CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`21-892
`
`ADMINISTRATIVE and CORRSPONDENCE
`DOCUMENTS
`
`

`

`Patent Information/Certification
`29 Apr 2005
`
`1
`
`Patent Information - Para!!raDb I Certfication
`
`In acordace with Title 21 of
`
`the Code of Federal Regulations, Par 314, Section 50 paragrh (i) (21 CFR
`314.50(i)J and'Par 314, Section 53, parh (c) (21 CFR 314.53(c)), InKne Pharacutical Company,
`informaton for the patent described in this application. InKne
`certfies that this patent informaton has not be previously submitted to the U.S. Food and Drug
`Admnistaton for the application for which approval is being sought: NDA 21-892.
`
`Inc (InKne) is subnùtting the followig
`
`(1) General requirements
`
`(i) Patnt number and the date on which th~ patent wil expire
`
`Patent Number:
`Date of Patent:
`Date of Expiration:
`
`5,616,346
`April 0 I, 1997
`May 18,2013
`
`(ii) Type of
`
`patent
`
`Patent number 5.616,346 is a method of use patent.
`
`(ii) Name of
`
`the patent owner
`
`Craig A. Aronchick, MD.
`903 Bryn Mawr Avenue
`Penn Valley. PA 19072
`
`(iv) Not Applicable
`
`(2) Formulation, composition, or method of
`
`use patents
`
`(i) OrigiIal declaration
`
`The undersigned declares that patent no. 5,616,346 covers the method of use of
`_ M (sodium phosphate monobasic monohydrate. USP and sodium
`phosphate dibl1ic anhydrous. USP). formerly INKP-I02. This product is the
`subject of this application for which approval is being sought: NDA 21-892
`
`-"
`?f-
`
`(ii) Amendmeiit of .
`
`patnt informaton upon approval
`
`InKine Pharmactical Company, Inc shall amend the original patent
`declaration by letter within 30 days after the date of approval of. this
`application
`
`(3) No relevant patents - This section not applicale
`
`ohn Cullen, J.D.
`Senior Vice Prsident & Genera Counl
`InKne Pharacutical Company, Inc.
`
`aLh. ii Zo s -~
`
`--
`
`,.
`
`

`

`EXCLUSIVTY SUMMARY FOR NDA # 21-892 SUPPL # N/ A
`
`Page 1
`
`Trade Name: OsmoPrepTM
`Generic Name: sodium phosphate monobasic monohydrate, USP änd sodium phosphate dibasic
`anhydrous, USP
`
`Applicant Name: Salix Pharmaceuticals, Inc. HFO # HFD- 1 80
`
`Approval Date If Known: March 16, 2006
`
`P ART I IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`i. An exclusivity determination wil be made for all original applications, but only for certain
`you answer "yes" to one
`
`supplements. Complete P ARTS II and II ofthis Exclusivity Summary only if
`
`or more of
`
`the following question about the submission.
`
`a) Is it an original NDA?
`YES / X / NO / /
`
`b) Is it an effectiveness supplement?
`
`If yes, what type? (SEl, SE2, etc.)
`
`YES / / NO /X/
`
`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 ofbi?availability or bioequivalence data,
`answer "no.")
`
`YES / X / NO / /
`
`.~'l.
`
`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 bioavailabil.ity 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:
`
`Form OGO-011347 Revised 10/13/98
`cc: Original NDA Division File HFO-93 Mary Ann Holovac
`
`--,
`
`

