過(guò)濾技術(shù)及應(yīng)用

1、質(zhì)保處質(zhì)保處2016.04 過(guò)濾知識(shí)及原理過(guò)濾知識(shí)及原理 過(guò)濾器的使用及維護(hù)過(guò)濾器的使用及維護(hù) 完整性測(cè)試完整性測(cè)試 自動(dòng)完整性測(cè)試儀自動(dòng)完整性測(cè)試儀 Important differences in the types of filters used in Bioprocesses. 生物制藥中使用的不同類型過(guò)濾器及生物制藥中使用的不同類型過(guò)濾器及其特性其特性 Why we use membrane filters for critical application 關(guān)鍵應(yīng)用中為什么使用膜過(guò)濾器關(guān)鍵應(yīng)用中為什么使用膜過(guò)濾器 How to recognize filtration problem

2、s and perform basictroubleshooting 怎樣理解過(guò)濾中的問(wèn)題和解決簡(jiǎn)單故障怎樣理解過(guò)濾中的問(wèn)題和解決簡(jiǎn)單故障 Size Exclusion大小排除大小排除 Particles are too large to pass through the “pore” 基于大小來(lái)分離基于大小來(lái)分離 Examples are termed entrapment,sieving, surface capture 例如攔截例如攔截,篩分篩分,表面捕獲表面捕獲 Adsorption吸附吸附 Particles stick to the filter bychemical / elec

3、trical attraction 顆粒由于化學(xué)顆粒由于化學(xué)/電荷作用粘附在濾器上電荷作用粘附在濾器上 Mechanisms can be affected by: 截流機(jī)制可以被以下因素影響：截流機(jī)制可以被以下因素影響： Fluid characteristics 流體特性流體特性 Operating conditions 操作條件操作條件 Particle type 顆粒類型顆粒類型 Filter type 過(guò)濾膜類型過(guò)濾膜類型 Viscosity粘度粘度 Chemical / Ionic content 化學(xué)化學(xué)/離子成分離子成分 Comments Slow flow allows mo

4、re contact較慢流速有較多接觸較慢流速有較多接觸 Mixing/Contact time can be critical混合混合/接觸時(shí)間有較大影接觸時(shí)間有較大影響響 Only affect adsorptive retention 只影響吸附截留只影響吸附截留 - NOT size exclusion 不影響大小排除不影響大小排除 Particle speed / velocity 顆粒速度顆粒速度 Applied pressure過(guò)濾壓力過(guò)濾壓力 Comments建議建議 Slow flow is good選擇低流速選擇低流速 better retention at slower

5、flow越低的流速越低的流速,越好的截留越好的截留 Matrix movement is bad結(jié)構(gòu)移動(dòng)是不利的結(jié)構(gòu)移動(dòng)是不利的 particles and fibers can bereleased from depth filters 顆粒和纖維能從深層過(guò)濾器析出顆粒和纖維能從深層過(guò)濾器析出 Velocity/Differential Pressure can have a major effect on adsorptive retention - Little to no effect on size exclusion 速度速度/壓差對(duì)吸附截留有壓差對(duì)吸附截留有重要影響重要影響,對(duì)大

6、小排除影響相當(dāng)小對(duì)大小排除影響相當(dāng)小 Deformable (soft)可變形顆?？勺冃晤w粒 Non-deformable (hard)不可變形顆粒不可變形顆粒 Comments建議建議 Under pressure soft particles canintrude into the filter structurecausing more effective filter blinding 在壓力下軟性顆粒會(huì)進(jìn)入過(guò)濾膜內(nèi)并導(dǎo)致更多的過(guò)濾堵在壓力下軟性顆粒會(huì)進(jìn)入過(guò)濾膜內(nèi)并導(dǎo)致更多的過(guò)濾堵塞塞 例如例如:凝膠凝膠 Hard particles form open cakes 硬顆粒形成一層餅例

