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`SENJU EXHIBIT 2267
`LUPIN v SENJU
`IPR2015-01105
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`#151142-203.01 Letter Final Report
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`Page 2 of 65
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`ADDENDUM 1
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`Protocol #15! 142-203
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`Protocol Deviation Recording Forms (Form No. 99—QA-004)
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`CONFIDENTIAL
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`PROL0337790
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`H511-=i2~20J.Dl M111.-r Final Report
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`Page 3 of65
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`Novembet 23. 2015
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`PROTOCOL #lSI 142-203
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`A NON-GLP ANTIMICROBIAL PRESERVAHVES EFFECTIVENESS EVALUATION OF SIX
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`PRODUCTS WHEN CHALLENGED WITH FOUR MICROORGANISM SPECIES BASED ON
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`EUROPEAN PHARMACOPOEIA METHOD 5.1.3.
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`icon
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`SSCI (SPONSOR)
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`3065 Kent Avenue
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`BIOSCIENCE LABORATORlESfi'lNC. (TESTING FACIUTY)
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`BIOSCIENCE U\BOR4KT0RlI3.$. INC.
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`pR0|_0337-(91
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`M51 I42-203.0] l.e11erFimI Report
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`This Document has been copyrighted by Bioscience Laboratories, Imc., and is considered
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`confidential between Biosoienee Laboratories, Inc. (Testing Facility) and SSCI (Sponsor). This
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`permission from Biosoience Laboratories. Inc. Pennission to release the Protocol and Study
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`Results to the United States Foot} and Drug Administration (FDA) is explicitly granted.
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`PROTOCOL M51141-203
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`rm 2 of 1|
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`BIOSCIENCE LABORATORIES. INC.
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`#151142-203.01 Leiief Final Report
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`Page 19 of 65
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`ADDENDUM 2
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`Data Tables 1 Through 18
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`=-151 I-1'.?—2fJ_1 HI
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`Protocol #151 142203
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`January 07. 2015
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`TM IA.B_L.E_I
`Test Product #3: Prolensa
`bromfenac ophthalmic solution 0.07%.
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`Bron-rfenac Sodium (unstressed)
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`Test Product #4: Prolensam bromfenac ophthalmic solution 0.07% (wfv)
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`Bromfenar: Sodium (4 weeks @ 60°C})
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`Lot Number 249031
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`Challenge
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`Initial
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`Aspergfllus bmslflensls
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`5
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`8.6818 x10
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`Acceptance
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`0European Pharmacopoeia '?.0. 5.1.3. EFFACACY OF ANTIMICROBIAL PRESERVATION. 01.-’20l l:S0l{]3. Acceptance Criteria,
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`Table 5.1.3.1, Parenteral preparations, eye preparations. Intrauterine preparations and inrramammary preparations: The criteria for
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`fungi is a 2 103:1} reduction following 7 days of exposure to the test product with no recovered Colony Forming Units (CFU) recovered
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`aflnr 28 days: nfexpnsure tn the product.
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`Protocol #151142-203
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`Protocol #15 I 142-203
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`January 0?, 2016
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`TABLE 8
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`Test Product #3: Prolensam bromfenac ophthalmic solution 0.07%.
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`Bromfenac Sodium (unstressed)
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`Lot Number 240031
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`Test Product #4: Prolcnsam bromfenac ophthalmic solution 0.07% (w.’v}
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`Bromfenac Sodium (4 weeks @ 60°C)
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`Lot Number 240031
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`Challenge
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`Microorggnism
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`(ATCC #)
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`I it! I
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`Poplimtion
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`{CFUML
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`of Product)
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`Day(s-)
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`Following
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`Inoculation
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`Candida efbicans
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`5
`:r?L
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`(ATCC #10231]
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`(CFU.-"n1L)
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`0Europ-can Pharmacopoeia 7.0. 5.1.3. EFFACACY OF ANTIMICROBIAL PRESERVATION. 0Ir‘20II:50I03. Acceptance
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`Criteria, Table 5.1.3.1, Parenrerm’ preparations, eye preparations, intrauterine preparations and fnrramammary preparations:
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`The criteria for fungi is a 2 logic reduction foilow-ing '7 days of exposure to the test product with no recovered Coiony Forming
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`Units {CFU} recovered alter 28 days of exposure to the product...
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`Protocol #151142-203
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`#151142-203.01 Lefiet Final Report
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`Protocol #151 142-203
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`January 07, 2016
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`TABLE 9
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`Test Product #3: Prolensam bmmfenac ophthalmic solution 0.07%.
