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`RESEARCH
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`CHEMISTRY REVIEW(S)
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`Reference ID: 3694741
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`Reference ID: 3705748
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MARY GRACE LUBAO
`02/23/2015
`
`Reference ID: 3705748
`
`

`

`CHEMISTRY REVIEW
`
`NDA 206-276
`
`Pazeo
`(olopatadine hydrochloride
`ophthalmic solution), 0.7%
`
`Alcon Research, Inc.
`
`Libaniel Rodriguez, Ph.D.
`Division of Transplants & Ophthalmology Drug Products
`HFD-590
`
`Reference ID: 3694741
`
`

`

`CHEMISTRY REVIEW
`
`Table of Contents
`
`Table of Contents.......................................................................................................................... 2
`
`Chemistry Review Data Sheet...................................................................................................... 4
`
`The Executive Summary .............................................................................................................. 8
`
`I. Recommendations......................................................................................................................8
`A. Recommendation and Conclusion on Approvability.......................................................... 8
`B. Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements, and/or Risk
`Management Steps, if Approvable...................................................................................... 8
`
`II. Summary of Chemistry Assessments.........................................................................................8
`A. Description of the Drug Product(s) and Drug Substance(s) ............................................... 8
`B. Description of How the Drug Product is Intended to be Used.......................................... 10
`C. Basis for Approvability or Not-Approval Recommendation ............................................ 10
`
`III. Administrative.........................................................................................................................12
`A. Reviewer’s Signature ........................................................................................................ 12
`B. Endorsement Block ........................................................................................................... 12
`C. CC Block........................................................................................................................... 12
`
`Chemistry Assessment................................................................................................................ 12
`
`I. Review Of Common Technical Document-Quality (Ctd-Q) Module 3.2: Body Of Data.......12
`3.2.S DRUG SUBSTANCE [olopstsdine hydrochloride,
`] 12
`3.2.S.1.. General Information 12
`
`3.2.S.2. Manufacture 15
`
`3.2.S.3 Characterization 13
`
`3.2.S.4. Control of Drug Substance 18
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`3.2.S.5. Reference Standards or Materials 23
`
`3.2.S.6. Container Closure System 24
`
`3.2.S.7. Stability 25
`
`Reference ID: 3694741
`
`(b) (4)
`
`

`

`CHEMISTRY REVIEW
`
`P
`
`DRUG PRODUCT [Name, Dosage form]
`
` 26
`
`3.2.P.1. Description and Composition 26
`
`3.2.P.2. Pharmaceutical Development 29
`
`3.2.P.3. Manufacture 36
`
`3.2.P.4. Control of Excipients 40
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`3.2.P.5. Control of Drug Product 56
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`3.2.P.6. Reference Standards or Materials 80
`
`3.2.P.7. Container closure System 84
`
`3.2.P.8. Stability 86
`
`3.2.P.8.1 Stability Summary and Conclusion 86
`
`3.2.P.8.2 Post-Approval Stability Protocol and Stability Commitment 92
`
`3.2.P.8.3 Stability Data 93
`
`A APPENDICES 101
`3.2.A.1. Facilities and Equipment
`
`3.2.A.2. Adventitious Agents Safety Evaluation
`
`3.2.A.3. Novel Excipients
`
`R REGIONAL INFORMATION ...................................................................................... 101
`3.2.R.1 Executed Batch Records
`
`3.2.R.2 Blank Manufacturing Batch Records
`
`3.2.R.3. Method Validation Information
`II. Review Of Common Technical Document-Quality (Ctd-Q) Module 1 ................................101
`A. Labeling & Package Insert............................................................................................. 102
`B. Environmental Assessment Or Claim Of Categorical Exclusion.................................... 108
`
`III.
`
`List Of Deficiencies To Be Communicated....................................................................N/A
`
`Reference ID: 3694741
`
`

