CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`209089Orig1s000
` 209090Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`505(b)(2) ASSESSMENT
`
`NDA # 209089
`
`Application Information
`NDA Supplement #: S-
`Efficacy Supplement Type SE-
`
`Proprietary Name: Xyzal Allergy 24HR
`Established/Proper Name: levocetirizine dihydrochloride
`Dosage Form: tablets
`Strengths: 5 mg
`Applicant: UCB, Inc.
`
`Date of Receipt: March 31, 2016
`
`PDUFA Goal Date: January 31, 2016
`
`RPM: Sherry Stewart
`Proposed Indication(s): Partial RX to OTC switch for the following:
`
`Action Goal Date (if different):
`
`
`Uses: temporarily relieves these symptoms due to hay fever or other upper respiratory allergies:
`• runny nose
`
`• sneezing
`
`• itchy, watery eyes
`
`• itching of the nose or throat
`
`GENERAL INFORMATION
`
`1)
`
`Is this application for a recombinant or biologically-derived product and/or protein or peptide
`product OR is the applicant relying on a recombinant or biologically-derived product and/or
`protein or peptide product to support approval of the proposed product?
` YES
`
` NO
`
` If “YES “contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`Reference ID: 4045813
`
`Page 1
`Version: January 2015
`
`

`

`INFORMATION PROVIDED VIA RELIANCE
`(LISTED DRUG OR LITERATURE)
`
`2) List the information essential to the approval of the proposed drug that is provided by reliance
`on our previous finding of safety and efficacy for a listed drug by reliance on published
`literature, or by reliance on a final OTC monograph. (If not clearly identified by the
`applicant, this information can usually be derived from annotated labeling.)
`
`Source of information* (e.g.,
`published literature, name of listed
`drug(s), OTC final drug
`monograph)
`
`Information relied-upon (e.g., specific
`sections of the application or labeling)
`
` *each source of information should be listed on separate rows, however individual
`literature articles should not be listed separately
`
`3) The bridge in a 505(b)(2) application is information to demonstrate sufficient similarity
`between the proposed product and the listed drug(s) or to justify reliance on information
`described in published literature for approval of the 505(b)(2) product. Describe in detail how
`the applicant bridged the proposed product to the listed drug(s) and/or published literature1.
`See also Guidance for Industry Providing Clinical Evidence of Effectiveness for Human Drug
`and Biological Products.
`Bridge for nonclinical information has been previously established per NDA 22064 and
`NDA 22157. The pending OTC NDA cross references these approved RX NDAs.
`
`RELIANCE ON PUBLISHED LITERATURE
`
`4)
`
`(a) Regardless of whether the applicant has explicitly stated a reliance on published literature
`to support their application, is reliance on published literature necessary to support the
`approval of the proposed drug product (i.e., the application cannot be approved as labeled
`without the published literature)?
` NO
` YES
`If “NO,” proceed to question #5.
`
`(b) Does any of the published literature necessary to support approval identify a specific (e.g.,
`brand name) listed drug product?
` NO
` YES
`If “NO”, proceed to question #5.
`If “YES”, list the listed drug(s) identified by name and answer question #4(c).
`
`(c) Are the drug product(s) listed in (b) identified by the applicant as the listed drug(s)?
` NO
` YES
`
`1For 505(b)(2) applications that rely on a listed drug(s), bridging studies are often BA/BE studies comparing the proposed product to the listed drug(s) Other examples include: comparative
`physicochemical tests and bioassay; preclinical data (which may include bridging toxicology studies); pharmacokinetic/pharmacodynamic (PK/PD) data; and clinical data (which may
`include immunogenicity studies) A bridge may also be a scientific rationale that there is an adequate basis for reliance upon FDA’s finding of safety and effectiveness of the listed drug(s)
`For 505(b)(2) applications that rely upon literature, the bridge is an explanation of how the literature is scientifically sound and relevant to the approval of the proposed 505(b)(2) product
`Page 2
`
`Reference ID: 4045813
`
`Version: January 2015
`
`

