CENTER FOR DRUG EVALUATION AND RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`22511Orig1s000
`
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`
`NDA # 022511
`
`
`
`
`
`SUPPL #
`
`
`
`
`
`HFD #
`
`Trade Name Vimovo
`
`Generic Name naproxen and esomeprazole magnesium delayed release tablets
`
`
`
`
`
`Applicant Name Pozen
`
`
`Approval Date, If Known April 30, 2010
`
`PART I
`
`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.
`
`
`
`
`
`
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`
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`
`
`
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`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)(2)
`
`c) 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:
`
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`Page 1
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`

`

`
`d) Did the applicant request exclusivity?
`
`3 years
`
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`
`
` YES
`
`
`
`NO
`
`
`
`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).
`
`
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`Page 2
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`

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`
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`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# 020067
`NDA# 021153
`NDA# 021689
`NDA# 021957
`
`
`NDA#
`
`
`
`NDA#
`
`
`
`NDA#
`
`
`
`
`
`
`
`
`
`
`
`
`
`EC Naprosyn
`Nexium (esomeprazole magnesium) Delayed Relaease Capsules
`Nexium IV (esomeprazole sodium) for Injection
`Nexium (esomeprazole magnesium) for Delayed-Release Oral
`Suspension
`Nexium (esomeprazole magnesium) Delayed Release for Oral
`Suspension
`Aleve (naproxen sodium)
`Aleve-D Sinus and Cold (naproxen sodium and pseudoephedrine
`hydrochloride)
`Anaprox (naproxen sodium)
`Naprelan (naproxen sodium)
`Naprosyn (naproxen sodium)
`Naprosyn (naproxen sodium)
`Naproxen Sodium
`NaprPac 250 mg, 375 mg and 500 mg (lansoprazole and
`naproxen)
`Treximet (naproxen sodium and sumatriptan succinate)
`
`Page 3
`
`NDA# 022101
`
`NDA# 020204
`NDA# 021076
`
`NDA# 018164
`NDA# 020353
`NDA# 017581
`NDA# 018965
`NDA# 021920
`NDA# 021507
`
`NDA# 021926
`
`
`
`
`
`

`

`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`
`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
`
`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 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:
`
`
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`Page 4
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`

`

`
`
`(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?
`
`
`(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
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 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?
`
`
`
`
`
`
`
` If yes, explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`Page 5
`
`

`

`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:
`
`
`
`(c)
`
`
`Investigation
`#1
`
`PN400-
`105
`
`Investigation
`#2
`
`PN400-
`114
`
`Investigation
`#3
`
`PN400-
`301
`
`Investigation
`#4
`
`PN400-
`302
`
`Investigation
`#5
`
`PN400-
`307
`
`Investigation
`#6
`
`PN400-
`309
`
`An Open-label, Randomized, Two-Way Crossover Study to
`Evaluate the Relative Bioavailability of Naproxen Following a
`Single Oral Dose of PN 400 (375 mg Naproxen/20 mg
`Esomeprazole) Versus EC-NAPROSYN® 375 mg in Healthy
`Subjects
`A Randomized, Open-Label, 4-Way Crossover Study to Evaluate
`Naproxen and Esomeprazole Plasma Levels in Healthy Subjects
`Following Oral Administration of PN 400, Enteric-Coated Naproxen
`500 MG Plus Enteric-Coated Esomeprazole 20 MG, Enteric-Coated
`Naproxen 500 MG Alone, and Enteric-Coated Esomeprazole 20
`MG Alone
`A 6-month, Phase 3, Randomized, Double-Blind, Parallel-Group,
`Controlled, Multi-Center Study to Evaluate the Incidence of Gastric
`Ulcers Following Administration of Either PN 400 or Naproxen in
`Subjects who are at Risk for Developing NSAID-Associated Ulcers
`
`A 6-month, Phase 3, Randomized, Double-Blind, Parallel-Group,
`Controlled, Multi-Center Study to Evaluate the Incidence of Gastric
`Ulcers Following Administration of Either PN 400 or Naproxen in
`Subjects who are at Risk for Developing NSAID-Associated Ulcers
`
`Randomized, Double-Blind, Parallel Group, Placebo-Controlled,
`Multi-Center Study , Evaluating the Efficacy of PN 400 BID AND
`Celecoxib 200 MG QD in Patients with Osteoarthritis of the Knee
`
`Randomized, Double-Blind, Parallel-Group, Placebo-Controlled,
`Multi-Center Study , Evaluating the Efficacy of PN 400 BID AND
`Celecoxib 200 MG QD in Patients with Osteoarthritis of the Knee
`
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`
`
`
`
`
`Page 6
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`