`

`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`Chemistry Review Data Sheet
`
`1. NDA :
`
`206-276
`
`2. REVIEW #:
`
`1
`
`3. REVIEW DATE: September 22, 2014
`
`4. REVIEWER:
`
`Libaniel Rodriguez
`
`5. PREVIOUS DOCUMENTS: N/A
`Previous Documents
`
`6. SUBMISSION(S) BEING REVIEWED:
`
`Document Date
`
`Submission(s) Reviewed
`
`Document Date
`
`
`
`NDA original July 31, 2014
`
`7. NAME & ADDRESS OF APPLICANT:
`
`Name:
`Address:
`
`Representative:
`
`Telephone:
`
`Alcon Research, Ltd.
`6201 South Freeway
`Mail Stop: TC-Fort Worth, TX 7613-2099
`USA
`Naj Sharif, PhD; Global Regulatory Project
`Manager
`817-568-6494
`
`8. DRUG PRODUCT NAME/CODE/TYPE:
`
`a) Proprietary Name: PAZEO
`b) Non-Proprietary Name (USAN): olopatadine hydrochloride ophthalmic solution, 0.7%
`c) Code Name/# FID
`d) Chem. Type/Submission Priority (ONDC only): 505(b) (1)
` Chem. Type:
`5
` Submission Priority:
`
`Priority
`
`9. LEGAL BASIS FOR SUBMISSION: New Drug Application, 505(b)(1)
`
`10. PHARMACOL. CATEGORY:
`inhibitor of
`
`Relatively selective histamine H1 antagonist and an
`
`Reference ID: 3694741
`
`Page 4 of 108
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`(b) (4)
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`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
` the release of histamine from the mast cells.
`
`11. DOSAGE FORM:
`
`Ophthalmic Solution
`
`12. STRENGTH/POTENCY:
`
`0.7%
`
`13. ROUTE OF ADMINISTRATION:
`
`Topical Ocular
`
`14. Rx/OTC DISPENSED:
`
`Rx
`
`15. SPOTS (SPECIAL PRODUCTS ON-LINE TRACKING SYSTEM): Not a SPOTS product
`
`16.
`
` CHEMICAL NAME, STRUCTURAL FORMULA, MOLECULAR FORMULA,
`MOLECULAR WEIGHT:
`
` USAN/INN Name:
`
`Olopatadine Hydrochloride
`
` Chemical Names:
`
`- (Z)-11-[3-(Dimethylamino)propylidene]-6,11-
`dihydrodibenz[b,e]oxepin-2-acetic acid, dihydrodibenz
`hydrochloride
`
` - 11-[(Z)-3-(Dimethylamino)propylidene]-6,11- [b,e]oxepin-2-
` acetic acid, hydrochloride
`
` Company or Laboratory Code: AL-4943(A) [Alcon]
`
`
`
` Other Non-Proprietary Name(s):
`
`None
`
` Chemical Abstracts Service (CAS) Registry Number:
`(hydrochloride)
`
`140462-76-6
`
` 113806-05-6 (base)
`
` Structural Formula
`
`
`
` Molecular Formula: C21H23NO3.HCI
`
`Reference ID: 3694741
`
`Page 5 of 108
`
`(b) (4)
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`(b) (4)
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`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
` Relative Molecular Mass:
`
`373.88 gm/mol
`
`17. RELATED/SUPPORTING DOCUMENTS:
`
`A. DMFs:
`
`DMF #
`
`Holder
`
`Item Referenced
`Olopatadine Hydrochloride
` Drug Substance
`
`Status2 Date Review
`Code
`Completed
`1
`1 Adequate 09-11-2014
`
`LOA Date
`12-18-2013
`
`05-11-2009
`10-07-2010
`10-07-2010
`01-31-13
`
`3
`Adequate
`Adequate
`3
`
`12-19-2012
`09-15-2014
`09-08-2014
`09-21-2013
`
`1111
`
`1 Action codes for DMF Table:
`1 – DMF Reviewed.
`Other codes indicate why the DMF was not reviewed, as follows:
`2 –Type 1 DMF
`3 – Reviewed previously and no revision since last review
`4 – Sufficient information in application
`5 – Authority to reference not granted
`6 – DMF not available
`7 – Other (explain under "Comments")
`
`2 Adequate, Inadequate, or N/A (There is enough data in the application, therefore the
`DMF did not need to be reviewed)
`
`B. Other Documents:
`
`DOCUMENT
`
`APPLICATION NUMBER
`
`DESCRIPTION
`
`Reference ID: 3694741
`
`Page 6 of 108
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`18. STATUS:
`
`ONDQA:
`CONSULTS/ CMC
`RELATED
`REVIEWS
`
`EES
`
`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`RECOMMENDATION
`
`DATE
`
`REVIEWER
`
`Overall recommendation
`Approval
`
`01-27-2015
`
`OC
`
`01-20-2015,
`Alcon, TX
`11-18-2014,
`Alcon,
`Covreur
`
`
`
`Pharm/Tox
`Biopharm
`EA
`Microbiology
`
`Approval
`Approval
`Categorical Exclusion granted
`Approval
`
`12-31-2014
`12-23-2014
`This review
`01-06-2015
`
`Dr. Aaron M. Ruhland
`Dr. Banu Sizanli Zolnik
`Dr. Libaniel Rodriguez
`Dr. Stephen Langille
`
`Reference ID: 3694741
`
`Page 7 of 108
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`(b) (4)
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`