`

`d) Did the applicant request exclusivity?
`
`Page 2
`
`YES / / NO /X/
`
`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?
`
`No
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRCTLY TO
`THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. Has a product with the same active ingredient(s), dosage form, strength, route of administration, and
`dosing schedule, previously been approved by FDA for the same use?(Rx to OTC switches should be
`answered NO-please indicate as such)
`
`YES / / NO / X /
`
`If yes, NDA #
`
`Drug Name
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRCTLY TO THE SIGNATUR BLOCKS ON
`
`PAGE 8..._._. q..
`
`3. Is this drug product or indication a DESI upgrade?
`
`YES / / NO /X/
`
`IF THE ANSWER TO QUESTION 3 is "YES," GO DIRCTLY TO THE SIGNATURE BLOCKS ON
`PAGE 8 (even if a study was required for the upgrade).
`
`-. ~,
`~
`
`PART II FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`
`(Answer either #1 or #2 as appropriate) ,
`
`i. Single active ingredient product.
`
`moiety as the drug under consideration? Answer "yes" if
`
`Has FDA previously approved under section 505 ofthe Act any drug product containing the same active
`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
`the compound requires metabolic conversion (other than deesterification of
`an esterified form of the drug) to produce an already approved active moiety.
`
`approved. Answer "no" if
`
`YES / X / NO / /
`
`--
`
`,
`
`Page 2
`
`

`

`If "yes," identify the approved drugproduct(s) containing the active moiety, and, ifknown, the NDA
`#(s).
`
`NDA# 21-097, Visicol Tablets
`
`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 anyone of the active moieties in the drug
`fore-approved active moiety and one
`an OTC
`monograph, but that was never approved under an NDA, is considered not previously approved.)
`
`previously approved active moiety, answer "yes." (An active moiety that is marketed under
`
`product? If, for example, the combination contains one never-be
`
`If "yes," identify
`
`the approved drug product(s) containing the active moiety, and, if
`
`known, the
`
`NDA #(s).
`
`YES II NO / /
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO.
`
`SIGNATURE BLOCKS ON PAGE 8. IF "YES" GO TO PART III.
`
`THE
`
`PART III THREE-YEAR EXCLUSIVITY FOR NDA'S AND SUPPLEMENTS
`
`clinical investigations (other than bioavailability studies) essential to the approval of
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`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."
`
`investigations" to mean investigations conducted on humans other than bioavailability studies.) If
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical
`the
`application contains clinical investigations only by virte of a right of reference to clinical investigations
`the answer to 3(a) is "yes" for any
`investigation referred to in another application, do not complete remainder of summary for that
`investigation.
`
`in another application, answer "yes," then skip to question 3(a). If
`
`IF ''NO,'' GO DIRECTLY
`
`TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`YES /X/ NO/ /
`
`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 I) no clinical investigation is necessary to support the supplement or application in
`light of previously approved applications (Le., information other than clinical trials, such as
`bioavailability data, would be suffcient to provide a basis for approval as an ANDA or 505(b)(2)
`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 suffcient to support approval of the application,
`without reference to the clinical investigation submitted in the application.
`--,
`
`application because of what is already
`
`

`

`(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 supplemènt?
`YES / X / 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:
`
`Page 4
`
`(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
`the application?
`
`support approval of
`
`YES / / NO / X /
`
`(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 app.Iicable, answer NO.
`
`If yes, explain:
`
`YES / / NO / X /
`
`(2) If the answer to 2(6) is "no," are you aware of pubiish~d st~dies 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 / X /
`
`~~
`
`If yes, explain:
`
`(c) If the answers to (b)( I) and (b )(2) were both "no," identify the clinical investigations
`submitted in the application that are essential to the approval:
`
`· Investigation 1: Study INKP-l 02-04-0 1 (Phase 3 study)
`
`· Investigation 2: Study INKP-i 02-03-0 1 (Phase 2 study)
`
`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.
`
`--
`
`,
`
`Page 4
`
`

`

`Page 5
`
`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,
`an"swer "no. ")
`
`Investigation # 1
`
`Investigation #2
`
`YES/ /
`
`YES / /
`
`NO / X/
`
`NO IX /
`
`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 / X /
`. ~. '.._-.-._. . ~
`
`NO IX /
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a similar
`investigation was relied on: '
`
`'~
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application or
`supplement that is essential to the approval (i.e., the investigations listed in #2( c), less any that
`are not "new"):
`
`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 iIwestigation, I) the applicant was the sponsor of the
`IND named in the form FDA 1571 fied 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.
`
`--
`
`,
`
`Page 5
`
`