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`Bromfenac Sodium (unstressed)
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`Lot Number 240031
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`Test Product #4: Proiensam brornfcnac ophthalmic solution 0.07% (w.’v}
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`Bromfenac Sodium (4 weeks @ 60°C)
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`
`Lot Number 24003}
`
`
`
`
`
`C“'"°"g°
`
`Microorganism
`(ATCC #)
`
`
`Initial
`
`Population
`
`(CF"U2'mI.
`
`
`of Product)
`
`
`
`Dayts)
`
`Foliowing
`
`Inoculation
`
`
`Pseudamonas aemginoxa
`
`{ATCC #902?)
`
`
`
`
`
`
`
`1.7070 x [0
`
`6
`
`
`
`
`
`
`
`
`
`
`
`3.§.3
`
`
`
`
`
`Ofiumpean Phannacopoeia 7.0. 5.1.3. EFFACACY OF ANTIMICROBIAL PRESERVATION. {]lf2011:5UlO3. Acceptance Criteria,
`
`
`
`
`
`
`
`
`
`
`
`Table 5.1.3.1, Parenteral preparations, eye preparations, intrauterine preparations and lmmmammary preparations: Criteria A for
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`bacteria is a 3 log"; reduction following 24 hours of exposure to the test product with no recovered Colony Forming Unilo (CFU)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`recovered after 28 days of exposure to the product.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Population
`
`Recovered
`
`(CFU."mL)
`
`
`.55
`
`Reduction
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`<l.{J0x10'
`
`¢I.D0x 10'
`
`<I.{)0x 10'
`
`
`-=1.00x 10'
`
`
`c1.00x 10'
`
`<1.00 x 10'
`
`<1.00 :4; 10'
`
`<l.00 x 10'
`
`H
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`5.232
`5.2322
`
`5.2322
`
`5.2322
`
`5.2322
`
`
`
`
`
`
`
`
`
`
`
`5.2322
`
`
`5.2322
`
`
`
`
`
`5.2322
`
`
`
`
`
`Acceptance
`Criteria
`
`
`
`
`YE
`
`YES
`
`
`
`
`
`YES
`
`YES
`
`
`
`YES
`
`
`YES
`
`
`
`YES
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`99 999494’
`
`99.999404.
`
`99.999494.
`
`YES
`
`99.99949/o
`
`Protocol #15] 142-203
`Page 8 of IS
`
`
`
`
`
`
`
`CONFIDENTIAL
`
`
`
`PROL0337815
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`
`
`PAGE27OF65
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`PAGE 27 OF 65
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`#151142-203.01 Lefier Final Report
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`Page 28 of 65
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`Protocol #151142-203
`
`January 0'7, 2016
`
`
`
`
`
`
`
`TABLE. II!
`
`
`leg; Egodygg Q3: Prulensa' " bromfenac ophthalmic solution 0.07%.
`
`
`
`
`
`
`
`
`Bromfenac Sodium (unstressed)
`
`
`
`Lot Number 240031
`
`
`
`
` : Prolensam bromfenac ophthalmic solution 0.07% {w/V)
`
`
`
`
`
`
`
`
`
`Bromfenac Sodium (4 weeks @ 60°C)
`
`
`
`
`
`Lot Number 240031
`
`
`
`
`
`
`Challenge
`
`Microorganism
`(“CC 3’
`
`
`
`
`
`
`i’o::1!ltaiI:on
`
`CFU, L
`
`o{f ProdT1‘ct
`
`
`
`
`Day(s)
`
`Following
`
`Inoculation
`
`
`
`
`
`Prague‘
`
`
`
`Population
`Recovered
`
`
`
`l‘
`
`E?3
`
`
`
`
`
`(CFU.-"mL)
`=o
`
`
`
`
`
`Staphyfococcu: aw-ens
`
`{ATCC #6538}
`
`
`
`
`
`
`5
`
`
`
`1.9767 x 10
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`<1.010'
`
`<l.0Dx 10'
`
`<1.0Dx 10'
`
`
`
`(1 '00 " 10'
`-:1.00x 10'
`
`<1.00 1: 10'
`
`
`I
`
`
`
`
`
`
`
`
`
`5.2959
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`5.2959
`
`5.2959
`
`5.2959
`
`5.2959
`
`
`
`
`
`
`
`YES
`
`was
`
`was
`
`
`YES
`<1.oo x 10'
`
`
`
`
`
`0European Pharmacopoeia 7.0. 5.1.3. EFFACACY OF ANTIMICROBIAL PRESERVATION. 0ll201l:5(}203. Acceptance Criteria,
`
`
`
`
`
`
`
`
`
`
`
`Table 5.1.3.1, Parenteral preparations, eye preparations, intrauterine preparations and intramammary preparations: Criteria A for
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`bacteria is a 3 10310 reduction following 24 hours of exposure to the test product with no recovered Colony Fanning Units (CFU)
`
`
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`
`
`
`
`
`
`
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`
`
`
`recovered alter 28 days of exposure to the product.
