respond by 12noon PM today Oct 30. 2017
`Monday, October 30, 2017 10:20:59 AM
`image002.png
`High
`
`Dear Yasameen,
`Please refer to NDA 210259 acalabrutinib. We have the following additional edit to the label.
`
`Under Section 5.5 Atrial Fibrillation and Flutter of the PI, please modify the last sentence, as
`follows: monitor for atrial fibrillation and atrial flutter and manage as appropriate.
`
`Please send the revised label back in tracked changes via email to myself and Ashley by 12noon PM
`today, October 30, 2017.
`
`Once the team reviews and confirms the labeling is agreed upon, we will let you know so you can
`submit officially to the NDA file.
`
`Kindly confirm receipt.
`
`Thank you,
`Theresa
`
`
`Theresa A. Carioti, MPH
`Chief, Project Management Staff
`
`Center for Drug Evaluation and Research
`Office of Hematology and Oncology Products
`Division of Hematology Products
`U.S. Food and Drug Administration
`Telephone: 301-796-2848
`Email: Theresa.Carioti.@fda.hhs.gov
`
`
`
`
`
`
`
`From: Yasameen Qazen [mailto:yasameen.qazen@acerta-pharma.com]
`Sent: Thursday, October 26, 2017 10:47 AM
`To: LucciVaughn, Ashley <Ashley.LucciVaughn@fda.hhs.gov>
`Cc: Carioti, Theresa <Theresa.Carioti@fda.hhs.gov>
`Subject: Re: Sponsor Response Required: Fourth FDA USPI Review/ NDA 210259/ Acalabrutinib/
`Acerta Pharma BV/ Response required via email by 12 PM EST Friday, October 27, 2017
`
`Hi Ashley
`
`
`
`
`
`Reference ID: 4173992
`
`

`

`
`The correction was made in the version submitted yesterday. Can you verify that it was
`received?
`
`
`Thank you
`
`Best regards,
`Yasameen Qazen
`
`From: LucciVaughn, Ashley <Ashley.LucciVaughn@fda.hhs.gov>
`Sent: Thursday, October 26, 2017 7:43:58 AM
`To: Yasameen Qazen
`Cc: Carioti, Theresa
`Subject: Sponsor Response Required: Fourth FDA USPI Review/ NDA 210259/ Acalabrutinib/ Acerta
`Pharma BV/ Response required via email by 12 PM EST Friday, October 27, 2017
`
`Good Morning Yasameen,
`
`Clinical has reviewed your request for the administrative change. They have requested you make the
`following correction and resubmit the label electronically to the NDA:
`
`
`Cytopenias
`Inform patients that they will need periodic blood tests to check blood counts during
`tre