High Volume Water Bath Sterilizer Quality Risk Control

Large volume injection can be absorbed quickly and exert effect rapidly by intravenous injection directly or carrying drugs into the blood in clinical use, which have generally been accepted by patients. It can also be used for emergency treatment of critically-ill patients who are unconscious. However, it would cause great harm to the health of patients if it existed quality problems with entering into the blood directly, especially when the test items like sterile, pyrogen or bacterial endotoxin are unqualified. So the sterilization process of injection is the core of the production process.The sterilization process of large volume injection is mainly carried out by moist heat sterilization whose sterilization medium is steam or water. Due to the existence of non-condensable gas and temperature blind corner, the steam sterilization is gradually eliminated. The appendix on sterilization in the GMP 2010 is clearly defined that the circulating steam method is not the final sterilization. Hot water was used as the medium for sterilization instead of steam, which well overcome the shortcomings of steam sterilization. For uniform heating and accurate temperature control, it is being widely used. Water bath sterilizer is the key production equipment in the production process of large volume injection to ensure the quality of products. Hence the water bath sterilizer plays a very important role in the final sterilization technology of products.As the world’s largest population, China has a large demand for large volume injection. With the continuous development of the national medical system reform, large volume injection enterprises expand the batch production to increase the output and reduce production costs. With the infusion volume increased, the volume requirements for sterilizer has gradually become larger. At present, the maximum volume of sterilizer has been more than 100 m3.The Chinese Food and Drug Administration (CFDA) has realized the risks of products quality caused by the increase of sterilizer volume since the second half of 2011 and clearly defined the sterilizer volume over 40 m3 as high volume water bath sterilizer. The CFDA requires all provinces, cities and bureau pay close attention to the risk control of high volume water bath sterilizers, and commission the Chinese medical equipment Engineering Association to organize experts and business representatives to conduct research on high volume water bath sterilizers. They draft water bath sterilizer selection (basic or general technical requirements) which was released on July 19,2012. After the official release, the responses were good. The inspection center of CFDA guided and approved the requirements in 2013, and released it on its website.Firstly, this paper introduces the origin of quality risk management, the classification of the common tools of quality risk management, and the application of quality risk management tools and management work in our company.Secondly, the cause and effect diagram (fishbone diagram) was used to identify product quality risks of high volume water bath sterilizer from the aspects of man, machine, material, method, environment and measurement, etc. Then failure mode and effect analysis (FMEA) was used to evaluate and score for the risks in the three aspects of seriousness, possibility and findability. The score greater than 28 or the score of seriousness equal to 5 points is identified as high risk; the score 11-27 is identified as medium risk; the score less than or equal to 10 is identified as the low risk. Subsequently, we take mesures to reduce high and medium risks and evaluate and score again until the risk has been reduced to the acceptable levels.Finally, the performance of large volume water bath sterilizer was confirmed after risk reduction. After the analysis of the test like the no-loading heat distribution, the full loading heat distribution, the full load heat penetration, and the biological indicator test, large volume water bath sterilizers were put to use. Then as the representatives, the glucose injection and hydrochloride levofloxacin sodium chloride injection were chosen, and the indicators of quality were summarized. Subsequently, the trend was analyzed by using Hart control charts and other statistical tools.Conclusion:All measures of risk reducing were effective; the high and medium risks were reduced to acceptable level; the data were eligible to confirm the performance of sterilizers; the quality indexs of glucose injection and hydrochloride levofloxacin sodium chloride injection were in the acceptable range and reach the expectations.