诊断试剂加速稳定性试验方案Attachment-VII-Test-Protocol-for-Accelerated-Stability-Test20160202[1]
体外诊断试剂运输稳定性研究方案
体外诊断试剂运输稳定性研究方案体外诊断试剂是一种用于检测人体样本中生化指标、疾病标志物等的试剂，其质量和稳定性对于检测结果的准确性至关重要。
而试剂在运输过程中受到温度、湿度、震动等不利环境因素的影响，可能导致试剂的降解和失效。
因此，需要进行体外诊断试剂运输稳定性的研究，以保证试剂在运输过程中的稳定性和可靠性。
本研究旨在评估体外诊断试剂在运输过程中的稳定性，具体方案如下：1.样品选择从市场上随机选取一批体外诊断试剂，包括不同制造商和不同类型的试剂。
确保选取的试剂能够涵盖常见的体外诊断试剂。
2.环境条件设置模拟实际运输环境，设置不同的温度、湿度和震动条件。
可以参考国内外相关标准和规范，确定合适的环境参数。
例如，可设置不同温度（常温、低温、高温）、湿度（相对湿度20%-80%）、震动（低频、中频、高频）条件。
3.运输箱选择选择合适的运输箱，确保能够满足运输过程中的要求。
运输箱的选取应考虑到绝缘性、隔热性、防潮性和防震性等因素。
4.试剂包装将选取的试剂进行适当的包装，以保护其在运输过程中不受到外界环境的影响。
包装材料可以使用常见的防潮、防震材料，如聚乙烯泡沫、吸湿剂等。
确保包装材料不会对试剂产生污染或化学反应。
5.试剂运输将包装好的试剂放入运输箱中，根据预设的环境条件，进行试剂的运输。
运输过程中，需保证运输箱的密封性和稳定性，避免温度、湿度和震动的剧烈变化。
6.试剂检测在运输过程结束后，对试剂进行检测，评估其稳定性。
检测指标可以包括试剂的活性、纯度、保存条件等。
对于常见的体外诊断试剂，可以通过比较运输前后的检测结果，评估试剂在运输过程中的稳定性。
7.数据分析和结果评估根据试剂检测结果，进行数据分析和结果评估。
参考相关标准和规范，对运输过程中的试剂稳定性进行评价，确定是否满足要求。
8.结论和建议根据研究结果，给出相应的结论和建议。
如果试剂在运输过程中的稳定性较好，可以提出合理的运输条件和建议；如果试剂的稳定性存在问题，可以提出相应的改进措施，如调整包装材料、改善运输环境等。
诊断试剂加速稳定性试验方案
Test Protocol for Accelerated Stability Test1.Test ObjectiveThe accelerated stability test is performed to determine the valid period of the Advanced Quality TM One Step Ebola Test.2.PrincipleThe test was based on the model Arrhenius Model of high temperature accelerated test. The acceleration factor is expressed as:AF=exp {(Ea/k)* [(1/Tu)-(1/Ts)]+ (RHu^n-RHs^n)},where,Ea: the start energy (eV),K: the boltzmann's constant and k=8.6*10E-5eV/K,T: the absolute temperature,RH: the relative humidity (in%) ,The subscript u: the normal state,The subscript s: was the acceleration state (e.g. Rhu ^ n referred to the n power of relative humidity under normal state),n: generally n was 2.Since the product is packed in aluminum foil bags, the humidity factor was not considered; the product is stored under 2-30℃, and the temperature of accelerated stability test is 50℃, then the acceleration factor AF = exp [(0.8 * 10 ^ 5 / 8.6) * (1 / (273 + 30) - 1 / (273 + 50))] = 6.69242, and it can be calculated that, for 24 months of valid period, the time for accelerated test at 50℃ is: 24 months/6.69242=3.586 months.3. Materials and Methods3.1 Materials3.1.1 Advanced Quality TM One Step Ebola Test, lot number:Lot #1: Lot #2: Lot #3:3.1.2 LOD quality control 1, prepared by NP antigen 1 from Wuhan Institute of Virology, CAS;LOD quality control2, prepared by NP antigen 2 (from Fitzgerald Industries):3.2 Steps3.2.1 Store the three batches of reagents at 50℃ for up to 4 months;3.2.2 When stored at 50℃ for 0 months, 1 months, 2 months, 3 months, 4 months, the three batches of reagents were tested by the quality controls, to investigate products’ performance characteristics of quality controls.3.2.3 Testing with quality controls:The test result of LOD quality control 1 was positive;The test result of LOD quality control 2 was positive;4. Test Results4.1 Test result of storage at 50℃Lot No.Test result0 month storage1 months storage2 months storage3 months storage4 months storage5. Conclusions。
诊断试剂加速稳定性试验方案
