Endotoxin test of rubber stoppers

Do we need to do endotoxin test for Ready for Sterilization rubber stoppers. Pl. post me any reference related to that.

I could be wrong but I suspect the test executed post sterilisation, pre - use would be more useful.

Containers and closures should be rendered sterile and, for parenteral pharmaceutical drug products, nonpyrogenic. The process used will depend primarily on the nature of the container and/or closure materials. The validation study for such a process should be adequate to demonstrate its ability to render materials sterile and non-pyrogenic. Written procedures should specify the frequency of revalidation of these processes as well as time limits for holding sterile, depyrogenated containers and closures.

Rubber closures (e.g., stoppers and syringe plungers) can be cleaned by multiple cycles of washing and rinsing prior to final steam or irradiation sterilization. At minimum, the initial rinses for the washing process should employ at least Purified Water, USP, of minimal endotoxin content, followed by final rinse(s) with WFI for parenteral products.

Normally, depyrogenation can be achieved by multiple rinses of hot WFI. The time between washing, drying (where appropriate), and sterilizing should be minimized because residual moisture on the stoppers can support microbial growth and the generation of endotoxins. Because rubber is a poor conductor of heat, extra attention is indicated in the validation of processes that use heat with respect to its penetration into the rubber stopper load . Validation data from the washing procedure should demonstrate successful endotoxin removal from rubber materials.

A potential source of contamination is the siliconization of rubber stoppers. Silicone used in the preparation of rubber stoppers should meet appropriate quality control criteria and not have an adverse effect on the safety, quality, or purity of the drug product.

Contract facilities that perform sterilization and/or depyrogenation of containers and closures are subject to the same CGMP requirements as those established for in-house processing. The finished dosage form manufacturer should review and assess the contractor’s validation protocol and final validation report. In accord with 211.84(d)(3), a manufacturer who establishes the reliability of the supplier’s test results at appropriate intervals may accept containers or closures based on visual identification and Certificate of Analysis review.

Where ever Endotoxin tests are required at critical control points during the processing , such tests must be recorded to prove that materials are Endotoxin free.

1 Like