CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`205029Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`1.3.5 Patent exclusivity
`Epinephrine Injection, USP 1:1000 (mg/ml.)
`
`Confidential
`Belcher Pharmaceuticals. LLC
`
`1.3.5.2 Patent certification - updated 7 March 2013
`
`In accordance with Section 21 CFR 314.50 i
`the following Patent Certification for
`1:1000 [mg/mL]):
`
`1 Belcher Pharmaceuticals, LLC (Belcher) makes
`proposed trade name (epinephrine injection, USP
`
`As part of this NDA (205029), Belcher references listed drug data contained in CorePharma,
`LLC’s NDA (20800) pertaining to Twinject, an approved epinephrine (0.3 mg/mL) product for
`use in the emergency treatment of severe allergic reactions.
`
`There is one method of manufacturing patent that applies to the production of the active
`pharmaceutical ingredient, i.e., epinephrine. Paragraph (i)(l)(iii)(2) of 21 CFR 314.50 states that
`“an applicant is not required to make a certification with respect to any patent that claims only a
`method of manufacturing the drug product for which the applicant is seeking approval.” As such,
`no patent certification for this method of manufacturing patent has been made.
`
`On October 31, 2012, Belcher had certified that there were no relevant patents related to
`Twinject or Belcher’s proposed epinephrine product for use in septic shock.
`
`On February 20, 2013, the Agency sent Belcher an information request for patent certification on
`two unexpired patents, 7297136 and 7621891, associated with Twinject (NDA 20800), as listed
`in the Orange Book. Belcher now makes such paragraph IV patent certification per the Agency's
`request in accordance with 21 CFR 314.50(i)(l)(i)(A)(4).
`
`Belcher’s proposed epinephrine drug product will be supplied in ampoules made available for
`continuous intravenous infusion upon dilution and does not include a delivery device. Both
`patents 7297136 and 7621891 consist of apparatus claims only for an injector device (i.e.,
`autoinjector) for delivery of one or two doses. Patent 7297136 does not claim delivery of
`epinephrine. Patent 7621891, which is a continuation-in-part of patent 7297136, does claim
`delivery of epinephrine by this particular autoinjector. Belcher’s proposed drug product does not
`consist of such a pre-filled injector device intended for self-administration. Therefore, Belcher’s
`proposed epinephrine drug product will not infringe on device patents 7297136 and 7621891.
`
`Paragraph IV Certification
`
`I, Mihir Taneja of Belcher Pharmaceuticals, LLC, certify that Patent No. 7297136 and Patent No.
`7621891 will not be infringed by the manufacture, use, or sale of-(epinephrine
`injection, USP 1:1000 [mg/mLD for which this application is submitted.
`
`To this effect, I and Belcher have complied with the requirements under 314.52(a) with respect
`to providing a notice to each owner of the patent or their representatives and to the holder of the
`approved application for the drug product which is claimed by the patent or a use of which is
`claimed by the patent and with the requirements under 314.52(c) with respect to the content of
`the notice. These notices were sent out on February 27, 2013.
`
`Reference ID: 3605853
`
`Page 1 of 2
`
`

`

`1.3.5 Patent exclusivity
`Epinephrine Injection, USP 1:1000 (mg/mL)
`
`Confidential
`Belcher Pharmaceuticals. LLC
`
`Delivery receipts for each of these notices, sent to the following, are attached:
`
`0 Owner of Patents 7,621,891 and 7,297,136:
`Ron Wyrick, President
`Washington Biotech Corporation
`4503 E Red Roan Drive
`
`Spokane, WA 99217-9734
`
`0 Holder of Twinject NDA 20800:
`Amedra Pharmaceuticals LLC
`
`Christopher Worrell, CEO
`2 Walnut Grove Dr., Suite 190
`
`Horsham, PA 19044-7707
`
`Sincerely,
`
`M» 42......
`
`Mihir Taneja
`Vice President
`
`Belcher Pharmaceuticals, LLC
`
`6911 Bryan Dairy Road
`Largo, FL 33777
`(727) 471-0850
`mihirt@belchergharma.com
`
`Reference ID: 3605853
`Reference ID: 3605853
`
`Page 2 of2
`
`