Test Protocol for Accelerated Stability Test1.Test ObjectiveThe accelerated stability test is performed to determine the valid period of the Advanced Quality TM One Step Ebola Test.2.PrincipleThe test was based on the model Arrhenius Model of high temperature accelerated test. The acceleration factor is expressed as:AF=exp {(Ea/k)* [(1/Tu)-(1/Ts)]+ (RHu^n-RHs^n)},where,Ea: the start energy (eV),K: the boltzmann's constant and k=8.6*10E-5eV/K,T: the absolute temperature,RH: the relative humidity (in%) ,The subscript u: the normal state,The subscript s: was the acceleration state (e.g. Rhu ^ n referred to the n power of relative humidity under normal state),n: generally n was 2.Since the product is packed in aluminum foil bags, the humidity factor was not considered; the product is stored under 2-30℃, and the temperature of accelerated stability test is 50℃, then the acceleration factor AF = exp [(0.8 * 10 ^ 5 / 8.6) * (1 / (273 + 30) - 1 / (273 + 50))] = 6.69242, and it can be calculated that, for 24 months of valid period, the time for accelerated test at 50℃ is: 24 months/6.69242=3.586 months.3. Materials and Methods3.1 Materials3.1.1 Advanced Quality TM One Step Ebola Test, lot number:Lot #1: Lot #2: Lot #3:3.1.2 LOD quality control 1, prepared by NP antigen 1 from Wuhan Institute of Virology, CAS;LOD quality control2, prepared by NP antigen 2 (from Fitzgerald Industries):3.2 Steps3.2.1 Store the three batches of reagents at 50℃ for up to 4 months;3.2.2 When stored at 50℃ for 0 months, 1 months, 2 months, 3 months, 4 months, the three batches of reagents were tested by the quality controls, to investigate products’ performance characteristics of quality controls.3.2.3 Testing with quality controls:The test result of LOD quality control 1 was positive;The test result of LOD quality control 2 was positive;4. Test Results4.1 Test result of storage at 50℃5. Conclusions。
药物稳定性加速实验
稳定性实验一、目的和要求1．了解应用化学动力学方法预测注射液稳定性的原理。
2．掌握应用恒温加速实验法测定维生素C 注射液的贮存期的方法。
二、仪器和材料仪器：恒温水浴，酸式滴定管（25ml ）,锥形瓶（50～250ml ）等。
材料：维生素C 注射液（2ml ∶0.25g ），0.1mol ∕L 碘液，丙酮，稀醋酸，淀粉指示液等。
三、实验内容（一）试验方法1、放样 将同一批号的V C 注射液样品（2ml ∶0.25g ）分别置4个不同温度（如70、80、90和100℃）的恒温水浴中，间隔一定时间（如70℃为间隔24h ，80℃为12h,90℃为6h ，100℃为3h ）取样，每个温度的间隔取样次数均为5次。
样品取出后，立即冷却或置冰箱保存，供含量测定。
2、V C 含量测定方法 精密量取样品液1ml ，置150ml 锥形瓶中，加蒸馏水15ml 与丙酮2ml ，摇匀，放置5分钟，加稀醋酸4ml 与淀粉指示液1ml,用碘液（0.1mol∕l）滴定，至溶液显蓝色并持续30秒不褪。
每1ml 碘液（0.1mol∕l）相当于8.806mg 的V C （C 6H 8O 6）,分别测定各样品中的V C 的含量, 同时测定未经加热试验的原样品中V C 含量，记录消耗碘液的毫升数。
（二）实验数据处理1．数据整理 由于含量测定所用的是同一种碘液，故不必考虑碘液的精确浓度，只要比较消耗碘液的毫升数即可。
将未经加热的样品（表1－1中时间项为0）所消耗碘液的毫升数（即初始浓度）作为100％相对浓度，各加热时间内的样品所消耗碘液的毫升数与其相比，得出各自的相对浓度百分数（C 相，％）。
实验数据如表 －1。
表 －1 70℃恒温加速试验各时间内样品的测定结果2．求4种试验温度的V C 氧化降解速度常数（k 70~k 100） 用回归方法求各温度的k 值时，先将各加热时间（x ）与其对应的lg(C 相，％)值（y ）列表（表 －2）表16－2 加热时间及其相对浓度（％）对数值的回归计算表（70℃）用具有回归功能的计算器，将x 和y 值回归，直接得出截距，斜率和相关系。
药品稳定性试验整体解决方案
稳定性试验整体解决方案注：此插图最好有博迅全系列试验箱整体照片我们上海博迅公司专业从事箱体制造20余年。
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体外诊断试剂的稳定性试验
体外诊断试剂的稳定性试验欧洲标准（EN1364：2002）与英国标准具有同等效力（CEN——欧洲标准委员会）序言此英国标准为EN13640：2002文件官方英文版本英国制定的这个文件是在技术委员会CH/69授权下制定的。
在体外诊断这块，它负责：——帮助查询者理解文件内容——向欧洲委员会上报查询者对该文件的解释，修改建议，并保持该文件的权威。
——关注国际和欧洲的进展并在该文件中颁布。
可以技术委员会秘书处申请获得委员会列出的组织名单参考英国标准所参考的资料部分可在BSI标准的目录“国际统一标准索引”找到，或在BSI标准电子目录软件中点击“Find”就可找到。
该标准主旨不是要包揽一项合同的所有条款，使用者要正确使用该标准。