`CHEMISTRY REVIEW
`Executive Summary Section
`
`The Chemistry Review for NDA 206-276
`
`The Executive Summary
`
`I.
`
`Recommendations
`
`A.
`
`Recommendation and Conclusion on Approvability
`
`The NDA provides adequate information to assure the identity, strength, purity,
`and quality of the drug product. All CMC issues have been resolved satisfactorily
`and
`there are no outstanding
`issues. The Office of Compliance (OC)
`recommended the drug substance manufacturing facility,
`, for approval on
`, and the drug product
`manufacturing facilities, Alcon Research, LTD., Fort Worth, Texas and Alcon-
`Covreour nv, Puurs, Belgium, on January 20, 2015 and November 8, 2014
`respectively, The Overall recommendation for approval was issued on January
`27, 2015 (see copies of OC reports attached to this review). This NDA is
`recommended for approval from the CMC perspective, Micro, PharmTox and
`Biopharm reviews also recommend approval of the NDA.
`
`B.
`
`Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements,
`and/or Risk Management Steps, if Approvable
`
`N/A
`
`II.
`
`Summary of Chemistry Assessments
`
`A. Description of the Drug Product(s) and Drug Substance(s)
`
`Drug Product: Olopatadine Hydrochloride Ophthalmic Solution, 0.7%, is a sterile,
`preserved, multi-dose ophthalmic solution formulation containing 0.77% w/w
`olopatadine hydrochloride. The formulation is developed as a topical ocular allergy
`product for QD treatment of chronic allergic inflammatory conditions.
`
`The active ingredient, olopatadine hydrochloride, in the proposed formulation is
` in the US approved products, PATADAY™, 0.2% (NDA 21-545) and
`PATANOL Ophthalmic Solution, 0.1% (NDA 20-688).
`
`
`
`Olopatadine Hydrochloride Ophthalmic Solution, 0.7% was formulated with the
`objective to increase the overall concentration of olopatadine in the conjunctiva to
`increase the magnitude and duration of efficacy in the treatment of allergic
`conjunctivitis. To meet this objective, Alcon has submitted this NDA for a product
`with a formulation containing new excipients and a higher concentration of
`olopatadine..
`
`Reference ID: 3694741
`
`Page 8 of 108
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`

`CHEMISTRY REVIEW
`Executive Summary Section
`
`
`The aqueous solubility of olopatadine at physiological pH
`) in the proposed
` The increased solubility of olopatadine base (0.7%
`aqueous formulation is achieved through the addition of the excipient,
`hydroxypropyl-γ-cyclodextrin (HP-γ-CD). The pH of the formulation is 7.2 which is
`closer to physiologic pH 7.4 and is similar to the pH of Alcon’s marketed products
`Patanol 0.1% and Pataday 0.2% (pH 7.0).
`
`Olopatadine Hydrochloride Ophthalmic Solution, 0.7% solution contains: Active:
`7.76 mg olopatadine hydrochloride equivalent to 0.7 mg olopatadine. Inactives:
`povidone; hydroxypropyl-gamma-cyclodextrin; polyethylene glycol 400;
`hydroxypropyl methylcellulose; boric acid; mannitol; benzalkonium chloride 0.015%
`(preservative); hydrochloric acid/sodium hydroxide (to adjust pH); and purified
`water.
`
`The excipient, hydroxypropyl-γ-cyclodextrin has not previously been approved in the
`US for use in any ophthalmic drug products. All pertinent CMC information
`regarding manufacture, raw materials, characterization, controls (raw materials and
`final hydroxypropyl-γ-cyclodextrin) and stability of the new solubilizing excipient
`has been provided in this application to support its use in the formulation. The data
`and information provided were reviewed and the conclusion of the review was that
`the quality of the proposed new excipient is adequate and that the use of this excipient
`does not have any adverse effect on the quality of the final drug product.
`
`Olopatadine Hydrochloride Ophthalmic Solution, 0.7% is supplied in a low density
`polyethylene (LDPE) white oval bottle with LDPE dispensing plug and
`polypropylene (PP) closure. This container/closure system is the same as the
`container/closure systems used in the related, approved ophthalmic drug products
`PATANOL and PATADAY from the same applicant. The product has a 2.5 mL fill
`trade size and a 0.5 mL fill sample size. The filled containers are labeled and the 0.5
`mL sample size is placed in a
`.
`
`The shelf life for this drug product is 104 weeks (24 months) and it is supported by
`the updated 78 weeks of stability data provided. Extensions of the shelf life for this
`drug product will be made through incoming annual reports, based on real time data.
`
`Drug Substance: Olopatadine hydrochloride, a structural analog of doxepine, is a
`potent, selective and topically effective anti-allergic/antihistaminic molecule. Because
`of these characteristics, it is considered valuable in the management of
`
`allergic conjunctivitis.
`
`Olopatadine hydrochloride is a white crystalline powder.
`olopatadine hydrochloride are clear, colorless
`substance is soluble in
`
`
` The drug
`
`
`Olopatadine hydrochloride has no polymorphs and does not have a chiral
`
`Reference ID: 3694741
`
`Page 9 of 108
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`

