CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`202895Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`ACTION PACKAGE CHECKLIST
`
`NDA # 021976
`202895
`BLA # N/A
`
`NDA Supplement # 8-020
`S-000
`
`BLA STN # N/A
`
`Proprietary Name: Prezista
`Established/Proper Name: darlmavir
`Dosage Form:
`Tablets and Oral Suspension
`
`_
`_
`_
`IfNDA, Efficacy Supplement Type. SE 05
`
`Applicant: Tibotec, Inc
`Agent for Applicant (if applicable): N/A
`
`RPM: Linda C. Onaga, MPH
`
`Division: DAVP
`
`NDAs:
`
`505
`
`2 Ori
`
`'
`
`lNDAs and 505
`
`2 NDA su
`
`laments:
`
`NDA Application Type: E 505(b)(1) D 505(b)(2) Listed d1ug(s) relied upon for approval (include NDA #(s) and drug
`Eflicacy Supplement: E 505(b)(1) U 505(b)(2)
`name(s)):
`
`(A supplement can be either a (b)(l) or a (b)(2)
`regardless of whether the original NDA was a (b)(l)
`or a (b)(2). Consult page 1 of the 505(b)(2)
`Assessment or the Appendix to this Action Package
`Checklist.)
`
`Provide a brief explanation of how this product is difler-t from the listed
`drug.
`
`0 User Fee Goal Date is December 30 2011
`
`If no listed drug, explain.
`I] This application relies on literature.
`I] This application relies on a final OTC monograph.
`D Other (explain)
`
`Two months prior to each action: review the information in the
`505
`2 Assessment and submit the draft to CDER 0ND 10 for
`
`clearance. Finalize the 505(b)(2) Assessment at the time of the
`approval action.
`
`On the day of approval, check the Orange Book again for any new
`patents or pediatric exclusivity.
`
`D No changes El Updated Date of check:
`
`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.
`
`0
`°.° Actions
`
`0
`
`Proposed action
`
`0
`
`Previous actions (specifv type and datefor each action taken)
`
`I The Application Information section is (only) a checklist. The Contents of Action Package section (beginning on page 5) lists the
`documents to be included in the Action Package.
`
`Version: 4/21/1 1
`
`Reference ID: 3060034
`
`

`

`Ifaccelerated approval or approval based on efficacy studies in animals, were promotional
`materials received?
`
`D Received
`
`Note: Promotional materials to be used within 120 days after approval must have been
`submitted (for exceptions, see
`ht_tp://www fda.gov/downloads/Drugs/GuidanceConmlianceRegiglatoglnfomlation/Guida
`nces/ucm069965.-
`. Ifnot submitted, -
`lain
`
`'2° Application Characteristics 2
`
`[2 Priority
`[I Standard
`Review priority:
`Chemical classification (new NDAs only):
`
`Type 3 (New Formulation)
`
`D Fast Track
`El Rolling Review
`D Orphan drug designation
`
`[I Rx-to-OTC full switch
`[I Rx—to-OTC partial switch
`El Direct-to-OTC
`
`NDAs: Subpart H
`D Accelerated approval (21 CFR 314.510)
`[I Restricted distribution (21 CFR 314.520)
`Subpart I
`[I Approval based on animal studies
`
`BLAs: Subpart E
`I] Accelerated approval (21 CFR 601.41)
`E] Restricted distribution (21 CFR 601.42)
`Subpart H
`El Approval based on animal studies
`
`X Submitted in response to a PMR
`El Submitted in response to a PMC
`E Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: I] MedGuide
`I] Communication Plan
`D ETASU
`I] REMS not required
`
`'3' BLAs only: Ensure RMS—BLA Product Information Sheetfor TBP and RMS—BLA Facility
`Information Sheetfor TBP have been completed and forwarded to OPI/OBI/DRM (Vicky D Yes, dates
`Carter
`
`v BLAs only: Is the product subject to oflicral FDA lot release per 21 CFR 610.2
`(approvals only)
`
`D Yes D No
`
`
`
`
`’3‘ Public communications (approvals only)
`
`0 Office of Executive Programs (OEP) liaison has been notified of action
`
`0
`Press Office notified of action (by OEP)
`
`0
`
`Indicate what types (if any) of information dissemination are anticipated
`
`
`
`FDA Talk Paper
`CDER Q&As
`Other DAVP listserv
`
`2 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. For
`example, if the application is a pending BLA supplement, then a new RMS—BLA Product Information Sheetfor TBP must be
`completed.
`
`Version: 4/21/11
`
`Reference ID: 3060034
`
`

