CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
`202270Orig1s000
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`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
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`EXCLUSIVITY SUMMARY
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`NDA # 202270
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`SUPPL # N/A
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`HFD # 510
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`Trade Name Janumet XR
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`Generic Name Sitagliptin/Metformin Hydrochloride Extended-Release Fixed Dose Combination
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`Applicant Name Merck Sharp and Dohme Corp.
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`Approval Date, If Known
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`PART I
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`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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`IS AN EXCLUSIVITY DETERMINATION NEEDED?
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`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
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` YES
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`NO
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`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
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`505(b)(1)
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`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.")
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` YES
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`NO
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`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.
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`The pivotal study to support this NDA was a clinical pharmacology study, P147, to
`establish bioequivalence between the to-be-marketed formulation of Janumet XR to the co-
`administration of sitagliptin and an approved metformin XR product (Glumetza). This study
`also compared the administration of two 50/500 mg Janumet XR tablets to the administration
`of one 100/1000 mg Janumet XR tablet.
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`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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`Not a supplement. This is an NDA for a new fixed-dose combination of sitaglitin and
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`Reference ID: 3080564
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`Page 1
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`metformin extended-release (Glumetza).
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`d) Did the applicant request exclusivity?
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`N/A
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`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
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` YES
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`NO
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`e) Has pediatric exclusivity been granted for this Active Moiety?
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` YES
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`NO
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`N/A
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` 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?
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`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
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`2. Is this drug product or indication a DESI upgrade?
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` YES
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`NO
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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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` YES
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`NO
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`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).
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`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(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
`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.
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`Reference ID: 3080564
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`Page 2
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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
`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.)
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`YES
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`NO
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`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`(metformin
`NDA# Glumetza
`hydrochloride extended
`release) Tablets
`NDA# Janumet (sitagliptin and
`metformin) Tablets
`NDA# Januvia
`(sitagliptin)
`Tablets
`NDA# Glucophage (metformin
`hydrochloride) Tablets
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`#(s).
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`NDA# N/A
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`NDA#
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`NDA#
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`021748
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`022044
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`021995
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`020357
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`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.
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`PART III
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`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."
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`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
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`Reference ID: 3080564
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`Page 3
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`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.
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`YES
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`NO
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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
`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.
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`(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?
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` YES
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`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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`NO
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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?
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` YES
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`NO
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`(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.
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` If yes, explain:
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` YES
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`NO
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`Reference ID: 3080564
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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
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
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` YES
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`NO
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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 submitted in the application that are essential to the approval:
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`Investigation #1: Study P036, "A Multicenter, Double-Blind, Randomized,
`Placebo- and Active-Controlled Factorial Study of MK-0431 and Metformin
`Coadministration in Patients With Type 2 Diabetes Mellitus Who Have Inadequate
`Glycemic Control"
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`Investigation #2: Study P020, "A Multicenter, Randomized, Double-Blind
`Study to Evaluate the Safety and Efficacy of the Addition of MK-0431 to Patients
`With Type 2 Diabetes Mellitus Who have Inadequate Glycemic Control on
`Metformin Therapy"
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`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`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
`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.
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`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.")
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`Investigation #1
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`Investigation #2
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`YES
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`YES
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`NO
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`NO
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`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA in which each was relied upon:
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`Reference ID: 3080564
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`Page 5
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`Investigation #1 was relied upon to support approval of NDA 022044 (Janumet).
`Investigation #2 was relied upon to support approval of NDA 021995 (Januvia) and NDA
`022044 (Janumet).
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`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?
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`YES
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`YES
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`NO
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`NO
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`Investigation #1
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`Investigation #2
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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:
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`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"):
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`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.
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`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?
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`!
`!
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`! NO
`! Explain:
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`Investigation #1
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`IND #
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`YES
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`Reference ID: 3080564
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`Page 6
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`Investigation #2
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`YES
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`! NO
`! Explain:
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`IND #
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`(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?
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`Investigation #1
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`YES
`Explain:
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`Investigation #2
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`YES
`Explain:
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`!
`!
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`! NO
`! Explain:
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`!
`!
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`! NO
`! Explain:
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`(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.)
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`YES
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`NO
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`If yes, explain:
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`=================================================================
`
`Name of person completing form: Raymond Chiang
`
`
`
`Reference ID: 3080564
`
`Page 7
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`