`CHEMISTRY REVIEW
`Executive Summary Section
`
`center.
`
`
`
`Olopatadine hydrochloride in the formulation is the same as in the US approved
`products, PATADAY™, 0.2% ophthalmic solution (NDA 21-545) and PATANOL
`Ophthalmic Solution, 0.1% (NDA 20-688),
`
`
`All CMC data and information necessary to assess the quality of olopatadine
`hydrochloride were provided in this application by reference to
`. Appropriate Letter of Authorization by
`, was provided. This DMF was previously reviewed on by Dr.
`Yong De Lu and found adequate in a review dated May 29, 2009. Updates to this
`DMF since the date of the last review were reviewed by this reviewer and the DMF
`was found to be adequate in support of this application on September 11, 2014. The
`retest date for the drug substance is
`stored at
`.
`
`
`
`
`
`B. Description of How the Drug Product is Intended to be Used
`
`ocular
`The drug product PAZEO, is intended for use in the treatment of
`itching associated with allergic conjunctivitis. The recommended dosing regime is
`one drop in each affected eye once a day.
`
`C. Basis for Approvability or Not-Approval Recommendation
`
`PharmTox, Microbiology and BioPharm recommend approval of this NDA
`application. The OC recommends all the facilities involved in the manufacturing of
`this drug product and substance for approval (see copy of OC conclusions attached at
`the end of this review). All other aspect of this application involving chemistry
`manufacturing and controls are acceptable. For these reasons, from the point of view
`of CMC, this application is recommended for approval.
`
`Product Quality Risk Assessment
`From Initial Quality Assessment
`Review Assessment
`
`Product
`Attribute/CQA
`
`Factors that
`can impact the
`CQA
`
`Assay for
`Olopatadine
`
`Quality of the
`incoming API;
`Analytical
`Method
`
`Risk Ranking
`(H) High
`(M) Medium
`(L) Low
`
`L
`
`Risk Mitigation
`approach
`
`Risk Evaluation
`
`Evaluate the
`incoming material
`Specification and
`CoA provided.
`Additionally
`
`Acceptable. Method is
`adequate and validation
`confirms that the method is
`suitable for its intended
`purposes.
`
`Reference ID: 3694741
`
`Page 10 of 108
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`