`

`Page 6
`the investigation was carried
`out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`a) For each investigation identified in response to question 3( c): if
`
`YES IX / NO / / Explain:
`
`(Investigation 1)
`
`YES IX / NO / ~ Explain:
`
`(Investigation 2)
`
`(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? N/ A
`
`Investigation # 1
`
`YES / _/ Explain _
`
`NO/~ Explain
`
`Investigation #2
`YES / ~ Explain_
`
`NO / ~ Explain
`
`(c) Notwithstanding an answer ()f"yes" to (a) or (b), areJli~re Q-Ih~U~i:sons 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 /X /
`
`-~
`
`If yes, explain:
`
`(See appended electronic signature pagej
`
`Tanya Clayton
`Regulatory Health Project Manager
`
`Brian E. Harvey, M.D., Ph.D.
`Division Director
`Division of Gastroenterology Products
`Offce of New Drug Evaluation II
`Center for Drug Evaluation and Research
`
`cc: Original NDA-DFS
`HFD-93 Mary Ann Holovac
`--
`
`,
`
`Page 6
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`/s/
`Tanya Clayton
`3/23/2006 01: 15: 44 PM
`
`Brian Harvey
`3/23/2006 02: 09: 52 PM
`
`'~
`
`--,
`
`

`

`PEDIATRIC PAGE
`(Complete for all APPROVED original applications and efficacy supplements)
`
`\. #: 21-892 Supplement Type (e.g. SE5): ~ Supplement Number: N/A
`Stamp Date:Mav 17,2005 Action Date: _
`
`Trade and generic names/dosage form: OsmoPrep (sodium phosphate monobas~oaAE;l:d sodium
`phosphate dibasic anhydrous, USP)
`
`Applicant: Salix Pharmaceuticals, Inc"
`
`Therapeutic Class: 38
`
`Indication(s) previously approved: N/ A
`
`Each approved indication
`
`"must have pediatric studies: Completed, Deferred, and/or Waived.
`
`Number of indications for this application(s):--
`
`Indication #1: c1eansinl! of the colon as a .preparation for colonoscopv in adults.
`
`Is there a full waiver for this indication (check one)?
`
`I&Yes: Please proceed to Section A.
`
`DNo: Please check all that apply: _Partial Waiver _Deferred _Completed
`NOTE: More than one may apply
`Please proceed to Section B, Section C, and/or Section D and complete as necessary.
`
`I Section A: Fully Waived Studies
`
`Reason(s) for full waiver:
`
`a Products in this class for this indication have been studied/labeled for pediatric population
`a Disease/condition does not exist in children
`.Too few children with disease to study .
`ere are safety concerns
`
`11Th
`
`llther: The drul! product does not represent a meaninl!ful therapeutic benefit over existinl! treatments for pediatric
`patients.
`
`If studies are fully waived. then pediatric information is complete for this indication. If there isanother indication, please see
`Attachment A. Otherwise, this Pediatric Page is complete and should be entered into DFS. .
`
`ISection B: Partially Waived Studies
`
`Age/weight range being partially waived:
`Min_
`Max_
`Reason(s) for partial waiver:
`
`kg-kg--
`
`moo_mo._
`
`yr._yr._
`
`Tanner Stage
`Tanner Stage
`
`o Products in this class for this indication have been studied/labeled for pediatric population
`o Disease/condition does not exist in children
`o Too few children with disease to study
`o There are safety concerns
`
`a Adult studies ready for approval
`
`

