LABORATORY CONTROL SYSTEM  实验室控制体系December 2005 CGMP GENERAL REQUIREMENT 	 FOR LABORATORY CONTROLS  针对实验室控制，CGMP 总体要求21 CFR 211.160 (b) Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity.  实验室控制应该包括建立科学合理的规范，标准，取样方案，确保所有部件，药品容器，盖子，在制材料，标签和药品符合适当的特性，质量，纯度标准CGMP GENERAL REQUIREMENT 	 FOR LABORATORY CONTROLS 实验室控制CGMP 总要求21 CFR 211.160 (b) (1) Laboratory controls shall include 实验室控制应该包括Determination of conformance to appropriate written specifications for the acceptance of each lot within each shipment of components, drug product containers, closures, and labeling used in the manufacture, processing, packing, or holding of drug products …………….…. 适当的书面规范对于每一批在装运的部件验收，药品器，盖子，和在药品制造，加工，包装，存放的标签应该一致。CGMP GENERAL REQUIREMENT 	 FOR LABORATORY CONTROLS 实验室控制CGMP 总要求21 CFR 211.160 (b) (2)	 Laboratory controls shall include 实验室应该包括Determination of conformance to written specifications and a description of sampling and testing procedures for in-process materials. Such samples shall be representative and properly identified. 取样程序的书面描述和在制材料的测试程序应该一致。像这样的样件应该具有代表性和可辨性CGMP GENERAL REQUIREMENT 	 FOR LABORATORY CONTROLS 实验室控制CGMP 总要求21 CFR 211.160 (b) (3)	 Laboratory controls shall include 实验室控制应该包括Determination of conformance to written descriptions of sampling procedures and appropriate specifications for drug products. Such samples shall be representative and properly identified.  取样程序的书面描述和药品合适的规格应该一致。像这样的样件应该具有代表性和可辨性。LABORATORY CONTROLS (Q7A) 实验室控制11.1 General Controls 总控制……There should be documented procedures describing sampling, testing, approval, or rejection of materials and recording and storage of laboratory data…………应有文档程序能描述材料取样，测试，批准，报废，以及实验室数据的记录和存储…………All specifications, sampling plans, and test procedures should be scientifically sound and appropriate to ensure that raw materials, intermediates, APIs, and labels and packaging materials conform to established standards of quality and/or purity……. ……所有的规格，取样计划，和测试程序都应该科学合理地确保原材料，中间体，APIs, 标签和包装材料满足所建立的质量和纯度标准……CGMP GENERAL REQUIREMENT 	 FOR LABORATORY CONTROLS 实验室控制CGMP 总要求Establishment of Sampling plans Specifications Standards Test procedures 建立：取样计划规范标准测试程序Testing for Components In-process materials Drug products (DS & DP) Containers and closures Labeling 测试：部件在制材料药品容器和盖子标签CGMP REQUIREMENT FOR 		LABORATORY CONTROLS 实验室控制CGMP 要求How Do We Establish a Laboratory Control System to Meet CGMP Regulation? 我们应该怎样建立实验室的控制系统以此来满足CGMP 规则STANDRD OPERATION PROCEDUR (SOP)			 实验室标准操作程序Global SOPs 全球SOPs 	-	Instrument, Method validation, Reagents 仪器，方法验证，和试剂-	Laboratory notebook, Documentation, etc. 实验手册，文档等等Local SOPs 国内SOPs 	-	Testing procedure, Calibration, etc. 测试程序，校对等等LABORATORY CONTROL SYSTEM  实验室控制系统General Requirement 总要求The Laboratory facilities should be adequate and have adequate equipment for the facilitation of its function 实验设施应该齐全，并且有足够的设备用于其功能的设施The responsible heads of various functional groups should have the necessary education, training, and experience to perform their functions 各职能组的负责人应该具备必要的教育，培训和经验以完成他们的功能The Procedures for the proper cleaning, maintenance and storage of lab glassware/utensils should be in place 清洗，维护，和实验室的器皿/烧瓶的存放的程序应该到位LABORATORY CONTROL SYSTEM  实验室控制系统General Requirement 总要求Laboratory reagents and other chemical supplies should be identified and given expiration dates (and/or marked with date of a bottle is opened)  实验室仪器其它化学物品应该查对和给定截止日期（或标明瓶子打开的日期）USP reference standard should be used if it is available. Otherwise, in-house primary standard should be established  如有可能，USP 参考标准应该采用。否则，过程质量原始标准应该建立。