CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`22-304
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`

`

`FM“ APPmed’ OMB No. 09100513
`Department of Health and Human Services
`Expiration Dete104/30/10
`.
`.
`.
`See OMB Smement an Page a.
`Food and Drug AdmII'IlSII‘aIIOI't
`PATENT INFORMATION SUBMITTED WITH THE __"__
`NDA NUMBER
`.
`FILING OF AN NDA, AMENDMENT, OR SUPPLEMENT
`22.30;
`For Each Patent That Claims 3 Drug Substance
`NAME OF AEPUCANT/ “DA HOLPER
`(Active Ingredient), Drug Product (Formulation and
`°“h°'M¢N¢""““ss°“ Pharmmm'mlsv h"-
`Composition) and/or Method of Use
`
`The following is provided in accordance with Section 505(b) and (c) of the Federal Food, Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME)
`TBD
`
`ACTIVE lNGREDIENT(S)
`Tapentadol HCL
`
`.
`
`DOSAGE FORM
`Tablets
`
`STRENGTHS)
`50mg. 75mg, 100mg
`
`required to be submitted to the Food and Drug Administration (FDA) with an NDA application.
`Thls patent declaration term is
`amendment. or supplement as required by 21 CFR 314.53 at the address prowded in 21 CPR 314.53(d){4).
`Within thirty (30) days alter approval at an NBA or supplement. or within-thirty.(30) days oi issuance of a new patent. a new patent
`declaration must be submitted pursuant to 21 CFR 314.53(c)(2)(ii) with all of the required intonnation based on the approved MBA
`or supplement. The Information submitted in'the declaration term submitted upon or after approval will be the only tntorrnalion relied
`upon by FDA tor Ilsttng a patent in the Orange Book.
`
`For hand-written or typewriter versions (only) of this report: If additional space is required for any narrative answer (i,e., one
`that does not require a ”Yes' or "No“ response), please attach an additional page referencing the question number.
`FDA will not list patent information it you file an incomplete patent declaration or. the patent declaration indiwtos the
`patent is not eligible for listing.
`———-———————__________—__—____________
`For each patent submitted for the pending NDA, amendment, or supplement referenced above, you must submit all the
`information described below. If you are not submitting any patents for this pending NDA, amendment, or supplement,
`com lete above section and sections Sand 6.
`
`a. United States Patent Number
`RE 39,5935 (Reissue of US 6.248.737)
`
`.
`
`d. Name ol Patent Owner
`Griinenlhal GmbH
`
`b.
`
`issue Date of Patent
`April 24, 2007
`US 6.248.737 issued June 19, 2(1)!)
`Address (of Patent Owner)
`Zieglerstr. 6. 52078
`
`c. Expiration Date of Patent
`June I9. 2018
`
`e. Name at agent or representative who resides or maintains
`a place of buslness within the United States authorized to
`receive notice oi patent certification under section
`505(b)(3) and (DIEMB) oi the Federal Food. Drug. and
`Cosmetic Act and 21 CFR 314.52 and 314 95 (a patent
`owner or NDA applicant/holder does not reside or have a
`place 01 business within me United States)
`9
`,
`
`CityiState
`Aachen
`
`ZIP Code
`Germany 52078
`
`FAX Number (If available)
`49 241 569 2655
`
`E-Mail Address (:1 available)
`Telephone Number
`patents®grunenthnLcom
`49 241 569 2590
`Address (of agent orrepresenlatrve named in 1.9.)
`Crowell & Morning, 9,0. Box 14300
`_
`City/State _
`Washington. DC.
`
`ZIP Code
`
`202-624-2500
`
`FAX Number (IT available) Telephone Number
`
`I.
`
`Is the patent reterenced above a patent that has been submitted previously lorthe
`approved NDA or supplement relerenced above?
`9. It the patent referenced above has been submitted prewously torlrsting. is the excitation
`date a new expiration date?
`FORM FDA 3542: (7/07)
`
`E~Matl Address (travaileble)
`jdevans®crowdt.cem
`
`[I Yes
`
`8 N0
`
`I] Yes
`
`D N0
`
`Page 1
`escoiaam (mum-m) HF
`
`

