空气和蒸汽混合式的灭菌方案洁定.ppt

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1、Air-Steam Mixture Sterilization Solution Delicate BFS containers and pre-filled syringes空气蒸汽混合灭菌解决方案应用于吹灌封和预灌装注射器产品的终端灭菌PDI Jinan September 2012PDI ， 2012年9月于济南Presentation by Hans Larsson/Kevin Qian Getinge主讲人：洁定公司 乐瀚森/钱鼎 Difficulties with terminal sterilization of your delicate containers 柔性容器终端灭菌

2、相对困难Important features on sterilization process灭菌过程的重要特征Fast process 过程迅速High degree of Sterility Assurance高度的无菌保证值No deformation on products 产品不变形 2Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Difficulties with terminal sterilization of your delicate containers 柔性容器终端灭菌相对困难How to choose? 如何选择Pr

3、ocess it quickly and to a high degree of Sterility Assurance, but then it will not be in good shape. 灭菌迅速并获得高的无菌保证值，但产品形状受到影响Process it quickly and ensure it remains in good shape, but it may not be fully sterile.灭菌迅速并保持产品形状，但不能完全灭菌Process it to a high degree of Sterility Assurance and remain in goo

4、d shape, but it will take a long time. 获得高的无菌保证值并保 持产品形状，但需要很长的灭菌时间At first glance you can only pick any two在快速处理、无菌保证和产品形状三者之间只能选择两项 3Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Steam Sterilization 蒸汽灭菌柜Traditional Steam Sterilizer 传统的蒸汽灭菌柜 Used for sterilization of many different products wit

5、hin Healthcare, Biomedical Research and Pharmaceutical Production 广泛应用于医疗、生物医学和制药行业 Used for a variety of products such as: 可用于不同的产品，比如： Hard goods (e.g. instruments, components, glassware parts)硬物（比如器械、部件、玻璃器皿） Porous / Wrapped Goods (e.g. textiles, Tyvek bags) 多孔/包裹物品 （比如织物、Tyvek袋子） Liquids, Paren

6、terals 液体、注射剂 Both for sterilization of products as well as decontamination of Bio-Hazardous waste. 可对产品灭菌，也可以对有生物危害的废物灭菌 4Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Why risk of deformation? 为何产品包装会产生变形What happens during heating of product in a Steam Sterilizer?在蒸汽灭菌过程中的加热阶段发生了什么？Steam is use

7、d to heat the product from the outside pressure in the chamber rises 蒸汽在容器外部对产品进行加热，灭菌器腔体压力不断上升Pressure in a sealed container rises as it is heated due to expansion of air and other factors 被加热的密闭容器由于气体膨胀及其他因素引起容器内部的压力上升 Total internal pressure will be sum of water vapor pressure and air pressure 内部

8、压力为水蒸汽压力和空气压力之和 5Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Why risk of deformation?为何产品包装会产生变形What happens during cooling of product in a Steam Sterilizer?在蒸汽灭菌过程中的冷却阶段发生了什么？Energy is only lost from container by transmission to environment need to remove steam from chamber 密闭容器能量的损失只能通过向腔体内传递

9、的方式 所以需要去除腔体内的蒸汽Replace the steam with air so that the containers do not explode 采用空气代替蒸汽，以防止密闭容器爆裂Radiation from external surfaces Slow cooling process 容器外表面热辐射 非常缓 慢的冷却过程Pressure in the sealed container is still very high 密闭容器内的压力仍然很高 The container can be sterilized in a steam sterilizer only if t

10、he container can withstand a pressure difference只有能承受内外压差的密闭容器才能在普通蒸汽灭菌器内进行灭菌 6Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Why risk of deformation?为何产品包装会产生变形Which Products can withstand a pressure difference? 哪些产品可以承受压差？LVP:s and parenteral in delicate containers cannot withstand a pressure di

11、fference柔性容器不能承受压差Some SVP:s like glass ampoules and crimp-capped vials can withstand a pressure difference. 一些玻璃安瓿和轧盖西林瓶能承受压差If you have the time to wait如果您有时间去等待的话 7Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Difficulties with terminal sterilization of your delicate containers柔性容器终端灭菌相对困难How

