IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`
`SENJU PHARMACEUTICAL CO., LTD.,
`BAUSCH & LOMB INCORPORATED and
`BAUSCH & LOMB PHARMA HOLDINGS
`CORP.,
`
`Plaintiffs,
`
`v.
`
`INNOPHARMA LICENSING, INC.,
`INNOPHARMA LICENSING, LLC,
`lNNOPHARMA, INC. and INNOPHARMA,
`LLC,
`
`Defendants.
`
`Civil Action No. 1: 14-cv-00667 (JBS)(KMW)
`Civil Action No. 1:14-cv-04149 (JBS)(KMW)
`Civil Action No. 1:14-cv-05144 (JBS)(KMW)
`Civil Action No. 1: 15-cv-00335 (JBS)(KMW)
`Civil Action No. 1: 14-cv-06893 (JBS)(KMW)
`Civil Action No. 1: 15-cv-03240 (JBS)(KMW)
`
`(Consolidated Actions)
`
`CONTAINS CONFIDENTIAL MATERIAL
`PURSUANT TO STIPULATED
`DISCOVERY CONFIDENTIALITY ORDER
`
`SLJpJ>LRMENTAL EXPERT REPORT OF DAUYL S. PAULSON, PH.D., M.A., M.S.,
`M.B.A.
`
`I.
`
`QUALIFICATIONS
`
`1.
`
`I, Daryl S. Pattison, Ph.D., M.A., M.S., M.B.A., submit this supplemental expert
`
`report at the request of Se1'\iu Pharmaceutical, Co., Ltd. ("Senju"), Bausch & Lomb Incorporated
`
`and Bausch & Lomb Pharma Holdings Corp. (collectively, "B+L'') in connection with the above
`
`captioned actions as an expert in the field of the evaluation of drug products. My qualifications
`
`in these areas, as well as other areas, are summarized in my expert reports dated December 24,
`
`2015, and established by my curriculum vitae, which was attached as Appendix A to my
`
`December 24, 2015, expert reports.
`
`2.
`
`I am submitting this supplemental expe11 report to provide a complete set of
`
`experimental data in the SSCI reports dated January 5, 2016, attached as Appendix A of this
`
`report.
`
`1
`
`
`
`SENJU EXHIBIT 2257
`INNOPHARMA v SENJU
`IPR2015-00902
`
`PAGE 1 OF31
`
`
`FOR THE DISTRICT OF NEW JERSEY
`
`SENJU PHARMACEUTICAL CO., LTD.,
`BAUSCH & LOMB INCORPORATED and
`BAUSCH & LOMB PHARMA HOLDINGS
`CORP.,
`
`Plaintiffs,
`
`v.
`
`INNOPHARMA LICENSING, INC.,
`INNOPHARMA LICENSING, LLC,
`lNNOPHARMA, INC. and INNOPHARMA,
`LLC,
`
`Defendants.
`
`Civil Action No. 1: 14-cv-00667 (JBS)(KMW)
`Civil Action No. 1:14-cv-04149 (JBS)(KMW)
`Civil Action No. 1:14-cv-05144 (JBS)(KMW)
`Civil Action No. 1: 15-cv-00335 (JBS)(KMW)
`Civil Action No. 1: 14-cv-06893 (JBS)(KMW)
`Civil Action No. 1: 15-cv-03240 (JBS)(KMW)
`
`(Consolidated Actions)
`
`CONTAINS CONFIDENTIAL MATERIAL
`PURSUANT TO STIPULATED
`DISCOVERY CONFIDENTIALITY ORDER
`
`SLJpJ>LRMENTAL EXPERT REPORT OF DAUYL S. PAULSON, PH.D., M.A., M.S.,
`M.B.A.
`
`I.
`
`QUALIFICATIONS
`
`1.
`
`I, Daryl S. Pattison, Ph.D., M.A., M.S., M.B.A., submit this supplemental expert
`
`report at the request of Se1'\iu Pharmaceutical, Co., Ltd. ("Senju"), Bausch & Lomb Incorporated
`
`and Bausch & Lomb Pharma Holdings Corp. (collectively, "B+L'') in connection with the above
`
`captioned actions as an expert in the field of the evaluation of drug products. My qualifications
`
`in these areas, as well as other areas, are summarized in my expert reports dated December 24,
`
`2015, and established by my curriculum vitae, which was attached as Appendix A to my
`
`December 24, 2015, expert reports.
`
`2.
`
`I am submitting this supplemental expe11 report to provide a complete set of
`
`experimental data in the SSCI reports dated January 5, 2016, attached as Appendix A of this
`
`report.
`
`1
`
`
`
`SENJU EXHIBIT 2257
`INNOPHARMA v SENJU
`IPR2015-00902
`
`PAGE 1 OF31
`
`
`
`II.
