IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`
`SENJU PHARMACEUTICAL CO., LTD.,
`BAUSCH & LOMB IN CORPORA TED and
`BAUSCH & LOMB PHARMA HOLDINGS
`CORP.,
`
`Plaintiffs,
`
`v.
`
`INNOPHAR.MA LICENSING, INC.,
`INNOPHARMA LICENSING, LLC,
`INNOPHARMA, INC. and INNOPHARMA,
`LLC,
`
`Defendants.
`
`Civil Action No. 1: 14-cv-00667 (JBS)(KMW)
`Civil Action No. I: 14-cv-04149 (JBS)(KMW)
`Civil Action No. 1: 14-cv-05144 (JBS)(KMW)
`Civil Action No. I: 15-cv-00335 (JBS)(KMW)
`Civil Action No. I: 14-cv-06893 (JBS)(KMW)
`Civil Action No. 1: 15-cv-03240 (JBS)(KMW)
`
`(Consolidated Actions)
`
`CONT AINS CONFIDENTIAL MATERIAL
`PURSUANT TO STIPULATED
`DISCOVERY CONFIDENTIALITY ORDER
`
`SUPPLEMENTAL EXPERT REPORT OF ADAM C. MYERS, Ph.D.
`
`I.
`
`INTRODUCTION
`
`I.
`
`I, Adam C. Myers Ph.D., submit this expe11 report at the request of Finnegan,
`
`Henderson, Farabow, Garrett & Dunner, LLP on behalf of Senju Pharmaceutical, Co., Ltd.
`
`("Senju"), Bausch & Lomb Incorporated and Bausch & Lomb Phanna Holdings Corp.
`
`(collectively, "B+L") as an expert in the field of the design, evaluation, and formulation of dn1g
`
`produc: M~ualificat:ns in these areas, as well as other areas, are summ:iz:~n ;expert- - - l
`
`,
`
`reports dated oe'cember 24, 2015, and established by my curriculum vitae, which was attached
`
`I
`
`'
`
`as Appendix A to my December 24, 2015, expert reports.
`
`II.
`
`DOCUMENTS AND INFORMATION CONSIDERE D IN FORMING OPINIONS
`
`In form ing my opinions, I had avai lable the documents cited herein, ·the
`2.
`.
`.
`documents cited in my December 24, 2015, expert reports as well as the publications listed on
`
`my curriculum vitae. I also based my opinions on my professional and academic experience in
`
`l
`
`
`
`SENJU EXHIBIT 2256
`INNOPHARMA v SENJU
`IPR2015-00902
`
`PAGE 1 OF30
`
`
`FOR THE DISTRICT OF NEW JERSEY
`
`SENJU PHARMACEUTICAL CO., LTD.,
`BAUSCH & LOMB IN CORPORA TED and
`BAUSCH & LOMB PHARMA HOLDINGS
`CORP.,
`
`Plaintiffs,
`
`v.
`
`INNOPHAR.MA LICENSING, INC.,
`INNOPHARMA LICENSING, LLC,
`INNOPHARMA, INC. and INNOPHARMA,
`LLC,
`
`Defendants.
`
`Civil Action No. 1: 14-cv-00667 (JBS)(KMW)
`Civil Action No. I: 14-cv-04149 (JBS)(KMW)
`Civil Action No. 1: 14-cv-05144 (JBS)(KMW)
`Civil Action No. I: 15-cv-00335 (JBS)(KMW)
`Civil Action No. I: 14-cv-06893 (JBS)(KMW)
`Civil Action No. 1: 15-cv-03240 (JBS)(KMW)
`
`(Consolidated Actions)
`
`CONT AINS CONFIDENTIAL MATERIAL
`PURSUANT TO STIPULATED
`DISCOVERY CONFIDENTIALITY ORDER
`
`SUPPLEMENTAL EXPERT REPORT OF ADAM C. MYERS, Ph.D.
`
`I.
`
`INTRODUCTION
`
`I.
`
`I, Adam C. Myers Ph.D., submit this expe11 report at the request of Finnegan,
`
`Henderson, Farabow, Garrett & Dunner, LLP on behalf of Senju Pharmaceutical, Co., Ltd.
`
`("Senju"), Bausch & Lomb Incorporated and Bausch & Lomb Phanna Holdings Corp.