12、to have it fast, sterile and in good shape? 如何实现快速灭菌、包材形状完好？ 8Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Processes available 可实现的灭菌方式 9Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Water Cascade 水浴式Why water? Water very good carrier of energy. Especially good during cooling phase. 为何采用水浴？水是

13、良好的能量载体， 特别在冷却过程中。Water is filled in the chamber and circulated during process. 水进入灭菌腔，并在整个过程中循环。Circulating water is heated with e.g. steam to heat up product 循环水被蒸汽加热，进而加热产品Possibility to add air support pressure可以加压力补偿Circulating water is cooled with e.g. cold water to cool down product循环水被冷却，进而冷

14、却产品Extremely fast process, but products are wet afterwards 灭菌过程非常快，但灭菌完成后产品是湿的。 Processes available可实现的灭菌方式 10Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Steam and air mixture 蒸汽和空气混合式Steam and Air mixed in process 在灭菌过程中蒸汽和空气混合Steam is used to heat up product蒸汽用于加热产品Dry pre-heating is optional

15、 预热可作为选项Possibility to add air support pressure - Fan makes the surrounding homogenous 可以加压力补偿 顶部风机使灭菌腔内环境更均一Air cooled by internal heat exchanger is used to cool down product. Air is circulated with fan 内部热交换器冷却腔内空气，进而冷却产品。 空气在风机的作用下在腔内循环 Process time can be very fast, depending on cooling system,

16、and products are dry afterwards 灭菌过程可以非常快速，产品在灭菌后为干燥状态 Temperature Gradient and F0 温度梯度和F0值 11Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Steam and air mixture 蒸汽和空气混合 Example on steam and air mixture sterilizer: 蒸汽和空气混合灭菌器示例 During heatup, product at the bottom heats more quickly than product

17、at the top 加热阶段，在灭菌底部的产品比顶部的产品升温快 Conversely, during cooling, the load at the bottom cools more quickly 相反，在冷却阶段，底部比顶部的冷却快The net result is that the total heating effect (F0 value) is the same所以整个过程的F0值是相同的This is a well accepted and understood principle, and customers validate their sterilizers acc

18、ordingly 这是广泛接受并能理解的原则，在灭菌器验证中完全实现If steam/air flow is horizontal, the same applies but with a temperature gradient horizontally如果蒸汽/空气的流向为水平，以上结论同样适用，但温度梯度是水平的。 Extensive testing 大量的测试 12Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Performing tests 性能测试Getting a “perfect” process requires exten

19、sive testing 取得完美的灭菌过程需要大量的测试How products are placed during the process 产品如何放置 “Stand-alone” products “站立式” Stacked products “堆积式”Process flow 过程流向 Vertical flow 垂直流向 Horizontal flow 水平流向Placement of load sensor 装载传感器的放置 Different locations to optimize cycle不同位置优化灭菌过程 Also important for safety对于安全性也

20、很重要 Extensive testing 大量测试 13Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 14Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Key Findings Temperature Control重要结论 温度控制Temperature Control 温度控制Placement of load sensors is critical to optimize the cycle in both preliminary study and lab testing. 装载传

21、感器的放置对优化灭菌过程非常关键，无论在初步研究阶段还是在实验室测试阶段An accurate load simulator (or “dummy” container) is key for sensitive loads. For each specific load a unique load simulator needs to be developed. 精确的装载模拟 （或称之为”仿制容器”）对于敏感性产品非常重要。对于每一个特殊装载都要进行装载模拟测试It is important to place the load sensor in the slowest product t

22、o make sure all products reach sterilization temperature.将装载传感器放置于温度上升最慢的产品是非常关键的，可以确认所有的产品都能达到灭菌温度Improving temperature spread has a significant impact on process time, in particular during cooling phase.提高热分布对灭菌时间，特别是冷却阶段有巨大的影响 Focus on low temperature spread only at those temperature ranges where

23、 it matters: slow heating and cooling above 90 C. 关注低温度分布，只有在温度范围发生问题，在90 C. 以上升降温缓慢。 15Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Key Findings Temperature Control重要结论 温度控制Temperature Control温度控制F0 accumulation during heating and cooling phase shall be considered when aiming for a fast cycle.