`

`1.3.5 Patent exclusivity
`Epinephrine Injection, USP 1:1000 (mg/mL)
`
`Confidential
`Belcher Pharmaceuticals. LLC
`
`1.3.5.2 Patent certification - updated 4 March 2013
`
`In accordance with Section 21 CFR 314.50('
`makes the following Patent Certification for
`injection, USP 1:1000 [mg/mu):
`
`’
`
`cher Pharmaceuticals, LLC (Belcher)
`proposed trade name (epinephrine
`
`As part of this NDA (205029), Belcher references listed drug data contained in CorePharma,
`LLC’s NDA (20800) pertaining to Twinject, an approved epinephrine (0.3 mg/mL) product for
`use in the emergency treatment of severe allergic reactions.
`
`There is one method of manufacturing patent that applies to the production of the active
`pharmaceutical ingredient, i.e., epinephrine. Paragraph (i)(1)(iii)(2) of 21 CFR 314.50 states that
`“an applicant is not required to make a certification with respect to any patent that claims only a
`method of manufacturing the drug product for which the applicant is seeking approval.” As such,
`no patent certification for this method of manufacturing patent has been made.
`
`On October 31, 2012, Belcher had certified that there were no relevant patents related to
`Twinject or Belcher’s proposed epinephrine product for use in septic shock.
`
`On February 20, 2013, the Agency sent Belcher an information request for patent certification on
`two unexpired patents, 7297136 and 7621891, associated with Twinject (NDA 20800), as listed
`in the Orange Book. Belcher now makes such patent certifications per the Agency's request in
`accordance with 21 CFR 314.50, paragraph (i)(i)(4).
`
`Belcher’s proposed epinephrine drug product will be supplied in ampoules made available for
`continuous intravenous infusion upon dilution and does not include a delivery device. Both
`patents 7297136 and 7621891 consist of apparatus claims only for an injector device (i.e.,
`autoinjector) for delivery of one or two doses. Patent 7297136 does not claim delivery of
`epinephrine. Patent 7621891, which is a continuation-in-part of patent 7297136, does claim
`delivery of epinephrine by this particular autoinjector. Belcher’s proposed drug product does not
`consist of such a pre-filled injector device intended for self-administration. Therefore, Belcher’s
`proposed epinephrine drug product will not infringe on device patents 7297136 and 7621891.
`
`I, Mihir Taneja ofBelcher Pharmaceuticals, LLC, certify that Patent NoI i297l36 and Patent No.
`
`7621891 will not be infringed by the manufacture, use, or sale of
`injection, USP 1:1000 [mg/mLD for which this application is submitte .
`
`epinephrine
`
`To this effect, I and Belcher have complied with the requirements under 314.52(a) with respect
`to providing a notice to each owner of the patent or their representatives and to the holder of the
`approved application for the drug product which is claimed by the patent or a use of which is
`claimed by the patent and with the requirements under 314.52(0) with respect to the content of
`the notice. These notices were sent out on February 27, 2013.
`
`Reference ID: 3605853
`
`Page 1 of 2
`
`

`

`1.3.5 Patent exclusivity
`Epinephrine Injection, USP 1:1000 (mg/mL)
`
`Confidential
`Belcher Pharmaceuticals. LLC
`
`Delivery receipts for each of these notices, sent to the following, are attached:
`
`0 Owner of Patents 7,621,891 and 7,297,136:
`Ron Wyrick, President
`Washington Biotech Corporation
`4503 E Red Roan Drive
`
`Spokane, WA 99217-9734
`
`0 Holder of Twinject NDA 20800:
`Amedra Pharmaceuticals LLC
`
`Christopher Worrell, CEO
`2 Walnut Grove Dr., Suite 190
`Horsham, PA 19044-7707
`
`Sincerely,
`
`M4" gwww
`
`Mihir Taneja
`Vice President
`
`Belcher Pharmaceuticals, LLC
`
`6911 Bryan Dairy Road
`Largo, FL 33777
`(727) 471-0850
`mihirt belcher harma.com
`
`Reference ID: 3605853
`Reference ID: 3605853
`
`Page 2 of 2
`
`