`

`NDA/BLA #
`
`Page 3
`
`O
`°.° Exclusivity
`
`0
`
`Is approval of this application blocked by any type of exclusivity?
`
`ENO
`
`D Yes
`
`O NDAs and BLAs: Is there existing orphan drug exclusivity for the “same”
`drug or biologic for the proposed indication(s)? Refer to 21 CFR
`31 6.3(b)(13) for the definition of "same drug”for an orphan drug (i. e.,
`active moiety). This definition is NOT the same as that usedfor ADA
`chemical classification.
`
`o
`
`(b)(2) NDAs only: Is there remaining S-year exclusivity that would bar
`efiecfive approval of a 505 (b)(2) application)? (Note that, even ifexclusivity
`remains, the application may be tentatively approved iit is otherwise ready
`for approval.)
`
`o
`
`(b)(2) NDAs only: Is there remaining 3—year exclusivity that would bar
`efiecfive approval of a 505(b)(2) application? (Note that, even ifexclusivity
`remains, the application may be tentatively approved ‘y‘it is othenvise ready
`for approval.)
`
`o
`
`(b)(2) NDAs only: Is there remaining 6—month pediatric exclusivity that
`would bar effective approval of a 505(b)(2) application? (Note that, even if
`exclusiw'ty remains, the application may be tentatively approved ifit is
`otherwise readyfor approval.)
`
`o NDAs only: Is this a single enantiomer that falls under the 10-year approval
`limitation of 505(u)? (Note that, even ifthe 10-year approval limitation
`period has not expired, the application may be tentatively approved ifit is
`otherwise readyfor approval.)
`
`‘3‘ Patent Information (NDAs only)
`
`0
`
`Patent Information:
`
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`which approval is sought.
`If the drug is an old antibiotic, skip the Patent
`Certification questions.
`
`0
`
`Patent Certification [505(b)(2) applications]:
`Verify that a certification was submitted for each patent for the listed drug(s) in
`the Orange Book and identify the type of certification submitted for each patent.
`
` O
`
`[505(b)(2) applications] If the application includes a paragraph 111 certification,
`it cannot be approved lmtil the date that the patent to which the certification
`pertains expires (but may be tentatively approved if it is otherwise ready for
`approval).
`
`
`
`I] Yes
`E No
`If, yes, NDA/BLA #
`date exclusivity expires:
`
`
`
`If yes, NDA #
`exclusivity expires:
`
`and date
`
`D Yes
`DNo
`If yes, NDA #
`and date
`exclusivity expires:
`
`If yes, NDA #
`exclusivity expires:
`
`and date
`
`El Yes
`ENO
`If yes, NDA #
`and date 10-
`year limitation expires:
`
`IX] Verified
`D Not applicable because drug is
`an old antibiotic.
`
`21 CFR 314.50(i)(1)(i)(A)
`El Verified
`
`21 C1311 314.5090)
`
`D No paragraph III certification
`Date patent will expire
`
`D N/A (no paragraph IV certification)
`I] Verified
`
`o
`
`[505(b)(2) applications] For each paragraph IV certification, verify that the
`applicant notified the NDA holder and patent owner(s) of its certification that the
`patent(s) is invalid, unenforceable, or will not be infringed (review
`documentation of notification by applicant and documentation of receipt of
`notice by patent owner and NDA holder). (Ifthe application does not include
`any paragraph IV certifications, mark "N/A " and skip to the next section below
`(Summary Reviews)).
`
`Reference ID: 3060034
`
`Version: 4/21/11
`
`