`
`(collectively, "B+L") as an expert in the field of the design, evaluation, and formulation of dn1g
`
`produc: M~ualificat:ns in these areas, as well as other areas, are summ:iz:~n ;expert- - - l
`
`,
`
`reports dated oe'cember 24, 2015, and established by my curriculum vitae, which was attached
`
`I
`
`'
`
`as Appendix A to my December 24, 2015, expert reports.
`
`II.
`
`DOCUMENTS AND INFORMATION CONSIDERE D IN FORMING OPINIONS
`
`In form ing my opinions, I had avai lable the documents cited herein, ·the
`2.
`.
`.
`documents cited in my December 24, 2015, expert reports as well as the publications listed on
`
`my curriculum vitae. I also based my opinions on my professional and academic experience in
`
`l
`
`
`
`SENJU EXHIBIT 2256
`INNOPHARMA v SENJU
`IPR2015-00902
`
`PAGE 1 OF30
`
`
`
`the area of drug formulation and analytics. I reserve the right to testify about these materials and
`
`experience. To the extent I am provided addi~ional documents or information, including any
`
`expert reports produced by InnoPhanna, I may offer further opinions.
`
`In addition to these
`
`materials, I may consider additional documents and information in forming any rebuttal
`
`opinions. Additionally, I may prepare demonstratives to illustrate any opinions I may present.
`
`Ill.
`
`STATEMENT OF OPINIONS EXPRESSED AND BASES AND REASONS
`THEREFOR
`
`3.
`
`Samples of B+L's Prolensa® product
`
`sourced from each manufacturer. Each manufacturer shipped the
`
`samples to Finnegan, Henderson, Farabow, Garrett & Dunner, LLP, who then shipped the
`
`samples to SSCI for testing. A portion of these samples were further shipped to BioScience
`
`Laboratories, Inc. These samples were evaluated for chemical stability at SSCI and for
`
`preservative efficacy at BioScience Laboratories, Inc. during the months of November 2015
`
`through January 2016. I was personally present during the chemical stability testing of these
`
`samples.
`
`4.
`
`SSCI has provided summary reports of both the chemical stability testing and
`
`preservative efficacy testing, which are attached as Appendix A. These reports describe the
`- - - -
`-
`-
`-
`analytical methodology to quantitate bromfenac free acid in the stressed and unstressed
`
`conditions. The chemical stability results are reported in the' document for all of the samples
`
`tested.
`
`5.
`
`SSCI is a cGMP facility providing contract product development services to the
`
`pharmaceutical industry. SSCI's service offerings include analytical testing (e.g., chemical
`
`stability), product development, and manufachtring. The chemical stability testing of B+L's
`
`Prolensa® product ~amples was performed in SSCI's cGMP quality control_ laboratory.
`
`2
`
`
`
`PAGE 2 OF 30
`
`
`
`6.
`
`Samples of B+L's Prolensa® product
`
`received, sto~ed, handled, and maintained according to SSCI' s cGf1P
`
`sample handling procedures. The samples were stored under ambient laboratory conditions in
`
`their original containers.
`
`7.
`
`A portion of the samples was used for unstressed analysis, and the remaining
`
`samples were stressed in an oven for four weeks at 60° C. The HPLC analyses to measure
`
`chemical stability were perfom1ed using an Agilent 1100 series chromatograph and· the
`
`chromatographic column was a Shiseido Capcell Pak Cl8.
`
`8.
`
`The SSCI reports correctly details the analytical testing that was performed and
`
`accurately reports the chemical stability test results, as well as the preservative efficacy test
`
`results.
`
`IV.
`
`COMPENSATION
`
`9.
`
`I am a salaried employee of AMRJ SSCI, LLC and its affiliates and I receive no
`
`additional compensation for this matter. No part of my compensation is contingent upon the
`
`outcome of this matter or any issue in it.
`
`V.
`
`PRIOR EXPERT TESTIMONY
`
`- t 0. · ··· During the·past four years;· I have not testified·as an· expert in-any cases.
`
`Date
`
`A'dam C. Myers, Ph.D.