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`Title: Regulatory Project Manager
`Date: 1.30.12
`
`
`Name of Office/Division Director signing form: Dr. Hylton Joffe signing off on behalf of Dr. Mary
`Parks
`Title: Cross-Discipline Team Leader
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`
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`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05
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`Reference ID: 3080564
`
`Page 8
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`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`02/01/2012
`
`HYLTON V JOFFE
`02/01/2012
`
`Reference ID: 3080564
`
`

`

`WW
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`Debmment Certification
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`As required by §306(k)(1) of 21 U.S.C. 335a(k)(l), we hereby certify that, in connection
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`with this application, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
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`(Merck), did not and will not use in any capacity the services of any person deban'ed
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`under subsections 306(a) or (b) of the Act.
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`Eéwv
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`
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`Richard J. Swanson, PhD.
`Director
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`Worldwide Regulatory Affairs
`
`(453T (0
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`Date
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`.‘1
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`WOW—mm
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`16-Sep-2010
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`Reference ID: 3083898
`Reference ID: 3083898
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`

`

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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
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`
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`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`INFORMATION REQUEST
`
`
`
`NDA 202270
`
`CERTIFIED MAIL
`RETURN RECEIPT REQUESTED
`
`Merck Sharp & Dohme Corp.
`Attention: Richard J. Swanson, Ph.D.
`Senior Director, Regulatory Affairs
`P.O. Box 1000, UG2C-50
`North Wales, PA 19454-1099
`
`
`Dear Dr. Swanson:
`
`Please refer to your New Drug Application (NDA) submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act for JANUMET XR (sitagliptin and extended-release metformin
`hydrochloride fixed-dose combination) Tablets, 100mg/1000mg, 50mg/500mg, and
`50mg/1000mg.
`
`FDA investigators have identified significant violations to the bioavailability and bioequivalence
`requirements of Title 21, Code of Federal Regulation, Part 320 in bioanalytical studies conducted
`by Cetero Research in Houston, Texas (Cetero).1 The pervasiveness and egregious nature of the
`violative practices by Cetero has led FDA to have significant concerns that the bioanalytical data
`generated at Cetero from April 1, 2005 to June 15, 2010, as part of studies submitted to FDA in
`New Drug Applications (NDA) and Supplemental New Drug Applications (sNDA) are
`unreliable. FDA has reached this conclusion for three reasons: (1) the widespread falsification of
`dates and times in laboratory records for subject sample extractions, (2) the apparent
`manipulation of equilibration or “prep” run samples to meet pre-determined acceptance criteria,
`and (3) lack of documentation regarding equilibration or “prep” runs that prevented Cetero and
`the Agency from determining the extent and impact of these violations.
`
`Serious questions remain about the validity of any data generated in studies by Cetero Research
`in Houston, Texas during this time period. In view of these findings, FDA is informing holders
`of approved and pending NDAs of these issues.
`
`The impact of the data from these studies (which may include bioequivalence, bioavailability,
`drug-drug interaction, specific population, and others) cannot be assessed without knowing the
`details regarding the study and how the data in question were considered in the overall
`development and approval of your drug product. At this time, the Office of New Drugs is
`
`
`1 These violations include studies conducted by Bioassay Laboratories and BA Research International specific to the
`Houston, Texas facility.
`
`Reference ID: 3010520
`
`