`

` Yes
`
` No
`
` Yes
`
` No
`
` Yes
`
` No
`
` Yes
`
` No
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Version: 4/21/11
`
`NDA/BLA #
`Page 4
`
`
` •
`
`
`
`[505(b)(2) applications] For each paragraph IV certification, based on the
`questions below, determine whether a 30-month stay of approval is in effect due
`to patent infringement litigation.
`
`Answer the following questions for each paragraph IV certification:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(1) Have 45 days passed since the patent owner’s receipt of the applicant’s
`notice of certification?
`
`
`
`(Note: The date that the patent owner received the applicant’s notice of
`certification can be determined by checking the application. The applicant
`is required to amend its 505(b)(2) application to include documentation of
`this date (e.g., copy of return receipt or letter from recipient
`acknowledging its receipt of the notice) (see 21 CFR 314.52(e))).
`
` If “Yes,” skip to question (4) below. If “No,” continue with question (2).
`
`(2) Has the patent owner (or NDA holder, if it is an exclusive patent licensee)
`submitted a written waiver of its right to file a legal action for patent
`infringement after receiving the applicant’s notice of certification, as
`provided for by 21 CFR 314.107(f)(3)?
`
`
`If “Yes,” there is no stay of approval based on this certification. Analyze the next
`paragraph IV certification in the application, if any. If there are no other
`paragraph IV certifications, skip the rest of the patent questions.
`
`If “No,” continue with question (3).
`
`
`(3) Has the patent owner, its representative, or the exclusive patent licensee
`filed a lawsuit for patent infringement against the applicant?
`
`
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice from the (b)(2) applicant (or the patent owner or
`its representative) stating that a legal action was filed within 45 days of
`receipt of its notice of certification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period (see 21 CFR 314.107(f)(2))).
`
`
`If “No,” the patent owner (or NDA holder, if it is an exclusive patent licensee)
`has until the expiration of the 45-day period described in question (1) to waive
`its right to bring a patent infringement action or to bring such an action. After
`the 45-day period expires, continue with question (4) below.
`
`(4) Did the patent owner (or NDA holder, if it is an exclusive patent licensee)
`submit a written waiver of its right to file a legal action for patent
`infringement within the 45-day period described in question (1), as
`provided for by 21 CFR 314.107(f)(3)?
`
`If “Yes,” there is no stay of approval based on this certification. Analyze the next
`paragraph IV certification in the application, if any. If there are no other
`paragraph IV certifications, skip to the next section below (Summary Reviews).
`
`If “No,” continue with question (5).
`
`
`
`
`Reference ID: 3060034
`
`

`

`NDA/BLA #
`
`Page 5
`
`(5) Did the patent owner, its representative, or the exclusive patent licensee
`bring suit against the (b)(2) applicant for patent infringement within 45
`days of the patent owner’s receipt of the applicant’s notice of
`certification?
`
`(Note: This can be determined by confirming whether the Division has
`received a written notice from the (b)(2) applicant (or the patent owner or
`its representative) stating that a legal action was filed within 45 days of
`receipt of its notice of certification. The applicant is required to notify the
`Division in writing whenever an action has been filed within this 45-day
`period (see 21 CFR 314.107(t)(2)). Ifno written notice appears in the
`NDA file, confirm with the applicant Whether a lawsuit was commenced
`within the 45-day period).
`
`If "No, " there is no stay ofapproval based on this certification. Analyze the
`nart paragraph IV certification in the application, Vany. Ifthere are no other
`paragraph IV certifications, skip to the next section below (Summary
`Reviews).
`
`If "Yes, " a stay ofapproval may be in eflect. To determine ifa 30—month stay
`is in eflect, consult with the 0ND ADRA and attach a summary ofthe
`response.
`
`
`
`6° Copy of this Action Package Checklist3
`
`December 16, 2011
`
`'2' List of oflicers/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 oflicers/employees
`
`'2' Copies of all action letters (including approval letter withfinal labeling)
`
`Action(s) and date(s)
`December 16, 2011
`
`6° Package Insert (write submission/communication date at upper right offirstpage ofPI)
`
`Most recent draft labeling. Ifit is division-proposed labeling, it should be in
`track-changes format.
`
`Original applicant-proposed labeling
`
`Example of class labeling, if applicable
`
`December 15, 2011
`
`March 30,- 2011 .
`N/A
`
`3 Fill in blanks with dates ofreviews, letters, etc.
`
`Version: 4/21/11
`
`Reference ID: 3060034
`
`