`

`RELIANCE ON LISTED DRUG(S)
`
`Reliance on published literature which identifies a specific approved (listed) drug constitutes
`reliance on that listed drug. Please answer questions #5-9 accordingly.
`
`5) Regardless of whether the applicant has explicitly cited reliance on listed drug(s), does the
`application rely on the finding of safety and effectiveness for one or more listed drugs
`(approved drugs) to support the approval of the proposed drug product (i.e., the application
`cannot be approved without this reliance)?
` NO
` YES
`If “NO,” proceed to question #10.
`
`6) Name of listed drug(s) relied upon, and the NDA #(s). Please indicate if the applicant
`explicitly identified the product as being relied upon (see note below):
`
`Name of Listed Drug
`
`NDA #
`
`Did applicant
`specify reliance on
`the product? (Y/N)
`
`Zyrtec (cetirizine )tablets
`
`Zyrtec (cetirizine ) oral syrup
`
`Zyrtec (cetirizine) chewable tablets
`
`NDA 19835
`
` NDA 20346
`
`NDA 21621
`
`Yes
`
`Yes
`
`Yes
`
`Applicants should specify reliance on the 356h, in the cover letter, and/or with their patent
`certification/statement. If you believe there is reliance on a listed product that has not been
`explicitly identified as such by the applicant, please contact the (b)(2) review staff in the
`Immediate Office, Office of New Drugs.
`
`7)
`
`If this is a (b)(2) supplement to an original (b)(2) application, does the supplement rely upon
`the same listed drug(s) as the original (b)(2) application?
` NO
` YES
` N/A
`If this application is a (b)(2) supplement to an original (b)(1) application or not a supplemental
`application, answer “N/A”.
`If “NO”, please contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`8) Were any of the listed drug(s) relied upon for this application:
`a) Approved in a 505(b)(2) application?
` NO
` YES
`If “YES”, please list which drug(s).
`Name of drug(s) approved in a 505(b)(2) application:
`
`b) Approved by the DESI process?
` NO
` YES
`If “YES”, please list which drug(s).
`Name of drug(s) approved via the DESI process:
`
`c) Described in a final OTC drug monograph?
`
`Page 3
`Version: January 2015
`
`Reference ID: 4045813
`
`

`

` NO
` YES
`If “YES”, please list which drug(s).
`
`Name of drug(s) described in a final OTC drug monograph:
`
`d) Discontinued from marketing?
` NO
` YES
`If “YES”, please list which drug(s) and answer question d) i. below.
`If “NO”, proceed to question #9.
`
`Name of drug(s) discontinued from marketing:
`NDA 20346 Zyrtec (cetirizine hydrochloride) syrup, 5 mg/5 mL
`
`i) Were the products discontinued for reasons related to safety or effectiveness?
` NO
` YES
`(Information regarding whether a drug has been discontinued from marketing for
`reasons of safety or effectiveness may be available in the Orange Book. Refer to
`section 1.11 for an explanation, and section 6.1 for the list of discontinued drugs. If
`a determination of the reason for discontinuation has not been published in the
`Federal Register (and noted in the Orange Book), you will need to research the
`archive file and/or consult with the review team. Do not rely solely on any
`statements made by the sponsor.)
`9) Describe the change from the listed drug(s) relied upon to support this (b)(2) application (for
`example, “This application provides for a new indication, otitis media” or “This application
`provides for a change in dosage form, from capsule to solution”).
`
`This application is for the L-enantiomer of the active ingredient that is being relied upon, and
`provides for a partial Rx-to-OTC switch.
`
`The purpose of the following two questions is to determine if there is an approved drug product
`that is equivalent or very similar to the product proposed for approval that should be referenced
`as a listed drug in the pending application.
`
`The assessment of pharmaceutical equivalence for a recombinant or biologically-derived product
`and/or protein or peptide product is complex. If you answered YES to question #1, proceed to
`question #12; if you answered NO to question #1, proceed to question #10 below.
`
`10) (a) Is there a pharmaceutical equivalent(s) to the product proposed in the 505(b)(2)
`application that is already approved (via an NDA or ANDA)?
`
`(Pharmaceutical equivalents are drug products in identical dosage forms intended for the
`same route of administration that: (1) contain identical amounts of the identical active drug
`ingredient, i.e., the same salt or ester of the same therapeutic moiety, or, in the case 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 of the 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, including potency and, where applicable, content uniformity,
`disintegration times, and/or dissolution rates. (21 CFR 320.1(c), FDA’s “Approved Drug
`Products with Therapeutic Equivalence Evaluations” (the Orange Book)).
`
`
`Reference ID: 4045813
`
`Page 4
`Version: January 2015
`
`