`

`For the parent referenced above, provide the following information on the drug substance. drug product and/or method of
`use that is the subject of the pending NDA, amendment, or supplement.
`
`
`
`Yes
`
`D No
`
`'
`
`
`
`
`
`
`2. Drug Substance (Active Ingredient)
`
`
`2.1 Does the patent claim the drug substance that is the active ingredient in the drug product
`descrbed in the pending NDA. amendment, or supplement?
`2.2 Does the patent claim a drug substance that is a difterent polymorph of the active
` Iuo
`
`D Yes
`ingredient descnbed in the pending NDA. amendment, or supplement? (593 attached note)
`
`
`2.3 It the answer to question 2.2 is 'Yes." do you certify that, as of the date ol this declaration, you have test data
`
`demonstrating that a drug product containing the polymorph will perform the same as the dmg product
`
`
`DNO
`described in the NBA? The type of test data required is described at 21 CFR 314.53(b).
`
` DYes
`
`
`2.4 Specify the polymorphic torm(s) claimed by the patent tor which you havethe test results described in 2.3.
`
`
`
`
`2.5 Does the patent claim only a metabolite at the active ingredient pending in the NDA or Supplement?
`
`(Complete the information in section 4 below it the patent claims a pending method of using the pending
`
`drug product to administer the metahohte.)
`_
`2.6 Does the patent claim only an Intermediate?
`
`
`
` 2.7 It the patent relerenced in 2.1 is a product-by-process patent. is the product claimed in the
`
`
`
`
`
`patent novel? (An answer is required only it the patent is a product’by-pmcess patent.)
`3. Drug Product (CompositionIFormulation)
`.
`3.1 Does the patent claim the drug product. as defined In 21 CFB 314.3, in the pending NDA,
`amendment. or supplement?
`3.2 Does the patent claim only an intermediate?
`
`[:1 Yes
`
`I] Yes
`
`D No
`
`E Yes
`
`D Yes
`
`E] No
`
`No
`
`
`
`
`
`3.3 II the patent relerenced in 3.1 is a promcbby-process patent. is the product claimed in the
`patent novel? (An answer IS required only if the patent is a produclvby-process patent.)
`4. Method of Use
`
`[I Yes
`
`D No
`
`
`
`
`
`
`
`
`
`Sponsors must submit the information in section 4 for each method of using the pending drug product for which approval]: being sought
`that is cleirned by the patent. For each pending method of use claimed by the patent. provide the following information:
`
`4.1 Does the patent claim one or more methods at use for which approval is being sought in
`
`
`
`E] No
`E Yes
`the pending NDA, amendment. or supplement?
`
`
`Does (00) the patent claimts) referenced in 4.2 claim a
`4.2 Patent Claim Numbor(s) (as fistedin the patent)
`
`S,86,88,90.93,94.95,96,98,|00. [03,105,106J to,
`pending method of use for which approval is being sought
`
`
`
`_
`>4 Yes
`”2,! NJ t7.l]6,l37,t38,|40
`in the pending NDA. amendment. or supplement?
`
`
`4.23 It the arswer to 4.2 is
`Use' (Submit in I alien or melhodoi use information as identified specifically in the approved labeling.)
`
`
`
`
`”€35 identity {Mill speci-
`TRADENAME is indicated for the relief of moderate to severe acute pain.
`holly the use will refer-
`'
`‘
`ence to the proposed
`
`
`labeling for the drug
`
`product.
`
`5. No Relevant Patents
`
`For this pending NDA. amendment. or supplement. there are no relevant patents that claim the drug substance (active ingredient),
`
`
`drug product (lonnulalion or composition) or method(s) of use. lor which the applicant is seeking approval and with respect to
`which a claim of patent infringement could reasonably be asserted it a person not licensed by the owner of the patent engaged In
`D Yes
`
`
`the manufacture. use. or sale of the drug product.
`
`FORM FDA 3542a (7/07)
`Page 2
`
`