7、如硬顆粒形成一層餅例如:沙子沙子 Pore rating孔徑孔徑 Structure結(jié)構(gòu)結(jié)構(gòu) Rigid or movable剛性或可移動(dòng)剛性或可移動(dòng) Comments Sterilizing filter common rating (legal definition)除菌過(guò)濾除菌過(guò)濾-公共孔徑公共孔徑(法規(guī)定義法規(guī)定義) Prefilters have nominal ratings - each manufacturer has their own standards and methods 預(yù)過(guò)濾預(yù)過(guò)濾-額定孔徑額定孔徑,每一個(gè)制造商有自己的定義和方法每一個(gè)制造商有自己的定義和方法0.

8、22 um Durapore Surface (3,000 x)0.22 um Durapore Cross-section (600 x) “Water Loving”親水親水 Wet spontaneously (or with little effort) with water Cellulosic materials(i.e. Regenerated cellulose, mixed cellulose ester, etc.)纖維素纖維素材料材料 Polycarbonate with additives (i.e. PVPP), Modified polysulfone, Nylon

9、, Modified polyvinylidenefluoride (PVDF)聚碳化合物聚碳化合物 Applications應(yīng)用應(yīng)用 Filtration and sterile filtration of aqueous or aqueous / organic solutions水或水水或水/有機(jī)溶液混合的過(guò)濾和除菌過(guò)濾有機(jī)溶液混合的過(guò)濾和除菌過(guò)濾 “Water hating”疏水疏水 Not spontaneously wetwith water. Water can remain or be “tricked”to enter filter水被截流或巧妙進(jìn)入膜水被截流或巧妙進(jìn)入膜 P

10、TFE -Polytetrafluoroethylene, PVDF -Polyvinylidene fluoridePolypropylene, Polysulfone,Polycarbonate Applications應(yīng)用應(yīng)用 Solvent, acid, base, and chemical filtration溶劑溶劑,酸酸,堿和化學(xué)品過(guò)濾堿和化學(xué)品過(guò)濾 Tank/Equipment vents, process gas, fermentation inlet/exhaust filters 罐罐/設(shè)備呼吸器設(shè)備呼吸器,工藝用氣工藝用氣,發(fā)酵進(jìn)氣發(fā)酵進(jìn)氣/排氣過(guò)濾排氣過(guò)濾 深層過(guò)濾器

11、深層過(guò)濾器 表面過(guò)濾器特性表面過(guò)濾器特性 膜過(guò)濾器膜過(guò)濾器 Fibrous (can shed fibers)纖維纖維(有纖維脫落有纖維脫落) Difficult to give an accurate pore size rating不能給出一個(gè)確切的空徑不能給出一個(gè)確切的空徑 Thick (3 -30 mm) & often adsorptive厚度厚度(3-30毫米毫米),通常有吸附通常有吸附 Give a percentage (i.e. 30 -70%) particle reduction只能給出顆粒減少的比例只能給出顆粒減少的比例 Have the greatest ca

12、pacity較大的承污能較大的承污能力力 Examples -Microfiberglass, String-wound, pad filters例如例如-玻璃纖維玻璃纖維,線繞式線繞式,壓壓板式板式 Fibers locked together by heat or membrane coating纖維用熱粘合或膜涂布纖維用熱粘合或膜涂布 Given a nominal rating or rated by the filter it protects可以給出公稱空徑可以給出公稱空徑 Thin (1 mm or less) & Slightly Adsorptive較薄較薄(小于小于

13、1毫米毫米),較小吸附較小吸附 Give a percentage (90 -99.9%) particle reduction給出顆粒減少的比例給出顆粒減少的比例(90-99.9%) Examples -Cellulose ester coated cellulose or polyesterweb例如例如-纖維素酯纖維素酯涂纖維或聚酯片涂纖維或聚酯片 Strong, Rigid NOT brittle堅(jiān)強(qiáng)堅(jiān)強(qiáng)，硬不易碎，硬不易碎 Tortuous pathway曲折的通道曲折的通道 Not all the retention on top 不是都截流在膜表面不是都截流在膜表面 Very h

