Document 5Lbzw5pqqjpEMneg95R0MnVvz
AR226-3066
TRADE SECRET
Study Title
LISP Biocompatibility Testing of H-22239 (Control Item)
and H-22240 (Test Item)
Contracting Laboratory
North American Science Associates, Inc. 2261 Tracy Road
Northwood, Ohio 43619-1397
for
Haskell
E. 1. du Pont de Nemours and Company Laboratory for Toxicology and Industrial Medicine
Elkton Road, P.O. Box 50 Newark, Delaware 19714
Study Monitor Susan A. MacKenzie, V.M.D., Ph.D., D.A.B.T.
Sttfdy Completed on January 17, 1997
Laboratory Project ID llaskcll Laboratory Report No. HLO-1997-00026
Paye 1 01'33
Company Sanitized. Does not contain TSCA CB(
t '.SP Bioconipatibility Tr.sliiit; 11! 11-322.19 (funtrol Hem> ;iiul 11-22240 (Ti.-si Hem)
GENERAL INFORMATION
Test Substance # I
Substance TestedSvnonvms/Qther ("pries-
NAmSA Lab. No..-
Physical Form: Purity: CompositionContaminants:
CAS Retfistiv No.:
H-22239 H-22239 (Control Item) 96T-16837-00 Blue fabric
Test Substance #2
Substance Tested: Synonyms/Other Codes:
NAmSA Lab. No.: Physical Form: Purity: Composition: Contaminants: CAS Registry No.: Study tnitiated-Completcd:
H-22240 H-22240 (Test Item) 96T-16836-00
Blue fabric
12/02/96-01/17/97
HLO-1997-08026
- 2Company Sanitized. Does not contain TSCA CBt WMs^sSSSSSS^
I 'S|' IliiiLoinpuiihilily lu.sling 1
H-22..<y (Control llemt und H--';;4l Tesi licrnt
DuPoni Central Research anil Development Haskell Laboralory lor rnxiculoyy and Industrial Medicine
HLO-1997-00026
January 17,1997
DuPoni Non-Woven Old Hickory. Tennessee
USP Biocompatibility Testing ofH-22239 (Control Item) and H.22240 (Test Item}
Attached you will find reports from North American Science Associates, Inc.
The results for the H-22239 and H-22240 samples are:
Test Results
Test Substance
Cylotoxicity (Ayarosc Overlay)
USP Intracutaneous
SC3
CSO"
USP Muscle Implantation
(7 day)
H-22239
Non-toxic
Pass
Pass
NS'
H-22240
Non-toxic
Pass
Pass
NS
a Sodium chloride extract h Cotton Seed oil extract c Not significant
^^0 Q ~VY\I^
Susan A. MacKenzie. V.M.D., Ph.D., D.A.B.T. Research loxicologist
-3-
Company Sanitized. Does not contain TSCA CBt
Ssss
l'()iit"i(JenHal
MdUJO-IIO
Lab No. P.O. No.
1-:. I. dii Pent de Nemours & Co. HASKELL LABORATORY
Ul-KTON RD. P.O. BOX 50 \hWARK. DL 19714-0050
A1T\: DR. SUSAN A. MACKENZIE:
ID No.
CYTOTOXICH Y AGAROSE OVERLAY, SOLID
96T 16837 00 LGX-593521
H-22239
Test Article: H-22239 (control item)
Test Article Description: Sheet 1 cnr piece
Exnerimental Procedure:
A monolayer of L-929 mouse fibroblast cells was grown 10 confluency and overlaid with Minimum Essential Medium supplemented with serum, antibiotics, neutral red. and 2% agarose. The test article, a 0.5 cm x 0.5 cm piece of 725871H as a positive control, and a 1.0 cm length piece of UP-1 as a negative control were placed on (he solidified overlay surface. Following incubation for 24 hours, the culture was macroscopically examined for evidence of cell decolorization to determine the zone of cell lysis. Any decolorized zone present was examined microscopically to confirm cell lysis.
Score
Nontoxic (N) Toxic (T)
Observations
Normal cell morphology in proximity to test sample.
Cellular death and degeneration associated with the area beneath the lest sample and possibly extended beyond the perimeter of the test sample. Where a zone of lysis was observed, the distance from the edge of the sample to the edge of the zone was measured and reported in millimeters (mm).
ompany Sanitized. Odes not contain TCA 6B1 p^ , ^ ^
f^WV| ,! B^AK^ 1,1R0 ^^B^ AK ^^& A^R
r R^& ^R &VJBIR
"'"''' /"1"I/''''" ^"""'^ '""'"'
'"- " *'''""' ""' '"''"'^
MG030-110
Lab No.
HLO-1997-00026
2261 Tracy Road Northwood. OH 43619 Phone 419*666^455 FAX 419*666*29S4
96T 16837 00
CYTOTOX1CITY - AGAROSE OVERLAY. SOLID
Results:
Test/Control Articles Test Article Negative Control: UP-1 NAmSA Positive Control: 725871H
Score N N T
Zone of Lysis (mm)
0 0 7
Results and conclusions apply only to the test article tested. No further evaluation of these results is made by NAmSA. Any extrapolation of these data to other samples is the responsibility of the sponsor.
Conclusion:
Comments: Record Storage:
The above test article was nontoxic for L-929 mouse fibroblast cells under the above described test parameters.
Placed the bluest side of the test article down on agarose.
All raw data pertaining to this study and a copy of the final report are to be retained in designated NAmSA archive files.
Test Article Received: 12-5-96
Date Prepared: 12-11-96
Date Terminated: 12-12-96
Company Sanitized. Does not contain TSCA CBI
nini
^
Date Completed iZ-n-^b
Approved By
Aiilhnn/tilioli lor duplica'"" .'! il'r. " l'"'' -<'.epl 111 wluilo. is reserved pen'ling NAmSA's wiitlen approval.
Confideniial TU013-800
HLO-1997-OC026
Lab No.
96T 16837 00
P.O. No. LGX-593521
STUDY TITLE: USP 1NTRACUTANEOUS TOXICITY STUDY IN THE RABBIT
(Extracts)
TEST ARTICLE:
H-22239 (control item)
IDENTIFICATION NO.:
H-22239
^
00^
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SPONSOR:
DR. SUSAN A. MA^CKENZIE
E. I. du Pom de Neimours & Co.
HASKELL LABOR/ATORY
ELKTON RD. P.O. BOX 50
NEWARK, DE
19714-0050
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226< Truy Ro*d NorltlWOOd. OH 43619
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Page 1 or 7
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TAHLH OF CONTENTS
lll.ii- I ^P-ODD.'I.
l-th N11.
