CJ ISO 10993 Biological evaluation of medical · PDF filef';~ ~ ~';'1 'CJ ISO 10993 Biological evaluation of medical devices May 2012 Nelson laboratories 'Cl 6280 South Redwood Road

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'CJ ISO 10993 Biological evaluation of medical devices

May 2012

Nelson laboratories

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6280 South Redwood Road

Salt lake City

Utah

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804 Green ValleyGreensboro, NC 27408USA

BURLINGTON LABS

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There are three basic tests every medical device must be subjected to: cytotoxicity,sensitization, and irritation. Each test screens for the presence of toxic, leachablematerials.The chemicals used in the manufacture of Burlington Maxima / ESD products listedbelow have been tested in finished products and pass the requirements ofbiocompatibility.

() Dianix Turq SBGTerasil Blue GLF

Terasil Navy S2GRL2Terasil Blue BFLR-02

Dianix Yellow AM-42Terasil Orange 4RLLumacron Blue LG

Terasil Pink 2GlAPermasil Violet BlNlumacron Red FSE

Disperse Blue FRlNTerasil Red 3Bl150Dianix Yellow S-6G

Chom Rubine 2GFl150Dianix Red EFB

Lumacron Bord EBllumacron Yellow E3G200

Perma Red BSN 200

Permasil Violet 2RB

Tricablanc EBF250Lonosperse Blue FBlN

Lonosperse Violet WRLDianix Red 177

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~ I',.Test Article 3: ~100mrn2perwell~I_~~-Test Afticlé 5i ~100mrr~perweJl

c')AcceptanCe Criteria: The United, States, Pharmacopeia' & National, Formuiary (USP , 87), states that thetestarticle tneets the ,te(¡uirerrelitsifthereacUvity grade is not greater than grade 2 or a mUd reactivity.TheANSl/AAMl/lSQ 10993-5 standard states that the achievement ota numerical grade greater than 2 isconsidered i:cytotoxii' effect. Nelson Laboratories acceptance criteria was based l,pon the negativecontr,,1 receiving "on reactivity grades and positive control receiving 3-4 'reactivity gradès (moderate to$E!vere).

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GOOO,~ABORATORY PRACTICES STATEMENTThe SJ~CstVçly referençêd in thj$ report was conduètedihoomp/iance withGood Laboratö 'ice (GlP) RegUlations sét förth ¡n"Title 21 Part 58 of theCode of Fêd~ta Tons of the Unîted StatèsQh~merica. Other portions ofthis study thátwete hot performed by or under the dlrectîon of SRC, includingthe cnatacter¡il,t1oh and $t8,DiUty testing of the tøst ~tliê!e whi,Ohis the

responsibilty oflhe Sponsor, are exempt from :this aGP statement.

Sincerely,

Nathaniel TerryTechnical,'ManagerBrulingtori LabsOffice Telephone:, 336-228-2420Email:.nathcmiel.terry(§burlington.com

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NEIlONLABORATORIES

Sponsor:Nathaniel Terry

Burlington Industries, Inc.906 Anthony St.

Burlington NC 27215

Functionality Processing for Test ArticlesIntended for Health Care Facilities GLP Report

.... ..... ....... .. . .... ........ ..... . . .. ... .. .. . . . . .. ................. . .. . .. . . .. ........ . .

Test Article: Burlington Maxima I ESD B101Burlington Maxima I ESD B102Burlington Maxima I ESD B103Burlington Maxima I ESD B104Burlington Maxima I ESD B105

Laboratory Number: 613916Study Received Date: 23 Dec 2011

Test Procedure(s): Standard Test Protocol (STP) Number:

Protocol Detail Sheet (PDS) Number:STP0159 Rev 02201104799 Rev 01

Summary: This report details the sterilization cycle performed on the test articles.

The test articles were retained at Nelson Laboratories, Inc. (NLI) for further testing. Test articles subject tosteam exposure are not for human use. The test articles should only be used for functionality,biocompatibility or other physical evaluations not involving human patients.

Procedure:Steam Exposure: The prepared test articles were placed into the steam sterilizer and sterilzed one time

. per parameters listed below:

Sterilizer Type:Preconditioning Pulses:Minimum Temperature:

Exposure Time:Dry Time:

Test Article Configuration:

Prevacuum3132°C4 minutes30 minutesUnwrapped test articles were placed into the chamber; test articles did notcontact each other during the cycle.

Jason C. Pope, B.S., ASQ CQA1: )-AoJ I)) \0

Study Completion DateP.O. Bo, 571830 i Murra, UT 8415', 830 USA ' 6280 Soulh Redwoud Road I Salt Lake C,ly. UT 84123-6600 U.SAwww.nelsonlabs.conl..fephone801?907500.Fa~8012907998.sales¡ßnelsonlabs.com

clb FRT0159.001 Rev 2

Page 1 of 2

These results relate only to the test artide listed in this report. Reports may not be reproduced except in their entirety. Subjec to NLI terms and conditions at WWnelsonlabs.com

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NEliONLABORATORIES

Laboratory Number613916Functionality Processing for Test Articles

Intended for Health Care Facilities GLP Report

Quality Assurance Statement.............................................................. a............................ l,O.................

Compliance Statement: The test was conducted in accordance with the USFDA (21 CFR Part 58)Regulations.

-ilott_ illIWIIf ..... tA ib it. ~_L ~' il '. Activity . ~ ¡¡- .---

Study Initiation

Audit Performed by Quality Assurance, IP '.Audit Results Reported to Study Director

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.._~""..'l_Date If - ir -:~:i29 Dec 2011

29 Dec 2011

29 Dec 2011

29 Dec 2011Audit Results Reported to Management

r:-:" ..,17'.. Lb. MI." ..Scientists'3 tb

-", - -,'lr¡¡ - A- ¡¡"" w- M_ ~Titlê' - --..I.. .. _....~'.I.. :Si_ _ _ _ __ --of .._- linm "~liMike Neilson

JásonC. Pope

Supervisor

Study Director

Data Disposition: The raw data and final report from this study are archived at NLI or an approved off-site location.

QUalitYAS~ 03 .iú\l 7.\1.Date

P.O Bo, 571830 I Murray. UT 84157-1830 USA. 6280 South RedwClod ¡load i Salt Lake C.ly. U r 841?:-6600 U.S.A

wNwne150"labs,com . Te!ephorie 801 2907500 . fa.. 80l 290 7998 . sa!es;ßoclson1abs,cumclb FRT0159.Qi Rev 2

Page 2 of 2

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Nathaniel TerryBurlington Industries, Inc.

906 Anthony St.Burlington NC 27215

NEUONLABORATORIES

ISO 10993 Part 10- Primary Skin Irritation Test in Rabbit..................................................... ...........................1-.......