`

`1.3.5 Patent exclusivity
`Epinephrine Injection, USP 1:1000 (mg/mL)
`
`1.3.5.2
`
`Patent certification
`
`31 October 2012
`
`Confidential
`Belcher Pharmaceuticals. LLC
`
`In accordance with Section 21 CFR 314.50('
`makes the following Patent Certification for
`injection, USP 1:1000 [mg/mL]):
`
`‘
`
`elcher Pharmaceuticals, LLC (Belcher)
`roposed trade name, (epinephrine
`
`As part of this NDA (205029), Belcher references listed drug data contained in CorePharma,
`LLC’s NDA (N020800) pertaining to Twinject, an approved epinephrine (0.3 mg/mL) product
`for use in the emergency treatment of severe allergic reactions.
`
`There is one method of manufacturing patent that applies to the production of the active
`pharmaceutical ingredient, ie, epinephrine. Paragraph (i)(l)(iii)(2) of 21 CFR 314.50 states that
`“an applicant is not required to make a certification with respect to any patent that claims only a
`method of manufacturing the drug product for which the applicant is seeking approval.” As such,
`no patent certification for this method of manufacturing patent has been made.
`
`In accordance with 21 CFR 314.50, paragraph (i)(l)(ii), Belcher certifies that to the best of its
`knowledge as of this date that there are no relevant patents related to Twinject or Belcher’s
`proposed epinephrine drug product, epinephrine injection, USP 1:1000 (1 mg/mL) for use in
`increasing systemic arterial blood pressure in acute hypotensive states associated with septic
`shock, and that patent information has not been submitted to the FDA for any patent that claims
`epinephrine on which investigations or literature references have been relied upon by Belcher for
`approval of this application.
`
`Sincerely,
`
`M 2w“
`
`Mihir Taneja
`Vice President
`
`Belcher Pharmaceuticals, LLC
`6911 Bryan Dairy Road
`Largo, FL 33777
`(727) 471 -0850
`mihirt@belchemharma.com
`
`Reference ID: 3605853
`
`Page 1 of 1
`
`

`

`1.3.5 Patent exclusivity
`Epinephrine Injection, USP 1:1000 (mg/mL)
`
`1.3.5.1
`
`Patent information
`
`Confidential
`Belcher Pharmaceuticals. LLC
`
`There are no patents claiming drug, drug product, or method of use for Belcher’s epinephrine
`drug product. Belcher Pharmaceuti
`s not currently have any patents related to its
`
`proposed epinephrine drugproductwmnephrine injection, USP 1:1000 (1 mg/mL)
`
`for use in increasing systemic arterta
`septic shock.
`
`oo pressure in acute hypotensive states associated with
`
`There is one method of manufacturing patent that applies to the production of the active
`harmaceutical in
`dient
`ie e ine brine. The Active In redient Manufacturer (AIM) is
`ee correspondin DMF No.
`
`ut orlzatlon etterto e c er
`
`armaceutlca s,
`
`ass:gnee of US Patent Number 6,218,575 with expiration date 26 July 202 ort e process for
`preparing adrenaline (epinephrine) by asymmetric hydrogenation.
`
`ection l.4.1).(#is the
`
`Reference ID: 3605853
`
`Page 1 of 1
`
`

`

`
`
`EXCLUSIVITY SUMMARY
`
`NDA # 205029
`
`
`
`
`
`SUPPL #
`
`
`
`Trade Name N/A
`
`Generic Name epinephrine injection 1 mg/mL
`
`Applicant Name Belcher Pharmaceuticals
`
`Approval Date, If Known 7/25/14
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`HFD # 110
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to
`one or more of the following questions about the submission.
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
`
`
`
`
` YES
`
`
`
`
`
`NO
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(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:
`
`
`Reference ID: 3600458
`
`
`Page 1
`
`