WiT lfK.170(l
SI'MMARV ...
INTRODUCTION . .
MATERIALS ...
MF.THODS
. . . RESULTS
. . . . C'ONCT.l.SION . . .
RECORD STORAGE
TABLE 1 LSP 1NTRACUTANEODS TOX1CITY OBSERVATIONS
^P-X S,te,,. o^ ,,,, ^^ ^ ^
NAmSA
H.*'M JrdJrr in leMin^ <'-f>..<i /or tfc^ .MfilnitI /*<-tirr JnJuurt
?.'(".' I'.l.- v Hfilll N'.il'i-i,.-..'1 (1H 4 It '1
* Al
.1 rt-fiCit-.'^''^
Auihc-ritatio" *"' Oui'l'ritiH'" nl this iBt1"" 1'" nrl ' '*>n)lf is tRSprvHO peniling NAmSA s wnltw a|pf0vn*
lUDl.l-KOl)
111.0-1997-0002(1
Lilh No.
VAT 16S37 (Ml
SUMMARY
The irst article. 11-222.19 (control ileini. 11 22239, wa'. cxii-acicd in 0.9% sodium chloride USP solution and cottonseed nil. Ml. These extracts were evaluated lor inlracuianeou.s loxicily in accordance with ihe guidelines ol" the curreni USP.
A 0.2 ml dose ol' llie appropriate lesi article extract was injected by the iniraculaneous route into rive separate sites on the right side ol llic back of each rabbit. Similarly, the corresponding blank vehicle was injected on the
tell side of the back of each rabbit. Two rabbits were used for each pair of extracts. Observations for erythema and edema were conducted at 24, 48, and 72 hours after iniraculaneous injection.
Under the conditions of ihis study, there was no evidence of significant irritation or toxicity from the extracts injected imracuianeously into rabbits. Each test article extract met the USP requirements.
Study and Supervisory Personnel:
Donald P. Barda, LAT Michael A. Safron, AAS (HT)
Patricia Mitchell
Barbara M. Monroe
Darcy Irons Cindy Harper
TinaM. Cox, BS, LAT
Approved by:
/ / / ( / (^f_______^-,...
Sicvcn J. HennanSky, PharmDPhD,;6ABT
Manager. Toxicology
I^^J?^ ZV-^-G
Date Completed
Company Sanitized. Does not contain TSCA CBI
^/las
XAmSA
,,
"
_
Hiirfrf Itailri in Ifllini! .S^iliri lor ilir .Miclual llrviri lailusli\
;';'fil liil.-v H.l"
Niilllir.i.i.l ClI I .ni.ri
I'lin. ..
""'
.1 ri.l,l,l-:u::
4"M.i,i,.;")'.<
Aulhorijalion toi rtuplK-nlw oi ihis 'epon. iiiroiil i" wtK^e i!, *(ison;ad oenrtmg NAmSA's wnliflii iip[iii>vfii
Paw 3 ol 7
I'lion mw)
iii.o-i'm-oou.'d
Lab 1^;).
'.lol lW<37iH>
1N1RODUTTJON
rile lest article identified below was extracted and the extracts were evaluated tbr biocompalibilily in accordance wnh the guidelines of (he current USP. The purpose of the study was to determine whether leachables extracted troni the material would cause local dermal iiril.tiii or toxic effects following injection into rabbit skin. The lest article was recciveil on Deixmhrr 5, 1996. The animals were injected on December 18, 1996, and the observations were concluded on Dt.i.cintvr 21. 1996.
MATERIAL::
The sample provided by the sponsor was identified and handled as follows:
Test Article:
H-22239 (control item)
Idem i Heal ion No:
H-22239
Storage Conditions:
Room temperature
Vehicles: Preparation:
0.9% sodium chloride USP solution (SC) coitonsced oil. NF (CSO)
A ratio of 120 cm-':20 ml (surface area of lest article to volume of vehicle) was used for each preparation. The test article was extracted in SC and CSO at 121C for 1 hour. The extraction vehicles without test article were
similarly prepared to serve as control blanks.
Condition of Extracts:
SC: CSO:
Test clear clear
Control clear clear
Sample Disposition:
Any remaining sample was discarded. METHODS
Test System:
Species:
Breed:
Source: Sex: Body Weight Range: Age: Acclimation Period:
Number of Animals: Identification Method:
Rabbit (Orvctolagus cuniculus) New Zealand White Myrtle's Rabbitry, Inc. No particular gender was prescribed for this lest No particular body weight range was prescribed for this test No particular age was prescribed for this lest Minimum 2 days Two per pair of extracts
Ear lag or tattoo
Justification of Test System:
The iniraculaneous injection lest in rabbits is specified in the current USP and has been used historically 10 evaluate biomaterial extracts.
Animal Management:
Husbandry:
Conditions conformed to Standard Operating Procedures which are based on the "Guide for the Care and Use of Laboratory Animals."
Food:
PR01-AB" High Phcr R.ihhil Diet was provided daily.
I'iiae 4 ol 7
V A
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H.illll lr,ldn in fridnj; Srfilin /> Ihr Mrilral l>rru r IlllluMrv
Attlhon/alion lof dupl.-atmn "I If"'. fHIio" nrnll in wtmln i*, ip-ion/tnl
|iefnting
\-'/f-.^ 11.11 y ll.i.-lil
N..I"II|.,.>;I (111 fl.ll.rl
Phiil'r I AX
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^nTSC^CBi
^zed.Po^01001
ysyiOS
I (.'111 1 mill
lll.l>-iy97-()U02f) Uib No. 96T 16837 00
W.iicr ('unl.iiiiin.iiils: Housing: Environmental:
l-iccly ivail.iblc. iniinicipiil (Toledo. Oil) w.ncr was delivered through an automatic
w.ilcring system.
Rr.ison.ibly expected coiiinininani.s in feed or water supplies did not have the potential to influence ihe outcome of this tes".
Animals were individually housed in st.i::'. .'
"
ucntitied by a card
indicating the l.ih number, animal number, lest code, sex, >ii>j u<m- L--.
The room temperature was monitored daily. 64-74F.
Ihe temperature range for the rabbit was
Facility: Personnel: Selection:
The room humidity was monitored daily. The humidity range for the rabbit was 30-70%.
The light cycle was controlled using an automatic timer (12 hours light, 12 hours dark).
