Biological reactivity USP
Biological reactivity tests of elastomerics, plastics and other polymeric materials that have direct or indirect contact with the patient were designed to determine the biological in vitro , in vivo response. Based on different plastics class various tests need to be conducted according to Table 1: Classification of Plastics of USP <88> , USP <87>.
Test protocols for biological reactivity testing are well defined by the U.S. Pharmacopeia, General Chapters <87> and <88>. These test protocols involve in vitro reactivity testing with mammalian cells and in vivo reactivity testing in animals, respectively. However, many Biopharmaceutical companies require only a Certificate of Compliance (COC) from equipment manufacturers that states the plastics, elastomers (or any other material) potentially in contact with the biopharmaceutical process meet U.S. Pharmacopeia Class VI Testing. It is the opinion of the Author that U.S. Pharmacopeia Testing per Class VI (one part of USP <88> testing), is not alone sufficient in determining the biological reactivity to that material. Additionally, the materials should be tested in accordance with USP <87>, in vitro testing with mammalian cells, to better determine potential reactivity that may decrease cell growth and, therefore, limit profit per batch.
| BODY CONTACT | CONTACT DURATION | |||
|---|---|---|---|---|
| Permanent (>30days) |
Prolonged (>24h to 30 days) |
Limited (>24h) |
||
| Surface devices | Skin | Class I | ||
| Mucosal membrane | Class V | Class III | Class I | |
| Breached or comprised surfaces | Class VI | Class V | Class III | |
| External communicating devices | Blood path, indirect | Class VI | Class V | Class IV |
| Dentin communicating | Class VI | |||
| Circulating blood | ||||
| Implant devices | Tissue or bone | Class VI | ||
| Blood | ||||
Biological reactivity testing has been performed to further increase yield. It is obvious that any material that reduces cell or microbial growth will affect yield. One such biological reactivity test applicable to and often requested by the Biotech Industry is the testing of elastomers, plastics, polymeric materials and their extracts as described in the U.S. Pharmacopeia General Chapter <88>. This in vivo testing consists of three (3) tests: Systemic, Intracutaneous, and Implantation. The materials and their extracts are then classified according to the test results as meeting Plastics Class I through Class VI. A summary of the tests are as follows:
| 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 on Sodium Chloride Injection | Mouse | 50 mL/kg | A(iv) |
| x | x | x | x | x | x | Rabbit | 0.2 mL /animal at eachof 10 sites | B | |
| x | x | x | x | x | Extract of Sample in 1 in 20 Solution of Alcohol in Sodium Chloride Injection | Mouse | 50 mL/kg | A(iv) | |
| x | x | x | x | x | Rabbit | 0.2 mL /animal at each of 10 sites | B | ||
| x | x | x | Extract of Sample in Polyethylene Glycol 400 | Mouse | 10g/kg | A(ip) | |||
| x | x | Rabbit | 0.2 mL /animal at each of 10 sites | B | |||||
| x | x | x | Extract of Sample in Vegateble Oil | Mouse | 50 mL/kg | A(ip) | |||
| x | x | x | Rabbit | 0.2 mL /animal at each of 10 sites | B | ||||
| x | x | Implant strips of Sample | Rabbit | 4 strips /animal | C | ||||
| x⭡ | x | Implant Sample | Rat | 2 Samples /animal | C | ||||
| ᵃ Test required for each class indicated by „x” in appriopriate columns. ᵇ Legend A (ip) – Systemic Injection Test (intraperitoneal); A (iv) – Systemic Injection Test (intravenous); B – Intracutaneous Test (intracutaneous); C – Implanation Test (intramuscular or⭡subcutaneous⭡UPS 35 implantation). |
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