`RESEARCH
`
`
`APPLICATION NUMBER:
`
`209606Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`EXCLUSIVITY SUMMARY
`
`NDA # 209606
`
`SUPPL #
`
`HFD # 161
`
`Trade Name IDHIFA®
`
`Generic Name enasidenib
`
`Applicant Name Celgene Corporation
`
`
`
`Approval Date, If Known August 1, 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: 4133109
`
`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?
`
`years (orphan drug exclusivity)
`years (new chemical entity)
`
`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
`
`Reference ID: 4133109
`
`Page 2
`
`(b)
`(4)
`
`
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`
`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."
`
`Reference ID: 4133109
`
`Page 3
`
`
`
`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
`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:
`
`
`
`
`
`Reference ID: 4133109
`
`Page 4
`
`
`
`(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?
`
` 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
`
`Reference ID: 4133109
`
`Page 5
`
`
`
`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
`
`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:
`
`
`Page 6
`
`Investigation #1
`
`IND #
`
`YES
`
`
`
`Investigation #2
`
`IND #
`
`YES
`
`
`
`
`
`Reference ID: 4133109
`
`
`
`
`
`
`(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?
`
`!!
`
`
`! 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: Jennifer J. Lee, PharmD
`Title: Regulatory Project Manager
`Date: July 19, 2017
`
`
`Name of Division Director signing form: Albert Deisseroth, MD
`Title: Supervisory Associate Division Director
`
`Reference ID: 4133109
`
`Page 7
`
`
`
`Reference ID: 4133109
`
`Page 8
`
`APPEARS THIS WAY ON ORIGINAL
`
`
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`JENNIFER J LEE
`08/01/2017
`
`ALBERT B DEISSEROTH
`08/01/2017
`
`Reference ID: 4133109
`
`
`
`ACTION PACKAGE CHECKLIST
`
`APPLICATION INFORMATION1
`NDA Supplement #
`If NDA, Efficacy Supplement Type:
`NDA # 209606
`(an action package is not required for SE8 or SE9 supplements)
`BLA Supplement #
`BLA #
`Proprietary Name: IDHIFA®
`Established/Proper Name: enasidenib
`Dosage Form: Tablet
`RPM: Jennifer J. Lee, PharmD
`
`Applicant: Celgene Corporation
`Agent for Applicant (if applicable):
`
`NDA Application Type:
`Efficacy Supplement:
`
` 505(b)(1)
` 505(b)(1)
`
` 505(b)(2)
` 505(b)(2)
`
`BLA Application Type:
`Efficacy Supplement:
`
` 351(k)
` 351(k)
`
` 351(a)
` 351(a)
`
`Division: Division of Hematology Products
`For ALL 505(b)(2) applications, two months prior to EVERY action:
`
` Review the information in the 505(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
`
` User Fee Goal Date is August 30, 2017
`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/ucm069965.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: 01/04/17
`
`Reference ID: 4133118
`
`
`
`NDA 209606
`Page 2
`
` Priority
` Standard
`Review priority:
`Chemical classification (new NDAs only): Isocitrate dehydrogenase 2 inhibitor
`(confirm chemical classification at time of approval)
`
` Fast Track
` Rolling Review
` Orphan drug designation
` Breakthrough Therapy designation
`(NOTE: Set the submission property in DARRTS and notify the CDER Breakthrough Therapy Program Manager;
`Refer to the “RPM BT Checklist for Considerations after Designation Granted” for other required actions: CST SharePoint)
`
` Rx-to-OTC full switch
` Rx-to-OTC partial switch
` Direct-to-OTC
`
`NDAs: Subpart H BLAs: Subpart E
`
` Accelerated approval (21 CFR 314.510)
` Accelerated approval (21 CFR 601.41)
`
` Restricted distribution (21 CFR 314.520)
` Restricted distribution (21 CFR 601.42)
` Subpart I Subpart H
`
` Approval based on animal studies
` Approval based on animal studies
`
` Submitted in response to a PMR REMS:
` Submitted in response to a PMC
` Submitted in response to a Pediatric Written Request
`
`Comments:
`
` MedGuide
` Communication Plan
` ETASU
` MedGuide w/o REMS
` REMS not required
`
` BLAs only: Is the product subject to official FDA lot release per 21 CFR 610.2
`(approvals only)
` Public communications (approvals only)
` Office of Executive Programs (OEP) liaison has been notified of action
`
`
`
`Indicate what types (if any) of information were issued
`
` Yes
`
` No
`
` No
`
` Yes
` None
` FDA Press Release
` FDA Talk Paper
` CDER Q&As
` Other – ASCO Burst
`
` Exclusivity
`Is approval of this application blocked by any type of exclusivity (orphan, 5-year
`
`NCE, 3-year, pediatric exclusivity)?