`

`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
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`
`
`
`
`
`
`
`
`
`
`
`
`NO
`
`NO
`
`NO
`
`NO
`
`NO
`
`NO
`
`
`
`
`
`
`
`
`
`
`
`
`
`Investigation #2
`
`Investigation #3
`
`Investigation #4
`
`Investigation #5
`
`Investigation #6
`
`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
`
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`Investigation #2
`
`Investigation #3
`
`Investigation #4
`
`Investigation #5
`
`Investigation #6
`
`
`
`
`
`
`
`
`
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`
`
`
`
`
`
`
`
`
`
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`
`
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`
`
`
`
`
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`
`
`
`
`
`
`
`
`
`
`NO
`
`NO
`
`NO
`
`NO
`
`NO
`
`
`
`
`
`
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`Page 7
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`

`
`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"):
`Investigation
`PN400-
`#1
`105
`
`An Open-label, Randomized, Two-Way Crossover Study to
`Evaluate the Relative Bioavailability of Naproxen Following a
`Single Oral Dose of PN 400 (375 mg Naproxen/20 mg
`Esomeprazole) Versus EC-NAPROSYN® 375 mg in Healthy
`Subjects
`A Randomized, Open-Label, 4-Way Crossover Study to Evaluate
`Naproxen and Esomeprazole Plasma Levels in Healthy Subjects
`Following Oral Administration of PN 400, Enteric-Coated Naproxen
`500 MG Plus Enteric-Coated Esomeprazole 20 MG, Enteric-Coated
`Naproxen 500 MG Alone, and Enteric-Coated Esomeprazole 20
`MG Alone
`A 6-month, Phase 3, Randomized, Double-Blind, Parallel-Group,
`Controlled, Multi-Center Study to Evaluate the Incidence of Gastric
`Ulcers Following Administration of Either PN 400 or Naproxen in
`Subjects who are at Risk for Developing NSAID-Associated Ulcers
`
`A 6-month, Phase 3, Randomized, Double-Blind, Parallel-Group,
`Controlled, Multi-Center Study to Evaluate the Incidence of Gastric
`Ulcers Following Administration of Either PN 400 or Naproxen in
`Subjects who are at Risk for Developing NSAID-Associated Ulcers
`
`Randomized, Double-Blind, Parallel Group, Placebo-Controlled,
`Multi-Center Study , Evaluating the Efficacy of PN 400 BID AND
`Celecoxib 200 MG QD in Patients with Osteoarthritis of the Knee
`
`Randomized, Double-Blind, Parallel-Group, Placebo-Controlled,
`Multi-Center Study , Evaluating the Efficacy of PN 400 BID AND
`Celecoxib 200 MG QD in Patients with Osteoarthritis of the Knee
`
`Page 8
`
`Investigation
`#2
`
`PN400-
`114
`
`Investigation
`#3
`
`PN400-
`301
`
`Investigation
`#4
`
`PN400-
`302
`
`Investigation
`#5
`
`PN400-
`307
`
`Investigation
`#6
`
`PN400-
`309
`
`
`
`
`
`
`

`

`
`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:
`
`
`Investigation #1
`
`
`
`IND # 076301
`
`
`
`
`
`
`
`
`
`YES
`
`
`
`
`
`
`
`
`
`Investigation #2
`
`
`
`IND # 076301
`
`
`
`
`
`
`
`
`
`
` Investigation #3
`
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`!
`!
`! NO
`
`
`
`Page 9
`
`
`
`
`
`
`
`YES
`
`
`
`
`
`
`
`
`IND # 076301
`
`
`
`
`
`
`
`Investigation #4
`
`IND # 076301
`
`
`
`
`
`
`
`
`Investigation #5
`
`IND # 076301
`
`
`
`
`
`
`
`
`Investigation #6
`
`YES
`
`
`
`
`YES
`
`
`
`
`YES
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IND # 076301
`
`YES
`
`
`
`
`
`
`
`
`