`
`3
`
`
`
`PAGE30F30
`
`
`
`Appendix A
`Appendix A
`
`PAGE 4 OF 30
`PAGE 4 OF 30
`
`
`
`
`
`PAGE 5 OF 30
`
`PAGE 5 OF 30
`
`
`
`
`
`PAGE 6 OF 30
`
`PAGE 6 OF 30
`
`
`
`
`
`PAGE 7 OF 30
`
`PAGE 7 OF 30
`
`
`
`
`
`PAGE 8 OF 30
`
`PAGE 8 OF 30
`
`
`
`
`
`PAGE 9 OF 30
`
`PAGE 9 OF 30
`
`
`
`
`
`PAGE 10 OF 30
`
`PAGE 10 OF 30
`
`
`
`
`
`PAGE 11 OF 30
`
`PAGE 11 OF 30
`
`
`
`
`
`PAGE 12 OF 30
`
`PAGE 12 OF 30
`
`
`
`
`
`PAGE 13 OF 30
`
`PAGE 13 OF 30
`
`
`
`
`
`PAGE 14 OF 30
`
`PAGE 14 OF 30
`
`
`
`
`
`PAGE 15 OF 30
`
`PAGE 15 OF 30
`
`
`
`
`
`PAGE 16 OF 30
`
`PAGE 16 OF 30
`
`
`
`
`
`PAGE 17 OF 30
`
`PAGE 17 OF 30
`
`
`
`
`
`55[1~
`
`A Division of Albany Molecul•r R .... rch Inc.
`
`3065 Kent Avenue
`West Lafayette, IN 47906-1076
`Phone: (765) 463-01 12
`Fax: (765) 463-4722
`E-mail: info@ssci-inc.com
`Web: www.ssci-inc.com
`
`Stability Evaluation of
`Bromfenac Sodium Drug
`Product Samples for Potency
`and Preservative Efficacy
`
`Project ID: EL20151326
`Report Date: 01/08/2016
`
`PAGE 18 OF 30
`
`
`
`
`
`TABLE OF CONTENTS
`
`SUMMARY ......................................................................................................................................................... . 3
`I.
`II. RESULTS AND DISCUSSION ........................................................................................................................... 3
`Ill. DATA TABLES ................................... ~ .............................................................................................................. 5
`Table I. Summary ofHPLC Data, Sequence 741881 ................................................................................................. 5
`Table 2. Summary of HPLC Data, Sequence 742199 ................................................................................................ . 6
`IV. EXPERIMENTAL ................................................................................................................................................ ?
`A. HPLC Method ..................................................................................................................................................... ?
`V. APPENDIX A: PRESERVATIVE EFFICACY DATA ...................................................................................... 8
`
`SSCI Report: Stability Evaluation of Compound 578 Drug Product Samples for Potency and Preservative Efficacy, 01/0812016
`page 2 of 13
`
`PAGE 19 OF30
`
`
`
`
`
`I. SUMMARY
`
`Bromfenac sodium ophthalmic solution drug products were sourced from Senju. A portion of
`the samples was used for unstressed (as received) analysis, and the remaining samples were
`stressed in an oven for four (4) weeks at 60°C. Samples from both the unstressed and stressed
`conditions were evaluated for potency and preservative efficacy.
`
`Potency was determined by HPLC w ith UV detection as detailed in Section IV.A. Percent
`recovery (percent initial) was calculated based on the potency after stress conditions relative to
`that of the unstressed sample. See Table I for the unstressed (as received) HPLC data and Table
`2 for the stressed sample HPLC data.
`
`Preservative efficacy was evaluated by BioScience Laboratories, lnc. Samples were evaluated
`for preservative efficacy as guided in the EP Preservative Effectiveness Test Method against the
`following organisms: Candida albicans (AA TCC# 10231 ), Aspergillus niger (AA TCC# 16404,
`also referred to as Aspergillus brasiliensis), Pseudomonas aeruginosa (AA TCC# 9027) and
`Staphylococcus aureus (AATCC# 6538). See Section V for the detailed experimental
`information.
`
`Section II contains results for both potency and preservative efficacy.
`
`II. RESULTS AND DISCUSSION
`
`Material was purchased from one (1) lot, which was used for all experiments and time points.
`Average results are summarized below, with the percent recovery calculated as the amount of
`active relative to the unstressed sample.
`
`l ot Number
`
`240031
`
`-
`
`Unstressed
`Concentration
`(mg/ml)
`Average= 0.7457
`High= 0.7466
`Low = 0.7451
`
`Stressed
`Concentration
`(mg/ ml)
`Average= 0.7445
`High = 0.7473
`Low= 0.7418
`
`% Recovery
`
`Average= 99.8
`High= 100.2
`Low= 99.5
`
`Stressed and unstressed samples were evaluated for preservative efficacy, with the following
`results.