`

`NDA 21-892
`Page 2
`
`o Formulation needed
`o Other:
`
`If studies are deferred, proceed to Section C. If studies are completed, proceed to Section D. Otherwise, this Pediatric Page is
`complete and should be entered into DFS
`
`¡Section C: Deferred Studies
`
`Age/weight range being deferred:
`
`kg--~ mo._
`
`MinMax_
`
`Reason(s) for deferral:
`
`mo._
`
`yr._yr._
`
`Tanner Stage
`Tanner Stage
`
`o Products in this class for this indication have been studied/labeled for pediatric population
`o Disease/condition does not exist in children
`o Too few children with disease to study
`o There are safety concerns
`o Adult studies ready for approval
`o Formulation needed
`Other:
`
`Date studies are due (mm/dd/yy):
`
`udies are completed, proceed to Section D. Otherwise, this Pediatric Page is complete and should be entered into DFS
`
`I Section D: Completed Studies
`
`Age/weight range of completed studies:.-
`
`MinMax_ k~kg-
`
`mo.
`mo.
`
`yr._yr._
`
`Tanner Stage
`Tanner Stage
`
`Comments:
`
`If there are additional indications, please proceed to Attachment A. Otherwise, this Pediatric Page is complete and should be entered
`into DFS
`
`This page was completed by:
`
`¡See appended electroiiic signature pagej
`
`Regulatory Project Manager
`
`cc: NDA
`HFD-950/Grace Carmouze
`(revised 9-24-02) FOR QUESTIONS ON COMPLETING THIS FORM CONTACT, PEDIATRIC TEAM, HFD-950
`301-796-7654
`
`

`

`Debanent Certficaon -lN-I02 (som phosphate tablets)
`29 Ape 2005
`
`Item 16 - Debarment Cerifcation
`
`InKine Pharaceutical Company, Inc. certfies tht it did not and will not us in any
`any pers debar under secton 306 ofthe Federl Food, Drug,
`and Cosmetic Act in connection with this application.
`
`serces of
`
`. capacity the
`
`On behalf of Ine Pharmceutical Company, Inc.
`
`Man Rose, M.D., J.D.
`Executive Vice President,
`Research and Development
`
`c¡!u!c.j-
`
`Date
`
`-l
`
`--,
`
`/'
`
`

`

`NDA REGULA TORY FILING REVIEW
`(Including Memo of Filng Meeting)
`
`NDA # 21-892
`
`Supplement #
`
`Effcacy Supplement Type SE-
`
`Trade Name: /-
`Established Name: sodium I?hosphate monobasic monohydrate, sodium phosphate dibasic anhydrous
`
`Strengths: 1.5 gram, oral tablet
`
`Applicant: Inkine I?harmaceutical
`Agent for Applicant: N/ A
`
`Date of Application: April
`
`29, 2005
`Date of Receipt: Apri129,2005
`Date clock started after UN: May 17,2005
`Date of Filing Meeting: July 6, 2005
`Filing Date: July 30, 2005
`Action Goal Date (optional):
`
`User Fee Goal Date: March 17, 2006
`
`Indication(s) requested: Cleansing of
`
`Type of Original NDA:
`OR
`Type of Supplement:
`
`the bowel as a preparation for colonoscopy in adults.
`(b)(l) 0
`(b)(l) 0
`
`(b)(2) ~
`(b)(2) 0
`
`~. .._.........."
`
`NOTE:
`(1) If you have questions about whether the application is a 505(b)(1) or 505(b)(2) application, see
`whether the original NDA
`the application is a (b)(2), complete Appendix B.
`indicate whether the NDA is a (b)(1) or a (b)(2)
`
`Appendix A. A supplement can be either a (b)(1) or a (b)(2) rêgardless of
`
`was a (b)(1) or a (b)(2). if
`
`the application is a supplement to an NDA, please
`
`(2) if
`
`application:
`o NDA is a (b)(l) application OR 0 NDA is a (b)(2) application
`P 0
`
`Resubmission after refuse to fie? 0
`
`Therapeutic Classification: S ~
`Resubmission after withdrawal? 0
`Chemical Classification: (1,2,3 etc.)
`Other (orphan, OTC, etc.)
`
`-.\:
`4"
`
`Form 3397 (User Fee Cover Sheet) submitted:
`
`YES ~
`
`NO 0
`
`User Fee Status:
`
`Paid ~ Exempt (orphan, government) 0
`Waived (e.g., small business, public health) 0
`
`NOTE: if
`
`the NDA is a 505(b)(2) application, and the applicant did not pay afee in reliance on the 505(b)(2)
`exemption (see box 7 on the User Fee Cover Sheet), confirm that a user fee is not required. The applicant is
`required to pay a user fee if (1) the product described in the 505(b)(2) application is a new molecular entity
`for a use that that has not been approved under section 505(b).
`Examples of a new indication for a use include a new indication, a new dosing regime, a new patient
`the applicant is claiming a new indication
`for a use is to compare the applicant's proposed labeling to labeling that has already been approved for the
`
`or (2) the applicant claims a new indication
`
`population, andan Rx-to-OTC switch. The best way to determine if
`
`Version: 12/15/2004
`This is a locked document. If you need to ad a comment where there is no field to do so, unlock the document using the following procedure. Click the
`~View . tab; drag the cursor down to 'Toolbars '; click on 'Forms. . On the forms toolbar. click the lock/unlock icon (looks like a padlock). This will
`, - allow you to insert text outside the provided fields. The form must then be relocked to permit tabbing through the fields.
`
`