`

`NDA 202270
`Page 2
`
`
`searching available documentation to determine which NDAs are impacted by the above
`findings.
`
`To further expedite this process, we ask that you inform us if you have submitted any studies
`conducted by Cetero Research in Houston, Texas during the time period of concern (April 1,
`2005 to June 15, 2010). Please submit information on each of the studies, including supplement
`number (if appropriate), study name/protocol number, and date of submission. With respect to
`those studies, you will need to do one of the following: (a) re-assay samples if available and
`supported by stability data, (b) repeat the studies, or (c) provide a rationale if you feel that no
`further action is warranted.
`
`Please respond to this query within 30 days from the date of this letter.
`
`This information should be submitted as correspondence to your NDA. In addition, please
`provide a desk copy to:
`
`
`Office of New Drugs
`Center for Drug Evaluation and Research
`10903 New Hampshire Avenue
`Bldg. 22, Room 6300
`Silver Spring, MD 20993-0002
`
`
`
`If you have any questions, call Raymond Chiang, Regulatory Project Manager, at (301) 796-
`1940.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Mary H. Parks, M.D.
`Director
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`Reference ID: 3010520
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`JULIE C MARCHICK
`09/06/2011
`J. Marchick signing for M. Parks
`
`Reference ID: 3010520
`
`

`

`
`Merck Sharp & Dohme Corp.
`Attention: Richard J. Swanson, Ph.D.
`Senior Director, Regulatory Affairs
`P.O. Box 1000, UG2C-50
`North Wales, PA 19454-1099
`
`Dear Dr. Swanson:
`
`We acknowledge receipt on August 3, 2011, of your August 3, 2011, resubmission of your new
`drug application submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for
`JANUMET XR (sitagliptin and extended-release metformin hydrochloride fixed-dose
`combination) Tablets, 100mg/1000mg, 50mg/500mg, and 50mg/1000mg.
`
`We consider this a complete, class 2 response to our July 22, 2011 action letter. Therefore, the
`user fee goal date is February 3, 2012.
`
`If you have any questions, call me, Regulatory Project Manager, at (301) 796-1940.
`
`
`
`ACKNOWLEDGE –
` CLASS 2 RESPONSE
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Raymond Chiang, M.S.
`Regulatory Project Manager
`Division of Metabolism and Endocrinology
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
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`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`
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`
`
`NDA 202270
`
`
`
`Reference ID: 3000646
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`08/15/2011
`
`Reference ID: 3000646
`
`

`

`From:
`To:
`Subject:
`Date:
`
`Chiang, Raymond
`"Swanson, Richard John";
`RE: XR quesiotns - follow up
`Friday, July 29, 2011 9:51:24 AM
`
`Hello Dr. Swanson,
`Please see response to your questions below.
`thanks,
`ray
`
`
`
`
`From: Swanson, Richard John [mailto:richard_swanson@merck.com]
`Sent: Thursday, July 28, 2011 9:05 AM
`To: Chiang, Raymond
`Subject: XR quesiotns - follow up
`
`Hi Ray
`we plan to submit the response to the CRL early next week but still need responses to a couple of the questions we
`had sent you
`
`1. all of the data we have on XR was submitted with the NDA - there have been no additional preclinical or clinical
`studies completed or ongoing. Please confirm that, since there are no additional data with XR, an updated safety
`analysis is not required and in response to the request for the safety analyses, etc, we can simply state that there is no
`additional data
`
`If there are no additional preclinical or clinical data to submit, an updated safety analysis is not required. However, you
`should explicitly state in your Complete Response submission that there are no additional data.
`
`2. Do you want us to submit the responses to the the Arecibo 483 (and the response to the question about the Near IR
`QBD method, which had not been part of the 483) as part of this response to you or should they go only to FDA
`inspector in Puerto Rico ( or should we send to both) ?
`
`Please officially submit your response to FDA and the FDA district office in Puerto Rico.
`
`If possible, we 'd like answers to these this week so we can put the package together to submit early next
`thanks
`rick
`
`
`From: Chiang, Raymond [mailto:Raymond.Chiang@fda.hhs.gov]
`Sent: Monday, July 25, 2011 1:44 PM
`To: Swanson, Richard John
`Subject: RE: Free to talk at 1 or 1:30 for a few minutes re XR?
`
`Dr. Swanson,
`Please submit the P147 CSR with your response to our our Complete Response (CR) letter.
`Please submit everything at once in response to the Complete Response (CR) letter.
`When you submit your labeling with the CR response, please clearly indicate what changes were made from the July 18,
`2011 submission (i.e. revised URL and revision of Figure 1). As always, please submit a tracked-changes version of
`the label (with changes noted from your July 18, 2011 submission).
`
`As per an earlier email, we were not be able to review your July 21, 2011 labeling submission because your July 18, 2011
`submission (also containing a revised package insert/Medguide) was used to make our revisions. If you wish to
`incorporate these changes to the package insert, you may request to do so in the next review cycle. Regarding updating the
`PI/MedGuide and cartons with the new URL. This will need to be reviewed by OSE and DDMAC, and also addressed in
`the next review cycle.
`
`thanks,
`ray
`
`
`Reference ID: 2981071
`
`