Summary: Enclosed is the final report for the testing we coordinated for you. The information is retainedby the testing laboratory.

t:::...~tëšt"IÍ';ic~le:~.~f ~;,;i-'~~ìPM"'" .d~Erur¡iñ-g' tõfVåxima;¿EStj1S'1 (j'i...i~~~.'i'fl"'.ii _:ili .¡¡.~~''''''~~"''"''''''.: .. ~ ~ ,.,,~. ..~'-,._..:."....__.. ._.....,,"~_,.-..-.,.. . H__;aNelson Laboratory Number: 614435~ '!.- "iL,. .iQ.~..',fi:L,_0!l,.JIi-~..T~

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Results: The test article did not cause skin irritation under the condition of this assay.

If you have any questions, please feel free to call or email any of our Subcontracting personnel at 801-290-7500 or subcontractingCânelsonlabs.com. Thank you for testing with Nelson laboratories, Inc.

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p.o. Box 571830 I Mi",oy, UT 84157-1830 U.SA . 6280 Soulh Redwood RQad I Sail Lake Gly, UT 84123-6600 U.S.A

www.nels.onlabs.com . Telephone 80\ 290 7500 . Fax 801 290 799B.. salesllnelsúnlabs.com F RM0641 Rev 02

These results relate only 10 the test article listed in 11116 renort Hepoi1s may not be reproducecl ex:ceplin their entirely. Sub¡eCIIO NU torms and conditions at \\'w.rlclsoiiiabs com

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STUDY TITLE:

FINAL REPORT

ISO 10993 Part 10 - Primary SkinIrritation Test in Rabbit

STUDY PROTOCOL NUMBER: 010972.046

STUDY NUMBER: D10972.046-13

TEST ARTICLE NAME: Burlington Maxima I ESD B101

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TEST ARTICLE LOT NUMBER: N/A

TEST FACILITY: Sinclair Research Center (SRC), LLC.

(AALAC Accredited)562 State Road DOAuxvasse, MO 65231, USAPhone: (573) 387-4400Fax: (573) 387-4404

SPONSOR: Nelson Laboratories, Inc.6280 South Redwood RoadSalt Lake City, UT 84123

NELSON REFERENCE NO.: 614435

'. .\ DATA REQUIREMENTS: GLP

DATE SAMPLE RECEIVED: 10-Jan-2012

STUDY INITIATION DATE: 10-Jan-2012

STUDY COMPLETION DATE: 3-Feb-2012

RESULTS SUMMARY: The test article did not cause skinirritation under the condition of this assay.

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~wa$áccording to SRC'~$OSahd Cèrttficat6.

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IACUC Protocol #ipproval Datè:

AMENDMENTS: N/A

25-Feb-2011

E)EVIATIQNS: N/A

~'~("'j~~ SRC Study No. D10972.046-13 Final Report Page 6 of 11

GENERAL OBSERVATIONAll animals were observed daily for general appearance.

DOSING SITE OBSERVATIONDermal observations of dosing sites were preformed at (1 :! 0.1) h post doseremoval, (24 :t 2) h, (48 :t 2) hand (72 :t 2) h post dose administration. Thescoring for erythema and edema was conducted according to the system givenin Table 1.

Table 1" Dermal Observation Scoring (24, 48 and 72 (:I 2)) hpost dose"

Reaction Irritation ScoreEryhema & Eschar Formation

No Erythema 0Very Slight Erythema (barely perceptible) 1

Well-Defined Erythema 2Moderate Erythema 3Severe Erythema (beet redness) to eschar formation

4Ipreventinagrading of erythema ,

Edema FormationNo Edema 0Very Slight Edema (barely perceptible) 1

Well-Defined Edema (edges of area well-defined by2

definite raising)Moderate Edema (raised approximately 1 mm) 3Severe Edema (raised more than 1 mm and extending

4beyond exposure area)Maximal possible score for irritation 8Other adverse chançies at the iniection sites shall be recorded and reported

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EVALUATION CRITERIAThe primary irritation index (PII) was determined as follows. Only scores at (24:t 2) h, (48:t 2) hand (72 :t 2) h observations were used for calculations. Afterthe 72 h grading, all erythema grades plus edema grades (24 :t 2) h, (48 :t 2) hand (72 :! 2) h were totaled separately for each test sample and blank for eachanimaL. The primary irritation score was calculated by dividing the sum of all thescores by 6 (two test! observation sites, three time points). To obtain the primaryIrritation index for the test sample add all the primary'irritation scores of theindividual animals and divide by the number of animals (generally three). Whenblank or negative control is used, calculate the primary irritation score for thecontrols and subtract that score from the score using the test material to obtainthe primary irritation score. For any response from test, record the maximumprimary irritation score for each animal, the time of onset of the response andthe time to maximum response. In case different extracts have been tested, theone giving the highest PII determines the response category.

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ce with the iso": Tast$ tor'

r'ôöd and Drug(órtb in2~CFRated1e$f'~.

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C)NEIiONLABORATORIES


Burlington Industries, Inc.906 Anthony 51.

Burlington NC 27215

ISO 10993 Part 10 Guinea Pig Buehler Sensitization Test. II.... l.............. .................. ............. ........................... .........


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Nelson Laboratory Number:.1'~ Tèslrn ii.¡r6:~~ '"

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614436:\..~f1

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Results: The test article (device) demonstrated NO sensitization reaction under the condition of thisassay.

r'"If you have any questions, please feel free to call or email any of our Subcontracting personnel at 801-290-7500 or subcontracting~nelsonlabs.com. Thank you for testing with Nelson Laboratories, Inc.

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PO. Bo, 571830 I Murray. UT 84 7-1830 U.SA . 6280 South Redwood Road I Salt Lake City. UT 84123-6600 U.SA

www.nelsonlabs.com . Telophone 801 2907500 . Fax 801 2907998 . salesl1nelsonlabs.com FRM061 Rev 02

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researchFINAL REPORT

STUDY TITLE: ISO 10993 Part 10 Guinea Pig BuehlerSensitization Test

PROTOCOL NUMBER: 010971.046

STUDY NUMBER: 010971.046-10






NELSON REFERENCE NO: 614436

DATA REQUIREMENTS: GLP




RESULTS SUMMARY: The test article (device) demonstrated NOsensitization reaction under the conditionof this assay.

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~a()Q~El~RAtORYPRAO'lOE ..~Me!N'rThe $RCstl.dYtefêr~n9éaiM/'i$repørtWascondl.. '.' .èôrtPliaiicewlth GoodLabori:toryRr~èti~e(I3LP)R~Yli:tì()iil?set. forth tnTitlt!~1. ,part5&ofthê..C()de .ofFederalRegtll'Etiônsofthe UhitedStatês' ofArnêrica.Ölhet.øprtions.öftHis.study

that were not.pêrfgtrnêí'l)yorunderthê dlteçtfonof'SeØi lnö(udlngthécharacterization and stabilty testing of thei test,¡¡rtcle(dêviee)which' Is theresponsibilitY of thø Sponsor,are exemptfromthi$ Gl.Pstatement.