`If so, specify the type
`
` Patent Information (NDAs only)
`
` No
`
`
` Yes
`
`
`
`Patent Information:
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`which approval is sought.
`
` Verified
` Not applicable because drug is
`an old antibiotic.
`
`CONTENTS OF ACTION PACKAGE
`Officer/Employee List
` List of officers/employees who participated in the decision to approve this application and
`consented to be identified on this list (approvals only)
`Documentation of consent/non-consent by officers/employees
`
` Included
`
` Included
`
`Reference ID: 4133118
`
`
`
`NDA 209606
`Page 3
`
` Copies of all action letters (including approval letter with final labeling)
`
`Approval; 8/1/2017
`
`Action Letters
`
`Labeling
`
` Package Insert (write submission/communication date at upper right of first page of PI)
` Most recent draft labeling (if it is division-proposed labeling, it should be in
`track-changes format)
` Original applicant-proposed labeling
`
` Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`submission/communication date at upper right of first page of each piece)
`
` Most-recent draft labeling (if it is division-proposed labeling, it should be in
`track-changes format)
`
` Original applicant-proposed labeling
`
` Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper right of first page of each submission)
`
` Most-recent draft labeling
`
` Proprietary Name
` Acceptability/non-acceptability letter(s) (indicate date(s))
`Review(s) (indicate date(s)
`
`
` Labeling reviews (indicate dates of reviews)
`
`Administrative / Regulatory Documents
`
` RPM Filing Review4/Memo of Filing Meeting (indicate date of each review)
` All NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`
` NDAs/NDA supplements only: Exclusivity Summary (signed by Division Director)
` Application Integrity Policy (AIP) Status and Related Documents
`http://www fda.gov/ICECI/EnforcementActions/ApplicationIntegrityPolicy/default.htm
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`Reference ID: 4133118
`
`See Action Letter 8/1/2017
`
` Included - 12/30/2016
`
` Medication Guide
` Patient Package Insert
` Instructions for Use
` Device Labeling
` None
`See Action Letter 8/1/2017
`
` Included
`Med Guide (6/8/2017)
`Patient Package Insert
`(12/30/2016)
`
` Included – container labels
`7/21/2017
`
`Letter 3/30/2017 (acceptability)
`Review 3/21/2017
`
`RPM: 2/28/2017
`DMEPA: 4/7/2017, 7/13/2017
`DMPP/PLT (DRISK): 6/27/2017
`OPDP: 6/28/2017
`SEALD:
` None
`CSS:
` None
`Product Quality: See Integrated
`Quality Assessment 5/31/2017
`Other:
` None
`
`2/28/2017
`
` Not a (b)(2)
`
` Completed (Do not include)
`
`
`
`NDA 209606
`Page 4
`
` Applicant is on the AIP
`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 designation granted 6/12/2014
`
` Yes
`
` No
`
` Yes
`
`
`
` 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)
`
`Reference ID: 4133118
`
` N/A
`
`
`
`
`
`
`
`8/1/2017, 7/26/2017, 7/21/2017,
`7/20/2017, 7/19/2017, 7/14/2017,
`7/7/2017 (2), 7/6/2017, 7/5/2017,
`7/3/2017, 6/30/2017 (2),
`6/20/2017, 6/14/2017 (2),
`6/12/2017, 6/8/2017, 6/7/2017,
`6/6/2017 (2), 6/5/2017 (2),
`6/2/2017 (2), 5/30/2017,
`5/12/2017, 5/5/2017, 5/3/2017,
`5/2/2017, 4/28/2017, 4/27/2017,
`4/26/2017 (2), 4/25/2017 (3),
`4/24/2017 (2), 4/6/2017, 4/4/2017,
`3/30/2017, 3/27/2017, 3/24/2017,
`3/15/2017, 3/9/2017, 3/2/2017,
`2/28/2017, 2/17/2017, 2/14/2017,
`2/7/2017, 2/1/2017, 1/27/2017,
`1/24/2017, 1/19/2017 (2),
`1/17/2017, 1/11/17, 1/6/2017,
`12/30/2016
`
`
`
` N/A or no mtg
`7/26/2016
` No mtg
`4/28/2017
`6/16/2017
`
`
`
`
`
`NDA 209606
`Page 5
`
` Advisory Committee Meeting(s)
` Date(s) of Meeting(s)
`
`Decisional and Summary Memos
`
