Most pharmaceutical manufacturers produce drugs in large vats of living cell cultures. For the production of these drugs, it is extremely important to ensure that these cell cultures are not exposed to any cytotoxic contaminants that may leach out of the seals. It is also imperative that cytotoxic contaminants not be present in the finished drug, especially for infants, and for patients who are pregnant or nursing.
Cytotoxicity O-ring testing
Before an O-ring is approved for the pharmaceutical industry, it needs to be tested for cytotoxicity (cell toxicity). This is usually tested in the United States per USP <87>, and internationally per ISO 10993-5. These two tests are very similar in methodology and criteria. Both cytotoxicity tests use L-929 mouse fibroblast cells, which are an industry-standard cell used for cytotoxicity testing. Cultures of these cells are produced in glass flasks prior to testing. Extracts are prepared using 3 test articles: the O-ring material, a negative control article (HDPE), and a positive control article (PVC for USP <87>, and powder-free latex gloves for ISO 10993-5). These extracts are then added to the cell cultures. Cells are incubated with the extracts and then examined after 48 hours. The grading scale is from 0 to 4, with 0 meaning cells are completely unaffected, and 4 meaning all cells are destroyed. For the test to be valid, the HDPE extract must have a grade of 0, and the PVC extract must have a grade of 3 or 4. The O-ring material meets the requirements if the biological response is less than or equal to grade 2. Materials that pass the requirements of USP <87> or ISO 10993-5 are generally considered non-toxic to cells.
Parker offers several O-ring compounds that have been tested for cytotoxicity.
|USP <87> Approved||ISO 10993-5 Approval|
|Ethylene Propylene (EPDM)||Ethylene Propylene (EPDM)|
This article was contributed by David Mahlbacher, applications engineer, Parker O-Ring Division