`

`Note that for proposed combinations of one or more previously approved drugs, a pharmaceutical
`equivalent must also be a combination of the same drugs.
`
` YES
`
` NO
`
`If “NO” to (a) proceed to question #11.
`If “YES” to (a), answer (b) and (c) then proceed to question #12.
`
`
`
`
` NO
`
`(b) Is the pharmaceutical equivalent approved for the same indication for which the
`505(b)(2) application is seeking approval?
` YES
`
`
`(c) Is the listed drug(s) referenced by the application a pharmaceutical equivalent?
` N/A
` YES
` NO
`Note: the pharmaceutically equivalent products are owned by the sponsor and cross referenced
`in this application.
`
`If this application relies only on non product-specific published literature, answer “N/A”
`If “YES” to (c) and there are no additional pharmaceutical equivalents listed, proceed to
`question #12.
`If “NO” or if there are additional pharmaceutical equivalents that are not referenced by the
`application, list the NDA pharmaceutical equivalent(s); you do not have to individually list all
`of the products approved as ANDAs, but please note below if approved approved generics are
`listed in the Orange Book. Please also contact the (b)(2) review staff in the Immediate Office,
`Office of New Drugs.
`
`Pharmaceutical equivalent(s):
`Xyzal tablets-NDA 22064
`Multiple approved ANDAs.
`
`11) (a) Is there a pharmaceutical alternative(s) already approved (via an NDA or ANDA)?
`
`(Pharmaceutical alternatives are drug products that contain the identical therapeutic moiety, or its
`precursor, but not necessarily in the same amount or dosage form or as the same salt or ester. Each
`such drug product individually meets either the identical or its own respective compendial or other
`applicable standard of identity, strength, quality, and purity, including potency and, where applicable,
`content uniformity, disintegration times and/or dissolution rates. (21 CFR 320.1(d)) Different dosage
`forms and strengths within a product line by a single manufacturer are thus pharmaceutical
`alternatives, as are extended-release products when compared with immediate- or standard-release
`formulations of the same active ingredient.)
`
`Note that for proposed combinations of one or more previously approved drugs, a pharmaceutical
`alternative must also be a combination of the same drugs.
`
` NO
` YES
`If “NO”, proceed to question #12.
`
`(b) Is the pharmaceutical alternative approved for the same indication for which the
`505(b)(2) application is seeking approval?
` YES
`
`
`
` NO
`
`Reference ID: 4045813
`
`Page 5
`Version: January 2015
`
`

`

`(c) Is the approved pharmaceutical alternative(s) referenced as the listed drug(s)?
` N/A
` YES
` NO
`
`If this application relies only on non product-specific published literature, answer “N/A”
`If “YES” and there are no additional pharmaceutical alternatives listed, proceed to question
`#12.
`If “NO” or if there are additional pharmaceutical alternatives that are not referenced by the
`application, list the NDA pharmaceutical alternative(s); you do not have to individually list all
`of the products approved as ANDAs, but please note below if approved generics are listed in
`the Orange Book. Please also contact the (b)(2) review staff in the Immediate Office, Office of
`New Drugs.
`
`Pharmaceutical alternative(s):
`
`PATENT CERTIFICATION/STATEMENTS
`
`12) List the patent numbers of all unexpired patents listed in the Orange Book for the listed
`drug(s) for which our finding of safety and effectiveness is relied upon to support approval of
`the (b)(2) product.
`
`Listed drug/Patent number(s): 6,455,533 for NDA 21621 Zyrtec chewable
`tablets
`
` No patents listed
`
` proceed to question #14
`
`13) Did the applicant address (with an appropriate certification or statement) all of the unexpired
`patents listed in the Orange Book for the listed drug(s) relied upon to support approval of the
`(b)(2) product?
` NO
` YES
`If “NO”, list which patents (and which listed drugs) were not addressed by the applicant.
`
`Listed drug/Patent number(s):
`
`14) Which of the following patent certifications does the application contain? (Check all that
`apply and identify the patents to which each type of certification was made, as appropriate.)
`
`No patent certifications are required (e.g., because application is based solely on
`published literature that does not cite a specific innovator product)
`
`21 CFR 314.50(i)(1)(i)(A)(1): The patent information has not been submitted to
`FDA. (Paragraph I certification)
`
`21 CFR 314.50(i)(1)(i)(A)(2): The patent has expired. (Paragraph II certification)
`
`Patent number(s):
`
`21 CFR 314.50(i)(1)(i)(A)(3): The date on which the patent will expire. (Paragraph
`III certification)
`
`Page 6
`Version: January 2015
`
`Reference ID: 4045813
`
`