Stdyalredor. ~i2 ... ....... ...... ~:.lr¡pÁ/~LUke;Zffang;M.D., M.Sc., Senior Scientist

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TEST DaVie! GHARACTeRIZATIONThE! Spon$orwa$'t$sQ¡tJnsiblèl~raii test dElvice Qhain the GLP n¡lg h$; TliElldentity, sirengtn, !'~.'¡.composition of devicewere SOlelY the . "Sponsör was Ie for supplyln'ftothé tesllng'labdeterminstlo y other$ thstm'sy have dlreetiyrperform.e' . inglaboratory, pnorta initiation of . '. . 'årthermQre, it wasthe reSpÓn$i ofthèSpansor to ensure thåt.the tést devicesubnìiltèdfOrLestingwas representativè oftlie final productthat Was $ubjected to'rrfaterislscharacterlatiion. . 'll i'equîrøments fdrhandnngpr ~(orGe¡Y.ete arranged in

advance Of récelp test device Wàs received in goodcond)tion.

sAMPi,e STORA .Test device .' " ~ion, storage. BOd dSÓPánd,the '.. s;tesponsiblefór èns

, " :-- -.-,. '. ,.. ,,' _ _ ., _ _ -;. .,., .'; _ . _ ',' _ . ::;,:,-. " - ::,.,. " --,',; - - -,.' ~ ,:: '-,' -, . -, - - -,.

AnaLysis: were providêd to SRC.

EXPERIMENTALOES,IGNSev . _en (17) atfult guinea plgs were used in the l1èin testihgfor .eaçh test

. sa including control testln this $tudy~ Tnestl./pyday Òis thefl($t dosing day.

Elevén (11) anlm$h!PNêrJJ in tlìe. testgtöl!p' ând sli(6) were in the~c.ohtrol group.The têstCfÐvice arìd cø,ntróldilvlèe wereddsedjn tw9 phasl!$ in tria proposeddu'ratlort Dermal sàoritig'wBs-perfòrré'd at"24 :b 2 andilS,:í'2 hôuh~post'ótiaiiengephase pàtch removaL. Animals werêeûthanizêd at termination. .

i!'trqn~,W~$iao~ording to SRcthåf .t(fSQ)s 'éncl Cértificate of

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INSTITUTIONAL ANIMAL OARE ANQUSe COMThe Pi:~tØèot a" ' '~: ticlì;ei:tsor i:rÇ)cedJ;rre~an¡rm~rs Qn thl, e r'évlewed and apprëNr"

initlatipn otsuch ûres.

IACUC Protoçol Approval Date: 7-Mar"2011

AMENDMENiiS:N/A

DEVIATIONS: N/A

HUSBANDRY

Acclimation: Preaeq'ìimated

Housing: The animals were;housedaccordlngto facilty SOP,

,êré Mönitoteêl arid'òlt6red¡ bot notEnvironment:

FoodìWater:

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Pink cloth with Iinrn,f(9fiallerìg&)

.CONTROL,DEvlcrteß~leARrION':~ ,:~' - ,;~~,._--~,,- .

'Uiè8¡:Pei"Pâtch Size (em)

;'2x3..2x,3.

ANIMAL SELECTJON AND QANOOMlZA1IONÀnimals Were seieoted'fbr study pasedon a physical examination pêrformed b,y aqu~iified member óf thtt'vetørinary staff. Thê selected aì)itoàlswere randomizedInto the treatment groups according to SRC SOP prior tö;Closèínitiation.

ANIMAL PRePA~TlaNThe hair on' the tElright flank areåfor'

gatea (..S)( 7cinlèftflånltgeprlaiie).was clippedprlor:t

.for induction phase,..sê administration.

TEST AND CONTROL DEVICE ADMINISTAATIONIiidlittion Phas4'(t?clÝ 0..17)

The patch of control or test device at - 2 x 3 em size was applied to the designatedleft dosing site of the cøntrolor test animals respectl' b doseadmlnistr~tioii. Dose areé Was wrapped ý¡ithelastic. . ~ ..' and secured with

hypoaUergenlc tape. Patch and dressíng were removed' al6:t 0.5 hours after

appUòatl9h. ProC$.durewas repeated three (3)tiÍ'ès' pet week for three (3)consèóutive weeks. .

GIillIerige phsse (13 day,sp,óstlast indlJctlon applicatIon)The patch of control ortèsldevice êt -gx 3 cm si~e w jeç to the deslgnçitedright dQsingsite Of the ÇòntÍ'olor test animals re$p. .'li: Clheiiie~ge dosè

phase. POsè arE~a was wråpp~d witheJàsUÓbandlågÉJ .... cl,recwith

hypoi:llergeni(j tapè. Patch 'and dréssing Wérerémoved at 6 ~ 0.5 hours afterapplicàtion.

TSRfJUNÄTIONAllanhrials wÉire èûthanlzed with' FâtalPlus(P 'injectiönst"erminRtiOn(day'36).

EVALUATIONCRlrT-et resUltswerÈf ' . inçidenCé and severity ofdJiesensitization reaction.In~idenCé Is defl ' .. , . ~fCEiitaQlfóf animals exhibiting a seasitizatlon reaction

at' esc . '.' NatIon tim~'~póint (24 aríd 48 hours) p ,C)Sèverity wascalcula ,Un: of the challéiige $0'0' i:~umber ofani' " time point. sevér,~ . (t)orgreater inthe .' '. . . :aUY hdlcate sensitizatIon. pròvidèd des oflèssthàn' one (1)

ate ot5served cóntröl animals,. then therêaotions .tl1è t!Istal1imåls 'Whiphexcsed the ricist ' control reèctlQnare prêsum d.Uê to sensitization. Inthe fÍriai'ái1alysis () , .' ,consíderatiort ls given to th . .' 1.1 pstterns, inte~sitY,duration, and charåcterof reàçtrons oftha test as compElre'with the controlconditio~. 1M skin.reeCLipnre$Ult is presented liS p6sitive (+) or negative (-).

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ASSAY VALIDITYThe assay was êQ'

irritation in cofitra'I'test.

èred valid based upon that there W!ls nó ê~cessive skin. åls .andthe test area consisted .'fnorrnal"sktnprior' to the

N/l:TIiOQ FQR OQNTROL.OF laIAsAlthöu'ghtheäti.dYc .' øt.QIlrçled, the uise of ácostudy per:šõrinelto mdermal scor'ing.còiìtròlle

,'ce'~ndfully trained

'mental bias.

AROHIVALÂcopy of the origin ort; original protocol (includin' "endmeiits, deviaítlons,requisijiÓriform and thnjents) 'ând all originål in-Ii, ,ay ~peë¡riC' råwd2lt~ as

well as .pertinent in:'lIfs . aêllitY data ate årchivecl at Sinclair' Research :Center L£C.

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qOMPLll\NCeTh~c~~ei' hQM~ing. lind l1.n~líng of tl\l ani . lianee with thø .ISO

1QS93-10: 201. ~icai E~ai,uátio . ~1b¡~test$foflrritatiònand Skin Sensi n, réport9Ø.in c .ab~. OrygAdministration GoOd Labörator, lfSY rêgulätlon~ setfôrthin21 CFR Part58 and inraGçtrdärièe tQ;the,global.. eolandthe. ed 1'estRequlsiliøn

I=orm, fac;IUttitéril : . ng proce~ures¡~fídW2., Pròtòcolamendments aíiCl dev If any, wére handled a acillt.SOP.