`
`SSCI Repon: Stability Evaluation of Compound 578 Drug Product Samples for Potency and Preservative Efficacy, 01/0812016
`page 3 of 13
`
`PAGE200F 30
`
`
`
`
`
`Organism
`
`Condition
`
`S. aureus
`
`1 -
`
`P.
`aeruginosa
`c.
`albicans
`
`A. niger
`
`Unstressed
`
`Stressed
`
`Unstressed
`
`Stressed
`
`Unstressed
`
`Stressed
`
`Unstressed
`
`Stressed
`
`Inoculum
`Count
`
`1.97667 X 106
`
`1.7070 X 106
`
`3.3953 X 105
`
`8.8837 X 105
`
`1
`<1.00 X 101
`
`<1.00 X 101
`<1.00 X 101
`<1.00 X 101
`..... -
`---
`--
`---
`
`28
`<1.00 X 101
`
`Cell Count (CFU/ml)
`Days After Inoculation
`14
`7
`<1.00 X 101 <1.00 X 101
`
`21
`---
`--
`<1.00 X 101
`<1.00 X 101 <1.00 X 101
`--
`<1.00 X 101
`<1.00 X 101 <1.00 X 101
`---
`<1.00 X 101 <1.00 X 10 1
`<1.00 X 101
`---
`< 1.00 X 101 < 1.00 X 101 <1.00 X 101
`--
`< 1.00 X 102 < 1.00 X 102 <1.00 X 102
`---
`<1.00 X 101 <1.00 X 101 <1.00 X 101
`--
`<1.00 X 101 <1.00 X 101 <1.00 X 101
`
`SSCJ Report: Stability Evaluation of Compound 5 78 Drug Product Samples for Potency and Preservative Ej]lcocy, 0 I /0812016
`page 4 of 13
`
`PAGE 21 OF 30
`
`
`
`
`
`III. DATA TABLES
`
`Table 1. Summary of HPLC Data, Sequence 741881
`
`lnj#
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`16
`17
`18
`19
`20
`
`Sample
`Description
`Blank
`Blank
`STDA
`STDA
`STDA
`STDA
`STDA
`STD B
`Blank
`STDA
`240031
`240031
`240031
`STDA
`
`LIMS
`
`LC Filename
`
`408677
`408677
`408705
`408705
`408705
`408705
`408705
`408706
`408677
`408705
`403486
`403489
`403490
`408705
`
`741882
`741883
`741884
`741885
`741886
`741887
`741888
`741889
`741890
`741897
`741898
`741899
`741900
`741901
`
`RT
`-
`-
`8.667
`8.668
`8.666
`8.666
`8.666
`8.665
`--
`8.666
`8.646
`8.648
`8.647
`8.663
`
`Area(mAU*s)
`
`-
`-
`4012.66
`4015.13
`4016.96
`4016.04
`4018.79
`4038.45
`-
`4019.73
`4556.16
`4548.27
`4547.03
`4016.40
`
`SSCI Report: Stability Evaluation of Compmmd 5 78 Drug Product Samples for Potency and Preservative E,ffiCIJcy, 0 110812016
`page 5 of 13
`
`PAGE 22 OF30
`
`
`
`
`
`Table 2. Summary of HPLC Data, Sequence 742l99
`
`Sample
`Descript ion
`Blank
`Blank
`STDA
`STDA
`STDA
`STDA
`STDA
`STD B
`Blank
`STDA
`STDA
`STDA
`STDA
`STDA
`STDA
`STDA
`STDA
`240031
`240031
`240031
`240031
`240031
`240031
`STDA
`240031
`240031
`240031
`240031
`STDA
`
`LIMS
`
`LC Filename
`
`RT
`
`408677
`408677
`408705
`408705
`408705
`408705
`408705
`408706
`408677
`408705
`408705
`408705
`408705
`408705
`408705
`408705
`408705
`403478
`403479
`403480
`403481
`403482
`403483
`408705
`403484
`403485
`403487
`403488
`408705
`
`742200
`742201
`742202
`742203
`742204
`742205
`742206
`742207
`742208
`742215
`742222
`742229
`742235
`742242
`742249
`742256
`742262
`742263