NAmSA is an AAALAC accredited facility.
Associates involved were appropriately qualified and trained.
Only healthy, thin-skinned animals free of mechanical irritation or trauma that could interfere with the test were selected.
Experimental Procedure:
Prior to treatment, each rabbit was clipped free of fur from the back and both sides of the spinal column to yield a .sufficient injection area. Two rabbits were prepared per pair of extracts. A 0.2 ml dose of test article extract was injected iniracutaneously into five separate sites on the right side of the back of each rabbit; 0.2 ml of the control blank was injected into Five separate sites on the corresponding left side of the back. Injections were spaced approximately 2 cm apart. The animals were relumed to their respective cages following the procedure.
Observations for erythema and edema were conducted at 24, 48. and 72 hours after injection. Reactions were scored on ;i 0 to 4 basis. Any reaction at the injection sites was also noted. The reactions were evaluated according to the following subjective rating scale:
ERYTHEMA (ER)
0 No erythema 1 Very slight (barely perceptible) 2 Well-defined (pink) 3 Moderate to .severe (red) 4 Severe (beet redness) to slight eschar
formation (injuries in depth)
EDEMA (ED)
0 No edema Very slight (barely perceptible)
2 Slight (edges of area well-defined by definite swelling)
3 Moderate (raised approximately 1 mm) 4 Severe (raised more than 1 mm, may
extend beyond the area of exposure)
The cumulative average erythema and edema score for each test extract and corresponding control blank was calculated. For each extract, a difference in average scores (test minus control blank) of 1.0 or less was considered to be acceptable. A difference of 0.6 to 1.0 indicated a slight, but acceptable, reaction. A difference > 1.0 was considered to be unacceptable. Additionally, the average score for each test extract and blank was calculated Cnr each interval. Any adverse reaction noted in the lest extract was compared to the
corresponding blank.
SC^CBi ;onlanT
Coropa^ s^d."'-010
KAinXA
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\\nrlif / fadri in Tn/inj? .Vrrrn-n fur ihf Mediftil tfrvue Iniluflry
??f.1 IiarvUn.iil Nntlhwnud OH 4J619
PhiiFw 4 rt.f>f,h.<145'.
f AX
4 I ).fif:.f,.;*-l*;4
Aulhnn/alion lin )nplh:fltniti ill KnS 'HpoH flr.opl in wiioly. i-1, feservori pending rslA/nRA s WritlBft flpptrtval
I'aiic 5 of 7
ll'iilVWHl
i.d-n'.'p-oi^t)
I. ah NI).
9(T loK37 00
Rl^ULTS Results of M'urrs lor iinlivulil.tl rahhils appear in Tabli.' I. i he I'indinfs are suminan/.ed below:
E'lrac! SC
cso
Average Tesi (-) Average CoiUrol = Diflerfn'-r = Assessment
O.U
0.0
0.0
Passed
1.0
1.0
0.0
Passed
The difference in average scores was considered acceptable. The difference between test and control average scores did not exceed 1.0 at any observation interval.
Results and conclusions apply only 10 the lest article tested. No further evaluation of these results is made by NAmSA. Any extrapolation of these data to other samples is the responsibility of the sponsor.
CONCLUSION
Under the conditions of this study, there was no evidence of significant irritation or toxicity from the extracts injected intracutaneously into rabbits. Each lest article extract met the LISP requirements.
RECORD STORAGE
All raw data pertaining to this study and a copy of the final report are to be retained in designated NAmSA archive Files.
Ooe^co.a.nTSC^
Company Sanded.
XAmS^Ait' -
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111.o-i 'm-DUo:^
l-ih No.
VDT K)K37 IHl
TAMJLi I'SP INTRAO! lANhOllS TOXICITY OBSERVATIONS
I l;ST KXTRACT
Sciiriiii! lnlcr\al (Hour-.l
RABBI 1' Nt'MBHR
9955S 99553 99558 99553
EXTRACT
sc sc cso cso
24
4K
l;R
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l;R
EU
0
0
0
0
0
0
0
0
I
I
1
1
I
1
1
1
72
ER
ED
0
0
0
0
1
1
1
1
ER = Erythema ED = Edema
SC = 0.9% sodium chloride USP solution CSO = cottonseed oil. NF
CONTROL BLANK Scunng Interval (Hours)
24
4K
7;
ER
ED
ER
ED
ER
ED
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
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Company
KAniSA
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STUDY TITLE: USP MUSCLE IMPLANTATION STUDY IN THE RABBIT
(1 Week)
TEST ARTICLE: H-22239 (control item)
IDENTIFICATION NO.: H-22239
SPONSOR:
DR. SUSAN A. MACKENZIE
E. I. du Pom dc Nemours & Co.
HASKELL LABORATORY ELKTON RD. P.O. BOX 50 NEWARK. DE I1)? 14-0050
KAniSA
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.
I
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H.irM J.ruJrr in Trains .Srrnrri !,,. ,h. ,.;dual l>,.,c, Indu-t,,
Wi Iiac<Hcai]
Norlliwoort OH lit. 19
l'hw-
''"'
4")-l>f,K.'145S
"3-66K.9-,-
Authofizalion tot dutjiicatitit' ol ltit& report, except in whole, lesetved pending MAmSA's wriiten approval
I I 1114 KU7
Sl MMAR't
INIRDDI'dlON
MATHRIAl-S MtiTHons RLSliLlS CONri.l-'SION RECORD STORAOt;
lAlU.hOl (ONH;NTS
111.0-m7-00()2i>
l..il) No
KiT |(>K37 (H)
P;nif Numh'.'r
Company Sanitized. Does not contain TSCA CB11
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Page 2 ol' ft
TL014-807
11LO-1997-00026
Lab No. 96T 16837 00
SUMMARY
The test article, H-22239 (control item), H-22239, was implanted in muscle tissue of the rabbit. The muscle tissue was evaluated for evidence of irritation or toxicity in accordance with the guidelines of the current USP.
Implant samples and USP negative control strips were loaded into needles and sterilized by steam. Rabbits were implanted and were (hen euthanatized 1 week later. Muscle tissues were excised and (he implant sites were examined macroscopically.
Under the conditions of this study, the macroscopic reaction was not significant as compared 10 the USP negative control implant material. The implanted test article met the USP requirements.