14、igh internal area 非常高的內(nèi)表面積非常高的內(nèi)表面積 65-75% porosity 65%-75%開(kāi)孔率開(kāi)孔率 Size exclusion particle retention does not change with flow or pressure 大小排除顆粒截流與流速和壓力無(wú)關(guān)大小排除顆粒截流與流速和壓力無(wú)關(guān)Sterilizing filters must have 99.99999% removal 無(wú)菌過(guò)濾器必須具有大于無(wú)菌過(guò)濾器必須具有大于99.99999%截流截流 Integrity testable (diffusion &/or bubble p

15、oint) 能做完整性測(cè)試能做完整性測(cè)試 Produced by Casting 鑄造膜 Nylon, Cellulose (mixed ester, regenerated), PVDF, Polysulfone 尼龍,纖維素(混合酯, 改良),聚偏二氟乙烯,聚砜 Produced by Stretching 拉伸膜 PTFE 聚四氟乙烯 Mainly made by casting membrane 主要由鑄造方式制造 Can be either hydrophilic orhydrophobic 可以是親水和疏水 Rated on the size of the smallest par

16、ticleit retains 孔徑是對(duì)最小的顆粒的截留 Very thin (100 - 260 um) 非常?。?00-260微米） Adsorption depends on materials 吸附與材料相關(guān) Examples例如 Cellulose ester纖維素酯 Regenerated cellulose改良纖維素 Nylon尼龍 Polysulfones聚砜 PVDF聚偏二氟乙烯 Slot shaped pores 狹窄的孔道 Very thin 非常薄 Often bonded to a supportmaterial 常常與支撐結(jié)合 Can have high prote

17、inadsorption 有較高的蛋白吸附 Examples例如 PTFE - Teflon聚四氟乙烯 Naturally hydrophobic天然疏水 Most hydrophobic polymer澄清(Millistak+ orPolygard)預(yù)過(guò)濾(Milligard orPolysep-II)最終(Durapore 0.22 or0.45m）深層表面膜 孔徑逐漸減小的過(guò)濾系列 Clarifying filter-澄清過(guò)濾 深層過(guò)濾 在過(guò)濾系列開(kāi)始是最大的 過(guò)濾容量 Prefilter-預(yù)過(guò)濾 Prefilter-預(yù)過(guò)濾-表面過(guò)濾 中等截留，中等載量 Final filter-除菌

18、過(guò)濾 除菌膜 最大的過(guò)濾截留率Performance ofFiltration Systems過(guò)濾系統(tǒng)性能Non-deformable types不可變形顆粒 Resin beads or fines樹(shù)脂粒 Drug crystals藥物晶體 Carbon fines炭粒 Diatomaceous Earth (D.E.)硅燥土 Form porous permeable cakes.在膜上形成可流通的餅Deformable types可變形顆粒 Proteins蛋白 Lipids脂 Sugar complexes糖復(fù)合物 Can move through the filter, breaku

19、p and compress into impermeablecakes.能穿過(guò)膜,破碎,壓縮* Happens with hard particles 發(fā)生在硬顆粒* Particles build up on the surface of the filter 顆粒堆積在過(guò)濾膜的表面 Happens with deformable particles 發(fā)生在可變形顆粒 Particles completely block the pore“ 顆粒完全堵塞膜“孔” Happens with little prefiltration OR particles slightly larger t

20、han the pore size 發(fā)生在缺少預(yù)過(guò)濾或顆粒略大于孔徑的情況 Happens with hard or deformable particles 發(fā)生在硬顆粒和可變形顆粒 Particles build up on the pore throat or opening 顆粒堆積在孔道或表面 Most common with biologicals 大多發(fā)生在生物化學(xué)顆粒 Gradual blockage most common 逐漸堵塞經(jīng)常發(fā)生 Everything was going alright, then all of a sudden the filter blocke