`

`NDA/BLA #
`
`Page 6
`
`Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`submission/communication date at upper right offirstpage ofeach piece)
`
`Most-recent drafi labeling. Ifit is division-proposed labeling, it should be in
`track-changes format.
`
`Original applicant-proposed labeling
`
`Medication Guide
`
`E Patient Package Insert
`E Instructions for Use
`[:1 Device Labeling
`D None
`
`December 15, 2011
`Sept-ber 9, 2011 (IFU)
`March 30, 201 1 (USP1 and USPPI)
`
`Example of class labeling, if applicable
`
`N/A
`
`Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper right offirstpage ofeach submission)
`
`0 Most-recent draft labeling
`
`Proprietary Name
`0 Acceptability/non-acceptability letter(s) (indicate date(s))
`0
`Review(s) (indicate date(s))
`
`Labeling reviews (indicate dates ofreviews and meetings)
`
`Administrative Reviews (e.g., RPMFiling ReviewMemo ofFiling Meeting) (indicate
`date ofeach review)
`All NDA (b)(2) Actions: Date each action cleared by (b)(2) Clearance Cmte
`:505 o 2 Assessment indicate date)
`
`I RPM June 23, 2011
`December 16, 2011
`
`El DMEPA December 13, 2011
`August 31, 2011
`
`El DRISK December 14, 2011
`September 28, 201 l
`September 6 2011
`
`I2] DDMAC September 2,2011
`July 26, 201 1
`
`August 5, 2011
`
`E Not a (b)(2)
`
`NDAs only: Exclusivity Summary (signed by Division Director)
`
`El Included
`
`
`
`0 Applicant is on the AIP
`
`o
`
`This application is on the AIP
`
`o Ifyes, Center Director’s Exception for Review memo (indicate date)
`
`
`O
`0..
`Application Integrity Policy (AIP) Status and Related Documents
`
`
`thQ://www fda.gov/ICECI/EnforcementActions/Applicationlntegg'gPolicy/defaulthtm
`
`
`
` I] Yes E No
`
`
`
`
`
`D Yes E No
`
`
`
`
`
` o Ifyes, 0C clearance for approval (indicate date ofclearance
`
`[I Not an AP action
`communication)
`
`4 Filing reviews for scientific disciplines should be filed behind the respective discipline tab.
`
`Version: 4/21/11
`
`Reference ID: 3060034
`
`

`

`Pediatrics (approvals only)
`0 Date reviewed by PeRC Auggt 17, 2011
`IfPeRC review not necessary, explain:
`Pediatric Page/Record (approvals only, must be reviewed by PERC before
`nalized)
`
`0
`
`Debarment certification (original applications only): verified that qualifying language was
`not used in certification and that certifications from foreign applicants are cosigned by
`US. agent (include certification)
`
`E Verified, statement is
`acceptable
`
`‘3' Outgoing communications (letters (except action letters), emails, faxes, telecons)
`
`'3'
`
`Internal memoranda, telecons, etc.
`
`N/A
`
`’3' Minutes of Meetings
`
`0
`
`Regulatory Briefing (indicate date ofmtg)
`
`Ifnot the first review cycle, any end-of-review meeting (indicate date ofmtg)
`
`E N/A or no mtg
`
`Pre-NDA/BLA meeting (indicate date ofmtg)
`
`O
`
`EOP2 meeting (indicate date ofmtg)
`
`E No mtg
`
`E No mtg
`
`o Other milestone meetings (e.g., EOPZa, CMC pilots) (indicate dates ofmtgs)
`
`N/A
`
`Advisory Committee Meeting(s)
`
`0 Date(s) of Meeting(s)
`
`O
`
`48-hour alert or minutes, if available (do not include transcript)
`
`E No AC meeting
`
`
`
`Oflice Director Decisional Memo (indicate datefor each review)
`
`Division Director Summary Review (indicate datefor each review)
`
`Cross-Discipline Team Leader Review (indicate datefor each review)
`
`PMR/PMC Development Templates (indicate total number)
`
`Decemberl42011
`
`MUSHSPRFmber 16 2011
`
`1
`
`Clinical Reviews
`
`0
`
`0
`
`0
`
`Clinical Team Leader Review(s) (indicate datefor each revieu)
`
`Clinical review(s) (indicate datefor each review)
`
`Social scientist review(s) (if OTC drug) (indicate datefor each review)
`
`December 13, 2011
`September 6, 2011
`May 9 2011
`
`Financial Disclosure reviews(s) or location/date if addressed in another review
`OR
`Ifno financial disclosure information was required, check here I] and include a
`review/memo explaining why not (indicate date ofreview/memo)
`
`Clinical Review - September 6,
`2011 Page 13
`
`Clinical reviews from immunology and other clinical areas/divisions/Centers (indicate
`date ofeach review)
`
`E None
`
`'2' Controlled Substance Staff review(s) and Scheduling Recommendation (indicate date of
`
`.
`
`5 Filing reviews should be filed with the discipline reviews.
`
`Version: 4/21/11
`
`Reference ID: 3060034
`
`

