清热解毒口服液GMP验证的研究
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摘要
2010年修订版《药品生产质量管理规范》发布以后,我们根据新版GMP进行自检,针对自检结果对清热解毒口服液生产线的配套系统、关键设备、人员培训和生产工艺进行相应升级改造和再验证,主要研究内容包括:
对空调净化系统进行自检,分析存在问题并提出检修和改造方案,最后从系统安装、运行和性能三方面对改造后的系统进行验证,证明改造后系统能更好的运行、操作和维护,保证洁净区的空气环境符合GMP要求。
对纯化水系统进行自检,针对出水管路乱、盲点多等缺陷提出管路改造方案,最后从系统安装、运行和性能三方面对改造后系统进行验证。验证表明,改造后的系统更适合纯化水生产、系统操作和维护保养,确认对整个循环系统未造成污染,各使用点的出水水质符合要求、供水正常。
经过自检,对存在问题的关键设备进行改造、人员培训和再验证,包括对口服液压滤系统滤材的筛选与验证,口服液配液罐增加容量后的验证,筛选、优化内包装后口服液灌轧机的验证,压力蒸汽灭菌器的维修后验证和对操作人员培训等活动。验证结果表明我公司关键设备经改造、优化后满足工艺规范要求,有利于保证药品质量、降低成本和提高生产效率。
在相关设备设施改造后对清热解毒口服液生产工艺进行优化和验证,通过对该产品各个工序、各个关键控制点的实验跟踪,结果表明利用升级改造后的设备和系统,按照优化后的生产工艺生产的口服液符合预定标准,且质量更稳定。
Accoring to the newest edition G MP revised in 2010, we have self-inspected, upgraded and revalidated the related system s, critical equipments, personnel training and process use for Qingrejiedu Oral Li quid production. The m ain study work are shown as following:
Studied on the potential pr oblem of air purifying system , and presented the optimized plan s econdly, and th en re validated the upgraded system including Installation Qualification, Operational Qualification and Perf ormance Qualification. Accroding to the revalidation, the upgraded system is m ore suitable for running, operation and maintanence, the purfied air in clean space can satisfy the requirement of GMP.
Self-inspected the water purifying system and analysed the problem such as blind area and orderless exsiting in the old system, and the optimized plan have been presented secondly, and then revalidated the upgraded system including Installation Qualification, Operational Qualification and P erformance Qualification. Accroding to the revalidation, the upgrad ed system is more suitable for running, operation and maintanence, satified the requirem ents for production, to evey process continuously and stably. According to the problem found during self-inspection for the critical equipment, Upgraded the Filtrating Material, Mixing Po t, Bottle Filling & Sealing Instrum ent, Pressurized S teamy S terilization Instrum ent, m eanwhile training the personnel to suitable for their work, lastly , revalidated all the upgraded equipm ent. Accroding to the revalidation, all the upgraded equipm ent is m ore econom ical, ef ficient and controllable for Oral Liquid producing while satified the requirement of GMP better.
Revalidation for the process of Heat Qingrejiedu Oral Liqu id production have been performed according to the up graded equipment and related system, the work scope, m ethod and flow for revalidation ha ve presented here. According to the revalidation, producing the Oral Liquid according to th e optim ized process b y upgraded equipment is more stable for control the quality of production.
According to the study, the optimized process and upgraded equipm ent is more controllable, economical and efficient for Oral Liquid production.