21、d” 一切正常,然后突然過(guò)濾器堵 塞了 流速下降 可能低于要求的流速(如灌裝速度) 壓力上升 可能超過(guò)過(guò)濾系統(tǒng)承受的壓差 過(guò)濾柱或管道/連接件 顆粒可能穿過(guò)過(guò)濾器 污染/堵塞下游過(guò)濾器 過(guò)濾成本改變 時(shí)間,產(chǎn)品和過(guò)濾器的成本 系統(tǒng)停止或更換過(guò)濾器 本道工序?yàn)V膜的選擇，孔徑，面積 操作條件（流速，溫度，壓力） 上道工序?yàn)V膜的選擇 產(chǎn)品本身的變化 產(chǎn)品過(guò)濾前作壓力流速實(shí)驗(yàn) 使用低的起始?jí)翰?1-2 psid or 0.1 bar 監(jiān)測(cè)和調(diào)整壓差 深層過(guò)濾:10-15PSID 表面過(guò)濾和膜過(guò)濾:30PSID 不超過(guò)制造商的規(guī)格 確保過(guò)濾在合時(shí)壓力下進(jìn)行 圓盤(pán)過(guò)濾器 13-293毫米直徑 傳統(tǒng)的濾器

22、可同時(shí)使用深層、表面濾膜 通常用于小批量過(guò)濾 成本低 分量重 安裝困難 占地面積大Stacked Disk層疊式圓盤(pán) Membrane bonded to both sides of a support disk 膜結(jié)合在圓盤(pán)支撐的兩邊 Support disks bonded together 圓盤(pán)支撐結(jié)合在一起 All filters work in parallel所有過(guò)濾器平行 Low hold-up volume殘液低 Easy to use & compact使用方便緊湊 Either replacement filter (Millidisk) or disposable

23、 device (Millipak) 有可替換的和一次性使用的過(guò)濾器 Non-metallic非金屬 Non-flexing structure不可變形構(gòu)造 Low resistance to back pressure 承受反壓低Pleated Cartridge折疊式 Membrane held between supportingmaterial膜在支撐材料間 Thermoplastic welding熱熔 2-5 materials of construction 2-5種結(jié)構(gòu)材料Good forward & reverse pressure resistance 較高的正/反

24、壓承受能力 Large surface area大過(guò)濾面積Multiply steamable多次蒸氣滅菌Variety of sizes, surface areas and o-ringconfigurations各種規(guī)格，表面積和形圈結(jié)構(gòu)Can have prefilter / final filter in the samecartridge能將予過(guò)濾和除菌過(guò)濾膜結(jié)合在同一過(guò)濾芯內(nèi) 濕潤(rùn)O型圈，易于安裝 檢查過(guò)濾外殼方向 inlet / outlet 不要過(guò)緊，合適的套筒不需要太大的力量 避免直接用手接觸過(guò)濾器 使用前沖洗過(guò)濾器 滅菌次數(shù)： CVGL除菌濾芯： 30 SIP 30 mi

25、n 135 C; 30 高壓滅菌60 min 126 C KVGL囊式除菌濾芯： 3 高壓滅菌60 min 126 C; 不能在線滅菌 Millidisk除菌濾器： 5 SIP 60 min 135 C; 5 高壓滅菌60 min 126 C 。 Aervent空氣/有機(jī)溶劑除菌濾器：150（100正向/50反向） SIP 30 min 145 C; Express聚醚砜除菌過(guò)濾器： 25 次正向（或22次正向，3次反向） 30min135 C; 一定要預(yù)先閱讀說(shuō)明書(shū)-實(shí)際工藝使用次數(shù)需要確認(rèn) Preventative Maintenance 預(yù)防性維護(hù)Oxidation氧化Integrity