`

`
`
`
`
`
`
`(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:
`
`
`
`! Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Investigation #1
`
`
`
`
`YES
`
`Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Investigation #2
`
`
`YES
`Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`!
`!
`
`! NO
`! 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:
`
`
`
`
`
`
`Page 10
`
`

`

`=================================================================
`
`Name of person completing form: Anna M. Simon
`Title: Regulatory Project Manager
`Date: 04/30/2010
`
`
`Name of Office/Division Director signing form: Donna Griebel, M.D.
`Title: Director
`
`
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05
`
`
`
`
`
`Page 11
`
`

`

`Application
`Type/Number
`--------------------
`NDA-22511
`
`Submission
`Type/Number
`--------------------
`ORIG-1
`
`Submitter Name
`
`Product Name
`
`--------------------
`POZEN INC
`
`------------------------------------------
`PN 400
`NAPROXEN/ESOMEPRAZOLE
`MAGNESIUM
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`Anna M SIMON
`04/30/2010
`
`DONNA J GRIEBEL
`04/30/2010
`
`

`

`
`
`
`505(b)(2) ASSESSMENT
`
`Application Information
`NDA # 022511
`NDA Supplement #: S-
`Efficacy Supplement Type SE-
`
`
`Proprietary Name: Vimovo
`Established/Proper Name: naproxen and esomeprazole magnesium
`Dosage Form: Delayed Release Tablets
`Strengths: 375 mg naproxen/20 mg esomeprazole and 500 mg naproxen /20 mg
`esomeprazole
`Applicant: Pozen
`
`Date of Receipt: June 30, 2009
`
`PDUFA Goal Date: April 30, 2010
`
`Action Goal Date (if different):
`
`Proposed Indication(s): Treatment of the signs and symptoms of osteoarthritis, rheumatoid
`arthritis and ankylosing spondylitis in patients at risk for developing NSAID-associated
`gastric ulcers.
`
`
`
`GENERAL INFORMATION
`
`
`
`
`
`1) Is this application for a recombinant or biologically-derived product and/or protein or
`peptide product OR is the applicant relying on a recombinant or biologically-derived
`product and/or protein or peptide product to support approval of the proposed product?
` YES
`
` NO
`
` If “YES “contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`
`
`Version March 2009
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`
`
`page 1
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`

`

`INFORMATION PROVIDED VIA RELIANCE
`(LISTED DRUG OR LITERATURE)
`
`2) List the information essential to the approval of the proposed drug that is provided by
`reliance on our previous finding of safety and efficacy for a listed drug or by reliance on
`published literature. (If not clearly identified by the applicant, this information can usually
`be derived from annotated labeling.)
`
`
`Information provided (e.g.,
`Source of information* (e.g.,
`pharmacokinetic data, or specific
`published literature, name of
`sections of labeling)
`referenced product)
`EC-Naprosyn (NDA 020067, Roche) Pozen referenced the Agency’s
`previous findings for safety and
`efficacy for EC-Naprosyn.
`
`
`
`
`
`
`
`
` *each source of information should be listed on separate rows
`
`3) Reliance on information regarding another product (whether a previously approved product
`or from published literature) must be scientifically appropriate. An applicant needs to
`provide a scientific “bridge” to demonstrate the relationship of the referenced and proposed
`products. Describe how the applicant bridged the proposed product to the referenced
`product(s). (Example: BA/BE studies)
`
`
`
`The scientific bridge to demonstrate the relationship of the reference listed drug to the new
`drug consisted of pharmacokinetic studies that compared the profiles of the naproxen in
`Vimovo to the currently marketed Naprosyn.
`
`RELIANCE ON PUBLISHED LITERATURE
`
`
`
`
`
`
`
`
`
`
`
`
`4) (a) Regardless of whether the applicant has explicitly stated a reliance on published
`literature to support their application, is reliance on published literature necessary to
`support the approval of the proposed drug product (i.e., the application cannot be approved
`without the published literature)?
` NO
`
` YES
`If “NO,” proceed to question #5.
`
`
`
`(b) Does any of the published literature necessary to support approval identify a specific (e.g.,
`brand name) listed drug product?
` NO
`
` YES
`If “NO”, proceed to question #5.
`If “YES”, list the listed drug(s) identified by name and answer question #4(c).
`
`
`
`(c) Are the drug product(s) listed in (b) identified by the applicant as the listed drug(s)?
`
` NO
` YES
`
`Version March 2009
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`page 2
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`

