Plastic Classes a | Tests To Be Conducted | ||||||||
I | II | III | IV | V | VI | Test Material | Animal | Dose | Procedureb |
x | x | x | x | x | x | Extract of Sample in Sodium | Mouse | 50 mL/kg | A (iv) |
x | x | x | x | x | x | Chloride Injection | Rabbit | 0.2 mL/animal at each of 10 sites | B |
x | x | x | x | x | Extract of Sample in 1 in 20 | Mouse | 50 mL/kg | A (iv) | |
x | x | x | x | x | Solution of Alcohol in Sodium Chloride Injection | Rabbit | 0.2 mL/animal at each of 10 sites | B | |
x | x | x | Extract of Sample in | Mouse | 10 g/kg | A (ip) | |||
x | x | Polyethylene Glycol 400 | Rabbit | 0.2 mL/animal at each of 10 sites | B | ||||
x | x | x | x | Extract of Sample in | Mouse | 50 mL/kg | A (ip) | ||
x | x | x | Vegetable Oil | Rabbit | 0.2 mL/animal at each of 10 sites | B | |||
x | x | Implant strips of Sample | Rabbit | 4 strips/animal | C | ||||
a
Tests required for each class are indicated by x in appropriate columns.
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b
Legend: A (ip)Systemic Injection Test (intraperitoneal); A (iv)Systemic Injection Test (intravenous); BIntracutaneous Test (intracutaneous); CImplantation Test (intramuscular implantation).
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Erythema and Eschar Formation | Score |
No erythema | 0 |
Very slight erythema (barely perceptible) | 1 |
Well-defined erythema | 2 |
Moderate to severe erythema | 3 |
Severe erythema (beet-redness) to slight eschar formation (injuries in depth) | 4 |
Edema Formation* | Score |
No edema | 0 |
Very slight edema (barely perceptible) | 1 |
Slight edema (edges of area well defined by definite raising) | 2 |
Moderate edema (raised approximately 1 mm) | 3 |
Severe edema (raised more than 1 mm and extending beyond the area of exposure) | 4 |
*
Excludes noninflammatory (mechanical) edema from the blank or extraction fluid.
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Form of Material | Thickness | Amount of Sample for Each 20 mL of Extracting Medium | Subdivided Into |
Film or sheet | <0.5 mm | Equivalent of 120 cm2 total surface area (both sides combined) | Strips of about 5 × 0.3 cm |
0.5 to 1 mm | Equivalent of 60 cm2total surface area (both sides combined) | ||
Tubing | <0.5 mm (wall) | Length (in cm) = 120 cm2/(sum of ID and OD circumferences) | Sections of about 5 × 0.3 cm |
0.5 to 1 mm (wall) | Length (in cm) = 60 cm2/(sum of ID and OD circumferences) | ||
Slabs, tubing, and molded items | >1 mm | Equivalent of 60 cm2total surface area (all exposed surfaces combined) | Pieces up to about 5 × 0.3 cm |
Elastomers | >1 mm | Equivalent of 25 cm2 total surface area (all exposed surfaces combined) | Do not subdivide2 |
1
When surface area cannot be determined due to the configuration of the specimen, use 0.1 g of elastomer or 0.2 g of plastic or other polymers for every 1 mL of extracting fluid.
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2
Molded elastomeric closures are tested intact.
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Extract or Blank | Dose per kg | Route* | Injection Rate, µL per second |
Sodium Chloride Injection | 50 mL | IV | 100 |
1 in 20 solution of Alcohol in Sodium Chloride Injection | 50 mL | IV | 100 |
Polyethylene Glycol 400 | 10 g | IP | |
Drug product vehicle | 50 mL | IV | 100 |
(where applicable) | 50 mL | IP | |
Vegetable Oil | 50 mL | IP | |
*
IV = intravenous (aqueous sample and blank); IP = intraperitoneal (oleaginous sample and blank).
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Extract or Blank | Number of Sites (per animal) | Dose, µL per site |
Sample | 5 | 200 |
Blank | 5 | 200 |
Capsule Width | Score |
None | 0 |
up to 0.5 mm | 1 |
0.61.0 mm | 2 |
1.12.0 mm | 3 |
Greater than 2.0 mm | 4 |