26、 failure完整性失敗 Filter blockage過(guò)濾膜堵塞Too many sterilization cycles太多滅菌次數(shù)Filter changeout can vary; 1 week to 1 year過(guò)濾器更換時(shí)間范圍很廣(從1周到1年)Need documentation需要文本支持Increased scrutiny應(yīng)不斷進(jìn)行檢查T(mén)here are two major retention mechanisms in liquids在流體過(guò)濾中有兩類過(guò)濾機(jī)理 Adsorption, Size Exclusion吸附,大小排除Three types of filters

27、 are commonly used in biopharmaceuticalfiltration三類過(guò)濾器普遍使用在生物制藥 Depth, Surface, Membrane深層,表面,膜過(guò)濾Filter materials are supplied as either過(guò)濾介質(zhì)以下列形式提供 Disc, Stacked Disc, Pleated Cartridge圓盤(pán),層疊式,柱式Filters block by either過(guò)濾堵塞可以是 Gradual, Total or Cake逐漸堵塞,完全堵塞Filtration problems can be solved過(guò)濾問(wèn)題可以被解決 M

28、onitoring and optimizing are key techniques監(jiān)測(cè)和優(yōu)化是關(guān)鍵技術(shù)Integrity Testing Theory完整性測(cè)試?yán)碚?為什么要對(duì)除菌濾器進(jìn)行完整性測(cè)試？ 完整性測(cè)試的方法有哪些？ 為什么可以用起泡點(diǎn)的方法代替細(xì)菌挑戰(zhàn)試驗(yàn)？ 什么時(shí)候進(jìn)行完整性檢測(cè)？ 起泡點(diǎn)測(cè)試原理是什么？ 擴(kuò)散流測(cè)試原理是什么？ 自動(dòng)完整性測(cè)試儀Common Sense通常理解 Filtration is often the most critical step in an operation 過(guò)濾通常是操作的關(guān)鍵步驟 Confirmation of manufacturer

29、s specifications 確認(rèn)制造規(guī)格 Detecting leaks due to o-rings, gaskets, seals 檢測(cè)O形環(huán),墊圈,密封墊的泄漏 Assuring the correct pore size filter 確認(rèn)正確的過(guò)濾孔經(jīng) Assuring integrity before sterilization 確認(rèn)滅菌前完整性 Assuring integrity after steaming or autoclaving 確認(rèn)蒸汽和消毒鍋滅菌后完整性Business Practice 商業(yè)慣例 Government Guidelines & Re

30、gulations法規(guī)要求 Part of corporate standard operating procedure公司標(biāo)準(zhǔn)操作規(guī)程 Auditing requirement審計(jì)需要 FDA Guideline指南(2003) Whatever filter or combination of filters is used, validation should include microbiological challenges to simulate worst-case production conditions”對(duì)于由一個(gè)或多個(gè)濾器組成的過(guò)濾系統(tǒng)，對(duì)它的驗(yàn)證都應(yīng)該包括在最差條件下進(jìn)

31、行的微生物挑戰(zhàn)試驗(yàn)Revision of annex 1 to EC Guide to GMP for sterile medicinal products(1997)歐盟對(duì)于無(wú)菌藥品GMP指南的附件一(1997版) “The integrity of the sterilized filter should be verified before use and should be confirmed immediately after use by an appropriate method such as a bubble point, diffusive flow or pressure

32、 hold test” 除菌過(guò)濾膜應(yīng)該在使用前及使用后立即采取合適的方法確認(rèn)其完整性,可以采用泡點(diǎn),擴(kuò)散流或壓力保持的方法.FDA Guideline on Sterile Drug Products Produced by Aseptic Processing (1987)FDA對(duì)于無(wú)菌操作生產(chǎn)的無(wú)菌藥品的要求(1987版) “Normally, integrity testing of the filter is performed after the filter unit is assembled and sterilized prior to use.” 完整性測(cè)試通常在過(guò)濾器安裝,

