CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
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`206439Orig1s000
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`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
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`EXCLUSIVITY SUMMARY
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`NDA # 206439
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`SUPPL #
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`HFD # 120
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`Trade Name Namzaric
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`Generic Name memantine HCl ER / donepezil
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`Applicant Name Forest Laboratories
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`Approval Date, If Known December 23, 2014
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`PART I
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`IS AN EXCLUSIVITY DETERMINATION NEEDED?
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`1. An exclusivity determination will be made for all original applications, and all efficacy
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`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer ”yes" to
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`one or more of the following questions about the submission.
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`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
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`YES X
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`NO [I
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`Ifyes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
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`505b2
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`0) Did it require the review of clinical data other than to support a safety claim or change1n
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`labeling related to safety? (If it required review only of bioavailability or bioequivalence
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`data, answer "r10. ")
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`YES [J
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`NOX
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`If your answer is "no" because you believe the study is a bioavailability study and, therefore,
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`not eligible for exclusivity, EXPLAIN why it is a bioavailability study, including your
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`reasons for disagreeing with any arguments made by the applicant that the study was not
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`simply a bioavailability study.
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`The sponsor provided two studies, a bioequivalence study, MD-PK-104, and a
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`bioavailability study, MDX—PK-IOS, for review. These studies are described by the sponsor
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`as a bioequivalence study and a bioavailability study, respectively.
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`If it is a supplement requiring the review of clinical data but it is not an effectiveness
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`supplement, describe the change or claim that is supported by the clinical data:
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`Reference ID: 3725556
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`Page 1
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`d) Did the applicant request exclusivity?
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`YES [:1
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`NO X
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`If the answer to (d) is ”yes,” how many years of exclusivity did the applicant request?
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`e) Has pediatric exclusivity been granted for this Active Moiety?
`YES X
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`NO [I
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`If the answer to the above question in YESI is this approval a result of the studies submitted in
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`response to the Pediatric Written Request?
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`1’10
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`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
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`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
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`2.
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`Is this drug product or indication a DESI upgrade?
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`YES D
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`NO X
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`IF THE ANSWER TO. QUESTION 2 IS "YES,” GO DIRECTLY TO THE SIGNATURE BLOCKS
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`ON PAGE 8 (even if a study was required for the upgrade).
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`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
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`(Answer either #1 or #2 as appropriate)
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`1. Single active ingredient product.
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`Has FDA previously approved under section 505 of the Act any drug product containing the same
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`active moiety as the drug under consideration? Answer "yes" if the active moiety (including other
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`esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this
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`particular form of the active moiety, e. g., this particular ester or salt (including salts with hydrogen or
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`coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate) has
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`not been approved. Answer "no" if the compound requires metabolic conversion (other than
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`deesterification of an esterified form of the drug) to produce an already approved active moiety.
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`YES [:1
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`NO x
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`Reference ID: 3725556
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`Page 2
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`If "yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
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`#(s).
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`NDA#
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`2. Combination product.
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`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
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`approved an application under section 505 containing M 93 of the active moieties in the drug
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`product? If, for example, the combination contains one never-before-approved active moiety and
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`one previously approved active moiety, answer "yes." (An active moiety that is marketed under an
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`OTC monograph, but that was never approved under an NDA,
`is considered not previously
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`approved.)
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`YES X
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`NO D
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`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
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`#(s).
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`NDA#
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`NDA#
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`Memantine hydrochloride ER
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`Aricept (donepezil)
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`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO THE
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`SIGNATURE BLOCKS ON PAGE 8.
`(Caution: The questions in part II of the summary should
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`only be answered “NO” for original approvals of new molecular entities.)
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`IF “YES,” GO TO PART III.
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`PART III
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`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
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`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
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`clinical investigations (other than bioavailability studies) essential to the approval of the application
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`and conducted or sponsored by the applicant." This section should be completed only if the answer
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`to PART II, Question 1 or 2 was "yes."
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`Reference ID: 3725556
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`Page 3
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`1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical
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`investigations" to mean investigations conducted on humans other than bioavailability studies.) If
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`the application contains clinical investigations only by virtue of a right of reference to clinical
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`investigations in another application, answer ”yes," then skip to question 3(a). If the answer to 3(a)
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`is "yes" for any investigation referred to in another application, do not complete remainder of
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`summary for that investigation.