`

`product described in the application. Highlight the diferences between the proposed and approved labeling.
`the applicant is claiming a new indicationfor a use, please contact the
`If you need assistance in determining if
`user fee staff
`
`NDA Regulatory Filing Review
`Page 2
`
`· (s there any 5-year or 3-year exclusivity on this active moiety in an approved (b)(I) or (b)(2)
`
`application? YES 0 NO is
`
`If yes, explain:
`
`.
`
`Does another drug have orphan drug exclusivity for the
`
`same indication? YES 0
`
`NO is
`
`· If yes, is the drug considered to be the same drug according to the orphan drug definition of sameness
`(2 1 CFR 3 l6.3(b)(l3))?
`
`YES 0
`
`NO 0
`
`.
`
`.
`.
`.
`
`.
`
`.
`
`If yes, consult the Director, Division of
`
`Regulatory Policy II, Offce of
`
`Regulatory Policy (HFD-007).
`
`Is the application affected by the Application Integrity Policy (AlP)?
`If yes, explain:
`
`If yes, has OC/DMPQ been notified of the submission?
`
`Does the submission contain an accurate comprehensive index?
`
`Was form 356h included with an a.uthorized signature?
`If foreign applicant, both the applicant and the U.S. agent must sign.
`
`YES 0
`YES 0
`is
`is
`
`YES
`
`'YES
`
`Submission complete as required under 21 CFR 314.50?
`If no, explain:
`
`YES
`
`is
`
`NO is
`
`NO 0
`NO 0
`NO 0
`NO 0
`
`Ifaaelectronic NDA, does it follow the Guidance? N/A 0 YES is NO
`If an electronic NDA, all forms and certifcations must be in paper and require a signature.
`the application were submitted in electronic format?
`
`Which parts of
`
`O ' y.
`
`0(
`
`Additional comments:
`
`. If an electronic NDA in Common Technical Document format, does it follow the CTD guidance?
`
`. N/A is YES 0 NO 0
`· Is it an electronic CTD (eCTD)? N/ A 0 YES 0 NO is
`If an electronic CTD, all forms and certifications must either be in paper and signed or be
`electronically signed.
`
`Additional comments:
`· Patent information submitted on form FDA 3542a? YES 0 NO is
`. Exclusivity requested? YES, Years NO ~
`
`NOTE: An applicant can receive exclusivity without requesting it; therefore, requesting exclusivity is
`not required.
`
`. Correctly worded Debarment Certification included with authorized signature? YES ~ NO 0
`If foreign applicant, both the applicant and the U.S. Agent must sign the certification.
`
`--
`
`, Version: 12115/04
`
`