`

`CHEMISTRY REVIEW
`Executive Summary Section
`
`L
`
`M
`
`L
`
`M
`
`H
`
`Evaluate Method.
`
`Check MBR for
`accuracy of the salts
`added.
`
`Analytical method
`for assay of BAK
`should be validated.
`If there is an
`overage used,
`evaluate the
`justification
`provided.
`Analytical method
`should be validated
`to capture the
`impurities. Calculate
`levels and if it exceeds
`Q3B qualification
`threshold, consult
`Pharm/Tox reviewer.
`Evaluate the need to
`control Extractables
`and leachables in the
`drug product
`Specification.
`Evaluate data and
`if loss is larger or
`equal to 5%,
`consider options
`available (such as
`shorter expiration
`date; alternate
`storage conditions
`if there is
`sufficient data for
`this route)
`Satisfactory
`validation
`
`Review of MBR confirms
`accuracy of weighings.
`
`Method was appropriately
`validated and found to be
`suitable for its intended
`purposes.
`No overages needed.
`
`Analytical method for
`impurities adequately validated
`and demonstrated to be suitable
`for intended purposes. No
`impurities levels were found or
`proposed above the Q3B
`qualification threshold.
`Extractables and leachables,
`when detected, were well below
`qualification thresholds. There
`was no need to include these in
`the Specification for the drug
`product.
`The average weight loss
`over a period of
`at long term storage
`conditions was
`%,
`well below the 5% loss for
`any action to be taken.
`Weight loss is monitored
`for information only, and it
`is not a parameter in the
`Specification Sheet for this
`drug product.
`Simulations and
`interventions conducted
`during media fills,
`Environmental
`monitoring
`
`
`
`Osmolality
`
`Incorrect
`weighing; loss
`of water on
`storage.
`Assay for BAK Assay Method
`
`Impurities
`Including
`Extractables
`
`Quality of raw
`material;
`container.
`
`Weight Loss
`
`Container
`closure
`properties
`
`Sterility
`This section of
`the Risk
`assessment
`was conducted
`by the
`microbiology
`reviewer.
`
`Reference ID: 3694741
`
`Page 11 of 108
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`

`

`CHEMISTRY REVIEW
`Executive Summary Section
`
`III. Administrative
`
`A. Reviewer’s Signature
`
`B. Endorsement Block
`
`Chemist Name/Date: Libaniel Rodriguez, Ph.D./January 28, 2015
`Chemistry Division Director/ Name/Date: Thomas Oliver, Ph.D./January 28, 2015
`Chemistry CMC Lead: Balajee Shanmugam, Ph.D./January 28, 2015
`ProjectManager Name/Date: Lois Almoza/January 28, 2015
`
`C. CC Block
`
`Reference ID: 3694741
`
`Page 12 of 108
`
`96 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
`
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`
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`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LIBANIEL RODRIGUEZ
`01/30/2015
`Updated Final Review, AP
`
`THOMAS F OLIVER
`01/30/2015
`
`Reference ID: 3694741
`
`

`

`CHEMISTRY REVIEW
`
`NDA 206-276
`
`Pazeo
`(olopatadine hydrochloride
`ophthalmic solution), 0.77%
`
`Alcon Research, Inc.
`
`Libaniel Rodriguez, Ph.D.
`Division of Transplants & Ophthalmology Drug Products
`HFD-590
`
`Reference ID: 3688760
`
`

`

`CHEMISTRY REVIEW
`
`Table of Contents
`
`Table of Contents.......................................................................................................................... 2
`
`Chemistry Review Data Sheet...................................................................................................... 4
`
`The Executive Summary .............................................................................................................. 8
`
`I. Recommendations......................................................................................................................8
`A. Recommendation and Conclusion on Approvability.......................................................... 8
`B. Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements, and/or Risk
`Management Steps, if Approvable...................................................................................... 8
`
`II. Summary of Chemistry Assessments.........................................................................................8
`A. Description of the Drug Product(s) and Drug Substance(s) ............................................... 8
`B. Description of How the Drug Product is Intended to be Used.......................................... 10
`C. Basis for Approvability or Not-Approval Recommendation ............................................ 10
`
`III. Administrative.........................................................................................................................12
`A. Reviewer’s Signature ........................................................................................................ 12
`B. Endorsement Block ........................................................................................................... 12
`C. CC Block........................................................................................................................... 12
`
`Chemistry Assessment................................................................................................................ 13
`
`I. Review Of Common Technical Document-Quality (Ctd-Q) Module 3.2: Body Of Data.......13
`3.2.S DRUG SUBSTANCE [olopstsdine hydrochloride,
`12
`3.2.S.1.. General Information 12
`
`3.2.S.2. Manufacture 15
`
`3.2.S.3 Characterization 13
`
`3.2.S.4. Control of Drug Substance 18
`
`3.2.S.5. Reference Standards or Materials 23
`
`3.2.S.6. Container Closure System 24
`
`3.2.S.7. Stability 25
`
`Reference ID: 3688760
`
`(b) (4)
`
`