`

`
`
`d) Did the applicant request exclusivity?
`
`
`
`
`
` YES
`
`
`
`NO
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`
`
` YES
`
`
`
`NO
`
` If the answer to the above question in YES, is this approval a result of the studies submitted in
`response to the Pediatric Written Request?
`
`
`
`
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`2. Is this drug product or indication a DESI upgrade?
`
`
`
`
`
` YES
`
`
`
`NO
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE BLOCKS
`ON PAGE 8 (even if a study was required for the upgrade).
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the same
`active moiety as the drug under consideration? Answer "yes" if the active moiety (including other
`esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this
`particular form of the active moiety, e.g., this particular ester or salt (including salts with hydrogen
`or coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate)
`has not been approved. Answer "no" if the compound requires metabolic conversion (other than
`deesterification of an esterified form of the drug) to produce an already approved active moiety.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`See attached list
`
`
`Reference ID: 3600458
`
`
`Page 2
`
`

`

`
`
`2. Combination product.
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`approved an application under section 505 containing any one of the active moieties in the drug
`product? If, for example, the combination contains one never-before-approved active moiety and
`one previously approved active moiety, answer "yes." (An active moiety that is marketed under an
`OTC monograph, but that was never approved under an NDA, is considered not previously
`approved.)
`
`
`
`
`
`YES
`
`
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`NDA#
`NDA#
`NDA#
`
`
`
`
`
`
`
`
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO THE
`SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary should
`only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`clinical investigations (other than bioavailability studies) essential to the approval of the application
`and conducted or sponsored by the applicant." This section should be completed only if the answer
`to PART II, Question 1 or 2 was "yes."
`
`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
`
`(This is a literature-based application.)
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`
`
`
`
`
`Reference ID: 3600458
`
`
`Page 3
`
`

`

`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved the
`application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical trials,
`such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or
`505(b)(2) application because of what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been sufficient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`by the applicant or available from some other source, including the published literature)
`necessary to support approval of the application or supplement?
`
`
` YES
`
`NO
`
`
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`(b) Did the applicant submit a list of published studies relevant to the safety and
`effectiveness of this drug product and a statement that the publicly available data would not
`independently support approval of the application?
`
`
`
`
`NO
`
`
`
` YES
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree
`with the applicant's conclusion? If not applicable, answer NO.
`
`
`
`
`
`
`
` YES
`
`
`
`NO
`
` If yes, explain:
`
`
`
`
`
`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
`
`
`
`
`
` YES
`
`
`
`NO
`
` If yes, explain:
`
`
`
`(c)
`
`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical
`
`
`Reference ID: 3600458
`
`
`Page 4
`
`

`

`
`
`investigations submitted in the application that are essential to the approval:
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The agency
`interprets "new clinical investigation" to mean an investigation that 1) has not been relied on by the
`agency to demonstrate the effectiveness of a previously approved drug for any indication and 2) does
`not duplicate the results of another investigation that was relied on by the agency to demonstrate the
`effectiveness of a previously approved drug product, i.e., does not redemonstrate something the
`agency considers to have been demonstrated in an already approved application.
`
`a) For each investigation identified as "essential to the approval," has the investigation been
`relied on by the agency to demonstrate the effectiveness of a previously approved drug
`product? (If the investigation was relied on only to support the safety of a previously
`approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`YES
`
`YES
`
`
`
`
`
`NO
`
`NO
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA in which each was relied upon:
`
`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support the
`effectiveness of a previously approved drug product?
`
`Investigation #1
`
`Investigation #2
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`YES
`
`YES
`
`
`
`
`
`NO
`
`NO
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`
`Reference ID: 3600458
`
`
`Page 5
`
`

`

`
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
`or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any
`that are not "new"):
`
`
`
`
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by"
`the applicant if, before or during the conduct of the investigation, 1) the applicant was the sponsor of
`the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor
`in interest) provided substantial support for the study. Ordinarily, substantial support will mean
`providing 50 percent or more of the cost of the study.
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`Investigation #1
`
`
`
`IND #
`
`
`
`
`
`
`
`
`
`YES
`
`
`Investigation #2
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`!
`!
`! NO
`! Explain:
`
`
`IND #
`
`
`
`
`
`
`
`
`
`
`
`
`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?
`
`Investigation #1
`
`YES
`
`Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`!
`!
`! NO
`! Explain:
`
`
`
`
`Reference ID: 3600458
`
`
`Page 6
`
`