`

`NDA Regulatory Filng Review
`Page 3
`
`NOTE: Debarment Certifcation should use wording in FD&C Act section 306(k)(1) i.e.,
`"(Name 0/ applicant) hereby certifes that it did no/and wil not use in any capacity the services 0/
`any person debarred under section 306 o/the Federal Food, Drug, and Cosmetic Act in connection
`with this application." Applicant may not use wording such as "To the best o/my knowledge. . . . "
`
`· Financial Disclosure forms included with authorized signature? YES iz NO 0
`(Forms 3454 and 3455 must be included and must be signed by the APPLICANT, not an agent.)
`NOTE: Financial disclosure is required/or bioequivalence studies that are the basis/or approval.
`
`. Field Copy Certification (that it is a true copy of the CMC technical section)? Y iz NO 0
`. PDUF A and Action Goal dates correct in COMIS? YES iz NO 0
`If not, have the document room staff correct them immediately. These are the dates EES uses for
`calculating inspection dates.
`
`. Drug name and applicant name correct in COMIS? If not, have the Document Room make the
`corrections. Ask the Doc Rm to add the established name to COMIS for the supporting IND if it is not
`already entered.
`
`. List referenced INO numbers: 56,291
`
`.
`
`.
`
`End-of-Phase 2 Meeting(s)? Date(s) August 23,2004
`If yes, distribute minutes before filing meeting~
`
`Pre-NDA Meeting(s)? Date(s) March 10,2005
`If yes, distribute minutes before filing meeting.
`
`Project Manaeement
`.
`
`Was electronic "Content of Labeling" submitted?
`If no, request in 74-day letter.
`
`NO 0
`
`NO 0
`
`YES iz
`
`NO 0 "~
`
`. All labeling (PI, PPI, MedGuide, carton and immediate container labels) consulted to OOMAC?
`
`YES iz NO 0
`to ODSIIO? N/A r8 YES 0 NO 0
`. Trade name (plus PI and all labels and labeling) consulted to ODS/DMETS? Y iz NO 0
`
`. Risk Management Plan consulted
`
`. MedGuide and/or PPI (plus PI) consulted to ODSIDSRCS? N/A r8 YES 0 NO 0
`.
`
`If a drug with abuse potential, was an Abuse Liability Assessment, including a proposal for
`scheduling, submitted?
`
`NI A r8
`
`YES o
`
`If Rx-to-OTC Switch application:
`.
`
`OTC label comprehension studies, all OTC labeling, and current approved PI consulted to
`
`ODSIDSRCS? N/A 0 YES 0
`
`Has DOTCDP been notified of
`
`the OTC switch application? YES 0
`
`.
`
`~-
`
`Version: 12115/04
`
`,
`
`NO o
`
`NO 0
`NO 0
`
`

`

`Clinical
`.
`
`If a controlled substance, has a consult been sent to the Controlled Substance Staff?
`YES 0
`
`NDA Regulatory Filng Review
`Page 4
`
`NO 0
`
`NO 0
`NO 0
`NO 0
`NO 0
`NO 0
`
`Chemistry
`.
`Did applicant request categorical exclusion for environmental assessment? YES r;
`YES 0
`If no, did applicant submit a complete environmental assessment?
`YES 0
`If EA submitted, consulted to Florian Zielinski (HFD-357)?
`r;
`YES 0
`
`.
`.
`
`Establishment Evaluation Request (EER) submitted to DMPQ?
`
`YES
`
`If a parenteral product, consulted to Microbiology Team (HFQ-805)?
`
`APPEARS THIS WAY
`ON ORIGINAL
`
`-:t-
`
`--
`
`, Version: 12115/04
`
`