对空调净化系统进行自检,分析存在问题并提出检修和改造方案,最后从系统安装、运行和性能三方面对改造后的系统进行验证,证明改造后系统能更好的运行、操作和维护,保证洁净区的空气环境符合GMP要求。
对纯化水系统进行自检,针对出水管路乱、盲点多等缺陷提出管路改造方案,最后从系统安装、运行和性能三方面对改造后系统进行验证。验证表明,改造后的系统更适合纯化水生产、系统操作和维护保养,确认对整个循环系统未造成污染,各使用点的出水水质符合要求、供水正常。
经过自检,对存在问题的关键设备进行改造、人员培训和再验证,包括对口服液压滤系统滤材的筛选与验证,口服液配液罐增加容量后的验证,筛选、优化内包装后口服液灌轧机的验证,压力蒸汽灭菌器的维修后验证和对操作人员培训等活动。验证结果表明我公司关键设备经改造、优化后满足工艺规范要求,有利于保证药品质量、降低成本和提高生产效率。
在相关设备设施改造后对清热解毒口服液生产工艺进行优化和验证,通过对该产品各个工序、各个关键控制点的实验跟踪,结果表明利用升级改造后的设备和系统,按照优化后的生产工艺生产的口服液符合预定标准,且质量更稳定。
Accoring to the newest edition G MP revised in 2010, we have self-inspected, upgraded and revalidated the related system s, critical equipments, personnel training and process use for Qingrejiedu Oral Li quid production. The m ain study work are shown as following:
Studied on the potential pr oblem of air purifying system , and presented the optimized plan s econdly, and th en re validated the upgraded system including Installation Qualification, Operational Qualification and Perf ormance Qualification. Accroding to the revalidation, the upgraded system is m ore suitable for running, operation and maintanence, the purfied air in clean space can satisfy the requirement of GMP.
Self-inspected the water purifying system and analysed the problem such as blind area and orderless exsiting in the old system, and the optimized plan have been presented secondly, and then revalidated the upgraded system including Installation Qualification, Operational Qualification and P erformance Qualification. Accroding to the revalidation, the upgrad ed system is more suitable for running, operation and maintanence, satified the requirem ents for production, to evey process continuously and stably. According to the problem found during self-inspection for the critical equipment, Upgraded the Filtrating Material, Mixing Po t, Bottle Filling & Sealing Instrum ent, Pressurized S teamy S terilization Instrum ent, m eanwhile training the personnel to suitable for their work, lastly , revalidated all the upgraded equipm ent. Accroding to the revalidation, all the upgraded equipm ent is m ore econom ical, ef ficient and controllable for Oral Liquid producing while satified the requirement of GMP better.
Revalidation for the process of Heat Qingrejiedu Oral Liqu id production have been performed according to the up graded equipment and related system, the work scope, m ethod and flow for revalidation ha ve presented here. According to the revalidation, producing the Oral Liquid according to th e optim ized process b y upgraded equipment is more stable for control the quality of production.
According to the study, the optimized process and upgraded equipm ent is more controllable, economical and efficient for Oral Liquid production.
引文
[1]李观欢,筑质量大堤迎世纪挑战,中国质量,1999, 2:7-7
[2]白慧良,李武臣,药品生产验证指南,北京:现代生物技术与医药科技出版中心,2003, 1:15-18
[3]任瑞莉,药品GMP发展史及实施GMP的工作程序,科技情报开发与经济, 2003, 4:2-2
[4] Human and veterinary drugs, Good Ma nufacturing Practices and proposed exemptions for certion OTC products, Fed.R eg.43, Part II, No.190, 29 th Sep.1978, pp45013-45089.
[5] Proposed rules, Current Good Manufact uring Practice in m anufacturing, packing, or holding, human and verterinary drugs, Fed.Reg.42, Part II, No.31, 13th Feb. 1976, pp6878-6894.
[6] Byers, Drug product quality as view ed by the Food and Drug Ainistration. Presented at the Co nference o n Quality Program s and Governm ent Regulations, Arlington,Va., 13th Apr. 1976, pp509-512.
[7] Proposed rules, hum an drugs, Current Good Manufacturing Practices in manufacture, processing, packing, or holding of Large Volume Parenterals and request for comm ents regarding Sm all V olume Parenterals, Fed.Reg.41, No.100, 1st June 1976, pp22202-22219.
[8] Chapman, K.G., The P AR approach to process validation, Pharm . Technol. 1984, 8(1), pp22-36
[9] Shepherd,R.E., FDA inspections of Large V olume and Sm all V olume Parenterals manufacturers. Presented to the M eeting of the Parenteral Drug Association, Chicago, 25th June 1976, Bull. P arenter. Drug Assoc, 30(5), pp209-213.