`742264
`742265
`742266
`742267
`742268
`742269
`742272
`742273
`742274
`742275
`742276
`
`··-
`--
`8.669
`8.670
`8.670
`8.670
`8.669
`8.669
`-·
`8.673
`8.676
`8.677
`8.681
`8.682
`8.684
`8.690
`8.691
`8.670
`8.670
`8.670
`8.673
`8.671
`8.672
`8.694
`8.676
`8.676
`8.678
`8.680
`8.701
`
`Area(mAU*s)
`-
`-
`4011.82
`4013.03
`4010.89
`4010.87
`4015.36
`4055.66
`-
`4015.87
`4019.08
`4018.56
`4017.59
`4019.84
`4017.62
`4017.27
`4023.48
`4537.86
`4545.41
`4541.65
`4522.94
`4555.21
`4556.05
`4024.68
`4541.95
`4541.17
`4524.65
`4523.19
`4024.02
`
`SSCI Repon: Stability E~oluotion ofCompmmd 578 Dmg Product Samples for Potency and Preservative Efficacy, 01108n0l6
`page 6 of 13
`
`PAGE 23 OF 30
`
`
`
`
`
`IV. EXPERIMENTAL
`
`A. HPLC Method
`
`HPLC analyses were performed using an Agilent 1100 series liquid chromatograph equipped
`with a diode array detector, degasser, quaternary pump, and autosampler. The chromatographic
`column was a Shiseido Capcell Pak C 18, 2. 1 x I 00.0 mm column with 5.0 lffil packing. The
`column temperature was set to 25°C, and the detector wavelength was 266 nm. The injection
`volume was 5.0 j.tL. The mobile phase was prepared by dissolving 7.9231 g of ammonium
`dihydrogen phosphate into 3000 mL of water, adding phosphoric acid to adj ust the pH to 7.30,
`and then mixing in I 000 mL of acetonitrile. The flow rate used was 1.5 mU minute, with a run
`time of 13 minutes per injection. Method performance was monitored for the following criteria,
`with the listed range of results.
`
`Criterion
`Precision (n=5 %RSD)
`Global %RSD
`Tai ling Factor (1 s standard injection)
`Plates ( l 51 standard injection)
`Percent Agreement
`
`Results
`0.05% - 0.06%
`0.06% - 0.11%
`1.8
`5251 - 5297
`100.6%- 101.1%
`
`SSCI Report: Stability EvalualiOII of Compound 5 78 Dn.g Product Samples for Potency and Preservative Efficacy, 0 110812016
`page 7 of 13
`
`PAGE240F30
`
`
`
`
`
`V. APPENDIX A: PRESERVATIVE EFFICACY DATA
`
`SSCI Report: Stability Evaluation of Compound 578 Drug Product Samples for Potency and Preservative Efficacy, 0 I /08/20 16
`page 8 of 13
`
`PAGE250F30
`
`
`
`
`
`1151142-20301 Lctwl'"~a>lll'l""'
`P•p2Sol"6l
`
`Pootocol Nl5 ll42-203
`Jonuary 07. 20 16
`
`Tf),U I.t: 1
`~.!!£!.V: ~rolcnsa'" hr<onf"'·' • ophU>almic solulioo 0 07%
`Bromfcooc Sodium(uostressed)
`Lot Numb<<> 240031
`
`Tat Poocluctl'~ Prolen,.•., bromfenac ophth:llmic solution 0.07% (wlv)
`BromfeMc Sodoum (~weeks@ 60"C))
`Lo1 Number 240031
`
`Challenge
`Mlero<~r&anlsm
`(ATCC #)
`
`lnlllal
`Population
`(CFU/mL
`of Product)
`
`Ooy(s)
`Followln~
`lnoculallon
`
`Product
`N
`
`Population
`Retovtrtd
`(Cf'U/mL)
`
`LOiiht
`Reduttlon
`
`Ac.uptflnce
`Criteril
`Met?