`

`NDA Regulatory Filing Review
`Page 5
`
`A TT ACHMENT
`
`MEMO OF FILING MEETING
`
`DATE: July 6, 2005
`
`Addendum, March 21, 2006: The referenced drug for this NDA is Visicol Tablets, 21-097. Visicol is also a
`505(b)(2) since they referenced published literature for their pre-clinical section.
`
`BACKGROUND: -- provides for cleaning of
`
`the bowel in preparation for colonoscopy in adults. This
`is an 505 (b )(2). The referenced drug is Visicol Tablets, NDA 2 1 -097.
`(Provide a brief background of the drug, e.g., it is already approved and this NDA is for an extended-release
`formulation; whether another Division is involved; foreign marketing history; etc.)
`
`ATTENDEES: Joyce Korvick, Brian Harvey, Ruyi He, Eric Brodsky, Liang Zhou, Ali AI-Hakim, Suresh
`Doddapaneni, Mushifiqur Rashid, Tarnal Chakraborti, Tanya Clayton
`
`ASSIGNED REVIEWERS (including those not present at fiing meeting) :
`
`Discipline
`Medical:
`Secondary Medical:
`Statistical:
`Pharmacology:
`Statistical Pharmacology:
`Chemistry:
`Environmental Assessment (if needed):
`B iopharmaceutical:
`Microbiology, sterility:
`Microbiology, clinical (for antimicrobial products only):
`DSI:
`. Regulatory Project Management:
`Consults:
`
`Other
`
`Reviewer
`Eric Brodsky
`
`Mushifiqur Rashid
`Tarnal Chakraborti
`
`Ali AI-Hakim
`
`Suliman AI-Fayoumi
`
`Kahery Malik
`Tanya Clayton
`DMETS, DDMAC
`
`-~
`
`Per reviewers, are all parts in English or English translation?
`Ifno, explain:
`
`YES rg
`
`NO 0
`
`CLINICAL
`
`FILE rg
`
`REFUSE TO FILE 0
`
`. Clinical site inspection needed?
`
`. Advisory Committee Meeting needed?
`
`YES, date if known
`
`YES t8
`
`NO 0
`
`NO. rg
`
`.
`
`If the application is affected by the AlP, has the division made a recommendation regarding
`whether or not an exception to the AlP should be granted to permit review based on medicái
`necessity or public health significanc~?
`
`N/A
`
`rg
`
`YES
`
`o
`
`NO
`
`o
`
`CLINICAL MICROBIOLOGY
`
`STATISTICS
`
`Version: 12/15/04
`
`--,
`
`N/ A t8
`N/A 0
`
`FILE 0
`FILE rg
`
`REFUSE TO FILE 0
`
`REFUSE TO FILE 0
`
`

`

`. B IOPHARMACEUTICS
`
`FILE f2
`
`. Biopharm. inspection needed?
`
`PHARMACOLOGY
`
`N/A 0
`
`FILE f2
`
`· GLP inspection needed?
`
`CHEMISTRY
`
`FILE f2
`
`· Establishment(s) ready for inspection?
`· Microbiology
`
`ELECTRONIC SUBMISSION:
`Any comments: Fully Electronic
`
`NDA Regulatory Filing Review
`Page 6
`
`REFUSE TO FILE 0
`YES 0
`NO f2
`REFUSE TO FILE 0
`YES 0
`NO f2
`REFUSE TO FILE 0
`YES 0
`NO 0
`YES 0
`NO f2
`
`REGULA TORY CONCLUSIONSIDEFICIENCIES:
`(Refer to 21 CFR 314.101(d) for fiing reqnirements.)
`
`The application is unsuitable for fiing. Explain why:
`
`The application, on its face, appears to be well-organized and indexed. The application
`appears to be suitable for fiing.
`
`o (
`
`3
`
`f2
`o
`
`ACTION ITEMS:
`
`No filing issues have been identified.
`
`Filing issues to be communicated by Day 74. List (optional):
`
`""
`
`1.0 If RTF, notify everybody who alrea~y received a consult request of RTF action. Cancel the EER.
`
`2.0 If
`
`fied and the application is under the AlP, prepare a letter either granting (for signature by Center
`Director) or denying (for signature by ODE Director) an exception for review.
`
`3.(3 Convey document fiing iss~es/no fiing issues to applicant by Day 74.
`
`Stats wil provide Information Request regarding the location of SAS fies.
`Clinical wil provide Information Request regarding Safety Follow-up.
`
`Tanya Clayton, B.S.
`Regulatory Project Manager, HFD- i 80
`
`Version: 12/15/04
`
`--
`
`,
`
`