`

`NDA/BLA #
`
`Page 8
`
`Risk Management
`REMS Documents and Supporting Statement (indicate date(s) ofsubmission(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 ifincorporated
`into another revien)
`
`DSI Clinical Inspection Review Summary(ies) (include copies ofDSI letters to
`im‘estigators)
`
`E None requested
`
`
`Clinical Microbiology Team Leader Review(s) (indicate datefor each revieuy
`
`E None
`
`Clinical Microbiology Review(s) (indicate datefor each review)
`
`DNoneMay252011
`.
`.
`'1 26, 2011
`
`Statistical Division Director Review(s) (indicate datefor each review)
`Statistical Team Leader Review(s) (indicate datefor each review)
`
`Statistical Review(s) (indicate datefor each review)
`
`
`
`Clinical Pharmacology Division Director Review(s) (indicate datefor each review)
`
`Clinical Pharmacology Team Leader Review(s) (indicate datefor each review)
`
`Clinical Pharmacology review(s) (indicate datefor each revieu)
`
`September 27, 2011
`
`December 8, 2011
`September 6, 2011
`.
`u
`'l 29, 2011
`
`‘3' DSI Clinical Pharmacology Inspection Review Summary (include copies ofDSI letters)
`
`D None August 5, 2011
`
`Pharmacology/Toxicology Discipline Reviews
`
`ADP/T Review(s) (indicate datefor each review)
`
`E None
`
`Supervisory Review(s) (indicate datefor each review)
`Pharm/tox review(s), including referenced 1ND reviews (indicate datefor each
`'
`
`E None
`D None I August 31, 2011
`May 26, 2011
`
`Review(s) by other disciplines/divisions/Centers requested by P/T reviewer (indicate date E None
`for each revien)
`
`Statistical review(s) of carcinogenicity studies (indicate datefor each revieu9
`
`6° ECAC/CAC report/memo ofmeeting
`3 DSI Nonclinical Inspection Review Summary (include copies ofDSI letters)
`
`E1111:2112) P/T review .a . e
`E None requested
`
`Reference ID: 3060034
`
`Version: 4/21/11
`
`

