`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`APPLICATION NUMBER:
`
`0206276Orig1s005
`
`
` PATADAY ONCE DAILY RELIEF (Extra Strength)
`Trade Name:
`olopatadine hydrochloride 0.7%
`Generic or Proper
`Name:
`
`
`Sponsor:
`
`Approval Date:
`
`Indication:
`
`
`Alcon Research, LLC
`July 13, 2020
`Temporarily relieves itchy eyes due to pollen,
`ragweed, grass, animal hair, and dander.
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`0206276Orig1s005
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Clinical Review(s)
`Product Quality Review(s)
`Non-Clinical Review(s)
`Statistical Review(s)
`Clinical Microbiology / Virology Review(s)
`Clinical Pharmacology Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`
`X
`
`
`
`
`X
`X
`
`
`
`
`
`X
`
`X
`
`
`

`

`
`
`
`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`0206276Orig1s005
`
`
`APPROVAL LETTER
`
`

`

`SUPPLEMENT APPROVAL
`
`NDA 206276/S-005
`
`Alcon Research, LLC
`Attention: Vincent Nanevie, MS, MBA, RAC
`Director, Global Regulatory Affairs - Vision Care
`6201 South Freeway
`Fort Worth, TX 76134-2099
`
`Dear Mr. Nanevie:
`
`Please refer to your supplemental new drug application (sNDA) dated and received
`September 13, 2019 and your amendments, submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for Pataday Once Daily Relief
`(olopatadine hydrochloride ophthalmic solution, 0.7%).
`
`This “Prior Approval” supplemental new drug application provides for the full
`prescription to over-the-counter switch of olopatadine hydrochloride 0.7% ophthalmic
`solution.
`
`APPROVAL & LABELING
`
`We have completed our review of this application, as amended. It is approved, effective
`on the date of this letter, for use as recommended in the enclosed agreed-upon
`labeling.
`
`LABELING
`
`Submit final printed labeling (FPL) as soon as they are available, but no more than 30
`days after they are printed. The FPL must be identical to the submitted labeling and
`must be in the “Drug Facts” format (21 CFR 201.66), where applicable.
`
`Submitted Draft Labeling
`Pataday® Once Daily Relief (Extra Strength)
`2.5 mL (0.085 Fl oz) 0.7% carton
`Pataday® Once Daily Relief (Extra Strength)
`2.5 mL (0.085 Fl oz) 0.7% immediate
`container
`Pataday® Once Daily Relief (Extra Strength)
`Two X 2.5 mL (0.085 Fl oz) 0.7% carton -
`Twin Pack
`Pataday® Once Daily Relief (Extra Strength)
`Sample 0.5 mL (0.017 Fl oz) 0.7% carton
`
`Date Submitted
`July 9, 2020
`
`June 25, 2020
`
`July 9, 2020
`
`July 9, 2020
`
`Reference ID: 4640163
`
`

`

`NDA 206276/S-005
`Page 2
`
`Pataday® Once Daily Relief (Extra Strength)
`Sample 0.5 mL (0.017 Fl oz) 0.7% immediate
`container
`Pataday® Once Daily Relief (Extra Strength)
`Sample 0.5 mL (0.017 Fl oz) 0.7% pouch
`
`June 25, 2020
`
`June 25, 2020
`
`The FPL should be submitted electronically according to the guidance for industry
`Providing Regulatory Submissions in Electronic Format — Certain Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD
`Specifications.1 For administrative purposes, designate this submission “Final Printed
`Labeling for approved NDA 206276/S-005.” Approval of this submission by FDA is not
`required before the labeling is used.
`
`DRUG REGISTRATION AND LISTING
`
`All drug establishment registration and drug listing information is to be submitted to FDA
`electronically, via the FDA automated system for processing structured product labeling
`(SPL) files (eLIST). At the time that you submit your final printed labeling (FPL), the
`content of labeling (Drug Facts) should be submitted in SPL format as described at
`FDA.gov.2 Information on submitting SPL files using eLIST may be found in the
`guidance for industry SPL Standard for Content of Labeling Technical Qs and As. In
`addition, representative container or carton labeling, whichever includes Drug Facts,
`(where differences exist only in the quantity of contents statement) should be submitted
`as a JPG file.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`new active ingredients (which includes new salts and new fixed combinations), new
`indications, new dosage forms, new dosing regimens, or new routes of administration
`are required to contain an assessment of the safety and effectiveness of the product for
`the claimed indication in pediatric patients unless this requirement is waived, deferred,
`or inapplicable.
`
`Because none of these criteria apply to your application, you are exempt from this
`requirement.
`
`1 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`2 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4640163
`
`