Study and Supervisory Personnel:
Martha Oswanski. BS, LAT Merle .. Hcinrke. BS, LAT
Jason A. Karsten
Tina M. Cox, BS, LAT
Approved by:
^ jJ ---------^
SievenJ. riermaiisky.PharmD, Ph&. DABT
Manager, Toxicology
Q^t^-7,ft^ Date Completed
/mm ^^-.0----------------------
bl)
Page 3 of 6
KAliiSAk .^| ^B
-
1I 1.;) --
Wurlil Uaiir in Tcslinic Service,
far the MArol Hence Industry
?261 ^'"^ HDa<)
Noilliwood. OH 43619
l'hm rA"
41B.666.94i5 4 "MWi-2954
Auttiorifllon tof duplical-on ol Ihia reoofl. except in whole, is reufved pending NAmSA's WTillen flpfifoval
TU014-K07
HLO-1997-00026
Lab No.
96T 16837 (X)
INTRODUCTION
The test article identified below was evaluated for biocompalibility in accordance with the guidelines of the
current USP. The purpose of the study was to evaluate (he potential for a local irritant or toxic response to material implanted in direct contact with muscle tissue. The test article was received on December 5, 1996. The animals were implanted on December 17, 1996, and muscles were explained on December 24, 1996.
MATERIALS
The sample provided by (he sponsor was identified and handled as follows:
Test Article:
H-22239 (control item)
Identification No:
H-22239
Storage Conditions:
Room temperature
Control Article:
Preparation:
Sample Disposition:
USP plastic 1 mm diameter negative control reference strips purchased by NAmSA from the offices of the US Phannacopeial Convention and cut into 10 mm sections.
A minimum of six sections of the test article per rabbit, each approximately 1 mm x 10 mm, were loaded into 16 gauge needles. The test article was cut into 1 mn. x 20 mm lengths and then folded in half to obtain 1 mm x 10 mm sections. For each rabbit, a minimum of four USP strips were loaded into the same size needles as used for the test article. Test and control articles were sterilized by steam.
Any remaining sample was discarded.
METHODS
Test System:
Species:
Breed:
Source: Sex:
Body Weight Range:
Age: Acclimation Period; Number of Animals: Identification Method:
Rabbit (Orvciolaeus cuniculus) New Zealand White
Myrtle's Rabbiiry, Inc. No particula: gender was prescribed for this test 3.2 kg to 3.3 kg at implantation No particular age was prescribed for this test Minimum 2 days
Two
Ear tag or tattoo
Justification of Test System:
The rabbit is suggested as an appropriate animal model for evaluating polymer materials by the current USP testing guidelines. The muscle tissue has been used historically because the response to implanted material is easily graded and compared to a known negative control material.
Animal Management:
Husbandry:
Conditions conformed to Standard Operating Procedures which are based on the "Guide for the Care and Use of Laboratory Animals."
Food:
PROLAB High Fiber Rabbit Diet was provided daily. Company Sanitized. Does not contain TSC-,,A. "'1
-
16 -
Wnrld l-fadrr in Teflinft Ktrvirfs
fur thi Midiral llmci Industry
2261 Tiacy Hoad
Norlhwood. OH 43619
Phone 419<66-945!>
FAX
41966-29&4
Aulhoruatlon lor duplicalion o) Ihu fepon. Bxcepi In whOtO. Is releivod pending NAmSA's written approval
Page 4 of 6
TU014-807
HLO-1997-00026
Lab No.
96T 16837 (X)
Waicr: Comaminanis: Housing:
Freely available, municipal (Toledo, OH) water was delivered through an automatic
watering system.
Reasonably expected contaminants in feed or water supplies did not have (he potential to influence the outcome of this test.
Animals were individually housed in stainless steel suspended cages identified by a card indicating the lab number, animal number, test code, sex, and dale implanted.
Environmental:
The room temperature was monitored daily. The temperature range for the rabbit was 64-74F.
The room humidity was monitored daily. The humidity range for the rabbit was 30-70%.
The light cycle was controlled using an automatic timer (12 hours light, 12 hours dark).
Facility: Personnel:
NAmSA is an AAALAC accredited facility. Associates involved were appropriately qualified and trained.
Selection:
Healthy, previously unused animals were selected.
Experimental Procedure:
The fur was clipped i".om the area over the paravertebral muscles and the rabbits were sedated with acepromazine maleale (0.2 ml/kg dose). After the muscle area was wiped clean with 70% alcohol, each paravertebral muscle was infiltrated with 1% lidocaine to achieve local anesthesia on both sides of the vertebral
column.
Needles containing test article were inserted into the muscle at a 45 angle. A stylet was placed in the needle and the needle was withdrawn, leaving the sample in the paravertebral muscle. Six test article sections were implanted in the right paravertebral muscle of each rabbit. In the opposite muscle, four USP negative control strips were similprly implanted.
Rabbits were returned to their respective cages following the procedure. Rabbits were observed daily for general health. Body weights were recorded prior to implantation and at termination.
At 1 week. the rabbits were we'ghed and euthanatized by an intravenous injection of a sodium pentobarbital based drug. The paravertebral muscles were dissected free and methodically cut to locate four of the test article sites and two of the USP negative control sites in each rabbit. Capsule formation or other evidence of irritation was scored using appropriate magnification and an auxiliary light source. Scores were assigned and recorded as
follows:
0 No capsule, no adverse reaction (other than minimal hemorrhage)
t Up to 0.5 mm capsule or reaction area 2 0.6 to 1.0 mm capsule or reaction area 3 1.1 to 2.0 mm capsule or reaction area 4 >2.0 nun capsule or reaction area
Average macroscopic scores for test implants were compared to average scores of the control sites.
Calculalic s were rounded off to the nearest 0.1. A Reaction Index difference of 0.0 to 0.5 in scores (test minus coniiol) was regarded as "not significant," 0.6 to 1.0 as a "trace." 1.1 to 2.0 as "slight," 2.1 to 3.0 as "moderate" and S3.1 as "marked." The requirements of the USP test were met if the difference between test and control score averages (macroscopic) was not greater than 1.0. The requirements of the test were not met
if the difference between the lest and control ;core for two (or more) implant sites exceeded 1 for any animal
implanted.
Company S^.OO^------1-^61
Page 5 of 6
KAuiKA
-
17 -
World leader in Testing Services for thf Medical he it c Industry
2261 Tiacy Road
NarthwocO OH 43619
Phono 419-66&-945!!!
FAX
4166fr?9SA
Auihori2lton lor duplication o) this repon. b.cepi m whole, is reserved pending NAmSA's wnillen appioval
TUO14-807
HLO-1997-00026 Lab No. 96T 16837 00
RESULTS
Clinical Observations: All animals appeared clinically normal throughout the duration of the study. Body
weight data for individual rabbits were considered acceptable.