`

`RELIANCE ON LISTED DRUG(S)
`
`
`
`
`
`Reliance on published literature which identifies a specific approved (listed) drug constitutes
`reliance on that listed drug. Please answer questions #5-9 accordingly.
`
`
`
`
`5) Regardless of whether the applicant has explicitly referenced the listed drug(s), does the
`application rely on the finding of safety and effectiveness for one or more listed drugs
`(approved drugs) to support the approval of the proposed drug product (i.e., the application
`cannot be approved without this reliance)?
`
` NO
` YES
`If “NO,” proceed to question #10.
`
`
`
`6) Name of listed drug(s) relied upon, and the NDA/ANDA #(s). Please indicate if the
`applicant explicitly identified the product as being relied upon (see note below):
`
`
`
`EC Naprosyn
`
`Name of Drug
`
`NDA/ANDA #
`
`NDA 020067
`
`
`
`Did applicant
`specify reliance on
`the product? (Y/N)
`Y (Form 356h)
`
`
`
`
`
`
`
`
`
`Applicants should specify reliance on the 356h, in the cover letter, and/or with their patent
`certification/statement. If you believe there is reliance on a listed product that has not been
`explicitly identified as such by the applicant, please contact the (b)(2) review staff in the
`Immediate Office, Office of New Drugs.
`
`7) If this is a (b)(2) supplement to an original (b)(2) application, does the supplement rely
`upon the same listed drug(s) as the original (b)(2) application?
` NO
`
` YES
` N/A
`If this application is a (b)(2) supplement to an original (b)(1) application or not a supplemental
`application, answer “N/A”.
`If “NO”, please contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`
`8) Were any of the listed drug(s) relied upon for this application:
`a) Approved in a 505(b)(2) application?
` NO
`
` YES
`If “YES”, please list which drug(s).
`Name of drug(s) approved in a 505(b)(2) application:
`
`
`b) Approved by the DESI process?
` NO
`
` YES
`If “YES”, please list which drug(s).
`Name of drug(s) approved via the DESI process:
`
`
`Version March 2009
`
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`

`

`c) Described in a monograph?
` YES
` NO
`
`If “YES”, please list which drug(s).
`
`
`Name of drug(s) described in a monograph:
`
`
`
`d) Discontinued from marketing?
` NO
`
` YES
`If “YES”, please list which drug(s) and answer question d) i. below.
`If “NO”, proceed to question #9.
`Name of drug(s) discontinued from marketing:
`
`i) Were the products discontinued for reasons related to safety or effectiveness?
`
` NO
` YES
`(Information regarding whether a drug has been discontinued from marketing for
`reasons of safety or effectiveness may be available in the Orange Book. Refer to
`section 1.11 for an explanation, and section 6.1 for the list of discontinued drugs. If
`a determination of the reason for discontinuation has not been published in the
`Federal Register (and noted in the Orange Book), you will need to research the
`archive file and/or consult with the review team. Do not rely solely on any
`statements made by the sponsor.)
`
`9) Describe the change from the listed drug(s) relied upon to support this (b)(2) application
`(for example, “This application provides for a new indication, otitis media” or “This
`application provides for a change in dosage form, from capsule to solution”).
`
`
`Application NDA 022511 provides for a combination product from the previously approved NDA
`020067 and NDA 021153.
`
`
`The purpose of the following two questions is to determine if there is an approved drug product
`that is equivalent or very similar to the product proposed for approval that should be referenced
`as a listed drug in the pending application.
`
`The assessment of pharmaceutical equivalence for a recombinant or biologically-derived product
`and/or protein or peptide product is complex. If you answered YES to question #1, proceed to
`question #12; if you answered NO to question #1, proceed to question #10 below.
`
`
`10) (a) Is there a pharmaceutical equivalent(s) to the product proposed in the 505(b)(2)
`application that is already approved (via an NDA or ANDA)?
`
`
`
`
`
`
`
`
`(Pharmaceutical equivalents are drug products in identical dosage forms that: (1) contain
`identical amounts of the identical active drug ingredient, i.e., the same salt or ester of the
`same therapeutic moiety, or, in the case of modified release dosage forms that require a
`reservoir or overage or such forms as prefilled syringes where residual volume may vary,
`that deliver identical amounts of the active drug ingredient over the identical dosing period;
`(2) do not necessarily contain the same inactive ingredients; and (3) meet the identical
`compendial or other applicable standard of identity, strength, quality, and purity, including
`potency and, where applicable, content uniformity, disintegration times, and/or dissolution
`rates. (21 CFR 320.1(c)).
`
`
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`
`
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`page 4
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`

