Research On The Quality Risk Maanagement In Production Of Freeze-dried Powder For Injection

International Conference on Harmonization released the guidance of Q9 Quality Risk Management in 2005.The guidance provides principles and examples of tools of quality risk management that can be applied to all aspects of pharmaceutical quality and provides scientific basis for pharmaceutical enterprises.In 2011,the concept of quality risk management was introduced to the new Good Manufacturing Practice for the first time in China.The new GMP requires that all pharmaceutical enterprises apply risk analysis to the all aspects of pharmaceutical quality using scientific knowledge and rich experience.In recent years,foreign regulatory institutions require that using quality risk management in pharmaceutical manufacturing for improving medicines quality and many overseas pharmaceutical enterprises have obtained the success,so Chinese pharmaceutical industry also has realized that it is important to carry out quality risk management.Freeze-dried powder is a kind of sterile powder for injection,and it is not terminally sterilized products,so it is a sort of high-risk drug in the pharmaceutical industry.Comparing with final sterilization,there are many variations in non-final sterilization.Microorganism control,prevention of endotoxin contamination and particulate contamination are complex in technology,so process control is particularly important.Therefore,introducing a risk-based approach to control risk in the production process of freeze-dried powder and ensuring the quality of products are imperative.Firstly,bibliometrics analysis is used for analyzing literatures on risk management of pharmaceutical production and explaining current research situation of domestic pharmaceutical industry through the trend of quantity of literatures and the content of research.Secondly,the thesis summarizes the idea which is the new exploration of FDA in quality risk management of pharmaceutical production and analyzes the quality metrics which are published in Request for Quality Metrics Guidance for Industry and other quality metrics are put forward.Moreover,the thesis summarizes the tools of quality risk management which are used in pharmaceutical manufacturing and comparing their applications,advantages,disadvantages and so on.And then chooses the risk management tool that is used in the production of freeze-dried powder for injection.On this basis,the assessment program is established which is based on literatures and foreign advanced standards,including the process,scoring,calculation of RPN and so on.Then using FMECA to assess risks of the production process of freeze-dried powder,which includes flows of people and goods,preparation before production and site-clearing after production,rubber stopper cleaning and sterilization,bottle washing and drying and so on.At last,risk assessors are endowed with weights by considering position,education background,working years and familiarity.So the weight coefficient was introduced to the FMECA which can correct deviation of risk assessment and optimize the program of quality risk management.