`

`CHEMISTRY REVIEW
`
`P
`
`DRUG PRODUCT [Name, Dosage form]
`
` 26
`
`3.2.P.1. Description and Composition 26
`
`3.2.P.2. Pharmaceutical Development 29
`
`3.2.P.3. Manufacture 36
`
`3.2.P.4. Control of Excipients 40
`
`3.2.P.5. Control of Drug Product 56
`
`3.2.P.6. Reference Standards or Materials 80
`
`3.2.P.7. Container closure System 84
`
`3.2.P.8. Stability 86
`
`3.2.P.8.1 Stability Summary and Conclusion 86
`
`3.2.P.8.2 Post-Approval Stability Protocol and Stability Commitment 92
`
`3.2.P.8.3 Stability Data 93
`
`A APPENDICES 101
`3.2.A.1. Facilities and Equipment
`
`3.2.A.2. Adventitious Agents Safety Evaluation
`
`3.2.A.3. Novel Excipients
`
`R REGIONAL INFORMATION ...................................................................................... 101
`3.2.R.1 Executed Batch Records
`
`3.2.R.2 Blank Manufacturing Batch Records
`
`3.2.R.3. Method Validation Information
`II. Review Of Common Technical Document-Quality (Ctd-Q) Module 1 ................................101
`A. Labeling & Package Insert............................................................................................. 102
`B. Environmental Assessment Or Claim Of Categorical Exclusion.................................... 108
`
`III.
`
`List Of Deficiencies To Be Communicated....................................................................N/A
`
`Reference ID: 3688760
`
`

`

`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
`Chemistry Review Data Sheet
`
`1. NDA :
`
`206-276
`
`2. REVIEW #:
`
`1
`
`3. REVIEW DATE: September 22, 2014
`
`4. REVIEWER:
`
`Libaniel Rodriguez
`
`5. PREVIOUS DOCUMENTS: N/A
`Previous Documents
`
`6. SUBMISSION(S) BEING REVIEWED:
`
`Document Date
`
`Submission(s) Reviewed
`
`Document Date
`
`
`
`NDA original July 31, 2014
`
`7. NAME & ADDRESS OF APPLICANT:
`
`Name:
`Address:
`
`Representative:
`
`Telephone:
`
`Alcon Research, Ltd.
`6201 South Freeway
`Mail Stop: TC-Fort Worth, TX 7613-2099
`USA
`Naj Sharif, PhD; Global Regulatory Project
`Manager
`817-568-6494
`
`8. DRUG PRODUCT NAME/CODE/TYPE:
`
`a) Proprietary Name: PAZEO
`b) Non-Proprietary Name (USAN): Olopatadine Hydrochloride
`c) Code Name/# FID
`d) Chem. Type/Submission Priority (ONDC only): 505(b) (1)
` Chem. Type:
`5
` Submission Priority:
`
`Priority
`
`9. LEGAL BASIS FOR SUBMISSION: New Drug Application, 505(b)(1)
`
`10. PHARMACOL. CATEGORY:
`inhibitor of
`
`Relatively selective histamine H1 antagonist and an
`
`Reference ID: 3688760
`
`Page 4 of 108
`
`(b) (4)
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`

`

`CHEMISTRY REVIEW
`Chemistry Review Data Sheet
`
` the release of histamine from the mast cells.
`
`11. DOSAGE FORM:
`
`Ophthalmic Solution
`
`12. STRENGTH/POTENCY:
`
`0.7%
`
`13. ROUTE OF ADMINISTRATION:
`
`Topical Ocular
`
`14. Rx/OTC DISPENSED:
`
`Rx
`
`15. SPOTS (SPECIAL PRODUCTS ON-LINE TRACKING SYSTEM): Not a SPOTS product
`
`16.
`
` CHEMICAL NAME, STRUCTURAL FORMULA, MOLECULAR FORMULA,
`MOLECULAR WEIGHT:
`
` USAN/INN Name:
`
`Olopatadine Hydrochloride
`
` Chemical Names:
`
`- (Z)-11-[3-(Dimethylamino)propylidene]-6,11-
`dihydrodibenz[b,e]oxepin-2-acetic acid, dihydrodibenz
`hydrochloride
`
` - 11-[(Z)-3-(Dimethylamino)propylidene]-6,11- [b,e]oxepin-2-
` acetic acid, hydrochloride
`
` Company or Laboratory Code: AL-4943(A) [Alcon]
`
`
`
` Other Non-Proprietary Name(s):
`
`None
`
` Chemical Abstracts Service (CAS) Registry Number:
`(hydrochloride)
`
`140462-76-6
`
` 113806-05-6 (base)
`
` Structural Formula
`
`
`
` Molecular Formula: C21H23NO3.HCI
`
`Reference ID: 3688760
`
`Page 5 of 108
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`

`CHEMISTRY REVIEW
`Chemistr