',l'A~onducts positive controls apprc))cimately every 6' months.

;'W~Sèòmi:leted on 25 Obt 2011 (SRC study number. methods. foethe positive eontral assay are similar to the

im~ls were s;:me strain from one vel1dor (Elm Hil). The. " troøhlorobenzené (DNOe for Induction phase and

. iì'f'a~tone. The negãtfvé control animals were exposed to

RESULTS

G(ll1étáIQbleJ'íitiont:AI¡anll1~ls)àppe~rèdnôrmalduring study. period (all doses succeeded).

. ~àre prEisentedin Table 2. The results (rom SRC'SO~1 dérmalobse",stionø are.t;îteŠéntedlnTable3.

eLUSION. ..... " ráensitization observed with ,elther cQntròl or test groups

at 24 . 48 hourhg post cha.llenQè phase. In tM flnai analysis of data,consideration wás gfVElhto theoVèräll patterns. Intensity, duration, and ch.aracter ofreactions tithe . coirparec: w~h the contrOl cannitions. The test article

(ç!evice). did not . . a !$er:$itization reaetion. .

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RIiPERSNCESSRCSOP: AC0202v7, Test lnltlation and Assignment, of Test System toÐqeriffentaIGroupSPlCSOP: ACö203v5, Animal Acquisition, Allocation, and Transportation andStudy Roøm RéseNatior' PrócéduresSRC SOP: AC0101v10¡ General Animal Care ProceduresSRC SUP: ACÓ1 08v4,RecQgnizingPain Stress or DistressS~CSOP: P .... '. pal ExaMination of Animals'

SRC 89p: ,a1 aòdy WeightsSRC soFf; '. , Skin irritation & Sensitization ScoringSRCSOP: ~R .. ...; V3,Oose Adminlsttatiòn ProceduresSRC SOP: PR &6¡"Afllma.! Sacrifice-EuthanasiaiSO 109QS-10:~ . iøfbgical Êvaluatlon of Medical Devices Part 10: Tests forIrritation and Skin $ensìtlzatloniSO 10993-1~;20ô~~üiQI . Evaluation of Medical Oevices Part 12: SamplePrépåtàttön àhd~R~fètén' Materials . .

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Nathaniel TerryBurlington Industries, Inc.

906 Anthony St.Burlington NC 27215

NEßONLABORATORIES

Agar Overlay GLP Report........................................................................................

Test Article: Burlington Maxima I ESD B101Burlington Maxima I ESD B102Burlington Maxima I ESD B103Burlington Maxima I ESD B 1 04Burlington Maxima I ESD B 1 05

Laboratory Number: 614437Study Received Date: 29 Dec 2011

Test Procedure(s): Standard Test Protocol (STP) Number:

Protocol Detail Sheet (PDS) Number:STP0031 Rev 07201104818 Rev 01

\.

Summary: The Agar Overlay test was designed to determine the cytotoxicity of diffusible componentsfrom materials or solutions. A layer of agar was added over a cell monolayer to act as a cushion toprotect the cells from mechanical damage while allowing the diffusion of leachable materials. The testarticles were then placed on top of the agar layer and incubated. The cell monolayers were examinedand scored based on the degree of cellular destruction, All test method acceptance criteria were met.

Results:

rv~.: J'!9~f!2~i2!.. ,m

Negative Control -

Polypropylene PelletsPositive Control -

'latex'Nåtural RUbber

Test Article 1

TesfArticle 21

Test Article 3

Test Article 4'

Test Article 5

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;: 100 mm2 per well

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a a a a

;: 1 00 rnm~ per well

~ 100 mm2 per well

~1 00 mm2 per well

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~ 100 mm2 per well

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a

a

a

a

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Acceptance Criteria: The United States Pharmacopeia & National Formulary (USP 87) states that thetest article meets the requirements if the reactivity grade is not greater than grade 2 or a mild reactivity.The ANSIlAAMIIISO 10993-5 standard states that the achievement of a numerical grade greater than 2 isconsidered a cytotoxic effect. Nelson Laboratories acceptance criteria was based upon the negativecontrol receiving "0" reactivity grades and positive control receiving 3-4 reactivity grades (moderate tosevere).

rYvvwStùdy Director

.no_

\)jQI r¡Christine Walton

/'1 .J"..: n ': ôlZ.Study Completion Date

PO. Bo, 571830 I Murray, ur 84157~1830 U.SA . 6280 Soulh Redwood Road ¡ Sail Lake City, UT 84123-6600 USAwww.f1eJsonlabs.com . Telephone 8012907500 . Fax 8012907998 . sa!es~nejsoniabs,(,om

clf FRTOO31.001 Rev 1

Page 1 of 3

These results re/ê'le only In the lesl arllc.u hSle(1ln lhis report Reports may iiot be Il'produced ÐlCePI in their erilirety SUbJêCI to NU terms and r.ondJlions al 'I'N. nelsonlHb:; com

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..................................... .......................... .................................................Laboratory Number 614437

Agar Overlay GLP Report

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Quality Assurance Statement

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........................................... l......... ...................................Compliance Statement: The test was conducted in accordance with the USFDA (21 CFR Part 58)Regulations.

t~.

llíI_'~'Mee¡¡" ,Activity. PI ~.. -:_oi'..

~ 4# . -:1' ( ~'" ~J¥ :~l\ ". __ _!i_ ~ mate~~

Study Initiation

. Audit Performed¡by,QuålityiAssurance" "'.: ,.''r' ii' 'ri -.: .- .iAudit Results Reported to Study Director

;l

A.udit ResúltsRêported to Managementj,'U- :t:; 'F .. .ù;,.- "j

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06 Jan 2012

,10'Ján2012:S' tti','t11 Jan 2012

1Ö:Ü~n 2012

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-U"" .. ¡ßScientists"'P_ .. ~

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~_.1 f!l ;r iJ i!~,'1 Title fr ,,'

~.. "' ~ lW L~jlP ~.- p.o~_~.. ~ ".J~

'...'i

Chad Summers

Chriliine Walton,

Supervisor

Study Diiector

Data Disposition: The raw data and final report from this study are archived at NLI or an approved off-site location.