`(Yu / No)O
`
`14
`
`A.stx.IJ:."''flus braslliwnsu
`(ATG'C ~ 16404)
`
`8.6818x IO'
`
`21
`
`28
`
`3
`
`4
`
`3
`
`4
`
`3
`
`4
`
`< I.OOx 101
`
`4.9386
`
`<l.OO x 101
`
`4.9386
`
`< I.OO x 101
`
`4.9386
`
`< 1.00xl01
`
`4.9386
`
`< l.OO x 101
`
`4.9386
`
`< I .OOxiO'
`
`4.9386
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`Pe.rce•t
`Reduetlon
`
`999988%
`
`9999&8%
`
`99.99&8%
`
`99.9988%
`
`99.9988%
`
`99.9988%
`
`O l!uroptl'Jl Phrun:ocnpoda 7.0 ~.JJ. fffACIIC Y O F ANTIMICROIIIAL PRESERVATIOI'I 0 1/2011 .50103. Acccpl•- Clitcroa,
`Table 5.1.3.1. Portllflrtll pr,parall'ons. eye pr~pomllons, inlf'OUIUUI~ prt.parotlonz and lntrvrrHJmtnary pre.pa.roJklns: ~ crntria for
`fungi is a 2 log,. reduction following 7 d.1ys of exposure 10 lhc len product with no recovered Colony F<>nnmg Unil$ (CFU) recovered
`after 28 days ofexpo\arc to the producL
`
`Prot<>«> I HIS I I42-203
`Poae 6 oi"IS
`
`SSCI Report: Stability Evaluation of Compound 578 Dn1g Product Samples for Potency and Preservative Efficacy, 0 1/0812016
`page 9 of 13
`
`PAGE260F 30
`
`
`
`
`
`MlS 1142-203 01 Lcner Fin11J Rq,Of1
`l'>J<26 of6l
`
`Protocol 1 1~1142-203
`January 07, 2016
`
`'I'J\1\l,f: 8
`l'cSI rroduct t) : Prolensa '" brumrcnno ophthalmic solulion 0.07%.
`Bromrcnac Sodium (un>1n:sse<l)
`Lot Number 240031
`
`I tll PI()(JUCI ct: Prtllr""' '" brom(cn~<O!Jhthillmic solutoon 0.07% (w/11)
`810r>~ Mdoo<1 (4 \lltclcl: @ 60'C)
`Lot Number 240031
`
`Challenge
`Mlcrooreonbm
`(ATCC#)
`
`lnlll•l
`Pop•lallon
`(CfU/mL
`of Produttl
`
`D•y(s)
`Following
`ln<><ularlon
`
`Pl"()duc:t
`II
`
`1•opul1tlon
`Recovered
`(CFUimL)
`
`Locoo
`Reducrloo
`
`Acc•ptln«!
`Criteria
`Mel?
`(Yu/NoiO
`
`Ctmdida albicatu
`(ATCCNI0231)
`
`3.3182x tO'
`CFU/1.0 mL
`
`r--
`
`14
`
`21
`
`-
`
`1 -
`
`28
`
`)
`
`4
`
`3
`
`4
`
`3
`
`4
`
`< 1.00 X 101
`
`4.5209
`
`<l.OOxlo'
`
`4.5209
`
`< !.OOx 101
`
`4.5209
`
`< 1.00x!01
`
`4.5209
`
`< 1.00 x 101
`
`4.5209
`
`< I.OOx 1o'
`
`4.S209
`
`YES
`
`YES
`
`YI!S
`
`YES
`
`YES
`
`YES
`
`Ptr<:tnt
`Rtduolloo
`
`99.!m0%
`
`99.9970%
`
`99.9970%
`
`99.9970%
`
`99.9970%
`
`99.9970%
`
`O F.«ope>n Phann""'flfl'O 7.0. l.L3. FFFACACY OF ANTIMICR081Al. PRLSERVATION . 01120tl.S010l. Acceptance
`'
`Criteria. Table 5.1.3.1, Port,ttrol preparation.t. t)'t prtparntions, lntrartttrlnt prtporalions and /ntromammary prepnr01Joru:
`The criteria for fungi is n 2 log10 rcdoction following 1 days of C>posure 10 !he lost product with no recovcr<d Colony Formlna
`Unit> (CFU) recovcn:d on..- 28 days of exposure to the product.
`
`Protocol #151142-203
`P•&• 7 of U
`
`SSCI Report: Stability Evaluation of Compound 578 Drug Product Samples for Potency and Preservative Efficacy, 01/0812016
`page 10 of 13
`
`PAGE27 0 F30
`
`
`
`
`
`1151142-lo:lOI Lc:kthoal R..(cid:173)
`f'Jae l7.C G$
`
`Prclocol #IS 1142-203
`Jonuary 07, 2016
`
`~
`Tool. Pruduot ~J: Prolcn .. "' ~"""("""'ophthalmic .solulion 0.07%.
`llromfenac Sodium (unstre.=d)
`Lot 'lumber 240031
`
`fiSIP!!Kluclf:!: Prolema"' lxomrenac ophihalmic soluloon 0.07% (wfv)
`Bromrenac Sodoum (4 weeks@ 60"C)
`Lot Number 24003t
`
`Challenge
`Mtcroora.anism
`(ATCC N)
`
`l nlliot
`Population
`(CFU/ml.