`

`
`
`
`
`
`
`
`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:
`
`=================================================================
`
`Name of person completing form: Russell Fortney
`Title: RHPM
`Date: 7/22/14
`
`Name of Office/Division Director signing form: Norman Stockbridge
`Title: Director, Division of Cardiovascular and Renal Products
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`
`Reference ID: 3600458
`
`
`Page 7
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`RUSSELL FORTNEY
`07/28/2014
`
`NORMAN L STOCKBRIDGE
`07/28/2014
`
`Reference ID: 3600458
`
`

`

`1.3.3
`
`Debarrnent Certification
`
`Epinephrine Injection, USP 121000 (mg/mL)
`
`Confidential
`
`Belcher Pharmaceuticals, LLC
`
`1.3.3
`
`DEBARMENT CERTIFICATION
`
`Belcher Pharmaceuticals, LLC hereby certifies that it did not and will not use in any capacity
`the services of any person debarred under section 306 of the Federal Food, Drug, and
`Cosmetic Act in connection with this application.
`
`4414: g;flv“
`
`Mihir Taneja
`Vice President
`
`Belcher Pharmaceuticals, LLC
`
`6911 Bryan Dairy Road
`Largo, FL 33777
`
`March 6,2013
`
`Date
`
`Reference ID: 3605853
`Reference ID: 3605853
`
`

`

`ACTION PACKAGE CHECKLIST
`
`APPLICATION INFORMATION
`
`NDA # 205029
`BLA #
`
`NDA Supplement #
`BLA Supplement #
`
`If NDA, Efficacy Supplement Type:
`(an action package is not requiredfor SE8 0r SE9 supplements)
`
`
`
`505(b)(2)
`NDA Application Type: E] 505(b)(1)
`Efficacy Supplement:
`I] 505(b)(1) El 505(b)(2)
`
`BLA Application Type: E] 351(k)
`Efficacy Supplement:
`[:1 351(k)
`
`I:I 351(a)
`[:I 351(a)
`
`0
`
`Review the information in the 505(b)(2) Assessment and submit
`the draft2 to CDER 0ND 10 for clearance.
`
`IXI No changes
`I:] New patent/exclusivity (notijfv CDER 0ND IO)
`
`
`Proprietary Name: N/A
`Applicant: Belcher Pharmaceuticals
`
`
`Established/Proper Name: epinephrine
`Agent for Applicant (if applicable): N/A
`
`
`
`Dosage Form:
`injection
`
`Division:
`
`
`
`For ALL 505(b)(2) applications, two months prior to EVERY action:
`
`
`
`
`
`
`
`
`
`0 Check Orange Book for newly listed patents and/or
`exclusivity (including pediatric exclusivity)
`
`
`
`Date of check: 7/22/14
`
`
`Note: Ifpediatric exclusivity has been granted or the pediatric
`information in the labeling of the listed drug changed, determine whether
`
`
`pediatric information needs to be added to or deletedfrom the labeling of
`
`
`this drug.
`
`
`> Actions
`
`Proposed action
`0
`0 User Fee Goal Date is 7/27/14
`
`0
`
`Previous actions (specifiz type and datefor each action taken)
`
`
`
`
`
`
`
`.AP
`
`I:ITA
`
`IE CR, 10/4/13
`
`El Received
`
`
`
`v If accelerated approval or approval based on efficacy studies in animals, were promotional
`materials received?
`
`
`Note: Promotional materials to be used within 120 days after approval must have been
`
`
`submitted (for exceptions, see
`
`
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida
`
`
`
`nces/ucm069965pdi). If not submitted, explain
`
`Application Characteristics 3
`
`9 v
`
`1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 2) lists
`the documents to be included in the Action Package.
`2 For resubmissions, 505(b)(2) applications must be cleared before the action, but it is not necessary to resubmit the draft 505(b)(2)
`Assessment to CDER 0ND 10 unless the Assessment has been substantively revised (e.g., new listed drug, patent certification
`revised).
`3 Answer all questions in all sections in relation to the pending application, i.e., if the pending application is an NDA or BLA
`ipplement, then the questions should be answered in relation to that supplement, not in relation to the original NDA or BLA. For
`example, if the application is a pending BLA supplement, then a new RMS—BLA Product Information Sheetfor TBP must be
`completed.
`
`Version: 6/23/2014
`
`Reference ID: 3605853
`Reference ID: 3605853
`
`

