88 BIOLOGICAL REACTIVITY TESTS, IN VIVO
The following tests are designed to determine the biological respon of animals to elastomerics, plastics, and other polymeric material with direct or indirect patient contact, or by the injection of specific extracts prepared from the material under test. It is esntial to make available the specific surface area for extraction. When the surface area of the specimen cannot be determined, u g of elastomer or g of plastic or other material for every mL of extraction fluid. Also, it is esntial to exerci care in the preparation of the materials to be injected or instilled to prevent contamination with microorganisms and other foreign matter. Three tests are described. The Systemic Injection Test and the Intracutaneous Test are ud for elastomeric materials, especially to elastomeric closures for which the appropriate Biological Reactivity Tests, In Vitro 87 have indicated significant biological reactivity. The two tests are ud for plastics and other polymers, in addition to a third test, the Implantation Test, to test the suitability of the materials intended for u in fabricating containers and accessories thereto, for u in parenteral preparations, and for u in medical devices, implants, and other systems.
The three tests are applied to materials or medical devices, if there is a need for classification of plastics and other polymers bad on in vivo biological reactivity testing.
For the purpo of this chapter, the definitions apply: the Sample is the specimen under test or an extract prepared from such a specimen. A Blank consists of the same quantity of the same extracting medium that is ud for the extraction of the specimen under test, treated in the same manner as the extracting medium containing the specimen under test. A Negative Control1 is a specimen that gives no reaction under the conditions of the test.
CLASSIFICATION OF PLASTICS
Six Plastic Class are defined (e Table 1). This classification is bad on respons to a ries of in vivo tests for which extracts, materials, and routes of administration are specified. The tests are directly related to the intended end-u of the plastic articles. The choice of extractants is reprentative of the vehicles in preparations with which the plastics are likely to be in contact. The Table 1 classification facilitates communication am
ong suppliers, urs, and manufacturers of plastics by summarizing the tests to be performed for containers for injections and medical devices if a need for classification exists.
Table 1. Classification of Plastics
Plastic Classa | Tests to be Conducted |
I | II | III | IV | V | VI | Test Material | Animal | Do | Procedureb |
x | x | x | x | x | 由此可见的近义词 x | Extract of Sample in Sodium Chloride Injection | Mou | 50 mL/kg | A (IV) |
x | x | x | x | x | x 妹妹的幸福生活 | Rabbit or Guinea Pig | mL/animal at each of 10 or 6 sites | B (IC) |
| x | x | x | x | x | Extract of Sample in 1 in 20 Solution of Alcohol in Sodium Chloride Injection | Mou | 50 mL/kg | A (IP) |
| x | x | x | x | x | Rabbit or Guinea Pig | mL/animal at each of 10 or 6 sites | B (IC) |
| | x | | x | x | Extract of Sample in Polyethylene Glycol 400 | Mou | 一年级的小蜜瓜 10 g/kg | A (IP) |
| | | | x | x | Rabbit or Guinea Pig | mL/animal at each of 10 or 6 sites | B (IC) |
| | x | x | x | x | 貌合神离Extract of Sample in Vegetable Oil | Mou | 50 mL/kg | A (IP) |
| | | x | x | x | Rabbit or Guinea Pig | mL/animal at each of 10 or 6 sites | B (IC) |
| | | x | | x | Implant strips of Sample | 洛神花茶的功效与作用Rabbit | 4 strips/animal | C |
| | | x | | x | Implant Sample | 冬天取暖Rat | 2 Samples/animal | 财务人员英文 C |
a Tests required for each class are indicated by “x” in appropriate columns. b Legend: A (IP)—Systemic Injection Test (intraperitoneal); B (IC)—Intracutaneous Test (intracutaneous); C—Implantation Test (intramuscular or subcutaneous implantation). |
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With the exception of the Implantation Test, the procedures are bad on the u of extracts that, depending on the heat resistance of the material, are prepared at one of three standard temperatures: 50, 70, and 121. Therefore, the class designation of a plastic must be accompanied by an indication of the temperature of extraction ., IV-121, which reprents a class IV plastic extracted at 121, or I-50, which reprents a class I plastic extracted at 50).
Plastics may be classified as USP Plastic Class I–VI only on the basis of the respon criteria prescribed in Table 1.
This classification does not apply to plastics that are intended for u as containers for oral or topical products, or that may be ud as an integral part of a drug formulation. Table 1 does not apply to natural elastomers, which are to be tested in Sodium Chloride Injection and vegetable oils only.
The Systemic Injection Test and the Intracutaneous Test are designed to determine the systemic and local, respectively, biological respons of animals to plastics and other pol
ymers by the single-do injection of specific extracts prepared from a Sample. The Implantation Test骆驼祥子作文 is designed to evaluate the reaction of living tissue to the plastic and other polymers by the implantation of the Sample itlf into animal tissue. The proper preparation and placement of the specimens under aptic conditions are important in the conduct of the Implantation Test.
The tests are designed for application to plastics and other polymers in the condition in which they are ud. If the material is to be expod to any cleansing or sterilization process prior to its end-u, then the tests are to be conducted on a Sample prepared from a specimen preconditioned by the same processing.
Factors such as material composition, processing and cleaning procedures, contacting media, inks, adhesives, absorption, adsorption and permeability of prervatives, and conditions of storage may also affect the suitability of a material for a specific u. Evaluation of such factors should be made by appropriate additional specific tests to determine the suitability of a material for its intended u.
USP Reference Standards 11— USP High-Density Polyethylene RS.
Extracting Media—