`

`6. Declaration Certification
`
`’
`
`6.1 The undersigned declares that this is an accurate and complete submission ofpatent information for the NDA,
`amendment, or supplement pencrrng under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-
`sensitive patent infonnatlon is submitted pursuant to 21 CFR 314.53. I attest that i am familiar with 21 CFR 314.53 and
`this submission complies with the requirements of the regulation. I verify underpenalty ofperjury that the foregoing
`is true and correct.
`
`
`
`
`
`
`
`
`
`Warning: A willfully and knowingly false statement is a criminal offense under 18 0.5.0. 1001.
`
`Agent, Representative or
`6.2 Authorized Signature of NDA Applicant/Holder or Patent Owner (Allomey.
`
`
`
`arherAulhon‘zed Official!) (Provide Inlonnatrbn below)
`
`%W'
`
`
`
`NOTE: Only an NDA applicant/holder may submit this declaration directly to the FDA. A patent owner who is not the NDA applicant!
`holder is authorized to sign the declaration but may not submit it directly to FDA. 2] CFR 314.53Ml4) and (dXd).
`
`
`Check applicable box and provide inlormation below.
`
`
`
`
`E] NDA Applicant/Holder
`
`NDA Applicant's/Holders Attorney. Agent (Representative) orother
`Authorized Olficlal
`
`D Patent Owner
`
`D Patent Owners 'Attomay. Agent (Representative) or Other Authorized
`Oflicial
`
`
`
`Name
`
`Ellen Coleni
`
`
`Address
`City/Slate
`
`
`
`Johnson & Johnson
`New Brunswick, NJ
`
`
`
`One Johnson & Johnson Plaza
`
`08933
`
`
`Telephone Nunber
`732-524-2359
`
`
`
`
`E-Marl Address (if available)
`FAX Number (if available)
`ecolcni@conrsjnj.com
`_
`732-524-5889
`————-—-——-————_—_______________
`
`
`
`
`
`
`
`
`
`
`
`An agency may nor conduct or sponsor. and aperson rs nor required In respond (0. a collection of
`
`
`infonnalian unless it dirplrrw a currently vulirl 0MB c'onrrol number.
`
`
`The publlc reporting burden for this collection of mformauon has been estimated mavmge 20 hours per response. including me Lime for reviewing instructions.
`searching existing dale sources. game-ins and maintaining the data needed. and completing and reviewing the collection oi" infomralion. Send commons regarding this
`burden estimate or any oLhcr aspect ot'Lhis collection of information. including suggestion for reducing this burden to:
`Food and Drug Administration
`CDER (l-l'FD-ODTJ
`5600 Fishers Lane
`Roclwille, MD 2085']
`
`
`
`FORM FDA 35423 (7/07)
`
`Page 3
`
`

`

`INFORMATION AND INSTRUCTIONS FOR FORM 3542a
`
`PATENT INFORMATION SUBMITTED WITH THE FILING
`OF AN NDA, AMENDMENT OR SUPPLEMENT
`
`lei Answer this question if applicable. If patent owner and NDA
`applicant/holder reside in the United States,
`leave space
`blank.
`
`2. Drug Substance (Active Ingredient)
`
`Complete all items in this section if the patent claims the drug
`substance that is the subject of the pending NDA. amendment, or
`supplement.
`
`2.4) Name the polymorphic form of the dmg identified by the
`patent.
`
`2.5) A patent for a metabolite of the approved active ingredient
`may not be submitted.
`If the patent claims an approved
`method of using the approved drug product
`to administer
`the metabolite, the pmnt may be submiued as a method of
`use panentdependingontheresponsestosectionht‘rhis form.
`
`2.7) Answer this question only if the patent is a product-by-
`pmcess patent.
`
`3. Drug Product (Composition/Formulation)
`
`Complete all items in this section if the patent clains the drug
`product that is the subject of the pending NDA, amendment, or
`supplement.
`
`3.3) An answer to this question is required only if the referenced
`patent is a product-by-process patent.
`
`4. Method of Use
`
`Complete all items in this section if the patent claims a method of
`use of the drug product that is the subject of the pending NDA.
`amendment. or supplement (pending method of use).
`
`4.2)
`
`For etch pending method of use claimed by the patent. identify
`by numberrhe clalm(s) in the patent that claim the pending use of
`the drug. An applicant my list together multiple patent claim
`numbersand infonmtion foreadrpendingnethodofuse, if
`applicable. However. each pending method of use must be
`separatelyliswdwithinthissecu'onofthe form.
`
`4.2a) Specify the part of the proposed dntg labeling that
`claimed by the patent.
`
`is
`
`describes the authorized signature.
`
`General Information
`
`infonnution to the agency the appropriate
`-To submit patent
`parent declaration form must be used. Two forms are-available
`for patent submissions. The approval status of your New Drug
`Application will detemtine which form you should use.
`
`patent
`submitting
`used when
`be
`should
`OFotm 3542::
`information with original NDA submissions. NDA amendments
`and NDA supplements prior to approval.
`
`supplemental
`oFutm 3542 should be used afler NDA or
`approval. This form is to be submitted within 30 days after
`approval of an application. This form should also be used to
`submit patent information relating to an approved supplement
`under 2l CFR 3l4.S3(d) to change the formulation. add a new
`indication or other condition of use, change the strength. or to
`make any other patented change regarding the drug. drug
`product, or any method of use.
`
`eFor-m 3542 is also to be used for patents issued after drug
`approval. Patents issued after drug approval are required to be
`submitted within 30 days of patent issuance for the patent to be
`considered "timely filed."
`
`form 3542 will he used for Orange
`OOnIy infomtation front
`Book publication purposes.
`0Forms should be submitted as described in 2! CFR 31453.
`Sending an additional copy of form 3542 to the Orange Book
`Staff will expedite patent publication in the Orange Book. The
`Orange Book Staff address (as of April 2007) is: Orange Book
`Staff. Office of Generic Drugs OGDIHFD-Glo, 7500 Standish
`Place, Rockville. MD 20855.
`
`n'l‘he receipt date is the date that the patent information is date
`stamped in the central document room. Patents are considered
`listed on the date received.
`
`Additional copies of these forms may be downloaded from the
`lntenret at: http:/Iwww.fda.gov/opacomlmotecltoiceslfdnfomlsl
`fdafonnshunl.
`
`First Section
`
`Complete all items in this section.
`
`1. General Section
`
`Complete all
`itself.
`
`items in this section with reference to the patent
`'
`
`lc) Include patent expiration date. including any Hatch-Waxmtn
`patent extension already granted. Do not
`include any
`applicable pediatric exclusivity. The agency will
`include
`pediatric exclusivities where applicable upon publication.
`
`Id)
`
`Include full address of patent owner. lf patent owner resides
`outside the US. indicate the country in the zip code block.
`
`5. No Relevant Patents
`
`Complete this section only if applicable.
`
`6. Declaration Certification
`
`Complete all items in this section.
`
`6.2) Authorized signature. Check one of the four boxes that best
`
`FORM FDA 35428 (7/07)
`
`Page 4
`
`