24、This is accepted from a sterility assurance level, but might not sufficient as temperature spread may lead to deformation of certain delicate containers. 对于一个快速灭菌过程，必须考虑加热和冷却阶段的F0值的积累。从无菌保障值来讲是被接受的，但也不充分，因为热分布会导致某些柔性包材变形During cooling phase, temperature spread at the end of cycle may be a safety iss

25、ue as late cooled / hot containers may explode when opening the door. 在冷却过程中，在灭菌过程的最后阶段，热分布可能产生安全问题，因为开门的时候热的容器可能会爆裂。 16Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Key Findings Pressure Control重要结论 压力控制Pressure Control 压力控制Support pressure is a key parameter, in particular if the load is not de

26、nsely packed or supported by loading accessories. 压力补偿是关键参数，特别是在装载不是特别紧密的情况下Support pressure needs to be adjusted during the course of the cycle. 在灭菌过程中压力补偿需要调节There are various strategies to control support pressure during the cycle and the most suitable pressure control is generally dependent on t

27、he design of the container as well as the container material. 有多种方式进行压力补偿，最适合的压力控制取决于容器的设计与材质 17Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Key Findings Other Parameters重要结论 其他参数Other Parameters 其他参数To optimize cooling time on a steam and air mixture sterilizer, it is necessary to: 为了优化冷却时间，必须具

28、备以下要素： Have sufficient cooling power 具有足够的冷却能力 Distribute the air uniformly within the load将空气均匀的分布在装载物上Characteristics of the BFS containers have a significant impact on their processability: 吹灌封容器的特性对灭菌过程中有很大的影响： Wall thickness/flexibility 容器壁厚/柔韧性 Head space/water level 液面上空间/液位 Weight of closure

29、. 容器的重量 18Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Key Findings Conclusion重要结论 结论Conclusion 结论Cycles need to be optimized for each type of container. 各种容器的灭菌循环都需进行优化Requires cooperation between BFS machine and sterilizer manufacturer. 需要吹灌封设备和灭菌设备的供应商进行技术合作Can be developed at site or in adva

30、nce.需要预先或者在现场进行优化 19 Nested Syringes 巢状注射器 Tests performed with 1 ,2 5 ml Nested syringes 用1 .2 5 ml的巢状注射器进行测试 4 4 8 nests per Rack (4 4 8 0 0 syringes) 每个灭菌架车装载4 4 8个注射器巢 （共4 4 8 0 0支注射器） Objective to develop an optimized process for Nested syringes 目标是优化灭菌过程 Lateral Air Flow Turbo option 水平气流 提供Tu

31、rbo选项 Criterias: 标准EN2 8 5 F0 spread 8 min F0差值为8 minVisually dry load 灭菌后负载目测干燥No movement of stopper 注射器插杆未移动 OPTIMIZED PROCESSING OF PRE-FILLED SYRINGES优化预灌装注射器的灭菌过程Development & Testing 优化及测试 20 Nested Syringes Temperature Distribution巢状注射器 热分布 Temperature monitoring from inside the syringes 在注射

32、器内部进行温度监控 Low temperature spread above 8 0 C 8 0 C 以上温差很小 Low temperature spread when F0 calculation starts ( 5 -6 C at 1 1 5 C ) 当F0开始积累时( 5 -6 C at 1 1 5 C ) ，温差很小 Low F0 spread (1 2 1 C ): 3 min with a total F0 of 3 0 min 小的F0差值(1 2 1 C ): 灭菌3 0分钟，F0差值小于3 min OPTIMIZED PROCESSING OF PRE-FILLED SY

33、RINGES优化预灌装注射器的灭菌过程Development & Testing 优化及测试 21 Nested Syringes Dry Load 干燥负载 Visible droplets on load and shelves after regular GEV process 在常规的GEV程序灭菌后在负载和层架上可见小的水滴 Adding preheat phase reduces droplets (but not completely dry) but increases temperature spread below 8 0 C 增加预热程序可以减少水滴（但不会完全干燥），但

34、提高了8 0 C 下的温度差 Adding Fan Drying removes droplets but increases temperature spread below 8 0 C 增加风扇干燥可以去除水滴，但提高了8 0 C 下的温度差OPTIMIZED PROCESSING OF PRE-FILLED SYRINGES优化预灌装注射器的灭菌过程Development & Testing 优化及测试 22 Nested Syringes Stopper Movement 插杆移动 Stopper movement measured before and after process i