`

`NDA/BLA #
`
`Page 9
`
`6° Product Quality Discipline Reviews
`
`
`
`o ONDQA/OBP Division Director Review(s) (indicate datefor each review) E None
`
`0
`
`Branch Chief/Tearn Leader Review(s) (indicate datefor each review)
`
`E None
`
`Product quality review(s) including ONDQA biopharmaceutics reviews (indicate
`datefor each renew)
`
`D None
`Product Quality September 29,
`$23311“ Q
`l'ty September 6, 20”
`P
`1 ct Quality May 2, 20”
`Biopharmaceutics September 1,
`201 l
`
`Microbiology Reviews
`E NDAs: Microbiology reviews (sterility & pyrogenicity) (OPS/NDMS) (indicate
`date ofeach review)
`D BLAs: Sterility assurance, microbiology, facilities reviews
`(DIVIPQ/MAPCB/BMT) (indicate date ofeach review)
`
`D Not needed
`August 10, 201 1
`
`Reviews by other disciplines/divisions/Centers requested by CMC/quality reviewer
`(indicate date ofeach review)
`
`Environmutal Assessment (check one) (original and supplemental applications)
`
`X Categorical Exclusion (indicate review date)(all original applications and
`all eflicaqv supplements that could increase the patient population)
`
`Product Quality Review :
`September 6, 2011
`
`'2' NDAs: Methods Validation (check box only, do not include documents)
`
`El Review & FONSI (indicate date of review)
`
`D Review & Environmental Impact Statement (indicate date ofeach review)
`
`Facilities Review/Inspection
`
`[I NDAs: Facilities inspections (include EER printout) (date completed must be
`within 2 years ofaction date) (only original NDAs and supplements that include
`a newfacility or a change that aflects the mamg’acturing sites‘)
`
`El BLAs: TB-EER (date ofmost recent TB—EER must be within 30 days ofaction
`date) (original and supplemental BLAs)
`
`Date completed: May 20, 2011
`E Acceptable
`D Withhold recommendation
`t app]:
`
`Date completed:
`B Acceptable
`D Withhold recommendation
`
`D Completed
`El Requested
`D Not yet requested
`E Not needed (per review)
`
`6 I.e., a new facility or a change in the facility, or a change in the manufacturing process in a way that impacts the Quality
`Management Systems of the facility.
`
`Version: 4/21/11
`
`Reference ID: 3060034
`
`

`

`NDA/BLA #
`Page 10
`
`Appendix to Action Package Checklist
`
`An NDA or NDA supplemental application is likely to be a 505(b)(2) application if:
`(1) It relies on published literature to meet any of the approval requirements, and the applicant does not have a written
`right of reference to the underlying data. If published literature is cited in the NDA but is not necessary for
`approval, the inclusion of such literature will not, in itself, make the application a 505(b)(2) application.
`(2) Or it relies for approval on the Agency's previous findings of safety and efficacy for a listed drug product and the
`applicant does not own or have right to reference the data supporting that approval.
`(3) Or it relies on what is "generally known" or "scientifically accepted" about a class of products to support the
`safety or effectiveness of the particular drug for which the applicant is seeking approval. (Note, however, that this
`does not mean any reference to general information or knowledge (e.g., about disease etiology, support for
`particular endpoints, methods of analysis) causes the application to be a 505(b)(2) application.)
`
`
`Types of products for which 505(b)(2) applications are likely to be submitted include: fixed-dose combination drug
`products (e.g., heart drug and diuretic (hydrochlorothiazide) combinations); OTC monograph deviations(see 21 CFR
`330.11); new dosage forms; new indications; and, new salts.
`
`An efficacy supplement can be either a (b)(1) or a (b)(2) regardless of whether the original NDA was a (b)(1) or a (b)(2).
`
`
`An efficacy supplement is a 505(b)(1) supplement if the supplement contains all of the information needed to support the
`approval of the change proposed in the supplement. For example, if the supplemental application is for a new indication,
`the supplement is a 505(b)(1) if:
`(1) The applicant has conducted its own studies to support the new indication (or otherwise owns or has right of
`reference to the data/studies).
`(2) And no additional information beyond what is included in the supplement or was embodied in the finding of
`safety and effectiveness for the original application or previously approved supplements is needed to support the
`change. For example, this would likely be the case with respect to safety considerations if the dose(s) was/were
`the same as (or lower than) the original application.
`(3) And all other “criteria” are met (e.g., the applicant owns or has right of reference to the data relied upon for
`approval of the supplement, the application does not rely for approval on published literature based on data to
`which the applicant does not have a right of reference).
`
`
`An efficacy supplement is a 505(b)(2) supplement if:
`(1) Approval of the change proposed in the supplemental application would require data beyond that needed to
`support our previous finding of safety and efficacy in the approval of the original application (or earlier
`supplement), and the applicant has not conducted all of its own studies for approval of the change, or obtained a
`right to reference studies it does not own. For example, if the change were for a new indication AND a higher
`dose, we would likely require clinical efficacy data and preclinical safety data to approve the higher dose. If the
`applicant provided the effectiveness data, but had to rely on a different listed drug, or a new aspect of a previously
`cited listed drug, to support the safety of the new dose, the supplement would be a 505(b)(2).
`(2) Or the applicant relies for approval of the supplement on published literature that is based on data that the
`applicant does not own or have a right to reference. If published literature is cited in the supplement but is not
`necessary for approval, the inclusion of such literature will not, in itself, make the supplement a 505(b)(2)
`supplement.
`(3) Or the applicant is relying upon any data they do not own or to which they do not have right of reference.
`
`
`If you have questions about whether an application is a 505(b)(1) or 505(b)(2) application, consult with your ODE’s
`ADRA.
`
`
`
`
`Reference ID: 3060034
`
`Version: 4/21/11
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LINDA C ONAGA
`12/16/2011
`
`Reference ID: 3060034
`
`

