FMEA法在冻干粉针剂生产过程中的风险管控

发布时间：2018-04-16 15:24

本文选题：风险管理 + 冻干粉针剂　；参考：《延边大学》2017年硕士论文

【摘要】：风险管理是以预防及控制风险因素为目的的科学方法,已经在诸多领域得到了有效应用。全球各个国家正在结合自身情况,致力于不断探索药品管理中存在的规律,从而建立更为完善、更为有效的管理制度,以保障产品质量。实施药品风险管理,首先要对其有一定的认识;其次,要不断切合自身独特的实际情况,制定出更为合理的管理制度,使药品质量风险的影响得到最大限度地降低。首先,据国家食品药品监督管理总局的数据统计,按照1998年修订的药品GMP认证,认证范围有冻干粉针的企业共有1468户,而按照2010年修订的药品GMP认证中,认证范围内有冻干粉针的企业却有480户。说明随着新版GMP认证的实施,要求对冻干粉针的生产过程更为严格,企业不易达到标准,从而通过GMP认证。在这480户企业中吉林省通过新版GMP认证的企业只有7户,而延边州却仅仅只有一户。本文介绍了冻干粉针剂独有的特点。其作为新型剂型产品具有稳定性好,可长期保存;加入对应的溶剂后能够迅速溶解,恢复药物特性;容易实现无菌操作。然而,使用有问题的冻干粉针产品后,可能产生血栓等问题,直接影响人的生命健康。因此,为了避免产品中产生可见异物,就要将风险管理应用到冻干粉针剂生产过程中,降低生产过程中失效模式的风险水平至可接受水平,从而生产出安全有效、稳定均一的产品。所以应用质量风险管理的科学方法和技术来预防、控制、降低或消除风险,已成为冻干粉针剂生产企业面临的重要难题。其次,本文详细介绍了与风险管理有关的理论。从风险管理的流程出发,从风险评估到风险控制,再到风险交流进行了概述。在风险管理工具中,失败模式与影响分析(FMEA)法通过计算风险优先系数能够得到定性或定量的分析,更为直观地看到风险水平的变化,因此本论文使用FMEA工具进行风险管理。最后,本文将FMEA法具体应用于A公司X冻干粉针剂的生产过程中,分析了冻干粉针剂生产过程中注射用水系统、空调系统、人流与物流、西林瓶的清洗与灭菌、胶塞与铝盖的处理、药液的配制、灌装、冻干、轧盖、贴签包装等环节的潜在失效模式,在原有控制措施下进行风险评估,对不能接受的风险点使用改进措施进行控制。并使用FMEA法对冻干粉针剂生产中注射用水系统、空调系统、生产过程中人物流、配制、洗瓶、胶塞清洗、灌装、冻干、灯检、包装等环节存在的高风险水平的风险点进行风险控制执行后的风险再评估。RPN数据表明,这些改进措施有效降低了风险水平至可接受水平,从而达到保障产品质量的目的。冻干粉针剂属于非最终灭菌的无菌制剂,必须对可能污染药品的尘埃粒子、微生物及细菌内毒素等风险采取有效的控制措施,最大限度地降低产品的污染风险,确保所生产的药品符合预定用途。
[Abstract]:Risk management is a scientific method aimed at preventing and controlling risk factors and has been effectively applied in many fields.Every country in the world is devoting itself to explore the law of drug management, so as to establish a more perfect and effective management system to ensure the quality of products.To implement drug risk management, we should first have a certain understanding of it; secondly, we should constantly adapt to our own unique actual situation and formulate a more reasonable management system to minimize the impact of drug quality risk.First, according to the statistics of the State Administration of Food and Drug Administration, according to the drug GMP certification revised in 1998, there are 1468 enterprises with lyophilized powder needles, and according to the revised drug GMP certification in 2010,Within the scope of certification there are freeze-dried powder needle enterprises have 480 households.It is shown that with the implementation of the new version of GMP certification, the production process of freeze-dried powder needle is more strict, and the enterprise is not easy to reach the standard, thus passing the GMP certification.Of the 480 enterprises, only 7 were certified by the new GMP in Jilin Province, while only one in Yanbian.This paper introduces the unique characteristics of lyophilized powder injection.As a new dosage form, it has good stability, can be preserved for a long time, can dissolve quickly after adding corresponding solvent, and can recover the characteristics of medicine, and it is easy to realize aseptic operation.However, the use of problematic lyophilized powder needle products may lead to problems such as thrombosis, which directly affect human life and health.Therefore, in order to avoid visible foreign bodies in the product, risk management should be applied to the production process of lyophilized powder injection, and the risk level of failure mode in the production process should be reduced to an acceptable level, so that the production is safe and effective.Stable and uniform products.Therefore, the application of scientific methods and techniques of quality risk management to prevent, control, reduce or eliminate risks has become an important problem faced by enterprises producing lyophilized powder injections.Secondly, this paper introduces the theory of risk management in detail.From the process of risk management, from risk assessment to risk control, and then to risk exchange are summarized.In the risk management tool, the failure mode and impact analysis (FMEA) method can get qualitative or quantitative analysis by calculating the risk priority coefficient, and can see the change of risk level more intuitively. Therefore, this paper uses FMEA tool to manage risk.Finally, this paper applies FMEA method to the production process of X lyophilized powder injection in company A, and analyzes the injection water system, air conditioning system, people flow and logistics, cleaning and sterilizing of Xilin bottle in the production process of freeze-dried powder injection.The potential failure modes of rubber plug and aluminum cap, preparation, filling, freeze-drying, rolling cover, labeling and packaging are evaluated under the original control measures, and the improvement measures are used to control the unacceptable risk points.The injection water system, air conditioning system, human logistics, preparation, flask washing, rubber plug cleaning, filling, freeze-drying, lamp checking in the production of lyophilized powder injection were carried out by FMEA method.The data of risk reassessment after the implementation of risk control in packaging and other links show that these improved measures can effectively reduce the risk level to acceptable level and thus achieve the purpose of ensuring product quality.The lyophilized powder injection is a non-final sterilizing sterile preparation. It is necessary to take effective measures to control the risks of dust particles, microorganisms and bacterial endotoxin that may contaminate the drug, so as to minimize the risk of contamination of the product.To ensure that the drugs produced are in accordance with the intended use.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R95

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