33、滅菌后使用前進(jìn)行PDA Technical Report # 26PDA技術(shù)報(bào)告26版 “It generally is regarded as a cGMP requirement that filters or filter systems routinely be integrity tested both prior to and after use.” 現(xiàn)行的GMP要求過(guò)濾器及過(guò)濾系統(tǒng)在使用前及使用后均需要進(jìn)行完整性測(cè)試 WHEN TO DO IT? Detect what? 什么時(shí)候做? 檢查什么？ Before sterilization faulty housings? 滅菌前

34、 外殼的問(wèn)題 Before use out-of-the box failures 使用前 包裝以外的問(wèn)題 After use sterilization induced failures 使用后 滅菌的影響 stress induced failures 壓力的影響金標(biāo)準(zhǔn)Regulatory & quality organizations need datafrom both to assure reliable and predictablefilter performance法規(guī)和質(zhì)量管理需要數(shù)據(jù)確?？煽亢皖A(yù)知過(guò)濾器性能 There must be a correlation b

35、etween a destructive and a non-destructive integrity test 破壞性和非破壞性測(cè)試兩者必須有關(guān)聯(lián) Regulatory requirement 法規(guī)需要 FDA Aseptic Guidelines FDA無(wú)菌指南 Validation justification for the use of a test 測(cè)試應(yīng)用的驗(yàn)證理由Integrity Testing Correlations完整性測(cè)試關(guān)聯(lián)What Non-Destructive Integrity Tests are Available?何種非破壞性測(cè)試合適?Bubble Poi

36、nt Introduction 起泡點(diǎn)介紹起泡點(diǎn)介紹Bubble point is the pressure at which gasdisplaces liquid from the largest set of filterpores and flows rapidly through the filter起泡點(diǎn)是氣體從濕潤(rùn)的最大膜孔擠出液體快速流出時(shí)的壓力Bubble point indicates the magnitude ofthe forces holding liquid in the filterstructure起泡點(diǎn)顯示過(guò)濾結(jié)構(gòu)內(nèi)保持液體的力的大小The oldest n

37、on-destructive integrity test最傳統(tǒng)的非破壞性測(cè)試泡點(diǎn)測(cè)試Bubble Point Test Applicability起泡點(diǎn)測(cè)試適用性Bubble Point Equation起泡點(diǎn)等式起泡點(diǎn)等式泡點(diǎn)的影響因素接觸角的影響Examples of the Effect of Contact Angle andSurfaceTension on Bubble Point Values接觸角和表面張力對(duì)起泡點(diǎn)值的影響實(shí)例Diffusion Testing Introduction擴(kuò)散流測(cè)試介紹 Gas dissolves in liquidheld in the por

38、es of a fullywetted membrane filter.氣體溶解在完全濕潤(rùn)的濾器膜孔內(nèi)的液體中 A pressure differential willgive a different gasconcentration across thefilter.膜壓差造成跨膜氣體濃度差 Results in gas flowthrough the liquiddissolved in the filter pores.結(jié)果使膜孔溶解的氣體流出擴(kuò)散流測(cè)試Diffusion Testing Equation擴(kuò)散測(cè)試方程擴(kuò)散測(cè)試方程A Reason for Diffusion Testing

39、什么情況下采用擴(kuò)散測(cè)試Diffusion Test Applicability擴(kuò)散測(cè)試適用性Factors Affecting Diffusion Tests擴(kuò)散測(cè)試的影響因素Example of Changed Diffusional Flow 舉例Example of Changed Diffusional Flow 舉例Example of Changed Diffusional Flow 舉例“Diffusion Testing” Summary 擴(kuò)散測(cè)試總結(jié)疏水濾膜采用有機(jī)溶劑進(jìn)行完整性測(cè)試的問(wèn)題HydroCorr Testing Hydrocorr測(cè)試測(cè)試HydroCorr Tes