`

`Attachment for Form 3542a (US. Patent No. RE 39,593)
`
`2.2
`
`Applicants understand the term “claim” as used in this question to mean a claim
`limited to one or more different polymorphs of the active ingredient described in
`. the NDA, and with this understanding, the answer is no. Accordingly, submission
`of the additional test date is not necessary.
`
`

`

`EXCLUSHHTYSUNHAARY
`
`NDA # 22-304
`
`SUPPL #
`
`HFD # 170
`
`Trade Name <none>
`
`Generic Name tapentadol
`
`Applicant Name Ortho-McNeil—Janssen-Pharmaceuticals, Inc.
`
`Approval Date, If Known 11/20/2008
`
`PART I
`
`IS AN EXCLUSIVITY'DETERNIINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III ofthis Exclusivity Summary only ifyou answer "yes" to
`one or more of the following questions about the submission.
`
`a) IS it a 505(b)(l), 505(b)(2) or efficacy Supplement?
`
`YES IXI
`
`NO [I
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(1)
`
`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 [1
`
`Ifyour 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:
`
`Page 1
`
`

`

`d) Did the applicant request exclusivity?
`
`YES [2}
`
`NO [:1
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`Five
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`YES [:1
`
`NO X]
`
`If the answer te the ebove geestien 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 I]
`
`'
`
`NO
`
`' IF THE ANSWER TO QUESTION 2 IS "YES," GO DRECTLY 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
`esten'fied forms, salts, complexes, chelates or clathrates) has been previously approved, but this
`particular form ofthe 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 [1
`
`NO-
`
`If"yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
`#(s).
`
`Page 2
`
`

`

`NDA#
`
`NDA#
`
`NDA#
`
`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 Q! E 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.)
`D
`E]
`
`YES
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
`#(s).
`
`7 NDA#
`
`NDA#
`
`NDA#
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART 11 IS "NO," GO DIRECTLY TO THE
`SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part H 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 ofexclusivity, an application or supplement must contain "reports ofnew
`clinical investigations (other than bioavailability studies) essential to the approval ofthe application
`and conducted or sponsored by the applicant. " This section should be completed only ifthe answer
`to PART H, 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). Ifthe answer to 3(a)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`
`Page 3
`
`

`

`summary for that investigation.
`
`YES
`
`[3
`
`NO E]
`
`H" "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" ifthe 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 ofpreviously 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 ofwhatis 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 ofpreviously 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?
`‘
`YEslj
`
`NOE]-
`
`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 ofpublished studies relevant to the safety and effectiveness
`offins drug product and a statement that the publicly available data would not independently
`support approval of the application?
`
`YES I]
`
`NO [1
`
`(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.
`
`YEslj
`
`NOE]
`
`If yes, explain:
`
`(2) If the answer to 2(b) is "no," are you aware ofpublished 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?
`
`YESE]
`
`Nolj
`
`Page 4
`
`