`

`Appendix A to NDA Regulatory Filng Review
`
`An application is likely to be a 505(b )(2) application if:
`
`NDA Regulatory Filing Review
`Page 7
`
`(1) it relies on literature to meet any of
`
`spo'nsor's drug product) to meet any of
`
`the approval requirements (unless the applicant has a
`written I-ght of reference to the underlying data)
`(2) it relies on the Agency's previous approval of another sponsor's drug product (which may be
`evidenced by reference to publicly available FDA reviews, or labeling of another drug
`the approval requirements (unless the application
`includes a written right of reference to data in the other sponsor's NDA)
`(3) it relies on what is "generally known" or "scientifically accepted" about a class of products to
`support the safety or effectiveness of the particular drug for which the applicant is seeking
`approvaL. (Note, however, that this does not mean any reference to general information or
`of analysis)
`
`knowledge (e.g., about disease etiology, support for particular endpoints, methods.
`
`causes the application to be a 505(b )(2) application.)
`(4) it seeks approval for a change from a product described in an OTC monograph and relies on
`the monograph to establish the safety or effectiveness of one or more aspects of the drug
`product for which approval is sought (see 21 CFR 330.11).
`
`Products that may be likely to be described in a 505(b )(2) application include combination drug
`products (e.g., heart drug and diuretic (hydrochlorothiazide) combinations), OTC monograph
`deviations, new dosage forms, new indications, and new salts.'- .,._._- -0_'
`
`If you have questions about whether an application is a 505(b)(1) or 505(b)(2) application, please
`consult with the Director, Division of Regulatory Policy II, Office of Regulatory Policy (HFD-007).
`
`'-
`1'-
`
`--,
`
`Version: 12/15/04
`
`

`

`NDA Regulatory Filing Review
`PageS
`
`Appendix B to NDA Regulatory Filng Review
`Questions for 505(b)(2) Applications
`
`1. Does the application reference a listed drug (approved drug)?
`
`YES r2
`
`NO 0
`
`If "No, " skip to question 3.
`
`2. Name oflisted drug(s) referenced by the applicant (if any) and NDA/ANDA #(s): NDA 21-097
`
`3. The purpose of
`
`this and the questions below (questions 3 to 5) is to determine if
`
`there is an approved drug
`product that is equivalent or very similar to the product proposed for approval and that should be
`referenced as a listed drug in the pending application.
`
`already approved? .YES r2
`
`(a) Is there
`
`a pharmaceutical equivalent(s) to the product proposed in the 505(b)(2) application that is
`NO 0
`
`(Pharmaceutical equivalents are drug products in identical dosage forms that: (1) contain identical amounts of
`the same therapeutic moiety, or, in the case of
`the identical active drug ingredient, i.e., the same salt or ester of
`modified release dosage forms that require a reservoir or overage or such forms as prefilled syringes where
`residual volume may vary, that deliver identical amounts ofthe active drug ingredient over the identical dosing
`period; (2) do not necessarily contain the same inactive ingredients; and (3) meet the identical compendial or
`other applicable standard of identity, strength, quality, and purity, in(;!ud.i~KP?!enExand, where applicable,
`1 (c))
`content uniformity, disintegration times, and/or dissolution rates. (21 CFR 320.
`
`If "No, " skip to question 4. Otherwise, answer part (b).
`
`(b) Is the approved pharmaceutical equivalent(s) cited as the listep drug(s)? YES r2
`(The approved pharmaceutical equivalent(s) should be cited as the listed drug(s).)
`
`NO 0
`
`-"5..~
`
`If "Yes, " skip to question 6. Otherwise, answer part (c).
`
`(c) Have you conferred with the Director, Division of
`
`(ORP) (HFD-007)? YES 0 NO r2
`
`Regulatory Policy II, Offce of
`
`Regulatory Policy
`
`If "No, " please contact the Director, Division of Regulatory Policy IL ORP. Proceed to question 6.
`YES 0
`
`4. (a) Is there a pharmaceutical altemative(s) already approved?
`
`NO 0
`
`individually meets either the identical or its own respective compendial or other i;pplicable standard of
`
`(Pharmaceutical alternatives are drug products that contain the identical