When an isolator for the aseptic process controlled under a positive pressure is used for high potency drugs, both of the robust containment system and the operation procedure are required to setle aseptic and safety issues. In this article, a visualization system for fine particles is proposed as a useful tool to evaluate the leakage from the containment system such as an isolator. Application of this visualization system will allow the behavior of particles scattering to be so clearly detected as to lead to easier fixing of the monitoring point for leaked particles. The test results has shown that this newly developed method has exactly been proved to be effective for resolving the challenging leakage issue by using such a reasonable and systematic risk management tool.
A thousand different excipients can be used when formulating pharmaceuticals and, as a rough estimate, excipients can comprise more than 90% of a medicinal product's weight. Excipients are no longer characterized as simple inert additives to the API, and the need for stringent, quality management of excipients has grown rapidly. In 2010, FDA noted five drug recalls due to dissolution failures ascribed to excipients. In one case, FDA issued an import alert and an advisory to drug and dietary supplement manufacturers warning of high levels of peroxide in the excipient crospovidone manufactured in China. In the warning, FDA explained that drug manufacturers who used excipients containing high levels of peroxides would observe a loss of drug potency and the formation of excessive impurities during the product's shelf life. This article discusses how the supplier of pharmaceutical raw materials should take a central role in ensuring excipient quality.
A jointly sponsored USP/ISPE survey of the pharmaceutical industry is presented and analyzed on the topic of the potential to use alternative methods of production (other than distillation) as the final purification process in the preparation of Water for Injection (WFI). The survey was prepared by USP Expert Committee members. It was reviewed, supported, and administered by the ISPE Critical Utilities Community of Practice (CU COP) leadership to the CU COP, and the results were collected and analyzed. The purpose of the survey was not only to acquire data related to the design, maintenance, and reliability of alternative non-distillation approaches for making WFI-quality water, but also to collect viable data from engineering end users so that the discussion could be removed from private unpublished anecdotes and brought to light-for better or worse-for eventual public dialogue among the industry, compendia, and regulatory groups. Typically, past discussions centered about the topic of “distillation vs Reverse Osmosis (RO) and/or UltraFiltration (UF)” as the final step and arbiter of microbiological and endotoxin control in WFI production. The current survey asked a series of different questions. Instead of focusing on the final purification step, the entire water system design, its operation and control strategies, and testing data was studied. Of the non-distillation systems that met all of the testing attributes of WFI, though validated as another type of water system, the analysis of the results shows a fascinating variability in the number and types of purification system designs, distribution designs, and sanitization strategies. The analysis also demonstrates that the goals of the survey were met, which were: 1. to expand the discussion to consider the entire water system and 2. achieve a meaningful dialogue based on data of real water systems.