[10]陈晓莉,药品生产工艺验证的研究,中国药事,2008, 12: 1122-1125
[11] 4th European Seminar of Quality Control in the Pharmaceutical and Cosmetic Industries, University of Geneva, Switerland, 25th -26th Sep. 1980:pp72
[12]曲维凤,制药企业GMP认证后员工的设备管理技能培训,中国药业,2007,6:24-24
[13]丁恩峰,高海燕,FDA最新工艺验证指南深度解析,医药工程设计, 2010,4:21-29
[14] Lockyer,K. and Oakland,J., The quest for quality ,2; How to sa mple success. Management Today,July, 1981:pp.75-77
[15]邓海根,制药企业GM P管理实用指南,北京:中国计量出版社,2000, 138-140
[16] Frederick J ,Carleton.validation of aseptic pharm aceutical processes [Z] ,1998:pp186
[17]邱怡,关立霞,王芳等,药品生产验证及实施,中国临床医药研究杂志,2004, 118: 126
[18]李玉兰,浅谈国际药品验证管理,中国药业,2004,13(7): 19-20
[19]姜成楠,吴昊,空气洁净技术应用研究,沈阳大学学报,2001,13(2):80-83
[20]许仲麟,药厂洁净室设计运行与GMP认证,上海:同济大学出版社,2011, 105-108
[21]张隽峰,王随林,刘强等,制药厂洁净区空调设计中几个问题的探讨,中国建设信息,2003,(F10): 70-73
[22]药品生产质量管理规范(2010年修订),北京:国家药品监督管理局,2010:105-106
[23]苏霖,制药设备与药品生产GMP规范,中国期刊方阵,2006(S1):426-429
[24]丁启圣,新型实用过滤技术,中国矿山工程,2005,34(1):11
[25]贺立中,美国药典24版中有关制药用水质量及检测方法的新规定,国外医药,2002(6):234-238
[26]姚宇,王多平,纯化水系统验证,医药工程设计,2001(6):24-27
[27]孙海岚,部冰,制药用水系统的设计及应用,科技创新导报, 2008 (02):98-99
[28]闻瑞梅,王在忠,高纯水的制备及检测技术,北京:科学出版社,1999:300-305
[29]国家药典委员会,中华人民共和国药典2010版二部,北京,中国医药科学出版社,2010:411-412
[30]张启阳,制药用水的生产和输送系统设计,科技资讯, 2009 (2):212-212
[31]袁松范,制药设备与GMP,上海医药情报研究,2003(4):128-130
[32]曹元,梁毅,浅析制药设备验证中的设计确认,医药工程设计, 20 09, (2):213-215
[33]王志敏,陈建国,陈远华,湿热灭菌柜的选用,医药工程设计,2003,8:3-5
[34]于瑞英,张文俊,文爱清,压力蒸汽灭菌柜重点阶段监测意义的探讨,中华医院感染学杂志, 2001, 3: 8
[35]黄福南,张美兰,灭菌柜的热分布测定和结构改进,中国医药工业杂志,1989, 5: 15
[36]李慧,杨忠华,药品生产工艺验证的应用思考,才智,2011, 22:51
[37]张元庆,浅谈药品生产工艺验证特点,中国中医药咨讯,2011,19:68
[38]游丹,陈瑜娜,企业GMP管理中人员培训的重要性,云南科技管理, 2006 (3):37-38
[2]白慧良,李武臣,药品生产验证指南,北京:现代生物技术与医药科技出版中心,2003, 1:15-18
[3]任瑞莉,药品GMP发展史及实施GMP的工作程序,科技情报开发与经济, 2003, 4:2-2
[4] Human and veterinary drugs, Good Ma nufacturing Practices and proposed exemptions for certion OTC products, Fed.R eg.43, Part II, No.190, 29 th Sep.1978, pp45013-45089.
[5] Proposed rules, Current Good Manufact uring Practice in m anufacturing, packing, or holding, human and verterinary drugs, Fed.Reg.42, Part II, No.31, 13th Feb. 1976, pp6878-6894.
[6] Byers, Drug product quality as view ed by the Food and Drug Ainistration. Presented at the Co nference o n Quality Program s and Governm ent Regulations, Arlington,Va., 13th Apr. 1976, pp509-512.