40、t Resistance to water intrusion水浸入法測(cè)試水浸入法測(cè)試HydroCorr Test Results測(cè)試結(jié)果HydroCorr Test Considerations測(cè)試的注意點(diǎn)測(cè)試的注意點(diǎn) Must have a leak-free system必須在一密閉系統(tǒng)內(nèi)進(jìn)行 Filters must be dry and clean過(guò)濾芯必須干燥且干凈 It is relatively easy to Hydrocorr test “very hydrophobic” membranes such as PTFE 對(duì)于疏水性很強(qiáng)的濾芯,例例PTFE材質(zhì)的膜材質(zhì)的膜,水

41、浸入法是相當(dāng)容易水浸入法是相當(dāng)容易 Successfully testing “l(fā)ess hydrophobic” membranes such as PVDF requires idealconditions that can be difficult to achieve in actual biopharmaceutical processes 在實(shí)際的生物制藥工藝中,測(cè)試一些疏水性不強(qiáng)的濾膜測(cè)試一些疏水性不強(qiáng)的濾膜,例例PVDF膜是比較困難膜是比較困難的的 Temperature changes should be minimized 盡量減少溫度的變化 Reference testi

42、ng is important 相關(guān)的參考比較重要 Must have a complete validation package 必須有一完整的驗(yàn)證文本 Values must be comprehensively correlated to microorganism challenge 數(shù)據(jù)必須與細(xì)菌挑戰(zhàn)相關(guān)完整性測(cè)試失敗處理措施潤(rùn)濕建議Summary總結(jié)總結(jié) Bubble point and Diffusion (or “Forward flow”) are BOTH validintegrity tests as per regulatory agencies.起泡點(diǎn), 擴(kuò)散流（或前

43、向流）和HydroCorr是法規(guī)認(rèn)可的完整性測(cè)試方法 The choice of an integrity test depends on the testing equipment,the filter manufacturer, the companys philosophy and the testingenvironment完整性測(cè)試的選擇倚賴測(cè)試裝置，過(guò)濾器制造商，公司體系和測(cè)試環(huán)境 Bubble point provides a direct correlation to bacterial retention, thecritical performance characteri

44、stic起泡點(diǎn)提供與細(xì)菌截留的直接關(guān)聯(lián)，重要的性能特性 Diffusion testing provides a sensitive way to determine integrity forlarger area filters擴(kuò)散測(cè)試提供一個(gè)敏感方法來(lái)測(cè)試大面積過(guò)濾器Automated Integrity Testers自動(dòng)完整性測(cè)試儀Why Do People Use Automatic Testers為何用戶會(huì)選用自動(dòng)測(cè)試儀Post SIP Integrity Testing SIP后的完整性測(cè)試后的完整性測(cè)試Revision of annex 1 to EC Guide to GM

45、P for sterile medicinal products(1997)歐盟對(duì)于無(wú)菌藥品GMP指南的附件一(1997版) “The integrity of the sterilized filter should be verified before use and should be confirmed immediately after use by an appropriate method such as a bubble point, diffusive flow or pressure hold test” 除菌過(guò)濾膜應(yīng)該在使用前及使用后立即采取合適的方法確認(rèn)其完整性,可以采

46、用泡點(diǎn),擴(kuò)散流或壓力保持的方法.FDA Guideline on Sterile Drug Products Produced by Aseptic Processing(1987)FDA對(duì)于無(wú)菌操作生產(chǎn)的無(wú)菌藥品的要求(1987版) “Normally, integrity testing of the filter is performed after the filter unit is assembled and sterilized prior to use.” 完整性測(cè)試通常在過(guò)濾器安裝,滅菌后使用前進(jìn)行PDA Technical Report # 26 PDA技術(shù)報(bào)告技術(shù)報(bào)告26版版 “It generally is regarded as