Macroscopic Observations: The findings for the macroscopic evaluation are shown below.
Weigiht (kg)
Rabbit
Number
DayO
Day 7
Site
1
99472
3.2
3.3
2
3
4
1
99474
3.3
3.6
2
3
4
Test
0 0 0 0
0 0 0 0
USP Negative Control
0 0
0 0
0.0
0.0
Macroscopically, there was no difference between the reactions of the test and control materials. This resulted in a macroscopic reactioii of "not significant* tissue contact irritation.
Results and conclusions apply only to the test article tested. No further evaluation of these results is made by NAmSA. Any extrapolation of these data to other samples is the responsibility of the sponsor.
CONCLUSION
Under the conditions of this study, (he macroscopic reaction was not significant as compared to the USP negative control implant material. The implanted test article met the USP requirements.
RECORD STORAGE
All raw data pertaining (o this study and a copy of the final report are to be retained in designated NAmSA
archive files.
^o^---------' Company sanl
- 18 -
World Lisiir in Ttlllsi Snfkti fat lilt Mt^lcal Unlit Infinity
2261 Tncy flaws
North.,od. OH 43619
Phon* 41E6<945S
FAX
41964S4
Autartsmen tor duplication rt Ous upon. awl * Kor, a r--nd Finding NAfflSA'i -mm ppnwl
Rage 6 of 6
HLO-1997-00026
B^B^ fl^R H
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"''"'''' ''"'r in T,-.linn Srivirv^"r lh'' w'""/ "" I'tilu-lr,'
Confidential
MG030-110
Lab No. P.O. No.
226 ITracy Road Northwood, OH 43619 Phone 419*666*94SS FAX 419*666*2954
96T 16836 00 LGX-593521
E. I. du Pent de Nemours & Co.
HASKELL LABORATORY ELK-TON RD. P.O. BOX 50 NEWARK, DE 19714-0050
ATTN: DR. SUSAN A. MACKENZIE
ID No.
H-22240
CYTOTOX1CITY - AGAROSE OVERLAY. SOLID
Test Article: H-22240 (test item)
Test Article Description: Sheet - I cm2 piece
Experimental Procedure:
A monolayer of L-929 mouse fibroblast cells was grown to confluency and overlaid with Minimum Essential Medium supplemented with serum, antibiotics, neutral red, and 2% agarose. The test article, a 0.5 cm x C.5 cm piece of 725871H as a positive control, and a 1.0 cm length piece of UP-1 as a negative control were placed on the solidified overlay surface. Following incubation for 24 hours, the culture was macroscopically examined for evidence of cell decolorization to determine the zone of cell lysis. Any decolorized zone present was examined microscopically to confirm cell lysis.
Score
Nontoxic (N) Toxic (T)
Observations
Normal cell morphology in proximity to test sample.
Cellular death and degeneration associated with the area beneath the test sample and possibly extended beyond the perimeter of the test sample. Where a zone of lysis was observed, the distance from the edge
of the sample to the edge of the zone was measured
and reported in millimeters (mm).
Company Sanitized. Does not contain TSCA CBI
19 -
Page I of 2
i i;'. r-i.i,-:'! in ,vlin;', (;-, 10','Tveff i-'t'llinii NAmSA"^ v.Titlr;n .ippioval
&^B^ A^R k^^^ fl^R B^& H^B KVJH^B
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HLO-1997-00026
2261 Tracy Road Northwood. OH 43619 Phone 419*666*9455 FAX 419^66*2954
MG030-110
Lab No. 96T 16836 00
CYTOTOXICITY - AGAROSE OVERLAY. SOLID
Results:
Test/Control Articles Test Article Negative Control: UP-1 NAmSA Positive Control: 725871H
Score N N T
Zone of Lvsis (mm)
0 0 6
Results and conclusions apply only to the test article tested. No further evaluation of these results is made by NAmSA. Any extrapolation of these data to other samples is the responsibility of the sponsor.
Conclusion:
Comments: Record Storage:
The above test article was nontoxic for L-929 mouse fibroblast cells under the above described test parameters.
Placed the bluest side of the test article down on agarosc.
All raw data pertaining to this study and a copy of the final report are to be retained in designated NAmSA archive files.
Test Article Received: 12-5-96
Date Prepared: 12-11-96
Date Terminated: 12-12-96
Company Sanitized. Does not contain TSCA CBl
bsi>i
Date Completed tZ-'n^fc
Approved By - 20 -
(fyiwf - as"y --t~.-w
I
'
Page 2 of 2
Aulliuri/ritiDri lor dii|ilr:;ilinii 11' 'lir, rr|iiul. Rxrnpl in whole, if. 'O.sen/od ii'.-iKliiiq NAmSA;: wrilIi'K ;i|)|)inval
STUDY TITLE: USP 1NTRACUTANEOUS TOXICITY STUDY IN THE RABBIT
(Extracts)
TEST ARTICLE:
H-22240 (test item)
IDENTIFICATION NO.:
H-22240
CO^'^
l5C^ 0^
t ^ DOi'es
5aft^1 c<^-
.tA^
SPONSOR:
DR. SUSAN A. MACKENZIE
E. I. du Font de Nemours & Co. HASKELL LABORATORY
ELKTON RD. P.O. BOX 50
NEWARK. DE
19714-0050
MinSSA - 21 World l^odir in Ttllil Srrflrri for Ilii Mtttrfl Ilimi l^mir,
?;6) Tncy Raid
Naittrood. OH 438(9
Phi,ne 4196e<4!i5
FAX
4198fr29S4
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. TU013.800
SUMMARY .
TABLE OP CONTENTs
Lab N9.
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96T168?60 ,,,,, .
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INTRODUC1 'ON ----------------------
MATERIAL! .-.--..-----.---------
METHODS ...........
RESULTS
.....
CONCLUSION .
.......--..-- .-........---
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RECORD STORAGE
...-.-............-..-....... ^ TABLE
| I - USPINITRACUTANEOUS TOXICrTY OBSERVATIONS .
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AuNvlUtW^dupUullondlhlintXHi.ciewilntiitnto.Hi
2l Trtd^ Hotd
North06d. OH 3BIB Phon* t6frIBS
FAX <lMeWt4
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TU013-800
HLO-1997-00026 Lab No. 96T 16836 00
SUMMARY
The lest article. H-22240 (lest item). H-22240, was extracted in 0.9% sodium chloride USP solution and cottonseed oil. NF. These extracts were evaluated for iniracuianeous (oxicily in accordance with the guidelines of the current USP.
