Abstract
Nonsterile parenteral products cause harm to patients, resulting in serious public health issues and great financial damage to drug manufacturers. To avoid such consequences, a contamination program should be deployed to ensure product sterility, and this can include periodic bioburden quantification and sterility testing. The use of traditional growth-based microbiological methods alone described in the current compendial guidelines for bioburden and sterility testing have been argued as unsatisfactory to determine the absolute absence of microorganism. This review aimed to investigate the advantages and drawbacks of the current conventional and the rapid microbiological detection methods. An inclusive review of literature was conducted to describe the microbial contamination in the sterile manufacturing of pharmaceuticals. An overview on the challenges and limitations of the traditional growth-based methods for bioburden assessment and sterility testing was presented. The conventional growth-based bioburden and sterility testing methods are the current mainstay technology in sterile pharmaceutical manufacturing. However, the rapid microbiological detection methods provide highly sensitive systems capable of verifying the absence of microbial contaminants including those with negligible counts of microbes in a short period of time, which might outweigh those of growth-based methods. Adoption of the rapid microbiological detection methods should be reconsidered as a future challenge in improvement of the sterility assurance of pharmaceutical products. However, their application in the large-scale manufacturing of pharmaceutical products may remain lagging because of limitations such as high expenses, the expertise, cost of test validation and the regulatory restrictions.