`

`NDA 206276/S-005
`Page 3
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`POSTMARKETING COMMITMENT
`
`As part of an Enhanced Pharmacovigilance Commitment, for a period of 3 years, submit
`as 15-day alert reports, all initial and follow-up postmarketing adverse event reports of
`nonprescription overuse and nonprescription misuse from all postmarketing sources,
`including consumer reports, solicited reports, foreign reports, and clinical study reports.
`As part of the periodic safety reports, provide a summary analysis of nonprescription
`overuse and nonprescription misuse adverse events, from postmarketing reports and
`those published in the medical literature, as well as a cumulative summary of these
`events.
`
`If you have any questions, call LCDR Jung Lee, Safety Regulatory Project Manager, at
`(301) 796-3599.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Karen Murry Mahoney, MD, FACE
`Acting Deputy Director
`Office of Nonprescription Drugs
`Acting Director
`Division of Nonprescription Drugs I
`Office of New Drugs
`Center for Drug Evaluation and Research
`
`ENCLOSURE(S):
`(cid:120) Carton and Container Labeling
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4640163
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`KAREN M MAHONEY
`07/13/2020 08:19:30 PM
`
`(
`
`Reference ID: 4640163
`
`

`

`
` CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`0206276Orig1s005
`
`
`LABELING
`
`

`

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`* NDC: 0065-0816-04
`
`Alcon 25 ml (0.085FL0Z)
`
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`
`
`
`Reference ID: 4640163
`
`

`

`
`
`Reference ID: 4640163
`
`

`

`
`
`Drug Facts
`
`Active ingredient
`Olopatadine (0.7%)...
`
`Use temporarily relieves itchy eyes due to pollen,
`ragweed, grass, animal hair and dander
`
`
`
`
`
`For external use only
`Do not use
`wif solution changes color or becomes cloudy
`
`wif you are sensitive to any ingredient in this product
`Inactive ingredients
`1 to treat contact lens related irritation
`
`benzalkonium chloride 0.015%,
`When using this product
`
`@ do not touch tip of container to any surface to avoid
`
`contamination
`m remove contact lenses before use
`@ wait at least 10 minutes before reinserting contact
`
`lenses after use
`
`@ do not wear a contact lens if your eye is red
`Stop use and ask a doctor if you experience:
`wisecall1-800-757-8195,
`
`w increased rednessof the eye
`witching worsens or lasts for more than 72 hours
`Keepout of reach of children.
`If swallowed,get medical help or contact a Poison
`Control Center right away.
`Directions
`@ adults and children 2 years of age and okder:
`@ put 1 drop in the affected eye{s) once dally
`w do not use more than 1 drop in each eye per day
`
`
`
`
`
`Pataday.
`
`
`EXTRA STRENGTH
`
`
`
`
`ONCE DAILY RELIEF
`Olopatadine hydrochloride
`ophthalmic solution 0.7%Antihistamine
`Eye Allergy Itch Relief
`
`Drug Facts (continued)
`1 if using otherophthalmic
`products while using this
`product, wait at least 5 minutes
`between each product
`m replace cap after each use
`w children under 2 years of age:
`consulta doctor
`Other information
`
`EXTRA STRENGTH
`
`ONCE DAILY RELIEF
`Olopatadine hydrochloride
`ophthalmic solution 0.7%
`Antihistamine
`
`(aAllergyItchRelief
`
`Works in Minutes
`
`Relief from Allergens:
`+ Pet Dander + Pollen
`* Grass » Ragweed
`
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`
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`this bottlehasa sealimprinted with Alcon
`around the neck. Do not useifsealis
`damaged or missing at timeofpurchase.
`EACH BOTTLE CONTAINS
`A30 DAY SUPPLY
`
`Eye Allergy itch Relief
`Works in Minutes
`For Ages 2 and Older
`———— FillLire ———
`AlconLaboratories,Inc.
`6201South
`Fort Worth,lexas76134
`Country ofOrigin:Japan
`ACTUALSIZE
`Carton contains ? ¥ 2.5m! hotties
`NDC: 0065-0816-01
`
`
`
`
`Alcon (0.085 FLOZEACH) sree
`
`LOT:
`
`
`i>mlbottles
`or email alcon.medinfo@alcon.com
`
`
`Reference ID: 4640163
`
`