`

`
`
`
`From: Swanson, Richard John [mailto:richard_swanson@merck.com]
`Sent: Monday, July 25, 2011 1:34 PM
`To: Chiang, Raymond
`Subject: RE: Free to talk at 1 or 1:30 for a few minutes re XR?
`
`OK, thanks Ray.
`
`We will have the P147 CSR amended completely by Friday and will send that to you by then (you already have the new
`tables and figures). I think the rate limiting step may be the 483 issues at the Arecibo manufacturing site - the site and
`the FDA officer have been discussing these things since April or May , we hope to resolve them this week but I don't
`know how realistic that is.
`
`
`As you work on these questions - can you also let know if you want us to submit new labeling and carton artwork with
`the revised URL or does that not matter . All we propose to do is substitute the revised URL for the old one. nothing
`else will change
`
`In addition, as before, If there's any way you can let us know when the labeling and cartons are approved, it would be
`appreciated so we can start printing in anticipation of the approval
`
`thanks
`rick
`
`
`From: Chiang, Raymond [mailto:Raymond.Chiang@fda.hhs.gov]
`Sent: Monday, July 25, 2011 1:27 PM
`To: Swanson, Richard John
`Subject: RE: Free to talk at 1 or 1:30 for a few minutes re XR?
`
`Hello Dr. Swanson,
`No need to call.
`I will get back to you regarding your questions.
`When you plan to respond to the CR?
`
`thanks,
`ray
`
`
`
`
`From: Swanson, Richard John [mailto:richard_swanson@merck.com]
`Sent: Monday, July 25, 2011 11:44 AM
`To: Chiang, Raymond
`Subject: Re: Free to talk at 1 or 1:30 for a few minutes re XR?
`
`Thanks
`Wanted to askabout the label we sumitted lasy week with the better figure as well as the proposal to use the
`new URL in labeling and packaging
`
`Also had couple of minor questions about how we should respond to the CRL
`
`eg- can we submit responses as we finish themor do they have to go all at once, we'd like to confirmthat no
`additional safety analysis is required since there have ben no addtional stuidesof XR since the NDA-allthe data
`we have was included in that, and who should we respond to about the NIR Questionsince that issue was not
`included in the 483 following the arecibo inspection
`
`Sent from my iPhone
`
`On Jul 25, 2011, at 11:33 AM, "Chiang, Raymond" <Raymond.Chiang@fda.hhs.gov> wrote:
`
`Reference ID: 2981071
`
`

