2017.3.28

2017

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Safety

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(biocompatibility) : The quality of not having toxic or injurious effects on biological systems

(systematic response)

(cellular response)

(tissue response)

(local response)

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- ISO 10993 http://www.iso.org/iso/iso_catalogue.htm- ASTM F748-95 http://www.astm.org

- FDA Guidance documents (G95-1) http://www.fda.gov/cdrh/g951.html

- CNS 14393:2004 http://www.cnsonline.com.tw/

CNS 14393FDA (G95-1)ISO 10993

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ISO 10993

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ISO 10993 Biological evaluation of medical devices

()

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ISO 10993

6

ISO 10993 :

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ISO 10993

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National Taipei University of Technology

ISO 10993

8

/

ISO 10993-8 ISO 10993-12

ISO 10993-1

ISO 10993-2

///ISO 10993-9 ISO 10993-13 ISO 10993-14 ISO 10993-15 /ISO 10993-16 ISO 10993-17 ISO 10993-18

ISO 10993-7

ISO 10993-3 ISO 10993-4 ISO 10993-5 ISO 10993-6 ISO 10993-10 ISO 10993-11

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:

National Taipei University of Technology

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10

ISO 10993

()

//

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11

A. (Limited)24

B. (Prolonged)24~30

C. (Permanent)30

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(ISO 10993-5 ) (ISO 10993-11) (ISO 10993-11) (ISO 10993-10) (ISO 10993-10) (ISO 10993-10) (ISO 10993-4) (ISO 10993-6)

(ISO 10993-11) (ISO 10993-3) (ISO 10993-3) (ISO 10993-9)

? ?

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ISO 10993

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FDA + ISO additional test for FDA

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ISO 10993-1

()

CytotoxicityISO10993-5

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ISO 10993-5 Test for in vitro Cytotoxicity

(L929 3T3)

? ?

>24

/

(Cytotoxicity)

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(Filter diffusion test)

(Direct contact test)

(Elution test)

: ()

/

0123

(Agar diffusion test)

(0.45m)

()

IrritationISO10993-10

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ISO 10993-10 Test for Irritation and Delayed-type Hyperseneitivity

(2Kg)

(

()

(Irritation)

National Taipei University of Technology

20

12345

12345

12345

12345

0.2ml

4

()

()

25mm2

25mm2

25mm2

25mm2

(Skin irritation)

(Intracutance reactivity)

()

SensitizationISO10993-10

National Taipei University of Technology

(1/2)

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ISO 10993-10 Test for Irritation and Delayed-type Hyperseneitivity

(300~500g)

-: (48h)(24h)

-: 33

/

(Hyperseneitivity)

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10SLS

+

8cm2 ()

1

2

3

7 day

48h

14 day

24h

ABC

+

+

0.1ml

6h

24h

6h

24h

6h

24h 14day

6h6h

24h

6h

24h

6h

24h

6h

24h

6h

24h

6h

(Bueher test) (maximization)

Implant EffectsISO10993-6

1. ()24h

2. ()24h

ISO 10993-6 Tests for local effects after implantation

(Subcutaneous)

(Muscle)

(Bone)

(12)

(12)

Muscle tissue from negative and positive reacting implants.

Minimal response

Severe response

http://www.devicelink.com/mddi/archive/98/08/013.html

():

() :

Systemic EffectsISO10993-11

1.

2. 30d30d()

3. 30d30d

()

ISO 10993-11 Tests for systemic toxicity

(acute toxicity) : < 24 hours (subacute) : 14-28 days (subacute/subchronictoxicity) : up to 90 days (chronic toxicity) : > 90 days

(oral) (dermal) (inhalation) (intravenous) (intraperitoneal)

:

/

Hemocompatibility

ISO10993-4

()(

)(thrombogenicity)(

)

ASTM F75616((NIH)

Autian)()

(

ELISA)C3aSC5b-9

ASTM F206519ASTM F1984

GenotoxicityISO10993-3

In vitro Ames test In vitro Chromosomal aberration TKIn vitro Mouse lymphoma In vivo micronucleus

DNA

ISO 10993-3 Tests for genotoxicity, carcinogenicity and reproductive toxicity

(mutagenicsubstancemutagen)(carcinogenicity)

(ISO 10993OEDC )

OECD : Organisation for Economic Co-operation and Development)

Ames

Salmonella typhimuriumhis

DNA DNA

CarcinogenicityISO10993-3

In vivo bioassay

Species: rat, mouse

Two year duration

Multiple dose groups

Histological tissue examination

Statistical analysis

Risk assessment

Re p r o d u c t i v e a n d d e v e l o p m e n t a l t o x i c i t y

ISO10993-3

1

2 ()

3

ISO10993-

ISO 10993-1

- MEM elution method

ISO10993-5 L929

-

ISO10993-4ASTM

- -

ISO10993-10

- -

ISO10993-10()

-

ISO10993-10

-

ISO10993-11

/- /

ISO10993-11(14~90)

-

ISO10993-11(>6)

- - LAL Test

USPLAL test

- - - - TK

ISO10993-3DNA

- - -

ISO10993-6

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ISO 10993-1 6 :

Equivalent

ISO 10993

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ISO 10993-1

?

?

1. 2.

/

/

ISO 10993

()

?

1.2.3.

?

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2

2

-

-

-

/

A.

B.

C.

D.

E.

F.

~Thankyou~