`

`NDA 205029
`
`Page 2
`
`[:I Priority
`Review priority: X Standard
`5
`Chemical classification (new NDAs only):
`(confirm chemical classification at time of approval)
`
`I] Fast Track
`D Rolling Review
`El Orphan drug designation
`[:I Breakthrough Therapy designation
`
`I:I Rx-to-OTC filll switch
`El Rx-to-OTC partial switch
`[:1 Direct-to-OTC
`
`NDAs: SubpartH
`E] Accelerated approval (21 CFR 314.510)
`E] Restricted distribution (21 CFR 314.520)
`Subpart I
`D Approval based on animal studies
`
`BLAs: Subpart E
`[:I Accelerated approval (21 CFR 601.41)
`E] Restricted distribution (21 CFR 601.42)
`Subpart H
`I:I Approval based on animal studies
`
`[:I Submitted in response to a PMR
`E] Submitted in response to a PMC
`C] Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: El MedGuide
`I: Communication Plan
`I:I ETASU
`1:] MedGuide w/o REMS
`E] REMS not required
`
`'3 BLAs only: Ensure RMS—BLA Product Information Sheetfor TBP and RMS—BLA Facilz'zy
`Information Sheetfor TBP have been completed and forwarded to OPI/OBI/DRM (Vicky
`Carter)
`
`E] Yes, dates
`
`Is the product subject to official FDA lot release per 21 CFR 610.2
`'3' BLAs only:
`(approvals only)
`
`El Yes
`
`[:I No
`
`1' Public communications (approvals only)
`
`0
`
`0
`
`Office of Executive Programs (OEP) liaison has been notified of action
`
`Indicate what types (if any) of information were issued
`
`0
`0.. Bxclusivity
`
`No
`
`I:] Yes
`None
`FDA Press Release
`
`
`
`FDA Talk Paper
`CDER Q&As
`Other
`
`
`
`o
`
`0
`
`Is approval of this application blocked by any type of exclusivity (orphan, 5—year
`NCE, 3-year, pediatric exclusivity)?
`If so, specify the type
`
`X] No
`
`[:1 Yes
`
`I
`
`Patent Information:
`
`
`
`Verify that form FDA-3 542a was submitted for patents that claim the drug for
`
`which approval is sought.
`
`
`
`
`
`
`Verified
`
`
`El Not applicable because drug is
`
`an old antibiotic.
`
`
`
`{CONTENTS OF ACTION. PACKAGE
`0
`I
`I f Officer/EmpIOyee List
`0
`l
`v List of officers/employees who participated in the decision to approve this application and
`consented to be identified on thi§.ll§1.(€?£3€f€¥fll€9.4.0.).
`
`
`
`Documentation of consent/non-consent by officers/employees
`
`Reference ID: 3605853
`Reference ID: 3605853
`
`
`
`
`
`
`
`Included
`
`Included
`
`Version: 5/14/2014
`
`..
`
`