体外诊断试剂的稳定性试验此欧洲标准是欧洲委员会（CEN）2001年12月27日制定并实施的：CEN成员国必须遵守CEN内部规则，在此规则的制约下，CEN各成员国采用此欧洲标准作为本国标准，但不能对该标准作任何改动。
最新条款和参考文件可向管理中心或CEN成员国申请获得。
该标准有三种官方版本（英语、法语、德语）。
CEN成员国可以把它翻译成本国语言版本，并上报管理中心以获得认可作为本国的官方版本。
CEN成员国是执行该标准的主体，它们是：澳大利亚、比利时、捷克、丹麦、芬兰、法国、德国、希腊、冰岛、爱尔兰、意大利、卢森堡、荷兰、马尔他、葡萄牙齿、西班牙、瑞典、瑞士和英国。
前言该文件（EN13640：2002）由技术委员会（简写TC）制定。
“体外诊断医用设备”部分由DIN 主持的秘书处负责。
通过出版同一文本或签注，各国可采用欧洲标准作为本国的标准。
在2002年9月前，那些标准相违反的款项必须取消。
此文件在欧洲委员会和欧洲自由贸易组织批令下由CEN制定，该文件支持欧盟指令。
与欧盟批令的关系见附见ZA附件A和ZA只具告知性，不作要求。
此标准包括一个参考资料根据CEN内部规定，下列国家的国标准机构必须实施欧洲标准：澳大利亚、比利时等（与上页所列相同）1、适用范围该欧洲标准适用于体外诊断药品，包括试剂产品，校准仪器、标准品和试剂盒，下面简称IVD 药品。
体外诊断试剂运输稳定性研究方案shipping Study Protocol
Shipping Study SOP1PurposeThe purpose of this procedure is to provide guidance and identify the requirements on applicable standards for shipping study on all XXX products、2ScopeThe scope of this procedure encompasses all shipping stability related activities of XXX products in R&D, QC/QA and Manufacturing Departments of XXX 、 The shipping stability testing of in vitro diagnostic (IVD) reagents includes Lateral flow products, calibrators, control materials and kits、3ReferenceEN13640: 2002 Stability Testing of In Vitro Diagnostic ReagentDesign Control SOPAccelerated Stability Study SOPXXX Gold Color Card (for LF)XXX’s Final QC Procedure for each product subjected to shipping study4Responsibilities4.1The Research and Development Department is responsible for conducting shipping studyincluding planning and conducting the actual shipping study activities, writing and routing study reports、R&D is also responsible for updating the shipping study determining if a simulated or real shipping study is needed for a product、 Also, The R&D is responsible for performing functional testing of simulated shipping study according to corresponding XXX’s Final QC Procedure, and provides the Functional Testing Record、4.2Quality Assurance is responsible for ensuring that the shipping study is performed inaccordance with this procedure、They are also responsible for maintaining the shipping study files、4.3Quality Control is responsible for performing functional testing of real shipping studyaccording to corresponding XXX’s Final QC Procedure, and provides the Functional Testing Record to R&D department as part of the shipping study report、4.4Manufacture Department is responsible for manufacturing products that require shippingstudy、5Materials:5.1Three batches of XXX Product for shipping study5.2Kit Box5.3Carton5.4Data Logger5.5QC standard (if applicable)5.6XXX Color Card (for Lateral Flow products)6Procedure6、1 R&D will select the shipping study protocol to use for the final product – either thesimulated shipping study protocol or the real shipping study protocol、6、2 Three lots of XXX Product will be manufactured and qualified for the shipping study、The prescribed number of units needed for the QC procedure will be randomly selected from thesetests, and evaluated for product performance using XXX’s final QC procedure、 This data will be used as the control or baseline data、6、2、1 Simulated shipping study protocola.3XFT/25℃:Perform 3 freeze/thaw cycles and at the last thaw, perform the QC testing、b.2 Days @ 55℃ /25 ℃:Place test strips in