`

`
`Application:
`
`
`
`
`Name of Drug:
`
`
`
`
`
`
`
`Applicant:
`
`
`
`
`
`
`
`
`
`
`
`
`NDA 202895
`NDA 21976/S-20
`
`Prezista® oral suspension, 100mg/mL
`Prezista® tablets, 75 mg, 150 mg, 400 mg, and 600 mg
`
`
`
`
`
`Tibotec, Inc
`
`Labeling Reviewed
`
`
`
`
`
`December 15, 2011
`
`December 15, 2011
`
`Division of Antiviral Products
`
`REGULATORY PROJECT MANAGER LABELING REVIEW
`
`
`
`Submission Date:
`
`
`Receipt Date:
`
`Submission Date of SPL: March 30, 2011 and June 28, 2011
`
`Type of Labeling Reviewed: WORD
`
`Material Reviewed:
`
`Last approved labeling for NDA 21976 (S-18) approved October
`19, 2011 and Proposed Labeling and Instructions for use for NDA
`202895 and NDA 21976/S-20 amended December 15, 2011
`
`
`Background and Summary Description:
`
`In response to FDA’s Written Request and PREA PMR 389-1, Tibotec submitted, an original
`NDA for Prezista oral suspension formulation. Because the oral solution formulation will share
`labeling with the tablet formulation, Tibotec submitted an efficacy supplement for the Prezista
`tablet formulation. The NDA data will support the use of Prezista in combination with other
`antiretroviral agents for the treatment of HIV-1 infection in pediatric populations from 3 to less
`than 6 years of age (10 kg to less than
` kg), 6 to less than 18 years of age (20 kg to less than 40
`kg), and treatment experienced and treatment naïve HIV-1 infected adult populations. The
`original NDA provides pharmacokinetic, safety, tolerability and virologic response data that
`supports weight-based dosing recommendations of Prezista in combination with ritonavir for
`treatment experienced HIV-1 pediatric patients 3 to < 6 years of age.
`
`
`
`
`
`Reference ID: 3059615
`
`1
`
`109 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following
`this page
`
`(b)
`(4)
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LINDA C ONAGA
`12/16/2011
`
`KAREN D WINESTOCK
`12/16/2011
`
`Reference ID: 3059615
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy Initiatives
`Division of Medical Policy Programs
`
`PATIENT LABELING REVIEW
`
`December 14, 2011
`
`Debra Birnkrant, MD, Director
`Division of Antiviral Products (DAVP)
`
`LaShawn Griffiths, MSHS-PH, BSN, RN
`Team Leader, Patient Labeling Team
`Division of Medical Policy Programs (DMPP)
`
`Barbara Fuller, RN, MSN, CWOCN
`Team Leader, Patient Labeling Team
`Division of Medical Policy Programs
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`DMPP Concurrence with submitted Instructions for Use
`
`Drug Name (established
`name):
`
`PREZISTA (darunavir)
`
`
`Dosage Form and Route: Oral Suspension
`
`NDA 202-895
`NDA 21-796/S-020
`
`Tibotec, Inc.
`
`2011-1372
`
`Application
`Type/Number:
`
`Applicant:
`
`OSE RCM #:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3058640
`
`1
`
`

