Increasing the probability of sterility of medicinal products

Abstract

Abstract Calculations show that official tests for sterility offer unacceptably low degrees of assurance of sterility. Some batches of heat treated articles with 10% contamination can pass the E.P. test on about 92% of occasions. It is proposed that viable counts be made on products immediately before the terminal inactivation procedure and that upper limits be set for the level of contamination. Samples of the product should be inoculated with spores of known resistance characteristics and also with samples of swabs from the production area. Such inoculated products should then be tested for absence of viable organisms, after being subjected to the terminal inactivation procedure. This test should be coupled with close environmental and process control and personnel education. It is recommended that these procedures replace the conventional test for sterility. The use of spores as direct and independent indicators of sterility, especially where the lethal conditions cannot be monitored instrumentally is recommended. A flexible approach is proposed for the use of the ‘lethality factor’ suitable for a terminal heat inactivation procedure; this would depend on the nature of the product and the standard of monitoring facilities and personnel. A change in the language is proposed. A medicinal product processed such that an acceptable probability of sterility exists, should be designated not as sterile but as safe.