35、s small 灭菌前后插杆移动很少 Stopper movement during the process is rather large! 在灭菌过程中插杆的移动相当大！ Inwards outwards appr. 2 -3 mm! But The GEV TS can control it with precision!但是GEV TS能够更精确的进行控制OPTIMIZED PROCESSING OF PRE-FILLED SYRINGES优化预灌装注射器的灭菌过程Development & Testing 优化及测试 23 Nested Syringes Biological ste

36、rilization efficacy 生物学灭菌效果 Biological indicator (cotton threads) placed inside rubber cap at the needle of the syringe 生物指示剂（棉线）放置于注射器针头一侧的橡皮帽内 Tests performed both with needles pointing upwards, downwards and horizontally 分别对针头向上、向下和水平方向进行测试 No growth in when needles were pointing upwards or horiz

37、ontally. Growth in one specimen where needle was pointing downwards 针头向上和水平放置时无微生物 生长，针头向下放置时有一个微生物生长 OPTIMIZED PROCESSING OF PRE-FILLED SYRINGES优化预灌装注射器的灭菌过程Development & Testing 优化及测试 24 Nested Syringes 巢状注射器 Temperature distribution throughout the load is very good 温度均一性非常好 Dryness of the load ca

38、n be controlled with additions in the process 负载的干燥度在灭菌过程中有很好的控制 Process times 1 0 0 min with Preheat and Fan Drying 灭菌时间大约为1 0 0 min，包括预热和风扇干燥时间OPTIMIZED PROCESSING OF PRE-FILLED SYRINGES优化预灌装注射器的灭菌过程Conclusions 结论What is most important for You?什么对您最重要？Getinge GEV TS Turbo is flexible! 洁定GEV最灵活！ 25

39、 Infusion Bags 输液袋 Heat Up 加热 Big Temperature spread initially 加热开始阶段的温差较大 Low temperature spread when F0 calculation starts ( 4 -7 C at 1 1 5 C ) 当F0开始累积时( 4 -7 C at 1 1 5 C )温差较小OPTIMIZED PROCESSING 优化的灭菌过程Development & Testing 优化与测试 26 Infusion Bags 输液袋 Lateral air flow Turbo options 水平气流 Turbo系列

40、可选 With ”Temperature controlled cooling” (Patent application published) we can control the Temperature spread during cooling 采用“冷却温度控制”的专利技术，洁定可以在冷却过程中很好的控制温差 Process times 7 5 min 2 hours (or more)程序时间7 5分钟-2小时OTHER APPLICATIONS INFUSION BAGS 其他应用 输液袋Conclusions 结论What is most important for You Get

41、inge GEV TS Turbo is flexible! 27 GEV TS Standard batteries of heat exchangers标准的串联式热交换器 Single speed fan 单速风扇 Modulating valve for heat exchangers热交换器调节阀 One steam inlet and drain per zone每个区域一个蒸汽入口和配水口GEV TS SERIES GEV TS系列TS Features 特点 28 GEV TS TURBO Standard batteries of heat exchangers标准的串联式热

42、交换器 Additional roof heat exchangers 顶部热交换器 Multi speed fan 多速风扇 Possibility to have a horizontal air/steam flow 具有水平空气/蒸汽流向 Modulating valve for heat exchangers 热交换器采用调节阀 Modulating valve for incoming steam蒸汽采用调 节阀 Two steam inlets per zone. One drain per zone.每个区域有两个蒸汽入口和一个排水口 Better performance th

43、an any competitor 优于任何竞争对手的性能优势 GEV TS SERIES GEV TS系列TS Turbo Features 特点 29Sep 2012 Hans Larsson - Getinge - PDI Jinan 2012 Questions? 问题？THANK YOU!HANS LARSSON / KEVIN QIANGETINGE SHANGHAI TRADING CO., LTD7 /F METRO PLAZA, 5 5 5 LOUSHANGUAN ROADSHANGHAI 2 0 0 0 5 1P.R. CHINA上海市长宁区娄山关路5 5 5号7楼 +4 6 2 1 6 2 2 8 6 1 6