` Office Director Decisional Memo (indicate date for each review)
`
`Division Director Summary Review (indicate date for each review)
`
`Cross-Discipline Team Leader Review (indicate date for each review)
`
`PMR/PMC Development Templates (indicate total number)
`
` Clinical Reviews
`
`Clinical
`
`
`
`
`
`Clinical Team Leader Review(s) (indicate date for each review)
`
`Clinical review(s) (indicate date for each review)
`
` and include a
`
`Social scientist review(s) (if OTC drug) (indicate date for each review)
`
` Financial Disclosure reviews(s) or location/date if addressed in another review
` OR
` If no financial disclosure information was required, check here
` review/memo explaining why not (indicate date of review/memo)
` Clinical reviews from immunology and other clinical areas/divisions/Centers (indicate
`date of each review)5
` Controlled Substance Staff review(s) and Scheduling Recommendation (indicate date of
`each review)
` Risk Management
`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 of each review and indicate location/date if incorporated
`into another review)
` OSI Clinical Inspection Review Summary(ies) (include copies of OSI letters to
`investigators)
`
`
`
`
` No AC meeting
`
`
`7/28/2017, Multidisciplinary
`Review (Section 18)
`See 7/28/2017 Multidisciplinary
`Review (Section 17)
`6/30/2017, See 7/28/2017
`Multidisciplinary Review (Section
`1)
`7/11/2017, See 7/28/2017
`Multidisciplinary Review (Section
`12)
`Total: 5 PMRs and 1 PMC
`
` No separate review
`See 7/28/2017 Multidisciplinary
`Review (Sections 2, 3, 4 and 7)
`5/30/2017, See 7/28/2017
`Multidisciplinary Review
`(Sections 2, 3, 4 and 7)
` None
`See 7/28/2017 Multidisciplinary
`Review (Sections 7.2.2, and 13.2)
`
`
`
` None
`
` N/A
`
`
`
`
`
`Review 6/27/2017
`
`5/17/2017
`
`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: 4133118
`
`
`
`NDA 209606
`Page 6
`
`Clinical Microbiology
` Clinical Microbiology Team Leader Review(s) (indicate date for each review)
`Clinical Microbiology Review(s) (indicate date for each review)
`Biostatistics
`
` None
`
` None
`
` Statistical Division Director Review(s) (indicate date for each review)
`
`Statistical Team Leader Review(s) (indicate date for each review)
`
`Statistical Review(s) (indicate date for each review)
`
` Clinical Pharmacology Division Director Review(s) (indicate date for each review)
`
`Clinical Pharmacology
`
` None
`
`Clinical Pharmacology Team Leader Review(s) (indicate date for each review)
`
`Clinical Pharmacology review(s) (indicate date for each review)
`
` OSI Clinical Pharmacology Inspection Review Summary (include copies of OSI letters)
`Nonclinical
` None
` Pharmacology/Toxicology Discipline Reviews
`
` ADP/T Review(s) (indicate date for each review)
`
`
`
`Supervisory Review(s) (indicate date for each review)
`
`
`
`Pharm/tox review(s), including referenced IND reviews (indicate date for each
`review)
` Review(s) by other disciplines/divisions/Centers requested by P/T reviewer (indicate date
`for each review)
` Statistical review(s) of carcinogenicity studies (indicate date for each review)
`
` ECAC/CAC report/memo of meeting
`
` No separate review
` None
`
` No separate review
`See 7/28/2017 Multidisciplinary
`Review (Section 16)
` No separate review
`See 7/28/2017 Multidisciplinary
`Review (Section 7)
`5/30/2017, See 7/28/2017
`Multidisciplinary Review (Section
`7)
`
` No separate review
`See 7/28/2017 Multidisciplinary
`Review (Section 6)
` No separate review
`See 7/28/2017 Multidisciplinary
`Review (Section 6)
`5/30/2017, See 7/28/2017
`Multidisciplinary Review (Section
`6)
`
`IRT-QT Review 3/30/2017
` None requested
`
` No separate review