'-lùuuÆ (g(J)rlQuality Assurance

IJ~(11A ;)OIjfDateU

P.O. 80' 571830 I Mú't'y, UT 84157-1830 U.S.A . 6280 South Renwood I,ooó I Soli Lake Cily. UT 84123-6600 U.SA

www.neisonlahs.com . Te!eptine 801!290 7500 . Fax 801 2907998 . sales1§nelsonlabs.comclf FRTOO31.001 Rev 1

Page 3 of 3

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..................................... .......................... ................ '0....... ........................ Sponsor:Nathaniel Terry


Burlington NC 272150'."""'\,

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NEIlONLABORATORIES

ISO 10993 Part 10- Primary Skin Irritation Test in Rabbit..................................... t.............. ....................................


l/"~'-Æ1""- -.." Y""jt"";"I'."-.~\'if,""" ""~f~..,:î.~~~ ~Ia$r~rtice.;~ ~'~llrl'Nelson Laboratory Number:

'll~~~'" "Pli .-,,, b"I'" ""i"i; ,-e~ '~.\l' ,~(' Testln,9 La ?'". "'~.,." - "'ri¡jif( Sf --lRlCtyl....,-._ .."-.. a ...

t:i _., it .e!i.lgtQñMeKlmã 1~i:'SPdlllQ~), g

614518'1' r 'll,.",_ ~.. - i"":"~,..~~\¡ ~i'!4::_ _ ~_ ....J~!!e'fli!¡ aese~c~ u;:'" i'1:;,~-

-.'!

Results: The test article did not cause skin irritation under the condition of this assay.

If you have any questions, please feel free to call or email any of our Subcontracting personnel at 801-290-7500 or subcontractingßìnelsonlabs.com. Thank you for testing with Nelson Laboratories, Inc.

(

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~Mindy Schvaneveldt, A.S.

JQeJ :2°I:iDate

p.o Elo, 571830 I Murr.y.UT 84157-1830 USA. 6280 South Redwood Road! Sail Lake eiy, UT 84123-6600 U.SA

www.nelsonlabs.com . Teiephone 801 2907500 . Fa), 801 2907998 . saleStWni~b:oniabs.com F RMOO41 Rev 02

C)These roslIHs relate only to Ihe lasl artrcle li5ted in ll)is rtJporl. Repoi1s may not be roprod\lCed excupt in their entirely. StibjOCI 10 NlI torms and condihons at YfWW nelsonlabs com

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STUDY TITLE:

FINAL REPORT

ISO 10993 Part 10 - Primary SkinIrritation Test in Rabbit



TEST ARTICLE NAME: Burlington Maxima I ESD 8102






(.~.'\:.

DATA REQUIREMENTS: GLP





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Quality Assurai;e,~Au,dito .'~" '

GOØOLABORATORY PRACTICES STATEMENTThe SRC stllCly réferençèd In thiS report Was COlidUQtédlti compliance withGQodLaborätå . . . .' (GLp) RegulåtiOrs set förthirtTitle 21 Part 58 ofthèCode Offédei:ai", . . tfQns of tne United StâtèsofAmì=tioa. Other portions ofthis studY thåtwøre n~t performed by orllOderthe diréctionof SRC. includingtheçh.áf:àótên~tlon' ånd$ta~bilty testing Qftheløst ~ftìolé, which is therespons.ibilty cfthaSponsor¡ äre exempt from this GOP ståtement.

StUdY' OireQtor: . ~/~. ..... ..o.ie:a&tdi%-~liReí~~aJ1~h M~Q\. M,Sc¡¡,$erlior S,çientišt .

" , "

CONTROL ARTICLEf,IDENTIFICATION

(:

TESTA~TIClE CHAAACTl;RIZATIONThe Sponsotwas, respqhsibleforall test arficlechríract . tíon data asspecifed in th'eGCPrègUlatiöns. TheidentitY, streng ":, purity, and

chemical compQ$ltion of the test artiCle were so!ely , .. bUity of the

Sponsor. The,$pO~$OtWliS resporisible fots ,. . g .' "thete:sting láboratoryresult~ of these ~~têrm,lhêtion$a.tid'any atflers at may l1á'ie directly impaGted

the téstil1g perfotrêd bY the tešting Îaboratory,prior to initiâtiOl1oftesting.Fu'rthermore, it was the resPonsibilty of the Sponsor to ensure that the testarticle sl;pJ1itted for testing 'Wás represèntátive ofthe final prQduct that wassUbjectea to Máterials ctrtáoterizaticm.Anyspedial requirejìîents for l1ancUing or

$loräge were arranged ¡nadvance ôf receipt and the test articÎe Was received ingood. conditièm.

SAMPi.i: STORAGe & SAFETYTe$tll~i .,' ipt;identificatiön, storage, and distribution was according to SRC

$OPand t ': nsorwas responsibie tor ensuring that MSDS and;CertiticateOf Anâlysis were pravidédlo SRC.

rEMIJiTtation reaction

..'nstùdies. ForpòtÈ!hUal dermal

( INSTITutlQ .The protdcÒIanimals:on thisinitiâtjoh ofsu:ch"

, e ANQ use OQllM'lrJ(IACUC)fs òl'ptòc-edlJ~' , 'thecare or use of

iewedand áppto . IAGUe prior to the

IAcue Protoåol Approv~I'Date:

AMÉNOfJENts: N/A

25-Feb..2011

DEVIATIONS: N/A

. ',\

''0/

No.ofrêstArticles Ueed

1~2.5x2.5

CONT~QL A~TIC"'EPRBPARATION. - - - . - '~--' -- ".' - - -" -. '- _.. - ,- ,-.. - .' -", -:, -,- - - - -' "_. - --~ .; . ,: - - - ,,, ;.; - .. - - -. -.

Oontr,ol Article ArnoulitUsØod(cmper patch)

, ,.2.5)(2.5

seJ.i:CTIOHØPANIMAL$AhirralsV(et~'¡seleatêdforstudY based ,ott a. phySicai, exarrinãtionperformedbyaql,aUfledrrernberQfthe veterinary staff.

ANIMALPREPARATIONAnimal hâi~ Ónj~àeK~area was clipped the day prior to dose administration.

1eST AN ~ "ARTI.CLE ADMINISTRATIONA ~2~5x. was áppliêdloplcally tdeachdó~e stte(two dosing siteSforcontröl and '..' article respectiVêIY). The two dosing sItes Were switched oneach;side of tne, animaL. Eactl pàrch was cQvered With a non;.òçclusive dressingànd wi'ClPpesJwlthà priatl'material. basing sitê$')Vere separatêd by at least1 ~5 em andWère m d"wÎth permanent marker after unwrappirig at4 hourspost dO,seadnìihistraUbn.' .

ASSAY VALIDity, The assaI" 'nsiClered valid based upon that there is no skin irritation in non.'teatedl' Nhkln of test arèa was Qormal pnortó, t~st~~mPle appliè,stion

~nd the afitrai non.-polar sQIVei'tdiå not SM'((:abòve à"sllght" irritantaÒd the oritroLpQlar solvent scores'as a negative.

METHOÐ FOI CONTROL OF BIASAlthough / ,sludy was not blinded, the use'ofa control article controiiedexperime al bias.