`of Product)
`
`On~(s)
`Follow I•&
`tnoeutollon
`
`Produt:t
`N
`
`Populollon
`Recovered
`(CI'U/mL)
`
`LotiO
`Reduellon
`
`Acceptance
`Crlter1•
`Met?
`!Y01 / NulO
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`YES
`
`Pucen1
`.R• ducllon
`
`999994%
`
`99.9994%
`
`99.9994%
`
`99.9994%
`
`99.9994%
`
`999994%
`
`99.9994%
`
`5.2322
`
`5.2322
`
`$.2322
`
`5.2322
`
`5.2322
`
`5.2322
`
`5.2322
`
`3
`
`<1.00 X tO'
`
`4
`
`J
`
`4
`
`<t.OO x to'
`<t.oo x to'
`<I.OOx 10'
`<1.00 X t01
`3
`<l.OOx t01
`----- -
`<l.OOx 10 1
`
`4
`
`)
`
`Pftudomonas at,lgfltOso
`(ATCC #9027)
`
`1.7070 X to'
`
`I
`
`1
`
`t4
`
`28
`
`99.9994%
`<l.OOx to'
`YES
`5.2322
`4
`OEuropcan Pharmcopocll 1.0. l.I.J. EfFACIICY OF 1\NTIMICRODIIIL rRESERVIITION 01120ll:SOI03. Ae«plan"" Crittno,
`Table 5.1.3 1. Porettttml prqJGroriQns, ~~ pnpdrotiotu, ilttrtlutuiM ~paratinN and iltll'dflttllt'llttDr:Y pnparolioltf: Critera A for
`I>Ktoria is a 3 Joe10 n:duc:Jion followina 24 houn of cxpasun: to lhe t<$1 producl With no recoverea Colony Fonnina Units (CFU)
`recovered after 28 doya or cxpooure 10 the prod""~
`
`Protucol NJS I I42-203
`Page 8 or 15
`
`SSCJ Report: Stability Evaluation of Compound 578 Dntg Product Samples for Potency and Preservative Efficacy, 0 1/08/2016
`page II ofl3
`
`PAGE280F 30
`
`
`
`
`
`IISII•l·20l01 ......... Finol1topon
`Po«< ll a(6.l
`
`l1i'Oiucol H151 142-203
`Jenuoty07. 2016
`
`ICJ<i'&h!<\ll.l: Prole,.•Jh~!!;!.!2 oplul\almi<: solution 0.07%.
`Bromfcn1c Sodium (unstrest<:d)
`Lot 1-oumbef 240031
`
`lntl'roc!U<tli4: Pw ""'" "' b<ro•fcnaeupbthol-nic solul•on 0.07% (wlv)
`B>omftOJ( Slld1Um (4 \\CCiul@ 60°C)
`Lot Numbor 240031
`
`Challenge
`Micnorea,nism
`(ATCCN)
`
`Initio!
`11opulotlon
`(CFU/mL
`orProduct)
`
`Da)'(s)
`Follow inc
`loocullllon
`
`Population
`Product Recovered
`u
`(CFUimL)
`
`Log10
`Reduction
`
`3
`
`4
`
`3
`
`4
`
`3
`
`<1.00 X 10'
`
`<(.00 X 10'
`
`<I.OOx 10
`
`<1.00 X 10
`<J.QQ X ]Q'
`
`5.2959
`
`5.29H
`
`5 2959
`
`5 2959
`
`5.2959
`
`4
`
`3
`
`5.2959
`
`5.2959
`
`Ateeptance
`Criteria
`Met?
`rYes / Nol O
`YES
`YES
`
`YES
`YES
`YES
`YeS
`
`YES
`
`Percent
`Rrductlon
`
`99 9995%
`
`99.9995%
`
`99.9995%
`
`99.9995%
`
`99.9995%
`
`99.9995%
`
`99.9995%
`
`I
`
`7
`
`StapltyloccccuJ nurcw.r
`(ATCC #6538)
`
`t 9767 x to•
`
`- -
`
`14
`
`28
`
`<J.oo x to'
`<1.00 X 101
`<LOO x to'
`99.9995%
`5 2959
`YES
`4
`Or 11ropun Pht>l!aOOIX'CII 7.0 ~.1.3 ErFAC,\C' Or ANTIMla\OBihl. PRESE'RVA OON. 0J/201l:.S0103. Aceeplance ( wma.