`See 7/28/2017 Multidisciplinary
`Review (Section 14)
` No separate review
`See 7/28/2017 Multidisciplinary
`Review (Section 5)
`5/30/2017, See 7/28/2017
`Multidisciplinary Review (Section
`5)
`
` None
`
` No carc
`
` None
`
` OSI Nonclinical Inspection Review Summary (include copies of OSI letters)
`
` None requested
`
`Reference ID: 4133118
`
`
`
`NDA 209606
`Page 7
`
`Product Quality
` Product Quality Discipline Reviews6
`
` None
`
`
`
`
`
`
`
`Tertiary review (indicate date for each review)
`
`Secondary review (e.g., Branch Chief) (indicate date for each review)
`
`Integrated Quality Assessment (contains the Executive Summary and the primary
`reviews from each product quality review discipline) (indicate date for each
`review)
`
` Reviews by other disciplines/divisions/Centers requested by product quality review team
`(indicate date of each review)
` Environmental Assessment (check one) (original and supplemental applications)
`
` Categorical Exclusion (indicate review date)(all original applications and
` all efficacy supplements that could increase the patient population)
`
` Review & FONSI (indicate date of review)
`
` None
`
` None
`Executive Summary: 6/19/2017
`Drug Substance: 5/22/2017
`Drug Product: 5/31/2017
`Process: 5/12/2017
`Facilities: 5/31/2017
`Biopharmaceutics: 6/1/2017
`
` None
`
`See Drug Product Review (page
`79) in Integrated Quality
`Assessment 5/31/2017
`
`
` Review & Environmental Impact Statement (indicate date of each review)
`
`
`
` Facilities Review/Inspection
`
` 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 efficacy
`supplements that require a manufacturing facility inspection(e.g., new strength,
`manufacturing process, or manufacturing site change)
`
` Acceptable: See Facilities
`Review in Integrated Quality
`Assessment 5/31/2017
` Withhold recommendation
` Not applicable
`
`6 Do not include Master File (MF) reviews or communications to MF holders. However, these documents should be made available
`upon signatory request.
`
`Reference ID: 4133118
`
`
`
`NDA 209606
`Page 8
`
`Day of Approval Activities
`
` For all 505(b)(2) applications:
` Check Orange Book for newly listed patents and/or exclusivity (including
`pediatric exclusivity)
`
`Finalize 505(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
` 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
`
` No changes
` New patent/exclusivity (Notify
`CDER OND IO)
`
` Done
`
` Done
`(Send email to CDER OND IO)
` Done
`
` Done
`
` Done
`
` Done
`
` Done
`
` Done
`
`Reference ID: 4133118
`
`
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`JENNIFER J LEE
`08/01/2017
`
`Reference ID: 4133118
`
`
`
`From:
`To:
`Subject:
`Date:
`
`Lee, Jennifer (CDER)
`"Penny Ng"
`RE: Enasidenib NDA 209606 Safety Reporting Post-approval
`Tuesday, August 01, 2017 10:49:00 AM
`
`Hi Penny,
`
`Yes, I can confirm that enasidenib is not considered part of a Part 3 combination product.
`
`In addition, in regards to your other question, the FDA Office of Media Affairs does not share any
`information regarding press releases and timing of releases with Applicants. Thanks for your
`understanding.
`
`Kind regards,
`Jennie
`
`From: Penny Ng [mailto:PNg@celgene.com]
`Sent: Tuesday, August 01, 2017 10:08 AM
`To: Lee, Jennifer (CDER)
`Subject: RE: Enasidenib NDA 209606 Safety Reporting Post-approval
`
`Good morning Jennie,
`
`Thank you again for following up on my question on the public communication, I appreciate your
`guidance as always.
`
`Regarding my question below, I understand from the FDA approval letter (received today) that the
`reporting requirement of the NDA is a follows:
`
`
`REPORTING REQUIREMENTS
`We remind you