a 55℃ oven for 2 days and then perform the QC testing、* DAY 0: Run 10 test strips each with three controls、** Continue testing every 3 months thereafter until the 39th Month、c.Humidity study:Place the pouched devices in the 30%, 60% and >=80% relative humidity environments for 48 hours、After 48 hours, perform QC testing on the devices exposed under the 3 different relative humidity conditions、d.Vacuum Test:Test units from each lot of product will be randomly selected and exposed to the reduced atmospheric pressure by placing the units under vacuum to a level of approximately 500 milliTorr for 24 hours、The prescribed number of units needed for the QC procedure will be randomly selected from these reduced pressure treated units and evaluated for product performance using XXX’s final QC procedure (Refer to Vacuum Testing SOP)、6、2、2 Real Shipping Study Protocola.Vacuum Test:Test units from each lot of product will be randomly selected and exposed to the reduced atmospheric pressure by placing the units under vacuum to a level of approximately 500 mTorr for 24 hours、The prescribed number of units needed for the QC procedure will be randomly selected from these reduced pressure treated units and evaluated for product performance using XXX’s final QC procedure (Refer to Vacuum Testing SOP)、b.Shipping Study:The prescribed number of products will be placed in 2 shipping carton、 Half of the boxes will be placed in the carton in an upright position and the other will be placed in an inverted position、 The Data Logger with new battery and cleared all memory on old data logged, activated and placed in each shipping carton、The logger will collect temperature and humidity readings every 10 minutes、 The shipping cartons will be sealed、 One carton will be shipped via air cargo and the other by sea cargo to an oversea destination predetermined by R&D、 The carton will be sent back to XXX from the destination upon arrival、Upon receipt of the returned cartons, QC will be responsible visually to inspect shipping box and its contains、 Special emphasis will be placed on the leakage if liquid reagents were included in the shipping study、 The prescribed number of test units for QC will be randomly selectedwith half of the of units from the upright and half from the inverted products in boxes、XXX final QC procedure for these prescribed tests will be performed、If there is no statistical difference between the intra-lot performance data of the shipping studied products and from the controls, the air shipped products and sea shipped products, then the shipping study data will support both air and sea transportation of the product to ourcustomers、7Data7、1 When shipping study is completed, the following data should be available:1) All raw data should be included in the final report、2)The QC testing data3)The vacuum study data4)Temperature and humidity data logged and retrieved from the data loggers5)Package visual examination record8Result8、1 The results of shipping study report should contain but not limited to the items listed below:1) A summary of the shipping study2)Simulated shipping study results3)Temperature and humidity data during shipment4)The vacuum study results5)Comparison of results (intra-lot, inter-lot, air vs、 sea, etc)6)Observations7)Conclusion。