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`YES
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`|:l
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`NO X
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`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
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`2. A clinical investigation is "essential to the approval” if the Agency could not have approved the
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`application or supplement without relying on that investigation. Thus, the investigation is not
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`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
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`application in light of previously approved applications (i.e., information other than clinical trials,
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`such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or
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`505(b)(2) application because of what is already known about a previously approved product), or 2)
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`there are published reports of studies (other than those conducted or sponsored by the applicant) or
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`other publicly available data that independently would have been sufficient to support approval of
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`the application, without reference to the clinical investigation submitted in the application.
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`(a) In light of previously approved applications, is a clinical investigation (either conducted
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`by the applicant or available from some other source, including the published literature)
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`necessary to support approval of the application or supplement?
`YES D
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`NO D
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`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
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`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
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`(b) Did the applicant submit a list of published studies relevant to the safety and effectiveness
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`of this drug product and a statement that the publicly available data would not independently
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`support approval of the application?
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`YES D NO D
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`(1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree
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`with the applicant's conclusion? If not applicable, answer NO.
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`YES I]
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`NO D
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`If yes, explain:
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`Reference ID: 3725556
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`Page 4
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`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted or
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`sponsored by the applicant or other publicly available data that could independently
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`demonstrate the safety and effectiveness of this drug product?
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`YES E]
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`NO D
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`If yes, explain:
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`(c)
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`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical investigations
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`submitted in the application that are essential to the approval:
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`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
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`studies for the purpose of this section.
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`3. In addition to being essential, investigations must be "new" to support exclusivity. The agency
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`interprets "new clinical investigation" to mean an investigation that 1) has not been relied on by the
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`agency to demonstrate the effectiveness of a previously approved drug for any indication and 2) does
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`not duplicate the results of another investigation that was relied on by the agency to demonstrate the
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`effectiveness of a previously approved drug product, i.e., does not redemonstrate something the
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`agency considers to have been demonstrated in an already approved application.
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`a) For each investigation identified as "essential to the approval," has the investigation been
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`relied on by the agency to demonstrate the effectiveness of a previously approved drug
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`product? (If the investigation was relied on only to support the safety of a previously
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`approved drug, answer "no.")
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`Investigation #1
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`Investigation #2
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`YES E]
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`NO [1
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`If you have answered "yes" for one or more investigations, identify each such investigation
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`and the NDA in which each was relied upon:
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`b) For each investigation identified as "essential to the approval", does the investigation
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`duplicate the results of another investigation that was relied on by the agency to support the
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`effectiveness of a previously approved drug product?
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`Reference ID: 3725556
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`Page 5
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`Investigation #1
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`Investigation #2
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`YES [3
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`NO [3
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`YES D
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`NO [I
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`If you have answered "yes" for one or more investigation, identify the NDA in which a
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`similar investigation was relied on:
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`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
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`or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any
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`that are not "new"):
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`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
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`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by"
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`the applicant if, before or during the conduct of the investigation, 1) the applicant was the sponsor of
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`the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor
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`in interest) provided substantial support for the study. Ordinarily, substantial support will mean
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`providing 50 percent or more of the cost of the study.
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`a) For each investigation identified in response to question 3(0): if the investigation was
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`carried out under an IND, was the applicant identified on the FDA 15 71 as the sponsor?
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`Investigation #1
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`YES I:
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`Explain:
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`(b) For each investigation not carried out under an IND or for which the applicant was not
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`identified as the sponsor, did the applicant certify that it or the applicant's predecessor in
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`interest provided substantial support for the study?
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`YESEI
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`Explain:
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`Investigation #2
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`(c) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that
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`the applicant should not be credited with having "conducted or sponsored" the study?
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`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to the
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`sponsored or conducted the studies sponsored or conducted by its predecessor in interest.)
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`If yes, explain:
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`Name of person completing form: Teresa Wheelous, R. Ph.
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`Title: Sr. Regulatory Project Manager
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`Date: April 3, 2015
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`Name of Office/Division Director signing form: Billy Dunn, MD
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`Title: Director, Division of Neurology Products
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`Reference ID: 3725556
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`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
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`Reference ID: 3725556
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`electronically and this page is the manifestation of the electronic
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`TERESA A WHEELOUS
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`04/03/2015
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`WILLIAM H Dunn
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`04/03/2015
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`ACTION PACKAGE CHECKLIST
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`APPLICATION INFORMATION1
` NDA-#7 20643.9
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`Proprietary Name: Namzaric
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`Applicant: Forest LabOratories
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`Established/Proper Name: memantine HCl ER / donepezil
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`Agent for Applicant (if applicable): Kathleen Waldron
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`Division: [Neurology Products .