`Table S.t.J I, Por~lllrrrrl prtpnralioru~ ,yr prtpo.mtiiJtU. lnlmuluine prrpanmons and IIIITOIIfQM'ItOIJ puparatio,u· Criteria A for
`bacteria is I 3 lot:•• reJuction rotlowmg 24 hours or cxpo.ure ID the lest product wilh no ICCO\Crod Colony Forrnina UOIIS (CFU)
`reooverod al\er 28 daysofexpotUfelo the product.
`
`Proloco l # lSI 142-203
`Pogo 9 of IS
`
`SSCI Report: Stability Evaluation of Compound 578 Drug Product Samples for Potency and Preservative Efficacy, 01/08/2016
`page 12 of 13
`
`PAGE290F 30
`
`
`
`
`
`MISII42·203 0 1 Lc"« l'in1l Report
`hl•19 of6)
`
`Prolocolll151142-203
`Januory 07,2016
`
`'fABI,t! II
`Ntutralizai>OI\ E1111luooon- Results
`IN l'r<><lllu.b.1 : PmlcnsaT>< bromfcnac ophthalmiC solution 0.07'11.
`&umrenac Sodium (unstressed)
`Lol Numbers 240031
`
`C~tlltn&e Mkrooratolam ATCC. N<utr•IIPIIoo Phase Mleroblal RttoYfry
`(A•trtgt CYUIPI11t)
`-
`
`A.i{Nrgilfus brasiliens I•
`
`113.00
`188.00
`
`R .. uua
`Poull'oiiO
`
`PMa
`t - -
`Pa.u
`
`CONTROL
`16404 t - ---
`TI:Sl
`- - -
`30.00
`CONTROL
`30.00
`TEST
`30.50
`CONTROL
`---
`n:sr
`34.00
`- 1-- ~NTROL
`-- --
`TESr
`23.50
`..
`8 1 no counts (Averai• (,FU/Piatc) nb•c•vcd for lho 1 I:ST san11~• do not vary by more !han a fac1or ar
`S ftom those recovered rrom the respective CONTROL s1unple; hence. I he neutralizing media are considered to be
`efl"ectaw:.
`
`1-
`
`Candula a/bicon•
`
`10231
`
`Pstudomonas aeruglmua
`- -
`Sutp/ty/()Cf)Cetl.t o11rw s
`
`9027
`
`6SJ8
`
`-
`
`24.00
`
`Past
`
`Pus
`
`I.6.ll.l&.ll
`Neutrnhzation Evaluation - Results
`:1<4! l'ro•h"'i l/1: Pr(>ICilllli'"' b•·on•f<nocophihlhnlc .olu1ion 0.07% (w/v)
`llromftnll< Sodium (4 <IIC:ek•@ 60•C)
`Lot Number 240031
`
`Challenge Mlcrooreul<m ATCCN Ncutuliuliol\ rhue Mk:robiaJ Ret on.ry
`(A vtroge CFU/Pialt)
`
`Results
`Pau/1'1110
`
`AsJI'rgillll.r bNuilltnsls
`
`16404
`
`CONTROL
`TEST
`
`Cnndltln nib/emu
`
`-
`
`PstuJomo,Jo.s a~n11h.aso
`
`CONTROL
`10231 - -
`TES r
`CONTROL
`
`9027
`
`Staphylocccci'S aur~us
`
`6538
`
`113.00
`21 3.50
`
`30.00
`36.00
`
`lO.SO
`
`) ~
`
`3S.SO
`2400
`
`-
`-
`
`Pass
`
`Pass
`
`,, .... ,
`
`Pa.lri6
`
`TEST
`---,~
`CONfROL
`TEST
`20.00
`0 I he counts (Average CfUIPiolc) ob><rv«l for the f ESl sam1•l• do nol vary h)/ more lb•n ,, fl1Clnr of
`5 fTotn !hose recovered from lilt respecti.e CONTROL ••mple; hcnct, !he ncutrahZin& med1a uc: considcn:~
`to be effecti\t>.
`
`Pro~ocol U151142-203
`Paac lOoflS
`
`SSCI Report: Stability Evaluation of Compound 578 Drug Product Samples for Potency and Presef'liOtive Efficacy, 0 I /0812016
`page 13 of13
`
`PAGE 300F 30
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