`

`
`
`
`EXTRA STRENGTH
`
`
`Pataday
`
`ONCE DAILY RELIEF
`
`
`Olopatadine hydrochloride
`
`ophthalmic solution 0.7%Antihistamine
`
`Eye Allergy Itch Relief
`
`Fee7Bleas)
`Drug Facts (continued)
`
`
`1 if using otherophthalmic
`Pataday.
`EXTRA STRENGTH
`products while using this
`
`Active ingredient
`Purpose
`product, wait at least 5 minutes
`Olopatadine (0.796)....scusuetsrsusseneeeeeeAntihistamine
`
`
`Pataday.
`between each product
`(equivalent to olopatadine hydrochloride 0.776%)
`
`
`m replace cap after each use
`
`w children under 2 years of age:
`Use temporarily relieves itchy eyes due to pollen,
`ragweed, grass, animal hair and dander
`
`Warnings
`For external use only
`Donot use
`
`wif solution changes color or becomes cloudy
`wif you are sensitive to any ingredient in this product
`
`Inactive ingredients
`1 to treat contact lens related irritation
`benzalkonium chloride 0.015%,
`
`Whenusing this product
`@ do not touch tip of container to any surface to avoid
`contamination
`m remove contact lenses before use
`@ wait at least 10 minutes before reinserting contact
`lenses after use
`@ do not wear a contact lens if your eye is red
`
`
`Stop use and ask a doctor if you experience:
`In the U.S., call 1-800-757-9195
`
`w increased redness of the eye
`witching worsens or lasts for more than 72 hours
`Keep out of reach of children.
`If swallowed,get medical help or contact a Poison
`Control Center right away.
`
`Directions
`@ adults and children 2 years of age and okder:
`
`STERILE
`@ put 1 drop in the affected eye{s) once dally
`w do not use more than 1 drop in each eye per day
`0.5 ml (0.017 FLOZ)
`
`
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`
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`Do notuse ifthe pouch Is
`damaged or missing at the
`time of use.
`
`Alcon Laboratories,Inc
`6201 South Freeway
`Fort Worth, Texas 76134
`Countryof Origin: Japan
`
`
`
`
`Other information
`
`ONCE DAILY RELIEF
`Olopatadine hydrochloride
`ophthalmic solution 0.7%
`Antihistamine
`Eye AllergyItch Relief
`Worksin Minutes
`
`Relief from Allergens:
`+ Pet Dander« Pollen
`
`
`* Grass » Ragweed
`or email alcon.medinfo@alcon.com
`
`
`Reference ID: 4640163
`
`

`

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`Reference ID: 4640163
`
`

`

`
`SeeCartonforUse,Warningsand Directions
`
`Pataday.
`
`SSae Alcon
`EyeAllergyItchRelief_ 0.5mb0.07FLO)
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`6201 South Freeway, FortWorth,TX76134
`
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`
`¢ Reference ID: 4640163
`
`

`

`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`0206276Orig1s005
`
`
`CROSS DISCIPLINE TEAM LEADER REVIEW
`
`

`

`Cross Discipline Team Leader Review
`
`Cross-Discipline Team Leader Review
`
`
`Date
`July 9, 2020
`From
`Francis E. Becker, M.D., F.A.C.P.
`
`years of age and older (same as proposed by Applicant One drop in theaffected eye(s) once daily,
`
`Pataday Once Daily Relief, “Extra Strength”
`Established or Proper Name
`Solution (ophthalmic use)
`Dosage Form(s)
`Temporarily relieves itchy eyes due to pollen, ragweed,
`Applicant Proposed
`grass, animal hair and dander/adults and children 2
`Indication(s)/Population(s)
`years of age and older
`
`One drop in theaffected eye(s) once daily, es
`Applicant Proposed Dosing
`Regi
`Approval: conditional upon strong labeling to help
`minimize overuse or misuse, coupled with postmarket
`commitment for Enhanced Pharmacovigilance
`Temporarily relieves itchy eyes due to pollen, ragweed,
`grass, animal hair and dander/adults and children 2
`
`Recommendation on Regulatory
`Action
`
`Recommended
`Indication(s)/Population(s) (if
`applicable
`RecommendedDosing
`Regimen(s)
`(if applicable
`
`1.
`
`Benefit-Risk Assessment
`
`CDER CrossDiscipline Team Leader Review Template
`Version date: October 10, 2017for all NDAs and BLAs
`
`Reference ID: 4638739
`
`