A 0.2 oil dose of the appropriate test article extract was injected by the intracutaneous route into five separate sites on the right side of the back of each rabbit. Similarly, the correspondingblank vehicle was injected on me
left side of the back of each rabbit. Two rabbits were used for each pair of extracts. Observations for erythema and edema were conducted at 24, 48, and 72 hours after intracutaneous injection.
Under the conditions of this study, (here was no evidence of significant irritation or toxicity from the extracts injected intracutaneously into rabbits. Each test article extract met the USP requirements.
Study and Supervisory Personnel:
Donald P. Baida, LAT Michael A. Safron, AAS (HT)
Patricia Mitchell
Barbara M. Monroe
Darcy Irons
Cindy Harper
Tina M. Cox, BS, LAT
Approved by:
Manager, Toxicology
(lidawh^'L-?,/-^
Date Completed
Company Sanitized. Does not contain TSCA CBI
/las
MmSjKif ,U_ _ &AJR W
- /-> -
H'orM Liaiir in TelUui Smicfl
for tin MtMnI Pnlf liifuttf
2261 Ticy Ro*o
Noxnwood. OH 43619
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"
"MtB.9455 'MMBM
AuthontMon tot duptiejlr> o* ihu noon. *ia(H In otiol*. rrd (undine MAmSA'i nnm opdwa!.
Page 3 of 7
TU013-800
HLO-1997-00026
Lab No. 96T 16836 00
INTRODUCTION
The test article identified below was extracted and the extracts were evaluated for biocompatibility ia accordance with the guidelines of the current USP. The purpose of the study was to determine whether leachables extracted from the material would cause local dermal irritant or toxic effects following injection into rabbit skin. The test anicle was received on December 5. 1996. The animals were injected on December 18, 1996. and the observations were concluded on December 21, 1996.
MATERIALS
The sample provided by the sponsor was identified and handled as follows:
Test Anicle:
H-22240 (test item)
Identification No:
H-22240
Storage Conditions:
Room temperature
Vehicles: Preparation:
0.9% sodium chloride USP solution (SC)
cottonseed oil, NF (CSO)
A ratio of 120 cm^ZO ml (surface area of test article to volume of vehicle) was used for each preparation. The test anicle was extracted in SC aid CSO at 121 C for 1 hour. The extraction vehicles without test anicle were
similarly prepared to serve as control blanks.
Condition of Extracts:
Sample Disposition:
SC: CSO:
Test clear clear
Any remaining sample was discarded.
METHODS
Control clear clear
Test System:
Species:
Breed: Source: Sex: Body Weight Range: Age: Acclimation Period: Number of Animals: Identification Method:
Rabbit (Orvctolagus cuniculus)
New Zealand White Myrtle's Rabbitry, me. No particular gender was prescribed for this test No particular body weight range was prescribed for this test No particular age was prescribed for this test Minimum 2 days Two per pair of extracts
Ear tag or tattoo
Justification of Test System:
The intracutaneous injection test in rabbits is specified in the current USP and has been used historically to evaluate biomaterial extracts.
Animal Management:
Husbandry:
Conditions conformed to Standard Operating Procedures which are based on the "Guide for (he Care and Use of Laboratory Animals."
Food:
PROLAB" High Fiber Rabbit Diet was provided daily.
Company Sanitized. Does not contain T5CA CBI
NAmSA
24
World t^aiir in Tilllsi Smicti for till Mtditsl lltftci Mutrjf
Aufhonitlcn lor duolKttion o! fhi upon. udl n Aok. x n
2261 Trcy Row)
Norlhoood. OH 43819
Phon* 4tBe.W55
FAX
41666^8f<
ing NAmSA'i onWn ipprmll
Page 4 of 7
TU013-800
HLO-1997-00026 Lab No. 96T 16836 00
Waier: Contaminants: Housing: Environmental:
Freely available, municipal (Toledo. OH) water was delivered through an automatic
watering system.
Reasonably expected contaminants in feed or water supplies did not have the potential to influence the outcome of this test.
Animals were individually housed in stainless steel suspended cages identified by a card indicating the lab number, animal number, test code. sex, and date dosed.
The room temperature was monitored daily. The temperature range for the rabbit was 64-74F.
The room humidity was monitored daily. The humidity range for the rabbit was 30-70%.
The light cycle was controlled using an automatic timer (12 hours light, 12 hows dark).
Facility: Personnel: Selection:
NAmSA is an AAALAC accredited facility.
Associates involved were appropriately qualified and trained.
Only healthy, thin-skinned animals free of mechanical irritation or trauma mat could
interfere with the test were selected.
Experimental Procedure:
Prior to treatment, each rabbit was clipped free of fur from the back and both sides of the spinal column to yield a sufficient injection area. Two rabbits were prepared per pair of extracts. A 0.2 ml dose of test article extract was injected intracutaneously into five separate sites on the right side of the back of each rabbit; 0.2 ml of the control blank was injected into five separate sites on the corresponding left side of me back. Injections were spaced approximately 2 cm apart. The animals were returned to their respective cages following the
procedure.
Observations for erythema and edema were conducted at 24, 48, and 72 hours after injection. Reactions were scored on a 0 to 4 basis. Any reaction at the injection sites was also noted. The reactions were evaluated according to the following subjective rating scale:
ERYTHEMA (ER)
0 No erythema 1 Very slight (barely perceptible) 2 Well-defined (pink) 3 Moderate to severe (red) 4 Severe (beet redness) to slight eschar
formation (injuries in depth)
EDEMA (ED)
0 No edema 1 Very slight (barely perceptible) 2 Slight (edges of area well-defined by
definite swelling) 3 Moderate (raised approximately 1 mm) 4 Severe (raised more than 1 mm. may
extend beyond the area of exposure)
The cumulative average erythema and edema score for each test extract and corresponding control blank was calculated. For each extract, a difference in average scores (test minus control blank) of 1.0 or less was
considered to be acceptable. A difference of 0.6 to 1.0 indicated a slight, but acceptable, reaction. A difference > 1.0 was considered to be unacceptable. Additionally, the average score for each test extract and
blank was calculated for each interval. Any adverse reaction noted in the test extract was compared to the
corresponding blank.
