Test

 
 
Sample Requirements
 BIOCOMPATIBILTY STUDY
STANDARD
<0.5 mm thickness
<0.5 mm thickness
irreguary shaped  solid devices 
irreguary shaped porous devices
  
ratio 6 cm2 /mL
ratio 3 cm2 /mL
ratio 0,2 /mL
ratio 0,1 g/mL
 liquids
Biological Evaluation Plan
ISO 10993-1
N/A
N/A
N/A
  N/A
 N/A
Chemical Characterization
Headpace GC-MS
ISO 10993-18
 1 sample (min.30 cm2)
 1 sample (min.15 cm2) 
 1 sample (min. 2 g) 
 1 sample (min. 1g) 
 1 sample (min.5 mL)
GC-MS
3 samples (min.30 cm2 each)
3 samples (min.15 cm2 each)
3 samples (min.2 g each)
3 samples (min. 1 g each) 
3 samples (min.5 mL each)
LC-MS
3 samples (min.30 cm2 each)
3 samples (min.15 cm2 each)
3 samples (min. 2g each)
3 samples (min. 1 g each) 
3 samples (min.5 mL each)
ICP-MS
3 samples (min.30 cm2 each)
3 samples (min. 15 cm2 each) 
3 samples (min. 2 g each)  
3 samples (min. 1 g each) 
3 samples (min.5 mL each)
Toxicological evaluation
 ISO 10993-17
 N/A
 N/A
 N/A
N/A
N/A
Cytotoxicity
MEM Elution
 ISO 10993-5
1 sample (min.120 cm2)
1 sample (min.60 cm2)
1 sample (min. 4g)
1 sample (min. 2 g)
1 sample (min.20 mL)
Direct Contact
3 samples (min.24 cm2 each)
3 samples (min.12 cm2 each)
3 samples (min.1 g each)
3 samples (min.1 g each)
3 samples (min.4 mL each)
Agar Diffusion
3 samples (min.24 cm2 each)
3 samples (min.12 cm2 each)
3 samples (min.1 g each)
3 samples (min.1 g each)
3 samples (min.4 mL each) 
Filter Diffusion
1 sample (min.120 cm2 each)
1 sample (min.60 cm2)
1 sample (min. 4g)
1 sample (min. 2g)
1 sample (min.20 mL)
MTT/XTT
1 sample (min.120 cm2 each)
1 sample (min.60 cm2)
1 sample (min. 4g)
1 sample (min. 2g)
1 sample (min.20 mL)
Sensitization
GPMT
 ISO 10993-10
6 samples (min.240 cm2 each)
6 samples (min.120 cm2 each)
6 samples (min. 8g each)
6 samples (min. 4g each) 
to be individually determined
LLNA
6 samples (min.50 cm2 each)
6 samples (min.25 cm2 each)
6 samples (min. 2g each)
6 samples (min. 1 g each)
 
to be individually determined 
Buehler
120 samples (pieces of 2.5 cm x 2.5 cm patches each)
to be individually determined
Irritation
In vitro irritation
 ISO 10993-23
2 samples (min.60 cm2 each)
2 samples (min.30 cm2 each)
2 samples (min.2 g each)
2 samples (min.1 g each) 
2 samples (min.10 mL each)
Intracutaneous reactivity
 ISO 10993-10
2 samples (min.60 cm2 each)
2 samples (min.30 cm2 each)
2 samples (min.2 g each)
2 samples (min.1 g each)
to be individualy determined
Animal Irritation Test
to be individually determined
Material mediated pyrogenicity
Material mediated pyrogenicity
ISO 10993-11
1 sample (min.1200 cm2 each)
1 sample (min.600 cm2 each)
1 sample (min. 40 g )
1 sample (min.20g)
to be indyvidualy determined
Endotoxin LAL
1 sample (min.12 cm2 each)
1 sample (min.6 cm2 each)
1 sample (min.1g each)
1 sample (min.1g)
   1 sample min. 2mL
Toxicity
Acute Systemic Toxicity
ISO 10993-1
2 sample (min.120 cm2 each) 
2 sample (min.60cm2 each)
2 sample (min. 4g  each)
2 sample (min. 2g  each) 
to be indyvidualy determined
Subacute toxicity
 to be indyvidually determined
Subchronic toxicity
to be indyvidually determined
Chronic toxicty
to be individually determined
Implantation
 4 week implantation
ISO 10993-6
 to be individually determined  
13 week implantation
 to be individually determined  
Hemocompatibility
Hemolysis (direct & indirect)