`

`Benefit-Risk Integrated Assessment
`
`Cross Discipline Team Leader Review
`
` I
`
` recommend approval of the prescription (Rx)-to-nonprescription (over-the-counter or OTC) switch of olopatadine hydrochloride ophthalmic solution 0.7%,
`for the temporary relief of itchy eyes; due to pollen, ragweed, grass, animal hair and dander in adults and children 2 years of age and older. To address
`concerns about potential overuse/misuse of this product by conusumers in the OTC environment, my recommendation for approval is conditional upon
`agreement with the Applicant for postmarketing follow-up which will include, in the Applicant’s annual and periodic reports, a summary of all experience
`with overuse and misuse cases (and their consequences). In addition, the Drug Facts label (DFL) should be strengthened to discourage misuse (e.g., “Put one
`drop in the affected eye(s) once daily. Do not exceed one drop per eye per day.”)
`
`Approval of this product for OTC use will provide an additional safe and effective therapeutic option for consumers to treat symptoms of allergic
`conjunctivitis. The less frequent (once daily) dosing compared to other OTC topical agents for the same indication, the dual mechanism of action
`(antihistamine and mast cell stabilizer), and the demonstrated efficacy and safety when dosed regularly (up to 6 weeks in clinical trials) will be of additional
`benefit to consumers in treating their ocular symptoms.
`
`Recent estimates suggest that 15-20% of the U.S. population (between 50 and 85 million Americans) suffer from allergic conjunctivitis. Symptoms include
`eye itching, redness, burning, and tearing; with itchy eyes being a primary symptom. Ocular symptoms of allergic disorders can have a profound impact on
`quality of life. Seasonal allergy sufferers may be unable to sleep at night, go outdoors, wear contact lenses, drive, or go to work. Tearing and ocular itching
`may be unbearable, and if untreated, ptosis, watery and mucous discharge, and photophobia could occur and lead to visual disturbances. Additionally,
`ocular infection is a possible consequence of frequent rubbing of irritated tissues.
`
`Treatment of allergic conjunctivitis must include identification and removal of the offending allergen, but this is often not possible. There are numerous OTC
`ophthalmic drops available for treatment of ocular allergy symptoms. However, effectiveness may be limited by the frequency of use required (up to 2 drops
`4 times daily) and potential side effects. Vasoconstrictor eye drops, for example, are associated with rebound vasodilatation and have warnings to “ask a
`doctor before use” for consumers with heart disease, high blood pressure, trouble urinating due to an enlarged prostate gland, or narrow angle glaucoma.
`Some consumers who resort to oral antihistamine therapy may suffer from somnolence, functional impairment, and increased occupational risks for
`accidents or injuries secondary to sedating effects.
`
`The efficacy of olopatadine 0.7% ophthalmic solution, one drop to affected eye(s) daily, for treatment of ocular itching has been adequately demonstrated in
`two pivotal trials (C-10-126 and C-12-053), and the safety profile of olopatadine products has been well characterized through clinical trials and
`postmarketing experience. The most common ocular adverse events (AEs) associated with olopatadine ophthalmic solutions across clinical trials included
`headache, blurred vision, and dry eye (and other ocular effects commonly associated with dry eye, e.g., abnormal sensation in the eye, pruritus, hyperemia,
`and ocular discomfort). Hypersensitivity is a known adverse event. Another potentially serious adverse event is corneal damage.
`
`Olopatadine ophthalmic solution has not been studied at doses higher than 0.7% once daily. Therefore, during the review cycle, the question arose as to
`whether, in the OTC environment where overuse or misuse of drug products by some consumers is anticipated, any adverse events might be seen in a
`higher frequency or severity if a consumer overuses the drug. Several options were considered to address this concern. The Clinical Reviewer, Dr. Steven
`CDER Cross Discipline Team Leader Review Template
`
`Version date: October 10, 2017 for all NDAs and BLAs
`
`2
`
`Reference ID: 4638739
`
`