`

`Patent number(s):
`
`Expiry date(s):
`
`21 CFR 314.50(i)(1)(i)(A)(4): The patent is invalid, unenforceable, or will not be
`infringed by the manufacture, use, or sale of the drug product for which the
`application is submitted. (Paragraph IV certification). If Paragraph IV certification
`was submitted, proceed to question #15.
`
`21 CFR 314.50(i)(3): Statement that applicant has a licensing agreement with the
`NDA holder/patent owner (must also submit certification under 21 CFR
`314.50(i)(1)(i)(A)(4) above). If the applicant has a licensing agreement with the
`NDA holder/patent owner, proceed to question #15.
`
`21 CFR 314.50(i)(1)(ii): No relevant patents.
`
`
`21 CFR 314.50(i)(1)(iii): The patent on the listed drug is a method of use patent
`and the labeling for the drug product for which the applicant is seeking approval
`does not include any indications that are covered by the use patent as described in
`the corresponding use code in the Orange Book. Applicant must provide a
`statement that the method of use patent does not claim any of the proposed
`indications. (Section viii statement)
`
`Patent number(s):
`Method(s) of Use/Code(s):
`
`15) Complete the following checklist ONLY for applications containing Paragraph IV
`certification and/or applications in which the applicant and patent holder have a licensing
`agreement:
`
`(a) Patent number(s): 6,455,533
`
`(b) Did the applicant submit a signed certification stating that the NDA holder and patent
`owner(s) were notified that this b(2) application was filed [21 CFR 314.52(b)]?
` NO
` YES
`If “NO”, please contact the applicant and request the signed certification.
`
`(c) Did the applicant submit documentation showing that the NDA holder and patent
`owner(s) received the notification [21 CFR 314.52(e)]? This is generally provided in the
`form of a registered mail receipt.
` NO
` November 18, 2016 submission YES
`If “NO”, please contact the applicant and request the documentation.
`
`(d) What is/are the date(s) on the registered mail receipt(s) (i.e., the date(s) the NDA holder
`and patent owner(s) received notification):
`
`Date(s): June 27. 2016
`
`Note, the date(s) entered should be the date the notification occurred (i.e., delivery
`date(s)), not the date of the submission in which proof of notification was provided
`
`Reference ID: 4045813
`
`Page 7
`Version: January 2015
`
`

`

`(e) Has the applicant been sued for patent infringement within 45-days of receipt of the
`notification listed above?
`
`Note that you may need to call the applicant (after 45 days of receipt of the notification)
`to verify this information UNLESS the applicant provided a written statement from the
`notified patent owner(s) that it consents to an immediate effective date of approval.
`
`YES
`
`NO
`
`Patent owner(s) consent(s) to an immediate effective date of
`approval
`
`Reference ID: 4045813
`
`Page 8
`Version: January 2015
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`SHERRY A STEWART
`01/24/2017
`
`Reference ID: 4045813
`
`

`

`505(b)(2) ASSESSMENT
`
`NDA # 209090
`
`Application Information
`NDA Supplement #: S-
`Efficacy Supplement Type SE-
`
`Proprietary Name: Children’s Xyzal Allergy 24HR (proposed)
`Established/Proper Name: levocetirizine dihydrochloride
`Dosage Form: oral solution
`Strengths: 0.5 mg/mL (2.5 mg/5mL)
`Applicant: UCB, Inc.
`
`Date of Receipt: March 31, 2016
`
`PDUFA Goal Date: January 31, 2016
`
`RPM: Sherry Stewart
`Proposed Indication(s): Partial RX to OTC switch for the following:
`
`Action Goal Date (if different):
`
`
`Uses: temporarily relieves these symptoms due to hay fever or other upper respiratory allergies:
`• runny nose
`
`• sneezing
`
`• itchy, watery eyes
`
`• itching of the nose or throat
`
`GENERAL INFORMATION
`
`1)
`
`Is this application for a recombinant or biologically-derived product and/or protein or peptide
`product OR is the applicant relying on a recombinant or biologically-derived product and/or
`protein or peptide product to support approval of the proposed product?
` YES
`
` NO
`
` If “YES “contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`Reference ID: 4045831
`
`Page 1
`Version: January 2015
`
`