`

`NDA 205029
`
`Page 3
`
`
`' " azA'ctidnijLétt‘ets, ‘
`
`,0 Copies ofall action letters (including approval letter withfinal labeling) m
`Labeling
`
`Package Insert (write submission/communication date at upper right offrst page ofPI)
`IE Included
`0 Most recent draft labeling (fit is dzvzszon-proposed labeling, it should betn
`trackchangeSformat)
`Original applicant—proposed labeling
`g Included
`
`0
`
`Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`submission/communication date at upper right offirst page ofeach piece)
`
`0 Most-recent draft labeling (ifit is division—proposed labeling, it should be in
`track—changes format)
`Original applicant—proposedlabelmg
`
`-
`
`v Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper right offirst page of each submission)
`
`o Most-recent draft labeling
`
`v Proprietary Name
`0 Acceptability/non-acceptability letter(s) (indicate date(s))
`0
`Review(s) (indicate date(s)
`
`
`
`
`
`I:I Medication Guide
`[:1 Patient Package Insert
`[:1 Instructions for Use
`[:1 Device Labeling
`None
`
`E] Included
`
`Ellncluded
`
`
`,
`
`Included
`
`..
`
`,.
`
`Unacceptable letter, 4/3/13
`Review, 4/2/13
`
`RPM: IE None
`DMEPA:
`8/7/13, 1/29/14,
`7/16/14
`
`None
`
`DMPP/PLT (DRISK):
`OPDP:
`None
`SEALD:
`None
`CSS:
`None
`
`Other: E] None
`
`3/12/13
`
`6/10/14
`
`E] Not a (b)(2)
`
`'3' Labeling reviews (indicate dates ofreviews)
`
`0O
`‘ RPM Filing Review4/Memo of Filing Meeting (indicate date ofeach review)
`00Oo
`' All NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`
`r Administrative ‘/ Reg‘u‘iatey Documents '
`
`'3' NDAS only: Exclusivity Summary (signed by Division Director)
`
`IX] Included
`
`6' Application Integrity Policy (AIP) Status and Related Documents
`ttp//www fda gov/ICECI/EnforcementActions/ApplIcationIntegriflPolicy/default.htm
`
`0 Applicantis onthe AIP
`
`D Yes
`
`No
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`'
`
`Version: 5/14/2014
`
`Reference ID: 3605853
`Reference ID: 3605853
`
`

`

`NDA 205029
`
`Page 4
`
`o
`
`This application is on the AIP
`0
`If yes, Center Director’s Exception for Review memo (indicate date)
`
`V
`
`[:1 Yes
`
`No
`
`0
`
`If yes, OC clearance for approval (indicate date ofclearance
`communication)
`
`El Not an AP action
`
`Pediatrics (approvals only)
`0 Date reviewed by PeRC 9/4/13
`If PeRC review not necessary, explain:
`
`Outgoing communications: letters, emails, and faxes considered important to include in
`the action package by the reviewing office/division (e.g., clinical SPA letters, RTF letter,
`etc.) (do not include previous action letters, as these are located elsewhere in package)
`Internal documents: memoranda, telecons, emails, and other documents considered
`important to include in the action package by the reviewing office/division (e.g.,
`
`Regulatory Briefing minutes, Medical Policy Council meeting minutes)
`
`
`Mmutes of Meetmgs
`lfnot thefirstrev1ew cycleany'end-ofrev1ew meetlng (indicate date ofmtg)
`.11.“..1Pre-NDA/BLAmeetmg (mdlcate date Ofmtg)
`
`Eopz meetmg (mdlcate date ofng)
`11....Mldcyc1e communicatisn (indicatedieéfmtg)
`
`I N/A or.no mtg
`X] No mtg
`
`E] No mtg
`IE N/A
`
`Late-c-ycle Meeting (indicate date ofmtg)
`IX] N/A
`Other milestone meetings (e.g., EOPZa, CMC pilots) (indicate dates ofmtgs) _
`
`Adv1sory Commlttee Meet1ng(s)
`D No AC meeting
`-
`Date(s) ofMeeting(s)
`
`'
`
`, Decisional and Summary Memos
`
`Office Director Decisional Memo (indicate datefor each review)
`
`X None
`
`0 v
`
`0 v
`
`Division Director SummaryReview(indicate datefor each review)
`Cross-D1sclplme Team Leader Review (Indicate datefor féfll review)
`PMR/PMC Development Templates (indicate totalnumber)
`
`9/28/13 7/25/14
`7/17/14
`IX] None
`
`Clinical review, page 9
`
`I No separate rev1ew i
`
`9/19/13 1/24/13
`
`9 v
`
`i Clinical Rev1ews
`0
`Clmlcal Team Leader Rev1ew(s) (indicate datefor each rev1ew)
`
`Cllnlcal rev1ew(s) (Indicate date for e