ISO 10993-4
 

 

 
6 samples (min 120 cm2 each)  
6 samples (min. 60 cm2 each)
6 samples (min. 4 g each) 
6 samples (min. 2 g each)
6 samples (min. 20 mL each)
Coagulation
3 samples (min 30 cm2 each)
3 samples (min 18 cm2 each)
3 samples (min. 1g  each)
3 samples (min 1 g each)
3 samples (min. 5 mL each)
Platelet Activation
3 samples (min 30 cm2 each)
3 samples (min 18 cm2 each)
3 samples (min. 1g each)
3 samples (min. 1g each)
3 samples (min. 5 mL each)
Complement  Activation
3 samples (min 30 cm2 each)  
3 samples (min 18 cm2 each)
3 samples (min. 1g each)
3 samples (min. 1g each)
3 samples (min. 5 mL each)
Hematology
3 samples (min. 30 cm2 each)
3 samples (min. 18 cm2 each)  
3 samples (min. 1g each)
3 samples (min. 1g each)
3 samples (min. 5 mL each)
Genotoxicity
AMES
ISO 10993-3
2 samples (min. 240 cm2 each)
2 samples (min. 120 cm2 each)
2 samples (min. 8g each)
2 samples (min 4g each)
2 samples (min 40 mL each)
MLA
ISO 10993-33
1 sample (min 240 cm2)
1 sample (min 120 cm2)  
1 sample (min. 8g)
1 sample (min. 4g)
1 sample (min. 40 mL)
Biological Evaluation Report
 
ISO 10993-1
 N/A
 N/A
 N/A
 N/A
 N/A

 

 

 

 

 

 

ISO 10993 – 1:2018 [E] Annex A
Medical device categorization by

 

Endpoints of biological evaluation

 
Nature of body contact Constant Duration>

Chemical information

Cyto

toxi

city

Sensitization

I

 Material mediated pyrogenicity

Acute Systemic

Toxicity

Suba

cute toxicity

Sub

chronic toxicity

 Chronic toxicity

Implan

tation

effects

Hemo

compa

tibility

Geno

toxi

city

Car

cino

geni

city

Repro

ductive

Develop

Mental toxicity

Degra

dation

 

 

Category

 

Contact

A – limited

(≤ 24h)

B – prolonged

(>24h to 30 d)

C – long term

(>30d)

Surface Medical Device

 

 

 

 

Surface Medical Device

 

   Intact Skin

 

A

 

 X E  E E

 

 
B X E E E
C X E E E

 

Mucosal membrane

 A X E E E
B X E   E E FDA

E

FDA

E

FDA

E

FDA
C X E E E FDA

E

FDA

 E E E
Breached or compromised surface A X E E E FDA

E

FDA
B X E E E FDA

E

FDA

E

FDA

E

FDA
C X E E E FDA

E

FDA

 E

E

FDA

E

FDA

Externally

communicating medical  device

 

Blood path indirect

 A E E E

E

FDA
B E E E

E

FDA

 

E

FDA

 
C X E E E

E

FDA
Tissue, bone, dentin A X E E E

E

FDA
B X E E E

E

FDA
C X E E E

E

FDA

 

Circulating blood

 A X E

E

FDA
B X E

E

FDA

 E
C X E E E

E

FDA

 E

                                     Implant

Medical

Device

 

          Tissue/bone

 A X E E E

E

FDA

E

FDA

 

 

 l l l l
B X E E E

E

FDA

 E E l g .
cm2
 E . s  each
C X E E E

E

FDA

 E E r ratio

 

 

 

 

 E

E

FDA

 s 2

 

Blood

 A X E E E

E

FDA

 E
to be individualy determined
 s

 

 

  each
3 samples (min 18 cm2 each)

E

FDA
3 samples (min 18 cm2 each)
1 sample (min.120 cm2 each)
3 samples (min 18 cm2 each)
B X E E E

E

FDA

 E E
6 samples (min. 2 g each)
 4 E E E 20
1 sample (min.20 mL)
 .
C X E E E

E

FDA

 E E E

E

FDA

 E E E

E

FDA

 6 2 samples (min. 40

 

 

 Sample R X – means preprequisite information needed for a risk assesment FDA – Additional FDA recommended endpoints for consideration E – means endpoint to be evaluated in the risk assesment