" 'ARØHIVAL~AcÓpyôfthè,~(j9inal,(eport,.originar. protocol (il'gl,deviatiönS,;,l'eliJ¡isitlonform ,andattachrnents) 'andiållraWdats'Sl!wi¡ili 'as pertinent' in..nfe fåcillty data are a'

CenterLLC~

endments,, in..Ufe study specific

edat Sinclair Research

COMPlIANCI:The care, housìn'Q ¡:nd hanpling of the animals 'Nere in compliance with the ISO1 Ò993..10: ~0'10Biôiogical Evafuatioh ofMediçal Devices Pârt 10: Tests forIrritatiQn and SkirfSensitization, reported in öompliance with u.s. Food and DrugAdministration, "d Laboratory Practice: (GLP) regulations set forth in 21 CFRPart 58 and, in a ~Q:rctance to the global protocol and the as.$oçiated TestRequisit¡on~òl1í façlltystandard opetatlngproçédures, and USDA Poliöy 12.Protocol amendments and deviations, ¡fa ny, wete handléd according to fç¡ciltySOP.

POSITive CQNTROL PATASinclair Résèarc; hterconducts positive conttols at least avery 6 months. Apositive control . às completed on 15 Sep 2011 (äRCStu~y# 010972.050-1). The usea methods for the positive control assay are simUàr to the reportedtast. The \J~e' . s were sam.e ~ttain fromdnè;,,,endpr ( 'øm~Reil.bitry).

The use , ' '20% Sodium bOdecyl Slilfäfe (80$) SaHnè: il'enegative,dóntrota Is were exposed tò soivents ¿nly.

GenelllIObservl,liøn$IAll ätiírnal$ âppeat~~'ñormai during study period (aii doses,sucaeeded).

Dèrmal:OOèrniáib ' ,8

v~lid~tionstudY

'and 8c;orlng:;ørès~htêd 1/1' Table 2. Dermal. ol;serV~ti(ms from SRC

12;050~1arè presented in Table3.

.'¡

ANALYS(SANDOÐNCLyaIONThe, déte'tnr ' "-" \iièi:hfinal satire (primary .testa observations at 24, 4a¡ :topics.1 ¡øn. Irftlie.finai~naltöthe . ensity¡ duration, acompared . I CONdlt¡Ol:l'S. The datalnöt cause a tatlon reaction. In oonciuslon,a non-irritant .

. .... on index) was 0.0 for the'coring after

'., . on was givenions Of the test

e test article. didartlalè was considered

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S ) 0 ie la t 0 - )r n ir e (I rl' it lr 1 ~c: ii F a b.. \, ...

-. .. .. . .

iUI m y: Er 10: d tt fi I1I pc f( th te in Wi ::0 'di 3ti I fc yc I. he nfi m ioi is ita e(

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in i3 I I I I I I I I I I fi r. I" J!ii n i3 I. I:in l!! :ei ar.. .. .. .. -

~e: iit ie !st rti e' ¡j 1 it i iW ' S n i ita )n n( 1'1 :i ( nc io of iis iS! y.

Y J I IVI ar qi Is1 m pi 3S fe fi e c I ( ei :iil ini )f ur iul :01 'ai n! pe ;01 iei it )1

9( 75 ) ( m g il il (Q :ili il l§ ;? 1 ar y( f( te in wi 11' lsI I L bc itc es Ini

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& li J ~I ¡ 21 t.. ..ut or ng ;0 'di ~t( r nc S Id A. )c

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F Bo) '18 1M iy, L 141 ,18: u.~ ., 10 ~ Ih f woo ~o. S.I ike f,U 41~ 66 U,:. me nlal :om Tel( one " 2 75 ,i 80 90 ,8 ale~ nel~ lab, ,n¡ RM 411 , O~

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researchSTUDY TITLE:

FINAL REPORT

ISO 10993 Part 10 . Primary SkinIrritation Test in Rabbit




c.' .






( DATA REQUIREMENTS: GLP





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IACUCprotóO~!~PRt¡óval Date:

AMBNOMi:H't$t N/A

i:)f:VIAl'IONS~: N/A

~-..

çóririg: , .~ntèdinTeblè 2.betmal,øb$srvations from SRC

..1 are prèsenteêHn Tâble"a. ';r~::~ .

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.......... .......................... .......................... ................................................ Sponsor:Nathaniel Terry


Burlington NC 272150... . úO j'" oJ

NEUONLABORATORIES

ISO 10993 Part 10 Guinea Pig Buehler Sensitization Test......................"...................... l.."... ....................... .............


a ~Test A_i1lçle:'

Nelson Laboratory Number:

Tesiingl:á6:-'U'. "l'

. r;' J3urlinglQn MaxiQ1fly;\ESQ.J31 02

614530

Sinclair Rësearch!f1' r~ ".' .. "." j,...

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If you have any questions, please feel free to call or email any of our Subcontracting personnel at 801-290-7500 or subcontractingcænelsonlabs.com. Thank you for testing with Nelson Laboratories, Inc.

(.... "'.:.... i

l~e rn 10\2-P.O. Box 571830 i Murra/, UT 84157-1830 U.S.A . 6280 South Redwood fload i Sail Lake City, UT 841Q3-6600 USA

www.nelsonlabs,com . Telephone 801 2907500 . Fa:i 80t 2907998 . salesrfnelsonJabs.com FRM061 Rev 02

.~~These results relate only to U'e lasl article listed inUils repôrt Hepôr1s may nôl be reproduced except in their enlirety. SlJbjccllo NU terms and conditions at W\\W nelsonlabs com

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researchFINAL REPORT

STUDY TITLE: ISO 10993 Part 10 Guinea Pig BuehlerSensitization Test

PROTOCOL NUMBER: 010971.046

STUDY NUMBER: D10971.046~11


(TEST ARTICLE LOT NUMBER: N/A




NELSON REFERENCE NO: 614530

( DATA REQUIREMENTS: GLP



STUDY COMPLETION DATE: 15-Mar-2012

RESULTS SUMMARY: The test article (device) demonstrated NOsensitization reaction under the conditionof this assay.

0"

GOOPLABORATORY PRACTIC $TATEMENTThe SRC,$fudy referenced irithis report wascond'. ntompJlance'WithGoodLaboratø¡y Prae (GLP) Regulalíonssetrorttiin Jltl~i1,'Part5Sof tl;ø

Fèderaì ~egu '. ,of the United States of ArrEirica other porti9'ns,oltlìthat were n'ot Pérlorrnecl by or under the dÎrectiotlofSRC; intìluding the .char¡acterjzation and stabilty testing of tlie test attl viCé) which is theresponsibilit of tlie Spon~ort are exempt from this statément.

Study Director: ~............D~LuKe'Zhang,M.D.t,M.SC., Senior Scientist

/óA'j;¿.. 0,'," ,

(0':')~/ Acolimstlon:

Housing:

ANINlAi.SEi.EQllO~,'AN,OAANDOMI~TIONAn¡m~ISwel'eselectedforstudybåseâ On'â,'phY~lcal~)(:aininaliOn. ¡;erfol1ed bya

q\.lified"mel'~e,l'oftJ'e vete.rlnarystaff., 'Thes~leotedanhnal$Were'.ranâomiì;edInto the treatrnentgroi.psaoeörding' to SRCSOR, prlortødos~,lnitiatlcm.

j\NIMALPRE:PAFlTIONIhe,halronthètt:rgetdQsingerea.,(-S)(7 cm.leftflank'areaJorlnduötiÕnphase,

righUlank area fo( ohallengephase) was.olippedprior to dose administration.

l-)1..,_/

TEST AN~ CÖNTROL DEvice ADMINISTRATIONInduction Pha$e (Day 0-17)

The pátèh of control or test devioe at - 2 x 3 cm size WaS applied to the designatedleft dosing site of the control oneat animals respectively at esohdose 'adminIstration. Dose area was Wi'appèd with elastic bandlge ::nd seouredwith

hypoallèrgenic tape. Patch and dressing were remøvedat á:t 0.5 hours afterapplioation, Procedure was. rèpeated three (3) times pet Week for three (3)conseèutlve weeks.