体外诊断试剂产品稳定性研究
法规要求
《体外诊断试剂注册管理办法》（国家食品药品监督管理总局令第5号）第十二条
客户需求
明确产品储存条件及有效期，并提示运输、储存和使用过程中可能对稳定性产品影响的因素
试验样品制备
实验室阶段试制 试生产阶段样品，应在符合质量管理体系要求的厂房中生产
技术指标要求
可测量性，避免主观性指标 指标不应仅局限于产品技术要求、成品出厂检定的范畴，度量指标应该是最能揭示一个产品在保存期限内其质量、安全或功效发生潜在的重大变化 充分考虑产品的特点，选择能够灵敏地反映产品质量变化情况的项目和指标进行稳定性研究
可参考已上市同方法学试剂的稳定性 如适用，可先进行加速破坏试验，对实时稳定性进行预测
间隔
以有效期12个月为例，稳定性研究做到15个月左右，可第3、6、9、11、12、13、14、15个月进行性能检测（不是绝对，遵循前松后紧原则）
实施方案
评价样品制备来源 技术标准与可接受限度 分析确定需要进行的稳定性类别 批次、时长、间隔
整理 by 吉林-免疫-流沙 版本：20170329
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稳定性研究
稳定性研究.mmap - 2017/3/29 - Mindjet
参考依据 研究目的 基本原则
研究方案
体外诊断试剂注册申报资料要求及说明（2014年第44号 附件3） Stability testing of in vitro diagnostic reagents（BS EN 13640:2002） Evaluation of Stability of in Vitro Diagnostic Reagents（EP25-A） In Vitro diagnostic medical devices——Evaluation of stability of in vitro diagnostic reagents （ISO 23640-2011 ） 临床检验体外诊断试剂稳定性评价（ 作者： 张妍 王治国 作者单位： 100730 北京,卫生部北京医院卫生部临床检验中心 ） 体外诊断试剂的稳定性测试（作者：张妍，王治国 《现代检验医学杂志》, 2012, 27(2):161-162） 关于体外诊断试剂的稳定性研究（作者：张丽 国家食品药品监督管理局 药品审评中心）
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Test Protocol for Accelerated Stability Test
1.Test Objective
The accelerated stability test is performed to determine the valid period of the Advanced Quality TM One Step Ebola Test.
2.Principle
The test was based on the model Arrhenius Model of high temperature accelerated test. The acceleration factor is expressed as:
AF=exp {(Ea/k)* [(1/Tu)-(1/Ts)]+ (RHu^n-RHs^n)},
where,
Ea: the start energy (eV),
K: the boltzmann's constant and k=8.6*10E-5eV/K,
T: the absolute temperature,
RH: the relative humidity (in%) ,
The subscript u: the normal state,
The subscript s: was the acceleration state (e.g. Rhu ^ n referred to the n power of relative humidity under normal state),
n: generally n was 2.
Since the product is packed in aluminum foil bags, the humidity factor was not considered; the product is stored under 2-30℃, and the temperature of accelerated stability test is 50℃, then the acceleration factor AF = exp [(0.8 * 10 ^ 5 / 8.6) * (1 / (273 + 30) - 1 / (273 + 50))] = 6.69242, and it can be calculated that, for 24 months of valid period, the time for accelerated test at 50℃ is: 24 months/6.69242=3.586 months.
3. Materials and Methods
3.1 Materials
3.1.1 Advanced Quality TM One Step Ebola Test, lot number:
Lot #1: Lot #2: Lot #3:
3.1.2 LOD quality control 1, prepared by NP antigen 1 from Wuhan Institute of Virology, CAS;
LOD quality control2, prepared by NP antigen 2 (from Fitzgerald Industries):
3.2 Steps
3.2.1 Store the three batches of reagents at 50℃ for up to 4 months;
3.2.2 When stored at 50℃ for 0 months, 1 months, 2 months, 3 months, 4 months, the three batches of reagents were tested by the quality controls, to investigate products’ performance characteristics of quality controls.
3.2.3 Testing with quality controls:
The test result of LOD quality control 1 was positive;
The test result of LOD quality control 2 was positive;
4. Test Results
4.1 Test result of storage at 50℃
5. Conclusions。