`

`Cross Discipline Team Leader Review
`
`Osborne, recommendedapprovalconditional upon strong labeling to help minimize overuse or misuse, coupled with postmarket safety follow-up.
`Postmarketsafety follow-up would be helpful to ensure that misuse is reported such that FDA cantake furtheraction if needed. Revisions to labeling would
`also be helpful, althoughit is acknowledgedthat evenif stronger labeling was developed and tested in consumerstudies, potential comsumer misuse cannot
`be completely mitigated. Another option which wasconsidered wasto require that the Applicant conduct a safety study at doses higher than 0.7% one drop
`daily. However, the Division of Ophthalmology (DO; formerly known andDivision of Transplant and Ophthalmology; DTOP) recommendedapprovalofthis
`application and contendedthat, based on the known chemical composition of olopatadine ophthalmic products as well as the results of animal studies,
`there are no safety concerns regarding overuse. Furthermore, Dr. Charles Ganley, Acting Director of Office of Specialty Medicine, pointed out that thereis
`no knownpathophysiologic mechanism to justify any safety concern from overuse.
`
`Based on the known pharmacokinetics of olopatadine ophthalmic products, systemic absorption and resulting systemic adverse events is not a concern.
`Local, ocular adverse events would presumably would beeasily identified by a consumer and result in discontinuing of the medication. The proposed DFL
`will be helpful in this regard as it includes instructions to “Stop use and ask a doctorif you experience!
`ee . eye pain, changesin vision,
`increased rednessof the eye, itching worsensor lasts more than 72 hours.” Ultimately, however, the necessity for labeling changes and subsequent
`consumerstudies, which, as noted above, would not be able to completely mitigate the risk of misuse, should be determined based on the degree of safety
`concern, which, as emphasized by our ophthalmology colleagues, is minimal. Therefore, approval of this application, with labeling languagethat, in the
`absence of required consumerstudies, would be reasonably expected to discourage misuse, coupled with assurance of adequate postmarketing safety
`monitoring, is the best option.It is acceptable in this case that, due to the unique chemical characteristics and safety profile of the product which provide
`adequate assuranceof safety for consumers, safety evaluation of higher than approved OTC dosesis not required. However, this approval should not be
`
`Benefit-Risk Dimensions
`
`
`
`construedas applicable to other drug products for which safety data at higher doses than OTC dosesarestill required.
`significantly disrupt normaldaily activities.
`
`
`
`|bimension Evidenceand Uncertainties Conclusionsand Reasons
`
`e Allergic conjunctivitis symptomsinclude tearing; redness; itching and
`burning; vasodilatation; and chemosis. Itchy eyes are a primary symptom.
`e Recent estimates suggest that 15-25% of the U.S. population, or between 50
`and 85 million Americans, suffer from allergic conjunctivitis or some form
`of ocular allergy (Obrien TP 2013)
`e Althoughnotlife-threatening, profound effect on quality oflife (Bielory L
`2008).
`e Can be debilitating; tearing and ocular itching may be unbearable; andif
`untreated, ptosis, watery and mucous discharge, and photophobia could
`occur and leadto visual disturbances.
`
`e Mild allergic conjunctivitis may presentitself as little more than a serious
`annoyance, but more severe formsof seasonal allergic conjunctivitis may
`
`Relief of eye itchiness dueto allergic
`conjunctivitis is important to consumersfor
`physiologic reasons and for physical comfort.
`Relief of symptomsofallergic conjunctivitis
`improves quality oflife for consumers.
`
`CDER Cross Discipline Team Leader Review Template
`Version date: October 10, 2017for all NDAs and BLAs
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`Reference ID: 4638739
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`Cross Discipline Team Leader Review
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`|bimension EvidenceandUncertainties Conclusionsand Reasons
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`warranted.
`
`e Should include identification and removalof the offendingallergen,if
`possible.
`e Various types of topical ocular agents (e.g., antihistamines, mast cell
`stabilizers, vasoconstrictors, combination products, dual-action agents with
`mast cell stabilizing and antihistamine properties, nonsteroidal anti-
`inflammatory drugs and topical steroids) have been prescribed.
`e Multiple antihistamine and vasoconstrictor eye drop solutions are currently
`marketed OTC.
`¢ Most OTC eye drops require frequent dosing (up to 1-2 drops 4 timesdaily).
`e Vasoconstrictors associated with rebound vasodilatation and have warnings
`to “ask a doctor before use” for consumerswith heart disease, high blood
`pressure, trouble urinating due to an enlarged prostate gland, or narrow
`angle glaucoma.
`e Olopatadineis a topical antihistamine with selective H1 receptor antagonist
`activity and mastcell stabilizing effects.
` |thas been marketed as an ophthalmic agent to treat symptomsofallergic
`conjunctivitis in the United States since 2015 (as Pazeo, 0.7%).
`e Since exposureto an offending allergen may not be avoidable and can
`occur on a continuousbasis, therapy that offers a longer duration of efficacy
`would offer advantages in symptom control
`
`e Patients may be unable to sleep at night, go outdoors, wear contact lenses,
`drive, or go to work.
`e Additionally, ocular infection is a possible consequence of frequent rubbing
`ofirritated tissues. Ocular infections are particularly likely to happen in
`children.
`
`e
`
`Pharmacotherapy has been the mainstay of
`treatment for conjunctival irritation.
`Frequency of dosing required and potential
`adverse events may limit consumeruse.
`Most sufferersself-treat for minoreyeirritations,
`whichhighlights the importance of OTC treatments
`for control of some of the symptoms.
`
`The effectiveness of the product has been
`established to treat symptomsrelatedto allergic
`conjunctivitis.
`This eye drop product provides an additional
`choice to consumers who experience such
`symptoms.
`This eye drop product hasboth antihistamine and
`mast cell stabilizing properties.
`Olopatadine hydrochloride hasa satisfactory safety
`profile in the prescription environment based on
`23 years ofclinical use for all olopatadine products
`and approximately 4 years for Pazeo in the
`postmarketing experiencein the United States.
`Adverseevents associated with olopatadine
`hydrochloride andits use as an ophthalmic solution
`
`For a risk assessmentin this application, the Applicant submitted a ISS forall
`olopatadine products and postmarket safety data from 2000-2018, supplemented by
`updates from PSURs, Periodic Adverse Drug Experience Reports (PADERs), and a 120-
`day safety update.
`The proposed OTClabeling has the essential warnings translated from the current
`Pazeo Rx label; additional warnings regarding pregnancy and breastfeeding are not
`
`CDER CrossDiscipline Team Leader Review Template
`Version date: October 10, 2017for all NDAs and BLAs
`
`Reference ID: 4638739
`
`