`

`If yes, explain:
`
`(0)
`
`Ifthe answers to (b)(1) and (b)(2) were both "no," identify the clinical 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 ofa previously approved drug for any indication and 2) does
`not duplicate the results ofanother investigation that was relied on by the agency to demonstrate the
`effectiveness of a previously approved drug product, i.e., does not redemonstrate something the
`agency considers to have been demonstrated in an already approved application.
`
`a) For each investigation identified as "essential to the approval," has the investigation been
`relied on by the agency to demonstrate the effectiveness of a previously approved drug
`product? (If the investigation was relied on only to support the safety of a previously
`approved drug, answer "no.")
`»
`
`Investigation #1
`
`YES I]
`
`NO I]
`
`Investigation #2
`
`'
`
`YES I]
`
`-NO 1:]
`
`Ifyou 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 [I
`
`NC El
`
`YES D
`
`NO [:1
`
`Page 5
`
`

`

`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`c) Ifthe 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 ofthe investigation, 1) the applicant was the sponsor of
`the 1ND 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(0): if the investigation was
`carried out under an 1ND, was the applicant identified on the FDA 1571 as the sponsor?
`
`!1
`
`Investigation #1
`
`,
`
`IND#'
`
`YES El
`
`1 NO [3
`! Explain:
`
`a
`
`!!
`
`1 NO I]
`! Explain:
`
`Investigation #2
`
`]ND#
`
`YES E]
`
`(b) For each investigation not carried out under an IND or for which the applicant was not 4
`identified as the sponsor, did the applicant certify that it or the applicant's predecessor in
`interest provided substantial support for the study?
`
`Page 6
`
`

`

`a D
`.
`. Explain:
`
`l1
`
`1 NO [I
`! Explain:
`
`.
`
`Investigation #1
`
`YES I]
`Explain:
`
`Investigation #2
`
`YES [:1
`Explain:
`
`(0) 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, ifall 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.)
`
`YESD
`
`NOE]
`
`If yes, explain:
`
`Name of person completing form: Matthew Sullivan
`Title: Regulatory Project Manager
`Date: November 19, 2008
`
`I Name of Office/Division Director signing form: Bob A. Rappaport
`Title: Director, Division of Anesthesia, Analgesia and Rheumatology Products
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/ 15/05
`
`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/
`
`_ Bob Rappaport
`11/20/2008 05:39:57 PM
`
`

`

`Supplement Number:
`
`~
`
`NDA Supplement Type (e.g. SE5):
`
`' PEDIATRIC PAGE
`(Complete for all filed original applications and efficacy supplements)
`
`.
`NDA/BLA#: 22304
`
`Division Name:DAARP
`
`PDUFA Goal Date: 11/20/08
`
`Stamp Date: 1/23/2008
`
`Proprietary Name:
`
`<none>
`
`Established/Generic Name: Tapentadol
`
`Dosage Form:
`
`Tablets (Immediate Release)
`
`Applicant/Sponsor:
`
`Johnson and Johnson
`
`Indication(s) previously approved (please complete this question for supplements and Type 6 NDAs only):
`
`(1)
`(2) __
`.(3) _
`
`
`(4)
`
`Pediatric use for each pediatric subpopulation must be'addressed for each indication covered by current
`application under review. A Pediatric Page must be completed for each indication.
`
`Number of indications for this pending application(s):1
`(Attach a completed Pediatric Page for each indication in current application.)
`
`Indication: Management of acute moderate to severe pain
`
`Q1: Is this application in response to a PREA PMR?
`
`Yes El Continue
`
`
`
`No
`_
`Supplement #:'___
`if Yes, NDA/BLA#:
`Does the division agree that this is a Complete response to the PMR? '
`[I Yes. Please proceed to Section D.
`I
`[I No. Please proceed to Question 2 and complete the Pediatric Page, as applicable.
`
`Please proceed to Question 2.
`PMR #:___
`
`02: Does this application provide far (If yes, please check all categories that apply and proceed to the next
`question):
`,
`,
`(a) NEW E active ingredient(s) (includes new combination); 1:] indication(8); El dosage form; D dosing
`regimen; or E] route of administration?*
`
`(b) E] No. PREA does not apply. Skip to signature block.
`
`* Note 152/ 0052' $5.6; 5'56; andSEfsl/b/II/Zss/ons may also tfl'ggerPRL-Ill.
`
`Q3: Does this indication have orphan designation?
`[:1 Yes. PREA does not apply. Skip to signature block.
`E No. Please. proceed to the next question.
`-
`
`Q4: Is there a full waiver for all pediatric age groups for this indication (check one)?
`[I Yes: (Complete Section A.)
`E No: Please check all that apply:
`[I Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`E Deferred for some or all pediatric subpopulations (Complete Sections C)
`D Completed for some or all pediatric subpopulations (Complete Sections D)
`I] Appropriately Labeled for some or all pediatric suprpulations (Complete Sections E)
`E] Extrapolation in One or More Pediatric Age Groups (Complete Section F)
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdeggmhsgflfdahhsgov) 0R AT 301-796-0700.
`
`