The instrument shall be properly calibrated and maintained  仪器应该恰当的校对和维护RECORD RETENTION 实验室档案的保存All records (batch, electronic chromatographic data for HPLC analysis of drug components and finished products) should be backed up and maintained for at least one year after the expiration date  所有档案（批次，药品成分高性能液体色普电子色析数据和产成品）在截止日期过后，应该至少保存一年。A system should be in place to manage raw data and laboratory notebooks  一系统应该有可能处理原始数据和实验笔记Daily use logbook should be kept for every instrument in laboratory  实验室里的每一仪器应该放着日常使用的日志。LABORATORY INSTRUMENTS 实验室仪器21 CFR 211.160 (b) (4)	 The calibration of instruments, apparatus, gauges, and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and previsions for remedial action in the event accuracy and/or precision limits are not met. Instruments, apparatus, gauges, and recording devices not meeting established specifications shall not be used 仪器，装置，检具，记录装置的校准，应该以合适的间隔与包含具体方向，进程，精确程度和为补救措施而做的准备的已有的书面计划一致，假如没有达到精确或准确程度。不满足已有规格的仪器，装置，检具，和记录装置不应该使用。LABORATORY INSTRUMENTS		 实验室仪器General 总概The laboratory instruments should be properly maintained and documented, and calibrated according to the written procedure(s)  实验室的仪器应该如实维护和归档，并且按照书面程序进行校对Use Logbook for instrument shall use hard bound book and be properly recorded and maintained  仪器上使用的日志要求使用硬面薄，并且做好记录和维护好CALIBRATION OF INSTRUMENTS		 实验室仪器校验Written Program (or SOP) 书面计划（或SOP ）- Specific directions 具体方向- Suitable intervals (schedule) 合适间隔（进程）- Parameters to be calibrated 校对参数- Acceptance criteria (limits) 验收标准（限度）- Previsions for remedial action 补救措施的准备Calibration Summary or Report 校准总结和报告VALIDATION  验证Overall policy should include validation process, cleaning procedures, analytical methods, in-process 	control test procedures, computerized system, and persons responsible for design, review, approval 总的政策应该包括验证程序，清洗程序，分析方法，在制控制测试程序，电算化系统和设计，评审，批准负责人All test methods used in a laboratory should be validated and documented before in use 所有的在实验室里使用的测试方法应该在使用之前就该被验证和归档USP test methods should be verified as suitable for actual use in testing of the product USP 测试方法应该被证实是有效的，实际在使用上适合于产品测试。VALIDATION  验证Computer systems for control of process, data collection, etc. should be validated and documented 电脑系统中的程序控制，数据收集等等，应该有效和归档All components, manufacturing materials, in-process materials, packaging material, and labeling should be inspected and tested according to written procedure(s) prior to release 所有的部件，制造材料，在制材料，包装材料和标签，在发布之前应该按照书面程序检验和测试STABILITY 稳定性试验Stability protocol and appropriate storage conditions for stability program should be established  针对稳定性计划，稳定性原型和合适的贮存条件应该建立Temperature and humidity of stability chamber should be validated and calibrated at regular intervals. Continuing chart recorder should be used to monitor temperature and humidity 具有稳定性的房间里的温度和湿度应该不间断的验证和校对Stability program should include meaningful and specific test methods (stability indicating methods) 稳定性计划应该包括有意义和具体的测试方法（稳定指数方法）STABILITY  稳定性实验Reserve samples should be properly retained. 	First three commercial batches should be placed on stability study and one batch per year thereafter (if produced) 存储的样件应该放好。前三次的商业批次应该进行稳定性研究，以后每年进行一批次（如果生产）Appropriate retest date should be established for APIs and shelf life for finished dosage forms 针对APIs 和完成了的剂量表格的贮存寿命，适量的重测试应该建立SUMMARY 总结A proper SOP system should be in place 正确的SOP 系统应该建立Records and documents should be properly maintained 记录和文件应该维护好Instrument should be properly maintained and calibrated 仪器应该如期地维护和校准Methods should be validated or verified 方法应该验证和证实Stability should be conducted to support retest or expiration date for products 稳定性应该能延续到能支持产品再测试和截止日期随时欢迎客户的任何新的和更深入的探讨* API 品种推荐/ANDA 申报和CGMP 认证支持/药品出口贸易渠道整合* * * * 谢谢！