`

`Cross Discipline Team Leader Review
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`
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`|bimension EvidenceandUncertainties Conclusionsand Reasons
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`andin the literature, has not been studied.
`
`are most commonly identified as headaches and
`eye symptoms.
`Safety of olopatadine hydrochloride ophthalmic
`solution 0.7%, in the prescription environment, is
`supportedbyclinical trial data (zero SAEs) and
`generally by postmarket safety data (26 SAEs over
`approximately 4 years, nonefatal).
`Warnings providedin the proposed OTClabeling
`mayhelp mitigate the risk of serious adverse
`events.
`
`Potential misuse of the 0.7% olopatadine eye drops
`exposes a consumerto a dose of olopatadinethat,
`based on information submitted by the Applicant
`
`Adverse events are predominantly non-serious, however a few, such as
`hypersensitivity and corneal damagearelisted in the Rx full prescribing information .
`However, an unknownforthis application is what will happen if a consumer
`does notfollow the proposed Drug Facts Label and misuses (overuses) the
`drug.In this instance the potential for adverse events is unstudied since the
`Applicant has not studied, noris it aware of any data, in which subjects were
`exposed to more than one dropin each affected eye per day. The longest
`duration for use was 6 weeks. This length of time may be adequate for
`seasonalallergic conjunctivitis, however not for perennial allergic
`conjunctivitis. Consumers may overuseby daily dose and by length of time of
`use.
`
`CDER CrossDiscipline Team Leader Review Template
`Version date: October 10, 2017for all NDAs and BLAs
`
`Reference ID: 4638739
`
`