`

`
`
`Dr. Swanson,
`Sure, give me a call.
`Can you tell me what you want to talk about.
`thanks,
`ray
`
`
`From: Swanson, Richard John [mailto:richard_swanson@merck.com]
`Sent: Monday, July 25, 2011 11:30 AM
`To: Chiang, Raymond
`Subject: Free to talk at 1 or 1:30 for a few minutes re XR?
`
`
`Notice: This e-mail message, together with any attachments, contains
`information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station,
`New Jersey, USA 08889), and/or its affiliates Direct contact information
`for affiliates is available at
`http://www.merck.com/contact/contacts.html) that may be confidential,
`proprietary copyrighted and/or legally privileged. It is intended solely
`for the use of the individual or entity named on this message. If you are
`not the intended recipient, and have received this message in error,
`please notify us immediately by reply e-mail and then delete it from
`your system.
`
`Notice: This e-mail message, together with any attachments, contains
`information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station,
`New Jersey, USA 08889), and/or its affiliates Direct contact information
`for affiliates is available at
`http://www.merck.com/contact/contacts.html) that may be confidential,
`proprietary copyrighted and/or legally privileged. It is intended solely
`for the use of the individual or entity named on this message. If you are
`not the intended recipient, and have received this message in error,
`please notify us immediately by reply e-mail and then delete it from
`your system.
`
`Notice: This e-mail message, together with any attachments, contains
`information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station,
`New Jersey, USA 08889), and/or its affiliates Direct contact information
`for affiliates is available at
`http://www.merck.com/contact/contacts.html) that may be confidential,
`proprietary copyrighted and/or legally privileged. It is intended solely
`for the use of the individual or entity named on this message. If you are
`not the intended recipient, and have received this message in error,
`please notify us immediately by reply e-mail and then delete it from
`your system.
`
`Notice: This e-mail message, together with any attachments, contains
`information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station,
`New Jersey, USA 08889), and/or its affiliates Direct contact information
`for affiliates is available at
`http://www.merck.com/contact/contacts.html) that may be confidential,
`proprietary copyrighted and/or legally privileged. It is intended solely
`for the use of the individual or entity named on this message. If you are
`not the intended recipient, and have received this message in error,
`please notify us immediately by reply e-mail and then delete it from
`your system.
`
`Reference ID: 2981071
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`07/29/2011
`
`Reference ID: 2981071
`
`

`

`From:
`To:
`Subject:
`Date:
`
`Chiang, Raymond
`"Swanson, Richard John";
`RE: NDA 202270 SDN30-- July 21, 2011 submission
`Friday, July 22, 2011 11:17:56 AM
`
`Hello Dr. Swanson,
`I reviewed your July 21, 2011 submission, which included a better rendition of
`Figure 1, as well as some minor editorial corrections to the Janumet XR package
`insert/MedGuide.
`
`Unfortunately, we will not be able to review this submission because your July
`18, 2011 submission (also containing a revised package insert/Medguide) was
`used to make our revisions. If you wish to incorporate these changes to the
`package insert, you may request to do so in the next review cycle. I also
`received your email regarding updating the PI/MedGuide and cartons with the
`new URL. This will need to be reviewed by OSE and DDMAC, and also
`addressed in the next review cycle.
`
`thanks,
`ray
`
`
`
`Reference ID: 2977579
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`07/22/2011
`
`Reference ID: 2977579
`
`

`

`From:
`To:
`cc:
`Subject:
`Date:
`
`Chiang, Raymond
`"Swanson, Richard John";
`Silverman, Robert E. (MRL);
`RE: Request regarding NDA 202270
`Monday, July 18, 2011 9:25:30 AM
`
`Hello Dr. Swanson,
`See information request below.
`thanks,
`ray
`
`
`
` July 11, 2011, response to our Form FDA 483
`We have reviewed
`and the following request below in black italics font.
`
`Please repeat the bioequivalence determination using the new reintegrated data
`and re-evaluate the study outcomes.
`
`We request you submit your response (i.e. new datasets) no later than noon,
`Thursday, July 21, 2011.
`
`Reference ID: 2974912
`
`(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/
`---------------------