`
`DOCUMENTS AND INFORMATION CONSIDERED IN FORMING OPINIONS
`
`3.
`
`Under my direction and control, BioScience Laboratories, Inc. conducted a
`
`Preservative Effectiveness Test ("PET")
`
`to evaluate and determine
`
`the antimicrobial
`
`preservatives effectiveness of several samples challenged with resistant microorganisms.
`
`In
`
`reviewing the PET results, I had available to me the documents cited herein, the documents cited
`
`in my December 24, 2015, expert reports as well as the publications listed on my curriculum
`
`vitae. The data tables for the PET were created using the raw data collected by the Study
`
`Director, Dan M. Dragotoiu, who conducted this comparative study and who holds a B.S. degree
`
`and has over ten years of professional and academic experience in the area of microbiology. I
`
`reserve the right to testify about BioScience Laboratories, Inc. test results and scientific expertise.
`
`To the extent I am provided additional documents or information, including any expert reports
`
`produced by InnoPharma, 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
`
`4.
`
`BioScience Laboratories, Inc. received from SSCI samples of B+L's Prolensa®
`
`product
`
`for PET. Upon receipt of
`
`these samples, BioScience Laboratories, Inc. stored, handled, and maintained according to
`
`BioScience Laboratories, Inc.'s current good manufacturing practice ("GMP") sample handling
`
`procedures as specifically outlined in their SOP L-0005. These samples were evaluated for
`
`preservative efficacy during the months of November 2015 through January 2016. BioScience
`
`Laboratories Study Director, Dan M. Dragotoiu, was personally present during the preservative
`
`efficacy testing of these samples.
`
`2
`
`
`
`PAGE2 OF31
`
`
`
`5.
`
`Summary reports of the preservative efficacy testing conducted by BioScience
`
`Laboratories, Inc. on these samples are attached as Appendix A. The report describes the
`
`analytical methodology to evaluate preservative efficacy of stressed and unstressed samples of
`
`B+L's Prolensa® product
`
`As set forth
`
`in the Ew-opean Pharmacopoeia, the following organisms were tested: Candida albicans
`
`(AATCC# 10231), Aspergillus niger (AATCC# 16404), Pseudomonas aeruginosa (AATCC#
`
`9027) and Staphylococcus aureus (AATCC# 6538). The preservative efficacy results are
`
`reported in the document for all of the samples tested.
`
`6.
`
`BioScience Laboratories, Inc. is a Good Laboratory Practice ("GLP")/GMP
`
`facility providing contract product development services to the pharmaceutical industry.
`
`BioScience Laboratories, Inc.'s service offerings include, but are not limited to analytical testing
`
`(e.g., preservative efficacy), product development, and manufactures label claims. The
`
`preservative efficacy testing of B+L's Prolensa® product
`
`samples was performed in BioScience Laboratories, Inc.'s GLP/GMP In-
`
`Vitro laboratory.
`
`7.
`
`The details of the analytical testing that was performed and the preservative
`
`efficacy test results obtained were provided to SSCI for incorporation in the SSCI reports
`
`(Appendix A).
`
`IV. COMPENSATION
`
`8.
`
`If called to testify to the facts stated herein, I will be compensated for my time
`
`preparing for and testifying in this matter at rate of $500.00 per. No part of my compensation is
`
`contingent upon the outcome of this matter or any issue in it.
`
`V.
`
`PRIOR EXPERT TESTIMONY
`
`9.
`
`During the past four years, I have not testified as an expert in any cases.
`
`3
`
`
`
`PAGE3 OF31
`
`
`
`0\ .... \\:-\ b
`Date
`
`--o~ s~~
`
`Daryl S. Paulson, Ph.D., M.A., M.S., M.B.A.
`
`4
`
`
`
`PAGE40F31
`
`
`
`Appendix A
`Appendix A
`
`PAGE50F31
`PAGE 5 OF 31
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`PAGE 18 OF 31
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`PAGE 18 OF 31
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`
`
`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 19 OF 31
`
`
`
`
`
`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 20 OF 31
`
`
`
`
`
`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
`
`PAGE 21 OF 31
`
`
`
`
`
`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 22 OF 31
`
`
`
`
`
`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 23 OF31
`
`
`
`
`
`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 240F 31
`
`
`
`
`
`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
`
`PAGE250F31
`
`
`
`
`
`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
`
`PAGE260F31
`
`
`
`
`
`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
`
`PAGE270F 31
`
`
`
`
`
`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
`
`PAGE280F31
`
`
`
`
`
`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
`
`PAGE290F 31
`
`
`
`
`
`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
`
`PAGE300F 31
`
`
`
`
`
`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 31 OF 31
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