`
`
`
`
`
`
`
`
`
`
`<1.00x 10'
`
`Acceptance
`
`Criteria
`
`
`
`
`
`
`
`S
`
`YES
`
`
`
`YES
`
`YES
`
`
`
`99.999596 I
`
`99.999596
`
`99.999598
`
`99.9995%
`
`
`
`99.9995%
`
`99.999596
`
`99.999593
`
`
`
`
`
`
`
`99.999596
`
`Protocol #151142-203
`
`
`Page 9 of I 5
`
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`CONFIDENTIAL
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`
`PROL0337816
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`PAGE 28 OF 65
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`#151142-203.01 Lefiet Final Report
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`Page 29 of 65
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`Protocol #151142-203
`
`January 07, 2016
`
`
`
`
`
`11
`T
`
`
`Neutralization Evaluation -— Results
`
`
`jljest Egguct #3: Prolenmm bromfenac ophthalmic solution 0.07%.
`
`
`
`
`
`
`Bromfenac Sodium (unstressed)
`
`
`
`Lot Numbers 240031
`
`
`
`
`
`
`.
`
`
`
`.
`
`
`
`
`
`
`
`
`
`Microbial Recovery
`
`
`
`
`
`Aspergiflus bmriliensls
`
`
`
`16404
`
`
`
`Candida olbicans
`
`
`
`10231
`
`
`Pseudamonas aeruginosa
`
`
`
`902'?
`
`
`
`Staphylococcus aureus
`
`
`
`6533
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`0
`
`
`
`
`
`
`
`
`
`
`
`
`
`TEST
`
`
`OThe counts (Average CFU:'Plate) observed for the TEST sample do not vary by more than a factor of
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`5 from those recovered from the respective CONTROL sample; hence, the neutralizing media are considered to be
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`effective.
`
`
`
`
`Results
`
`
`
`
`Pass
`
`
`
`Pass
`
`
`
`Pass
`
`
`
`Pass
`
`
`
`
`
`
`TABLE 12
`
`Neutraiization Evaluation — Results
`
`
`Test Pmguct #4: Prolensam bromfenac ophthalmic solution 0.07% (w!v}
`
`
`
`
`
`
`
`
`Bmrnfenao Sodium (4 weeks @ 60°C}
`
`
`
`
`
`Lot Number 24003!
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Aspergiflus brasiliertsix
`
`
`
`16404
`
`
`Candida albiccms
`
`
`
`Pseudomanas aerugittosa
`
`
`
`10231
`
`
`
`9027
`
`
`
`Staphylococcus mrreus
`
`
`
`
`6538
`
`
`.
`
`.
`
`
`
`
`
`
`
`TEST
`
`
`CONTROL
`
`
`TEST
`
`CONTROL
`
`
`TEST
`
`
`CONTROL
`
`
`
`Microbial Recovery
`
`
`
`
`T
`
`213.50
`
`
`Results
`
`
`Pass
`
`
`
`
`
`
`
`
`Pass
`
`
`
`IE!
`
`
`
`30.00
`
`36.00
`
`30.50
`
`35.50
`
`24.00
`
`20.00
`TEST
`
`
`0 The counts (Average CFUfPlale] observed for the TEST sample do not vary by more than a factor of
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`5 from those recovered fi'om the respective CONTROL sample; hence, the neutralizing media are considered
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`to be effective.
`
`
`
`
`
`
`Protocol #151142-203
`
`
`Page 10 of 15
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`
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`CONFIDENTIAL
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`PROL0337817
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`PAGE29OF65
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`#151142-203.01 Letter Final Report
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`HI I-13-I01 HI
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`I ‘ I I4?-201 HI lcncr Filul Rap-\r1
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`|‘l I I2 IN "1 I .-tut l nu] (hp.-:1
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