`

`Cross Discipline Team Leader Review
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`2. Background
`Alcon Research, LLC (the Applicant), a subsidiary of Novartis until April 9, 2019, submitted this NDA supplement for a full
`prescription (Rx) to over-the-counter (OTC) switch of olopatadine hydrochloride ophthalmic solution 0.77% (or olopatadine 0.7%) for
`the indication of temporary relief of itchy eyes due to pollen, ragweed, grass, animal hair and dander in adults and children 2 years of
`age and older. FDA approved NDA 206276, olopatadine hydrochloride ophthalmic solution 0.77% (or olopatadine 0.7%), with a
`proprietary name of Pazeo, on January 30, 2015, for use as a prescription drug for the treatment of ocular itching associated with
`allergic conjunctivitis (AC). The proposed dosing regiment for the OTC switch (One drop in the affected eye(s) once daily,
`), is the same dosing regimen approved for Rx use.
`
`
`
`
`On February 14, 2020, FDA approved the full switch of olopatadine 0.1% from Rx-to-OTC (sNDA 020688) with the OTC name of
`Pataday Twice Daily Relief (relief of itching and redness) and olopatadine 0.2% (sNDA 021545) with the OTC name of Pataday Once
`Daily Relief (no descriptor, relief of itching). In the current submission, the Applicant proposes the OTC name of Pataday Once Daily
`Relief with the labeling descriptor “Extra Strength” for the olopatadine 0.7% product.
`
`
`Table 1: Olopatadine Ophthalmic Solutions with Successful or Planned Rx-to-OTC Switches
`Rx Approval Year /
`OTC Approval
`1996 / Feb 14, 2020
`
`Rx Product
`Patanol (olopatadine 0.1%)
`
`OTC Names
`Pataday Twice Daily Relief
`
`
`NDA# /
`(IND#)
`020688 /
`(107178)
`021545 /
`(142363)
`206276
`(060991)
`
`
`Pataday (olopatadine 0.2%)
`
`2004 / Feb 14, 2020
`
`Pataday Once Daily Relief
`
`
`Pazeo (olopatadine 0.7%)
`
`2015 / Pending
`
`Pataday Once Daily Relief “Extra
`Strength”
`PDUFA July 13, 2020
`Electronically copied and reproduced from Dr. Osborne’s Clinical Review
`
`
`As the proposed OTC product is unchanged from the current Rx product, except for the proposed OTC labeling, no new clinical,
`preclinical, or CMC data were submitted. To support approval for the switch of Pazeo Rx to OTC status, the Applicant intends to rely
`on FDA’s prior finding of safety and efficacy for Pazeo (NDA 206276) and for olopatadine at multiple additional doses and routes of
`administration via cross reference to the approved NDAs for Pataday Twice Daily Relief (olopatadine 0.1%; NDA 020688, previously
`
`CDER Cross Discipline Team Leader Review Template
`Version date: October 10, 2017 for all NDAs and BLAs
`
`
`
`6
`
`Reference ID: 4638739
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`(b) (4)
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`(b) (4)
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`Cross Discipline Team Leader Review
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`marketed Rx under trade name Patanol), Pataday Once Daily Relief (olopatadine 0.2%; NDA 021545, previously marketed Rx under
`trade name Pataday), and olopatadine 0.6% nasal spray (currently marked Rx under trde name Patanase).
`
`Olopatadine is a topical antihistamine with selective H1 receptor antagonist activity and mast cell stabilizing effects. It is marketed as
`an ophthalmic agent for the prevention or treatment of ocular pruritus due to allergic conjunctivitis and as a nasal spray for the relief
`of the symptoms of seasonal allergic rhinitis (SAR). Olopatadine exhibits two distinct mechanisms of action. It inhibits histamine
`release from mast cells and is a relatively selective antagonist of H1 receptors. As a result, olopatadine prevents type 1 immediate
`hypersensitivity reactions. Topical ocular administration relieves the ocular pruritus associated with allergic conjunctivitis. Intranasal
`administration relieves symptoms associated with SAR.
`
`Disease or Condition
`
`Allergic conjunctivitis (ocular allergy) is a mast-cell mediated hypersensitivity reaction that can be an acute or chronic illness that
`involves inflammation of the conjunctiva. Symptoms of all forms of ocular allergy include tearing; itching and burning;
`vasodilatation; and chemosis (Singh et al, 2010). Most recent e