In the pharmaceutical industry, it is commonly known that controlling water content is one of the most important quality control factor for lyophilized Powder Injections. The level of water content will directly influence the drug’s potency within its shelf life. Since the only source of water content from primary packages normally originates from rubber stoppers, controlling water content in rubber stoppers becomes critically important. Based on nearly 20 years of butyl rubber stopper R&D and manufacturing experiences, we have gained substantial knowledge on how to control water content in rubber stopper for lyophilized powder injections. In order to achieve low water content level, the first stop is to monitor and control water content during manufacturing process. For example, increasing the temperature and time of the drying process can lower the water content level to some extent. On the other hand, setting stringent limits on main raw materials can help achieve the desired water content level in rubber stoppers. It is important to set strict quality control point, such as water content level, for the raw material suppliers. Superior temperature and moisture control on warehouses and clean rooms is also essential. In summary, low water level content of lyo-stoppers requires various quality control measures and methods.