`

`INFORMATION PROVIDED VIA RELIANCE
`(LISTED DRUG OR LITERATURE)
`
`2) List the information essential to the approval of the proposed drug that is provided by reliance
`on our previous finding of safety and efficacy for a listed drug by reliance on published
`literature, or by reliance on a final OTC monograph. (If not clearly identified by the
`applicant, this information can usually be derived from annotated labeling.)
`
`Source of information* (e.g.,
`published literature, name of listed
`drug(s), OTC final drug
`monograph)
`
`Information relied-upon (e.g., specific
`sections of the application or labeling)
`
` *each source of information should be listed on separate rows, however individual
`literature articles should not be listed separately
`
`3) The bridge in a 505(b)(2) application is information to demonstrate sufficient similarity
`between the proposed product and the listed drug(s) or to justify reliance on information
`described in published literature for approval of the 505(b)(2) product. Describe in detail how
`the applicant bridged the proposed product to the listed drug(s) and/or published literature1.
`See also Guidance for Industry Providing Clinical Evidence of Effectiveness for Human Drug
`and Biological Products.
`Bridge for nonclinical information has been previously established per NDA 22064 and
`NDA 22157. The pending OTC NDA cross references these approved RX NDAs.
`
`RELIANCE ON PUBLISHED LITERATURE
`
`4)
`
`(a) Regardless of whether the applicant has explicitly stated a reliance on published literature
`to support their application, is reliance on published literature necessary to support the
`approval of the proposed drug product (i.e., the application cannot be approved as labeled
`without the published literature)?
` NO
` YES
`If “NO,” proceed to question #5.
`
`(b) Does any of the published literature necessary to support approval identify a specific (e.g.,
`brand name) listed drug product?
` NO
` YES
`If “NO”, proceed to question #5.
`If “YES”, list the listed drug(s) identified by name and answer question #4(c).
`
`(c) Are the drug product(s) listed in (b) identified by the applicant as the listed drug(s)?
` NO
` YES
`
`1For 505(b)(2) applications that rely on a listed drug(s), bridging studies are often BA/BE studies comparing the proposed product to the listed drug(s) Other examples include: comparative
`physicochemical tests and bioassay; preclinical data (which may include bridging toxicology studies); pharmacokinetic/pharmacodynamic (PK/PD) data; and clinical data (which may
`include immunogenicity studies) A bridge may also be a scientific rationale that there is an adequate basis for reliance upon FDA’s finding of safety and effectiveness of the listed drug(s)
`For 505(b)(2) applications that rely upon literature, the bridge is an explanation of how the literature is scientifically sound and relevant to the approval of the proposed 505(b)(2) product
`Page 2
`
`Reference ID: 4045831
`
`Version: January 2015
`
`

`

`RELIANCE ON LISTED DRUG(S)
`
`Reliance on published literature which identifies a specific approved (listed) drug constitutes
`reliance on that listed drug. Please answer questions #5-9 accordingly.
`
`5) Regardless of whether the applicant has explicitly cited reliance on listed drug(s), does the
`application rely on the finding of safety and effectiveness for one or more listed drugs
`(approved drugs) to support the approval of the proposed drug product (i.e., the application
`cannot be approved without this reliance)?
` NO
` YES
`If “NO,” proceed to question #10.
`
`6) Name of listed drug(s) relied upon, and the NDA #(s). Please indicate if the applicant
`explicitly identified the product as being relied upon (see note below):
`
`Name of Listed Drug
`
`NDA #
`
`Did applicant
`specify reliance on
`the product? (Y/N)
`
`Zyrtec (cetirizine )tablets
`
`Zyrtec (cetirizine ) oral syrup
`
`Zyrtec (cetirizine) chewable tablets
`
`NDA 19835
`
` NDA 20346
`
`NDA 21621
`
`Yes
`
`Yes
`
`Yes
`
`Applicants should specify reliance on the 356h, in the cover letter, and/or with their patent
`certification/statement. If you believe there is reliance on a listed product that has not been
`explicitly identified as such by the applicant, please contact the (b)(2) review staff in the
`Immediate Office, Office of New Drugs.
`
`7)
`
`If this is a (b)(2) supplement to an original (b)(2) application, does the supplement rely upon
`the same listed drug(s) as the original (b)(2) application?
` NO
` YES
` N/A
`If this application is a (b)(2) supplement to an original (b)(1) application or not a supplemental
`application, answer “N/A”.
`If “NO”, please contact the (b)(2) review staff in the Immediate Office, Office of New Drugs.
`
`8) Were any of the listed drug(s) relied upon for this application:
`a) Approved in a 505(b)(2) application?
` YES
` NO
`If “YES”, please list which drug(s).
`Name of drug(s) approved in a 505(b)(2) application:
`
`b) Approved by the DESI process?
` YES
` NO
`If “YES”, please list which drug(s).
`Name of drug(s) approved via the DESI process:
`
`c) Described in a final OTC drug monograph?
`
`Page 3
`Version: January 2015
`
`Reference ID: 4045831
`
`