Aa>n TSC?^
fleieorf nHzed. Does
CO'.tupa"^'
KAlllXA - 25 World l^adsr tn TullHf Sitvlen for till MrilrjJ UlUn lnf*my
2261 Tracy RMJ
Nonhwood. OH 438)9
Phone 4I666-955
PAX
4t66&29S4
Aulhorlullon Id duplKlllon ol ihn npon. new In --10--. u i--Mind p*nding NAmSA't nHtun ppnnt
Page 5 of 7
TUO 13-800
HLO-1997-00026 Lab No. 96T 16836 00
RESULTS
Results of scores for individual rabbits appear in Table I. The findings are summarized below:
Extract SC
CSO
Average Test (-) Average Control = Difference == Assessment
0.0
0.0
0.0
Passed
1.0
1.0
0.0
Passed
The difference in average scores was considered acceptable. The difference between test and control average scores did not exceed 1.0 at any observation interval.
Results and conclusions apply only to the test article tested. No further evaluation of .these results is made by NAmSA. Any extrapolation of these data to other samples is the responsibility of the sponsor.
CONCLUSION
Under the conditions of this study, there was no evidence of significant irritation or (oxicity from the extracts injected intracuianeously into rabbits. Each test article extract met the USP requirements.
RECORD STORAGE
All raw data pertaining to this study ; archive files.
I a copy of the final report are to be retained in designated NAmSA
Company SanW^.D.e^o"""^'-'81
MmSBA 26 WotU Uaitt ill Tunas Ifmm far tin MlUcsl Onlti IsfulU)
22G1 Trcy Rout
Nodhwaod. OH 43619
Phone 419-6frMS5
FAX
4iafe9&4
*ilhanMIWIedufflicllonetlhiiport.ctffaih<il.iiMli^pft<^N<mSA'irMnalt^
Page 6 of 7
TUO 13-800
HLO-1997-00026 Lab No. 96T 16836 00 TABLE 1 USP 1NTRACUTANEOUS TOXIC1TY OBSERVATIONS
TEST EXTRACT Scoring Interval (Hours)
RABBIT NUMBER
99555 99557 99555 99557
EXTRACT
sc sc
cso cso
24
48
ER
ED ER ED
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
72
ER ED
0
0
0
0
1
1
1
1
ER = ED =
Erythema Edema
SC = 0.9% sodium chloride USP solution CSO = cottonseed oil, NF
CONTROL BLANK Scoring Interval (Hours)
24
48
72
ER
ED
ER ED
ER
ED
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
Sanitized. Does not contain TSCA FBI Company
MmSA
- 27 -
World Ija^tr l Tulmi .Strum for Ihi Ml^ital Dutci MUM)
AulhormUon IM i)uplic*lion ol ihn upon. ucw in ihol*. a >
2?6t Tracy Road
Northwood. OH 43819
Phone FAX
<lWi66.9Iii5 4lft66fre9!i4
Ing NAHISA'I wimn pproval
Page 7 of 7
Confidenlial TU014-807
HLO-1997-00026
Lab No.
96T 16836 00
P.O. No. LGX-593521
STUDY TITLE: USP MUSCLE IMPLANTATION STUDY IN THE RABBIT
(1 Week)
TEST ARTICLE: H-22240 (test item)
IDENTIFICATION NO.:
H-22240
Ooesn01.c.^'"^061
ulized.
Company5^
SPONSOR:
DR. SUSAN A. MACKENZIE
E. I. du Pont de Nemours & Co. HASKELL LABORATORY ELKTON RD. P.O. BOX 50 NEWARK, DE 197(4-0050
MmSSA
- 28 -
WarU l^adfr is TtiliHl Stulrti for tht MlUcal Dtvitl Infinity
2261 Ticy RoaK
Nonhwood OH 43619
Phone 4l9<66-9455
FAX
Jl66-;ai
AulhOTttllcn lof duplicilion of ttis npon. mpl in ho-, is rfcmo (widhg NAmSA'i nmlMi ni>l
TUO 14-807
SUMMARY .....
INTRODUCTION . .
MATERIALS .... METHODS ......
RESULTS .......
CONCLUSION . . . RECORD STORAGE
TABLE OF CONTENTS
HLO-1997-00026 Lab No. 96T 16836 00
Company Sanitized. Does not contain TSCA CB1
MmSIK - 29 W orld Uatit In Ttitlni Smitti for tin MtMcal llHlct Infinity
2261 Tttcy RIM)
Northwood. OH 43619
Ption* 41M66-945S
FAX
4ie684a54
AulhortiMon fw duplluiloi ol Ihu nport. <BW In iMiol*. u mMHM iwiding NAniSA-t iiniun ipprovll
TU014-807
HLO-1997-00026 Lab No. 96T 16836 00
SUMMARY
The lest article, H-22240 (test item). H-22240, was implanted in muscle tissue of the rabbit. The muscle tiuue was evaluated for evidence of irritation or toxicity in accordance with the guidelines of the current USP.
Implant samples and USP negative control strips were loaded into needles and sterilized by steam. Rabbits were implanted and were then euthanatized 1. week later. Muscle tissues were excised and the implant sites were examined macroscopically.
Under the conditions of this study, the macroscopic reaction was not significant as compared to the USP negative control implant material. The implanted test article met the USP requirements.
Study and Supervisory Personnel:
Martha Oswanski, VS. LAT Merle J. Heineke, BS, LAT
Jason A. Karsten Tina M. Cox, BS, LAT
Approved by:
Manager, Toxicology
Of&Umiffry.W^
Date Completed
^/nun
Company Sanitized. Does not contain TRC^ ^
MmSA
_ If) _
WorU Ijadrr In Tistiiit Sinlw fot iki MlUr*! Df<lei lUuitr)
2281 Tricy Rud
Northmod. OH *3G10
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'9<8.945S
'6tM95
AuftonuMn hM diWaiMm al ihr nport. mpl in --<or. r muwa pwdhg NAmSA'i WMn tpprovl
Page 3 of 6
TU014-807
HLO-1997-00026 Lab No. 96T 16836 00
INTRODUCTION
The test article identified below was evaluated for biocompatibility in accordance with the guidelines of the
current USP. The purpose of (he study was to evaluate the potential for a local irritant or toxic response to
material implanted in direct contact with muscle tissue. The test article was received on December 5, 1996. The animals were implanted on December 17, 1996, and muscles were explained on December 24, 1996.
MATERIALS
The sample provided by the sponsor was identified and handled as follows:
Test Article:
H-22240 (test item)
Identification No:
H-22240
Storage Conditions:
Room temperature
Control Article: Preparation:
USP plastic 1 mm diameter negative control reference strips purchased by NAmSA from the offices of the US Pharmacopeia! Convention and cut into 10 mm sections.