`

`Note that for proposed combinations of one or more previously approved drugs, a pharmaceutical
`equivalent must also be a combination of the same drugs.
`
` YES
`
`
`
`
` NO
`
` If “NO” to (a) proceed to question #11.
`If “YES” to (a), answer (b) and (c) then proceed to question #12.
`
`
` NO
`
`(b) Is the pharmaceutical equivalent approved for the same indication for which the
`505(b)(2) application is seeking approval?
` YES
`
`
`(c) Is the listed drug(s) referenced by the application a pharmaceutical equivalent?
` YES
` NO
`
`
`
`If “YES” to (c) and there are no additional pharmaceutical equivalents listed, proceed to
`question #12.
`If “NO” or if there are additional pharmaceutical equivalents that are not referenced by the
`application, list the NDA pharmaceutical equivalent(s); you do not have to individually list all
`of the products approved as ANDAs, but please note below if approved approved generics are
`listed in the Orange Book. Please also contact the (b)(2) review staff in the Immediate Office,
`Office of New Drugs.
`
`Pharmaceutical equivalent(s):
`
`
`11) (a) Is there a pharmaceutical alternative(s) already approved (via an NDA or ANDA)?
`
`(Pharmaceutical alternatives are drug products that contain the identical therapeutic moiety, or its
`precursor, but not necessarily in the same amount or dosage form or as the same salt or ester. Each
`such drug product individually meets either the identical or its own respective compendial or other
`applicable standard of identity, strength, quality, and purity, including potency and, where applicable,
`content uniformity, disintegration times and/or dissolution rates. (21 CFR 320.1(d)) Different dosage
`forms and strengths within a product line by a single manufacturer are thus pharmaceutical
`alternatives, as are extended-release products when compared with immediate- or standard-release
`formulations of the same active ingredient.)
`
`Note that for proposed combinations of one or more previously approved drugs, a pharmaceutical
`alternative must also be a combination of the same drugs.
`
` NO
`
` YES
`If “NO”, proceed to question #12.
`
`
`
`
`
` NO
`
`(b) Is the pharmaceutical alternative approved for the same indication for which the
`505(b)(2) application is seeking approval?
` YES
`
`(c) Is the approved pharmaceutical alternative(s) referenced as the listed drug(s)?
`
` NO
` YES
`
`If “YES” and there are no additional pharmaceutical alternatives listed, proceed to question
`#12.
`
`Version March 2009
`
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`page 5
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`

`

`If “NO” or if there are additional pharmaceutical alternatives that are not referenced by the
`application, list the NDA pharmaceutical alternative(s); you do not have to individually list all
`of the products approved as ANDAs, but please note below if approved generics are listed in
`the Orange Book. Please also contact the (b)(2) review staff in the Immediate Office, Office of
`New Drugs.
`
`
`Pharmaceutical alternative(s):
`
`
`PATENT CERTIFICATION/STATEMENTS
`
`
`12) List the patent numbers of all unexpired patents listed in the Orange Book for the listed
`drug(s) for which our finding of safety and effectiveness is relied upon to support approval
`of the (b)(2) product.
`
`Listed drug/Patent number(s):
`
` No patents listed
`
`
`13) Did the applicant address (with an appropriate certification or statement) all of the
`unexpired patents listed in the Orange Book for the listed drug(s) relied upon to support
`approval of the (b)(2) product?
`