`RPM: Teresa Wheelous, R Ph
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` NDA Application Type: ElfT505(b)(1) X 505(b)(2)
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`0 <1 Review the information in the>505(b)(2) Assessment and submit ‘-
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`o ' Check Orange Book for newly listed patents and/or
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`E] No changes
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`Date of check: 10/28/14
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`Note: Ifpediatric exclusivity has been granted or the pediatric
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`information in the labeling ofthe listed drug changed, determine whether
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`pediatric information needs to be added to or deletedfrom the labeling of
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`Ifaccelerated approvalorapproval based on efficacy studies1n animals, were promotional
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`Note: Promotional materials to be used within 120 days after approval must have been
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`submitted (for exceptions, see
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`ht_tp://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatorylnformation/Guida
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` Appl1cat1on Charactenstics
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`I The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 2) lists
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`the documents to be included in the Action Package.
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`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)
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`Assessment to CDER 0ND IO unless the Assessment has been substantively revised (e.g., new listed drug, patent certification
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`\nswer all questions in all sections in relation to the pending application, i.e., if the pending application is an NDA or BLA
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`ipplement, then the questions should be answered in relation to that supplement, not in relation to the original NDA or BLA. For
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`example, if the application is a pending BLA supplementfihen a new RMS—BLA Product Information-Sheetfor TBP must be
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`Version: 6/23/2014
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`NDA/BL-A #
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`[:1Priority
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`[:11Accelerated approval (21 CFR 314.510)
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`E] ZlRestricted distribution (21 CFR 314.520)
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`E] “Approval based on animal studies
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`Submitted1n response to a PMR
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`Submitted1n response to a Pediatric Written Request
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`[:1Approval based on animal studies
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`REMS:
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`I Communication Plan
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`[:11 REMS not required
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`.: Publ1c communicatlons (approvals only)
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`Is approval of this application blocked by any type of exclusivity (orphan, 5-year
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`Verify thatform FDA—3542a was submitted for patents that claim the drug for
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`CONTENTS OF ACTION PACKACE
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`'3‘ ListOfofficers/employees who participated1n the decision to approve this application and E/Included
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`[:3 Included
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`Version: 8/27/2014
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`fAéii’o‘fiéé) Aid (1516(5) "'ApfiiAV'aii .._.
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`or Most-recent draft labeling (if it is division-proposed labeling, it shouldbe in
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`track-changesformat) 12/18/14
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`H All NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`Cleared —1 1/13/14
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`[2],: Not a (b)(2)
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`J Application Integrity Policy (AIP) Status and Related Documents
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`4 Filing-reviews :forvscientific disciplines are NOT required to be included in the action package.
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`Version: 8/27/2014“
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`NDA/BL-‘A #
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`This application is on the AIP
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`If yes, Center Director’s Exception for Review memo (indicate date)
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`If yes 00- clearance for approval (indicate date ofclearance
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`K Pediatrics (approvals only)
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`0 Date reviewed by PeRC 12/03/2013,,
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`L Outgoing communications: letters, emails, andvfaxes considered important to include in the
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`Briefin; minutes,Medical Polio Council meetin; minutes)
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`Clinical Team Leader Review(s) — N/A
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`D No separate review 12/ 19/ 14
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`12/ 19/ 14 _
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`Q Financial Disclosure reviews(s) or location/date if addressedIn another review
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`cashrerjzw). . J N/A
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`investigators)
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`1:]No separate review
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`... Statlstlcal Rev16w(s) ”(indicate datéfor eaCh rewew) 1...0..."2....714
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`E] None requested
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`Version: 8/27/2014 -
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`[3No separate review
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`date for each review)
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`v Microbiology Reviews
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`_. (indicate. date ofeach Ieview)
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`"mall effcacy supplements that could increase the patientpopulatzon)
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`D Review & FONSI (indicate date of review)
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`Product Quality
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`1:] Review & Environmental Impact Statement (indicate date ofeach review)
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`only; do NQI include EER Detailed Report; date completed must be within 2
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`years of action date) (only original NDAs and supplements that include a new
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`Date completed:
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`E];2 BLAs: TB—EER (date of most recent TB—EER must be within 30 days of action
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`5 i.e., a new facility or‘a change in the facility, or a change in the manufacturingprocess in a way that impacts the Quality
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`NDA/BL‘A #
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`Page -7
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`v, For all 505(b)(2) applications:
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`0 Check Orange Book for newly listedpatents and/or exclusivity (including
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`Day of Approval Activities
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`6' Send approval email within one business day to CDER-APPROVALS
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`o '» Finalize -505(b)(2) assessment
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`'2'
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`‘3' Send a courtesy copy of approval let