A minimum of six sections of the test article per rabbit, each approximately
1 mm x 10 mm, were loaded into 16 gauge needles. Toe test article was cut
into 1 nun ;< 20 mm lengths and then folded in half to obtain 1 mm x 10 am
sections. For each rabbit, a minimum of four USP stripswere loaded into the same size needles as used for the test article. Test aid control articles were sterilized by steam.
Sample Disposition:
Any remaining sample was discarded.
METHODS
Test System:
Species: Breed:
Source: Sex:
Body Weight Range: Age: Acclimation Period: Number of Animals: Identification Method:
Rabbit (Orvctolapis cuniculus) New Zealand White Myrtle's Ranbitry, Inc. No particular gender was prescribed for this test 2.5 kg to 2.6 kg at implantation No particular age was prescribed for this test Minimum 2 days
Two
Ear tag or tattoo
Justification of Test System:
The rabbit is suggested as an appropriate animal model for evaluating polymer materials by the current USP testing guidelines. The muscle tissue has been used historically because the response to implanted material is easily graded and compared (o a known negative control material.
Animal Management:
Husbandry:
Conditions conformed to Standard Operating Procedures which are based on the "Guide for the Care and Use of Laboratory Anim, Is."
Food:
PROLAB* High Fiber Rabbit Diet was provided daily.
MmSA
_.-----""" - 31 -
2261 Trcy ROM)
NorthOTOd. OH <381B
WortS Ltadli la TfiHl Swiets for Ike Mittcal tmict Infinity
Phoni FAX
416SMS5 1a669i4
Ajlhcuaillai lor dupliciton ol ihh fpon. xcW m tiol*. a fufnd pfiding NAmSA'i mutin ipcirmil
Page 4 of 6
TU014-807
HLO-1997-00026
Lab No. 96T 16836 00
Waier:
Freely available, municipal (Toledo, OH) water was delivered through an automatic watering system.
Contaminants:
Reasonably expected contaminants in feed or water suppliesdid not have the potential to influence the outcome of this test.
Housing:
Animals were individmily housed in stainless steel suspended cages identified by a can!
indicating the lab number, animal number, test code, sex, and date implanted.
Environmental:
The room temp-rature was monitored daily. The temperature range for the rabbit was 64-74?.
The room humidity was monitored daily. The humidity range for the rabbit was 30-70%.
The light cycle was controlled using an automatic timer (12 hours light, 12 hours dark).
Facility:
NAmSA is an AAALAC accredited facility.
Personnel:
Associates involved were appropriatelyqualified and trained.
Selection:
Healthy animals were selected. To reduce me number of animals used for testing, and to comply with the directives of the NAmSA IACUC, rabbits on this study may have been used previously in an unrelated test model. Any previously evaluated test or control articles did not cause a response in the aninus. Complete history of animal mage is traceable in laboratory records. Animals used for previous evaluations are identified in
the report.
Experimental Procedure:
The fur was clipped from the area over the paravertcbral muscles and the rabbits were sedated with acepromazine maleate (0.2 ml/kg dose). After the muscle area was wiped clean with 70% alcohol, each
paravenebral muscle was infiltrated with 1% lidocaine to achieve local anesthesia on both sides of the vertebral
column.
Needles containing te-t article were inserted into the muscle at a 45 angle. A stylet was placed in the needle and the needle was withdrawn, leaving the sample in the paravenebral muscle. Six test article sections were implanted in the right paravenebral muscle of each rabbit. In the opposite mu<a;le. four USP negative control strips were similarly implanted.
Rabbits were returned to their respective cages following the procedure. Rabbits were observed daily for general health. Body weights were recorded prior to implantation and at termination.
At 1 week. the rabbits were weighed and euthanatized by an intravenous injection of a sodium pcntobarbital based drug. The paravenebral muscles- were dissected free and methodically cut to locate four of the test article sites and two of the USP negative control sites in each rabbit. Capsule formation or other evidence of irritation was scored using appropriate magnification and an auxiliary light source. Scores were assigned and recorded as
follows:
0 No capsule, no adverse reaction (other than minimal hemorrhage) 1 Up to 0.5 nun capsule or reaction area 2 0.6 to 1.0 mm capsule or reaction area 3 1.1 to 2.0 mm capsule or reaction area 4 >2.0 mm capsule or reaction area
Sompany Sanitized. Does not contain TSCA CB
MmM - 32 WarU Uadit in TllltHf Strflcis jw tin Midtcfl Dnici lulniuj
2261 Ttcy Ran)
Norlh-ooa. OH <3619
Ptione 4194W.94S5
FAX
41B4864B54
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TUOl4-g07
HLO-1997-00026
Lab No. 96T 16836 00
Avenge macroscopic scores for test implants were compared to average scores of the control lites. Calculations were rounded off to the nearest 0.1. A Reaction Index difference of 0.0 to 0.5 in scores (test minus control) was regarded as "not significant," 0.6 to 1.0 as a "trace," 1.1 to 2.0 as light,1' 2.1 to 3.0 is moderale- and (3.1 a& 'marked.' The requirements of (he USP test were met if the difference between test and control score averages (macroscopic) was not greater than 1.0. The requirements of the test were not nut if (he difference between the test and control score for two (or more) implant sites exceeded 1 for any aniiBd
implanted.
RESULTS
Clinical Observations: All animals appearedclinically normal throughout the duration of the study. Body weight data for individual rabbits were considered acceptable.
Macroscopic Observations: The findings for the macroscopic evaluation are shown below.
Weigyu(kg)
Rabbit
Number
DayO
Day 7
Site
1
98944*
2.6
2.8
2
3
4
1
99122*
2.5
2.8
2
3
4
Test
0 0 0 0
0 0 0 0
USP Negative Control
0 0
0 0
0.0
0.0
Previous use history traceable in laboratory records.
Macroscopically, there was no difference between the reactions of the test and control materials. This resulted in a macroscopic reaction of "not significant' tissue contact irritation.
Results and conclusions apply only to the test article tested. No further evaluation of these results is made by NAmSA. Any extrapolation of these data to other samples is the responsibility of me sponsor.
CONCLUSION Under die conditions of this study, the macroscopic reaction was not significant as compared to the USP negative control implant material The implanted test article met the USP requirements.
RgCQRP STQRAGE
Ail raw data pertaining to this study and a copy of the final report are to be retained la designated NAm&A archive files.
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