`

`NDAIBLA# 2230422304223042230422304
`
`.
`
`,
`
`Page 2
`
`Please note that Section F ma be used alone or in addition to Sections C, D, and/or E.
`
`5 Section A: Fully Waived Studies (for all pediatric age groups)
`,
`
`
`
`
`
`
`Reason(s) for full waiver. (check, and attach a brief justification for the reason(s) selected)
`L—J Necessary studies would be impossible or highly impracticable because: _
`1:] Disease/condition does not exist in children
`I] Too few children with disease/condition to study
`[:1 Other (9.9., patients geographically dispersed): __
`[:1 Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients AND is not likely to be used in a substantial number of pediatric patients.
`I] Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`E] Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`El Evidence strongly suggests that product would be ineffective and unsafe in all pediatric
`subpopulations (Note: if studies are fully waived on this ground, this information must be included in
`the labeling.)
`[:1 Justification attached.
`
`If there is another
`If studies are fully waived, then pediatric information is complete for this indication.
`indication, please complete another Pediatric Page for each indication. Othenlvise, this Pediatric Page is
`complete and should be signed.
`
`Section B: Partially Waived Studies (for selected pediatric subpopulations)
`
`Check subpopulation(s) and reason for which studies are being partially waived (fill in applicable criteria below):
`
`Note: If Neonate includes premature infants, list minimum and maximum age in “gestational age" (in weeks).
`
`Reason (see below for further detail):
`
`_
`
`failedA
`
`Not meaningful
`therapeutic
`benefit"
`
`Ineffective or
`unsafef
`
`Formulation
`
`[I No; [:1 Yes.
`Are the indicated age ranges (above) based on'weight (kg)?
`[:1 No; D Yes.
`Are the indicated age ranges (above) based on Tanner Stage?
`Reason(s) for partial waiver (check reason corresponding to the category checked above, and attach a brief
`justification):
`# Not feasible:
`
`E] Necessary studies would be impossible or highly impracticable because:
`E]
`Disease/condition does not exist in children
`
`Too few children with disease/condition to study
`I]
`Other (e.g., patients geographically dispersed): __
`C]
`* Not meaningful therapeutic benefit:
`[:I Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients in this/these pediatric subpopulation(s) AND is not likely to be used in a substantial number of
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cdemmhs@fda.hhs.gov) 0R AT 301-796-0700.
`
`

`

`NDA/BLA# 2230422304223042230422304
`
`Page 3
`
`pediatric patients in this/these pediatric subpopulation(s).
`
`1' Ineffective or unsafe:
`
`{3- Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if studies -
`are partially waived on this ground, this information must be included in the labeling.)
`El Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are partially waived on this ground, this information must be included in the labeling.)
`[:l Evidence strongly suggests that product would be ineffective and unsafe in all pediatric subpopulations
`(Note: if studies are partially waived on this ground, this information must be included in the labeling.)
`A Formulation failed:
`
`E] Applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for
`this/these pediatric subpopulation(s) have failed. (Note: A partial waiver on this ground may gm; cover
`the pediatric subpopulation(s) requiring that formulation. An applicant seeking a partial waiver on this
`ground must submit documentation detailing why a pediatric formulation cannot be developed. This
`submission will be posted on FDA’s website if waiver is granted.)
`
`L__I Justification attached.
`
`For those pediatric subpopulations for which studies have not been waived, there must be (1) corresponding
`study plans that have been deferred (if so, proceed to Sections C and complete the PeRC Pediatric Plan
`Template); (2) submitted studies that have been completed (if so, proceed to Section D and complete the
`PeRC Pediatric Assessment form); (3) additional studies in other age groups that are not needed because the
`drug is appropriately labeled in one or more pediatric subpopulations (if