`

` NO
` YES
`If “YES”, please list which drug(s).
`
`Name of drug(s) described in a final OTC drug monograph:
`
`d) Discontinued from marketing?
` YES
` NO
`If “YES”, please list which drug(s) and answer question d) i. below.
`If “NO”, proceed to question #9.
`
`Name of drug(s) discontinued from marketing:
`NDA 20346 Zyrtec (cetirizine hydrochloride) syrup, 5 mg/5 mL
`
`i) Were the products discontinued for reasons related to safety or effectiveness?
` YES
` NO
`(Information regarding whether a drug has been discontinued from marketing for
`reasons of safety or effectiveness may be available in the Orange Book. Refer to
`section 1.11 for an explanation, and section 6.1 for the list of discontinued drugs. If
`a determination of the reason for discontinuation has not been published in the
`Federal Register (and noted in the Orange Book), you will need to research the
`archive file and/or consult with the review team. Do not rely solely on any
`statements made by the sponsor.)
`9) Describe the change from the listed drug(s) relied upon to support this (b)(2) application (for
`example, “This application provides for a new indication, otitis media” or “This application
`provides for a change in dosage form, from capsule to solution”).
`
`This application is for the L-enantiomer of the active ingredient that is being relied upon.
`This application provides for a partial Rx-to-OTC switch.
`
`The purpose of the following two questions is to determine if there is an approved drug product
`that is equivalent or very similar to the product proposed for approval that should be referenced
`as a listed drug in the pending application.
`
`The assessment of pharmaceutical equivalence for a recombinant or biologically-derived product
`and/or protein or peptide product is complex. If you answered YES to question #1, proceed to
`question #12; if you answered NO to question #1, proceed to question #10 below.
`
`10) (a) Is there a pharmaceutical equivalent(s) to the product proposed in the 505(b)(2)
`application that is already approved (via an NDA or ANDA)?
`
`(Pharmaceutical equivalents are drug products in identical dosage forms intended for the
`same route of administration that: (1) contain identical amounts of the identical active drug
`ingredient, i.e., the same salt or ester of the same therapeutic moiety, or, in the case 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 of the 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, including potency and, where applicable, content uniformity,
`disintegration times, and/or dissolution rates. (21 CFR 320.1(c), FDA’s “Approved Drug
`Products with Therapeutic Equivalence Evaluations” (the Orange Book)).
`
`
`Reference ID: 4045831
`
`Page 4
`Version: January 2015
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`Note that for proposed combinations of one or more previously approved drugs, a pharmaceutical
`equivalent must also be a combination of the same drugs.
`
` YES
`
` NO
`
`If “NO” to (a) proceed to question #11.
`If “YES” to (a), answer (b) and (c) then proceed to question #12.
`
`
`
`
` NO
`
`(b) Is the pharmaceutical equivalent approved for the same indication for which the
`505(b)(2) application is seeking approval?
` YES
`
`
`(c) Is the listed drug(s) referenced by the application a pharmaceutical equivalent?
` N/A
` YES
` NO
`Note: the pharmaceutically equivalent products are owned by the sponsor and cross referenced
`in this application.
`
`If this application relies only on non product-specific published literature, answer “N/A”
`If “YES” to (c) and there are no additional pharmaceutical equivalents listed, proceed to
`question #12.
`If “NO” or if there are additional pharmaceutical equivalents that are not referenced by the
`application, list the NDA pharmaceutical equivalent(s); you do not have to individually list all
`of the products approved as ANDAs, but please note below if approved approved generics are
`listed in the Orange Book. Please also contact the (b)(2) review staff in the Immediate Office,
`Office of New Drugs.
`
`Pharmaceutical equivalent(s):
`Xyzal oral solution-NDA 22157
`Multiple approved ANDAs.
`
`11) (a) Is there a pharmaceutical alternative(s) already approved (via an NDA or ANDA)?
`
`(Pharmaceutical alternatives are drug products that contain the identical therapeutic moiety, or its
`precursor, but not necessarily in the same amount or dosage form or as the same salt or ester. Each
`such drug product individually meets either the identical or its own respective compendial or other
`applicable standard of identity, strength, quality, and purity, including potency and, where applicable,
`content uniformity, disintegration times and/or dissolution rates. (21 CFR 320.1(d)) Different dosage
`forms and strengths within a product line by a single manufacturer are thus p