OhaHeoge Phase (13 daY$ post last l~tlucttønappU(fállo'The Pát~~ of contròl or test device at -2 x 3 em size ," '. 'nght dO' ita: of the control or test animals respeetively e ' lange dose.phase.' . rea was wrsppød with elastic bønttage andseoured withhy,poallergeriictapei Patcflè'and dressingfwere rerJoved'at 6~'O,S hour!)Jiíf!erappllåation. '

Dermal Observations:DemiaÎ dbservatlon results are presented in Table 2. the results fromSRCvsUdåtiòn study 010971~060.1 dermal'oDservation$are~pttl.!liited in Tåble 3.

ANALY.ls AND CONCLUSIONfherèis no skinirritatîon orsensitlt.ation obsetved witn,eithèr control ,9rat 24 and 48 hour sèoringpost chaiieng!! phase,1 ~hefili alyslsdf.,

èònsideratinn wa~ given to the overall patterns, ir', . ... i Hon,aìidèhátacter ofreactions ofthe testes compared withtÌíecolìtrol cördltitiÌ'$. Thetêst article(device) dl4 not cause a sensitization reaction.

Table 2: Dermal Observâtlol1$:. ÇhaUengePhase. (OlmiãlSif "'llU~L ~. .........

~~,.~,..~". ..,"~J¡u:,' . '. '.,

14 RÖm:'Io.Urli d\fØ',IfQut'Xl~ö'rlf' f(è,,,lti'Animal 10 ~ ,~_ _ _ _ -.._ -' -', - . ~,- ..."'.c' ~." _.,

.Rltifit'll~íê'lltÖ' ITICihttlllfl""II"..........,i.'

.' ...... .~ " " ".' '. - ~- --, - ,.,." ..' ,d. '.~'.' ,... ..,Ißl "'-.

,o;è)titrgl,líøiIP .' . .".." "i' ..'

..' ," '7.d

0'1P1:5~3 0 . 0d. '.

..~ .' '. . '. ....' '. ... .'...

Ô1Jt!t~25 .0 '..'.

ø'..' .,... ..

...C1F~fß2ß (j .' (j'.. '. .... - ....

..C1f'4¡S21 . .. ö ø

... .'. .. . .-

.

~1.F~:5~å. ..

0,

Ö '". .. ....

.~1Ra:52~h..'~..' ..'

.....0 0 ..

$t;otQlncfa,nç;"(%). O:Q ..(,' '. h.,.......dOtQ.' . '. ~ / -d

. ". .S~~eiIJJiJ'è(f" (to . . I. ..O~Ö.

',... .,' ',~ ., ..,."re '.' .. .- '.

l'øjt,'lI:Ql!ø~ ,

'.. ':Z."",'11#1r$18" .'. '. ,Cl.. Zo.'J C.,.'

'.'"'"

f1F2'iS'¡Ur' .' .". n 0

.- "".... . , .....

Ttr$:520 .... '. 0 0.. .... ..

T1P4:5Z1....

0 0 ...' .. ..

TtPß:t146 0'. ......

0 .'.. .. '.' "...-.

TtÀ6:52ä 0 0 ..

11.Ë7:5áO 0 0.....

....... '. ..' .. .,

*tFß~53,1:. . .' .. 0 .' 0 - .

T'P9i532 0 0 .'

'~.". .

T1F10;5ßä.......

0.'

.......0..

-

J1F11;5~ ','. 0..' 0,. ..' -

,Sëørélnéi~el1ce(%) 0.0 .... 0,0 .. ..' ."'Sfive'rltVScol"e'.. .

'.O,Q 0;0'. ./ ..' . .'

'.".' Y''Ä__-:~ObSl!l'~tlO"S: Animal 529 atthe24hourscorewas ob~erved witfHt2mmspot oncralìial matgin. of dosesile,$Uglitly erylhélmlc.Remaindêrøf sitehaclhOat:normalobservstions. .

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rUiFeflí!NC:!$SRCSOP:,Ae02Ð2v7, ,Test,lnitiatiohåiid,Ässignmentof Test'Systert'toSxpe"rimerital,C3roupŠRCSQP: Aca~ø3v5, AnlmaIAcquisition,Anoeation,and'Transportatiòh'and'Stl;dyRooni Resérvation Procedures 'SRÇSPP: AC0101v10, 'Gt¡neraIAnimal'CarEtProcedures$RO.SOP:'A,ë01(j$v4, .Recogni¡zingPain .Stre$šor DistressSRCSQP: PR0201v~, Physical Examination of AnimalsSRGS()P:,PR0202v5, Animal,Body'Weights

SRQSOP:, PR02,èl7v3" Skin,lrritation&Seiisiti~atlòn'ScoringSRCSOP:PR02ClSva,Dose Administration ProceduresSRCSOP:PR0401 va" AnirtalSacnflce-EuthlimasiaISO '1(îS93"10:201ÖBlological,E,,aluatiOr'OfMèdical Devices' Part ,10: 'Tests for

Irritation, ànd SkinSensitizationISO,1(j993-12,:2007Biological,Ëvaluatlon,ofMedical Devices, Part12:.$amplePreparation' ând' Reterél'öe Materials

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NEIiONLABORATORIES



Burlington NC 27215

ISO 10993 Part 10 Guinea Pig Buehler Sensitization Test........................................................................................


BurlingtQ.nMçlx.irralÆSQ B 105

614533"',,' is "" (it

S!!!I~ir Research

Vi!¿ T~stÄÌtièlê:'Nelson Laboratory Number:

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If you have any questions, please feel free to call or email any of our Subcontracting personnel at 801-290-7500 or subcontractingßinelsonlabs.com. Thank you for testing with Nelson Laboratories, Inc.

~Date

These results relate only to the test article listed in this repoit Repoits may not be reproduced except in their entirely. Subject to NLI terms arid cOflcllllons at 'M nelsonlabs corn

FRM061 Rev 02

P.O, Bo' 571830 I Murray. UT 84157-1830 U,SA . 6280 South Redwood Road I Salt Lake City. UT 84123-8600 U.SA

www.ne!sonlabs.com . Telephone 801 2907500 . Fax 801 290 '1998 . sates(ßnelsonlabs.c:m

) ¡I

.'~"--~"sincl,a.ir

research

STUDY TITLE:

PROTOCOL NUMBER:

STUDY NUMBER:

TEST ARTICLE NAME:

TEST ARTICLE LOT NUMBER:

TEST FACILITY:

SPONSOR:

NELSON REFERENCE NO:

DATA REQUIREMENTS:

DATE SAMPLE RECEIVED:

STUDY INITIATION DATE:

STUDY COMPLETION DATE:

RESULTS SUMMARY:

FINAL REPORT

ISO 10993 Part 10 Guinea Pig BuehlerSensitization Test

010971.046

010971.046-14

Burlington Maxima I ESD B105

N/A

Sinclair Research Center (SRC), LLC.