[7] Proposed rules, hum an drugs, Current Good Manufacturing Practices in manufacture, processing, packing, or holding of Large Volume Parenterals and request for comm ents regarding Sm all V olume Parenterals, Fed.Reg.41, No.100, 1st June 1976, pp22202-22219.
[8] Chapman, K.G., The P AR approach to process validation, Pharm . Technol. 1984, 8(1), pp22-36
[9] Shepherd,R.E., FDA inspections of Large V olume and Sm all V olume Parenterals manufacturers. Presented to the M eeting of the Parenteral Drug Association, Chicago, 25th June 1976, Bull. P arenter. Drug Assoc, 30(5), pp209-213.
[10]陈晓莉,药品生产工艺验证的研究,中国药事,2008, 12: 1122-1125
[11] 4th European Seminar of Quality Control in the Pharmaceutical and Cosmetic Industries, University of Geneva, Switerland, 25th -26th Sep. 1980:pp72
[12]曲维凤,制药企业GMP认证后员工的设备管理技能培训,中国药业,2007,6:24-24
[13]丁恩峰,高海燕,FDA最新工艺验证指南深度解析,医药工程设计, 2010,4:21-29
[14] Lockyer,K. and Oakland,J., The quest for quality ,2; How to sa mple success. Management Today,July, 1981:pp.75-77
[15]邓海根,制药企业GM P管理实用指南,北京:中国计量出版社,2000, 138-140
[16] Frederick J ,Carleton.validation of aseptic pharm aceutical processes [Z] ,1998:pp186
[17]邱怡,关立霞,王芳等,药品生产验证及实施,中国临床医药研究杂志,2004, 118: 126
[18]李玉兰,浅谈国际药品验证管理,中国药业,2004,13(7): 19-20
[19]姜成楠,吴昊,空气洁净技术应用研究,沈阳大学学报,2001,13(2):80-83
[20]许仲麟,药厂洁净室设计运行与GMP认证,上海:同济大学出版社,2011, 105-108
[21]张隽峰,王随林,刘强等,制药厂洁净区空调设计中几个问题的探讨,中国建设信息,2003,(F10): 70-73
[22]药品生产质量管理规范(2010年修订),北京:国家药品监督管理局,2010:105-106
[23]苏霖,制药设备与药品生产GMP规范,中国期刊方阵,2006(S1):426-429
[24]丁启圣,新型实用过滤技术,中国矿山工程,2005,34(1):11
[25]贺立中,美国药典24版中有关制药用水质量及检测方法的新规定,国外医药,2002(6):234-238
[26]姚宇,王多平,纯化水系统验证,医药工程设计,2001(6):24-27
[27]孙海岚,部冰,制药用水系统的设计及应用,科技创新导报, 2008 (02):98-99
[28]闻瑞梅,王在忠,高纯水的制备及检测技术,北京:科学出版社,1999:300-305
[29]国家药典委员会,中华人民共和国药典2010版二部,北京,中国医药科学出版社,2010:411-412
[30]张启阳,制药用水的生产和输送系统设计,科技资讯, 2009 (2):212-212
[31]袁松范,制药设备与GMP,上海医药情报研究,2003(4):128-130
[32]曹元,梁毅,浅析制药设备验证中的设计确认,医药工程设计, 20 09, (2):213-215
[33]王志敏,陈建国,陈远华,湿热灭菌柜的选用,医药工程设计,2003,8:3-5
[34]于瑞英,张文俊,文爱清,压力蒸汽灭菌柜重点阶段监测意义的探讨,中华医院感染学杂志, 2001, 3: 8
[35]黄福南,张美兰,灭菌柜的热分布测定和结构改进,中国医药工业杂志,1989, 5: 15
[36]李慧,杨忠华,药品生产工艺验证的应用思考,才智,2011, 22:51
[37]张元庆,浅谈药品生产工艺验证特点,中国中医药咨讯,2011,19:68
[38]游丹,陈瑜娜,企业GMP管理中人员培训的重要性,云南科技管理, 2006 (3):37-38