`

`1 INTRODUCTION
`
`On March 30, 2011 Tibotec, Inc. submitted original NDA 202-895 for PREZISTA
`(darunavir) Oral Suspension which provides pharmacokinetic, safety, tolerability and
`virologic response data that supports weight-based dosing recommendations of
`PREZISTA in combination with ritonavir for treatment-experienced HIV-1 infected
`pediatric patients ages 3 to < 6 years. Labeling in the submission included expanded
`dosing recommendations for the age group 3 to < 6 years. DMPP completed a review
`of the Patient Package Insert on September 6, 2011, as requested by DAVP. On
`August 16, 2011 the Division of Antiviral Products held a teleconference with
`Tibotec, Inc. and requested that the Applicant submit Instructions for Use for the
`product.
`On September 28, 2011, DMPP completed a review of the proposed PREZISTA
`(darunavir) Oral Suspension Instructions for Use (IFU) submitted on September 14,
`2011. On December 12, 2011, Tibotec, Inc. submitted proposed revisions to the IFU
`for the Agency’s review and approval.
`
` 2
`
` MATERIAL REVIEWED
`• Draft PREZISTA (darunavir) Oral Suspension Instructions for Use (IFU)
`submitted on December 12, 2011.
`
`
`3 CONCLUSIONS
`The Applicant’s proposed IFU revisions are acceptable with the following comments:
`•
`In Figure A, the Applicant should change
` to “use”.
`•
`In Figure
` the Applicant should use a lowercase ‘b” in: “Closing the bottle”.
`
`
`4 RECOMMENDATIONS
`• Consult DMPP regarding any additional revisions made to the PI to determine if
`corresponding revisions need to be made to the IFU.
`
`Please let us know if you have any questions.
`
`
`
`
`
`
`Reference ID: 3058640
`
`2
`
`(b) (4)
`
`(b)
`(4)
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`BARBARA A FULLER
`12/14/2011
`
`LASHAWN M GRIFFITHS
`12/14/2011
`
`Reference ID: 3058640
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`Office of Medication Error Prevention and Risk Management
`
`Label and Labeling Memorandum
`
`December 13, 2011
`
`Loretta Holmes, BSN, PharmD
`Division of Medication Error Prevention and Analysis
`(DMEPA)
`
`Lubna Merchant, MS, PharmD
`Division of Medication Error Prevention and Analysis
`(DMEPA)
`
`Carol A. Holquist, RPh
`Division of Medication Error Prevention and Analysis
`(DMEPA)
`
`
`
`
`
`
`
`
`Date:
`
`Reviewer:
`
`
`
`Team Leader
`
`
`
`Division Director
`
`
`
`Drug Name and Strength:
`
`
`Application Type/Number: NDA 202895
`
`Applicant:
`
`OSE RCM #:
`
`
`Prezista (Darunavir) Oral Suspension
`100 mg per mL
`
`Tibotec, Inc.
`
`2011-1370
`
`Reference ID: 3057660
`
`

`

`
`
` 1
`
`
`INTRODUCTION
`This memorandum responds to a request from the Division of Antiviral Products (DAVP)
`for DMEPA’s evaluation of revised labels and labeling for Prezista oral suspension.
`
`2 BACKGROUND
`The Applicant submitted revised carton labeling and a revised syringe graphic on
`November 9, 2011 in response to recommendations from DMEPA that were forwarded to
`the Applicant on October 6, 2011 in an Information Request Letter. Additionally, the
`Applicant made changes to the container label (the location of the lot number and expiry
`was changed) that were not requested by DMEPA and submitted the revised container
`label containing those changes on November 30, 2011. DMEPA evaluated these labels
`and labeling (see Appendices A through C).
`
`3 CONCLUSIONS AND RECOMMENDATIONS
`The Applicant has implemented our recommendations for the carton labeling and syringe
`graphic and we find the revised carton labeling and syringe graphic submitted on
`November 9, 2011 acceptable. Additionally, we find the revised container label
`s