Nelson Laboratories, Inc.6280 South Redwood RoadSalt Lake City, UT 84123

614533

GLP

10-Jan-2012

10-Jan-2012

15-Mar-2012

The test article (device) demonstrated NOsensitization reaction under the conditionof this assay.

Date:~

c......-....,'. I

"-_/'

GOOD L.GORA TORY PRACTIOE,$ Si:A.ENTThe. SRC study refer'eMinthls reportwa&c~)nductécf in.pliance wlth Good

Laboratory Pra lations: aet forth in Títlé'~1 ~ârt 58 è;f the Code ofFédèraFR . .. . . States öfAmenøa ....lportions of this studythat,were nótpe . d'hy'of under the dlrec;tíön' of . dihgthe

èhåract~riZatio)i a' .$t .' 9 of thé, test de\iib~rwhiGh is thê responsibilty of

the Sponsot;ate exetn tlíiS GLP statement. . . . .

..~ := Dat: /UIßL.uke Zhang, M.D., M.Sc., Senior Soientist

St!;dy,pirectejr:

C,-.

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/..sAMPLE S.T~tdevicSOPamltAnaJysrs werÐ.

E¥pl;ftIMENTAL DESIGNs~v~ntéén(11)a 'sairøl.,lnoJu. .

JUS1iIFICAT:lØ'NFOR$l!lBCfrONOF'ti! T&STS¥$Tl!MThe gUfmáà pig. Is ~sa štandard model to" . J$ljGt dermal sensitizationreäCtiO'rt in huma rscommended by the .. sensitizàtlonstudies, For t '. .eguinea pig, was used 'evaluate thepotential dar ion' reaction of the test.~

IN$TITUTìONALANIMAL CARe AND USE COMThe protocøl anti , ments or procedu "

animals on this's . reviewed andappro\(adinijlâ,tlon ofsudli prø 'res, .

(IACUC)thé cate or use ofIAQUe prior to the

IACUC ProtdcolApprovalOate:

AM~NDMeNt$: N/A

DEVIATIONS:

7-Mar-20f1

,Oevi§l,ti'On: Protócol Section 7.3.1 qlnduction Phasew Page 60.the~Jetion requires removal of t or control patch after 6

outs post dose applicatic: the stu,dy, the testas inadvertehtly removedtès earlier than the

t. .lìne for a few test animals' . induction phase onJán!!áry 1eth, 18th and 20th. 2012.Effect on Study: None

IDENTIFICATION,QP TESTSYSTEM

11

(....J~/HUSBANDRY

Acclimation: Preàcclimated

The animals were hÓUSll~ according to facilty SOP._ _ ..' - _ JRoo'nítenìperätìJ~ ¡twere monitored andcontrolled while hu . . monitored, but nöt

ç.Qiitrø!l~ø.Food åndwater were provided aecòrdii'g to SRCSOP; Foo.d and water' analysis is maintained asfacilit recOrds and. t~ere weré noknowricQntàminants expected'to interfere wíth the testresults;

'RANDOMIZA tJ'QN~,, " udy based on a ph .

qualifieèffnêri , vøteritiary steff. Thes. . ' ,into the tresrinent gfoílps according to SRCSOP p'riør

inafton performed by aaiSWere ratidòmized

'dôše initiation.

ANIMAL. PIU~PA.RATIONTlì hair on the t~ , ing area (-5 x 7 om left f1ànK lfl!l:for induction phase.right flank areaför , fige phase) waS clìppedpri6rtodose administration.

,.. , L.í:!\VIOil ADMINistRATIONInduction P .. Ö..11)The patch of cOl1trpl ør test device at .. 2 x 3cm size was epplied to the designatedleft dO$ing $ltè of the cQhtrol or testatíimals respeoti doseadministration. Oose area was wrappedwlthelasti 'sé,Gured withhypoaiiêrgenlc,tá~.'Pátch and dressing w,ere rém~, , 5 hours post

appliaatlon.Procecluì'e was repeated three (3) tltie~'per w~ekfot three (3)

consecutive weéks:

Challeiige Çlháse. LTh'ep$fCh øl '. Vice ât "'2 x 3c ìiéd to the designatedright dOsing. sIte ohheoontrol, or test anirnels. lha cnálleilge dosephaSè~ Dose area Was wräpped withelåstÎd bandageánd secured with

hypoallergenictape~ Patch and dressingwereremoved at 6 :10.5 hours postappliöátioh.

". -

. nsitlzation . reaction.

.sensitization reactionëfgØ. $everity wase total humber of

. ane(1) or gre~ter in's of iess thanorìé (1)

;.tbøtest animals which~é dO'ê fò sér'sìtlzatión. In., patterns, intensity,

. Ith the Oontrol;d~r+)i orn~gàtive (-).

c..........)~-~.j

valld based upon thatønd the test ateá ê

liL ÐFBIASbliridêlQ, the use pfä

,

fd~rmåi scoring contl\

POSI'IIVe c .sincìálr' . ....Apositlye CO

010971.050-rep~rtedtést.

, i

ReSULTS

C:.nlral..iOl)..rvlltfons;Aiianimalsap~ared norrnal'durlng study' period '(all.dQ$es'$lì~çeéded).

Dermal Oi)sèfî:alions:Dermâl observation r.sults are presented in Table 2. Theresúíts' from SRCvaJidation študy Ð10911:Q5pi1 dermal òbservations arel',e$entedlnTablé3.

(......)\( . /¡~

ANAL. V$I$AN ONOLUSiONTherei$ nbs .' .... ørsensitization observed witb.'at 24 and :post challenge phase. In t~cc;nsiCtera. 'ven tô the overall patternsìinte'reactions of _compared with the control cònnot cause a sensitization reaction.

. her,;còntrQI or tesfgroups'is of data,

j and character of.. e t~st device did

C~.)

jmalAcquisition, Allocation,snd Ttansportàtion and'urt3s

;ehètal Anirnal Care Proèedures" ,. '¡zing Pain, stre-ss 01' Distr~ss,

at Exiamination of Anlmäis'j:ly Weights'ion & Sensltiz~tion ~èø1ing

. inistrâtion PtóoeUrh' "Sacrlflc:e..euthl!nasiaevaluation of Medioal Ðeviøe~ Part 10: Tests for

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#6305Empire Imports, Inc.

800-544-4744

WWerpiremport.com

Documents

CJ ISO 10993 Biological evaluation of medical · PDF filef';~ ~ ~';'1 'CJ ISO 10993 Biological evaluation of medical devices May 2012 Nelson laboratories 'Cl 6280 South Redwood Road