【正文】 ? Testing of large quantities of material may be required. 可能需要對(duì)大量的原料進(jìn)行測(cè)試。 ? The placebo material must be evaluated for lack of inhibitory effects on microanisms. 安慰劑原料必須進(jìn)行對(duì)微生物無抑制效應(yīng)的評(píng)估。 Disadvantages 缺點(diǎn) ? Sterility or microbial count testing must be performed in order to assess whether any microanisms are present. 必須執(zhí)行無菌或微生物計(jì)數(shù)測(cè)試，以評(píng)估是否存在微生物。 ? Placebo materials can be substantially less expensive than product or microbiological growth media, which can be a significant concern in large process equipment. 安慰劑物料的成本遠(yuǎn)低于產(chǎn)品或微生物生長(zhǎng)培養(yǎng)基， 在 較大的工藝設(shè)備中是顯著關(guān)注點(diǎn)。 Advantages 優(yōu)點(diǎn) ? Can use materials which are able to tolerate the actual processing conditions utilized in the aseptic process. 可使用 能 忍受無菌工藝使用的實(shí)際加工條件 的物料。 . Placebo Material Simulation 安慰劑物料模擬 A placebo material is substituted for the production materials and handled in a representative manner. The placebo material can be sampled for microbial count or sterility testing depending upon the acceptance criteria requirements of the protocol. 使用安慰劑物料來代替生產(chǎn)物料，以一種特定的方式處理。s growth promotion capability under routine operating conditions within the equipment. 由于關(guān)系到設(shè)備內(nèi)在正常操作條件下的培養(yǎng)基的促生長(zhǎng)能力，工藝模擬與實(shí)際工藝可能很少有類似之處。 ? Quantities of microbiological growth media required may be excessive. 可能需要大量的微生物培養(yǎng)基數(shù)量。 ? It adds increased risk of microbiological contamination of the facility by providing a major nutrient source when normal materials used may be innocuous or bactericidal. 另外，由于提供了一個(gè)營(yíng)養(yǎng)來源，增加了設(shè)施微生物污染的風(fēng)險(xiǎn)， 而正常使用的物料可能是無害的或殺菌的?？赡苄枰褂脺缁蠲福撬麄?cè)诖笙到y(tǒng)中的使用可能嚴(yán)格受限。 ? Less reliance on environmental conditions in the evaluation of the process. 在工藝評(píng)價(jià)時(shí)較少依賴于環(huán)境條件。微生物生長(zhǎng)培養(yǎng)基 可進(jìn)行微生物計(jì)數(shù)或無菌測(cè)試，由方案中要求的可接受標(biāo)準(zhǔn)決定。 See Appendix 1 for information on the selection, sterilization and use of test materials. 見附錄 1測(cè)試物料選擇、滅菌和使用的信息。一般原則，不能在系統(tǒng)中引入任何物質(zhì)，不管是培養(yǎng)基或安慰劑，可能在隨后的加工中帶來問題。例如，帶有結(jié)晶工序的無菌原料藥模擬，在早期步驟模擬階段可能需要液體物料，而結(jié)晶工序后的步驟需要粉末物料。如果選擇了一種測(cè)試物料，進(jìn)一步需要決定選擇液體或粉末物料。每種選擇都有一定的優(yōu)點(diǎn)和缺點(diǎn)。 4. TEST MATERIALS USED IN PROCESS SIMULATION 工藝模擬使用的測(cè)試物料 Independent of the decision on whether the aseptic process is to be simulated in total or in unit operation fashion, consideration must be given to the selection of a material to be utilized in the simulation. The choices are: a microbiological growth promoting media, placebo material, simulation without material or actual product material (generally an excipient). With each choice there are of course certain advantages and disadvantages. Materials that inhibit microbiological growth should not be used. If a test material is utilized, a further decision between a liquid or powder material is also required. Those firms that have chosen to segment the process simulation according to the various unit operations may elect to make different selections for the test material in different parts of their overall program. For example, in sterile BPC simulations with a crystallization step, a liquid material may be used during simulation of the early steps, and a powder material in those steps which follow the crystallization step. 不管決定是模擬整個(gè)無菌工藝或部分單元操作的形式，應(yīng)考慮模擬使用的物料的選擇。 ? The methods required to evaluate individual unit operations may require more handling of sterile materials to acmodate a segmented process simulation. 個(gè)別單元操作的評(píng)價(jià)方法可能需要對(duì)更多的滅菌材料進(jìn)行處理，以適應(yīng)細(xì)分過程的模擬方法。 Disadvantages 缺點(diǎn) ? Requires more time to perform than a total process simulation. 相比總工藝模擬該方法需要更長(zhǎng)時(shí)間。 ? In the event of failure of a portion of an individual simulation, only that simulation which failed may need to be repeated after corrective action has been taken. 在個(gè)別模擬發(fā)生故障時(shí)，僅僅只是失敗的那個(gè)模擬需要采取糾正措施 ? In some aseptic processes, this approach may resemble the actual process more closely. 在一些無菌加工過程，這種做法可能于實(shí)際的工藝更為密切。 Advantages 優(yōu)勢(shì) ? If contamination is detected, the corrective measures can focus on a smaller portion of the overall process. 如果發(fā)現(xiàn)污染，糾正措施可以側(cè)重于整個(gè)進(jìn)程的一小部分。在進(jìn)行模擬的幾個(gè)步驟中，一個(gè)驗(yàn)收標(biāo)準(zhǔn)的建立，必須來自各單元操作的經(jīng)驗(yàn)累積。 ? Will generally require the use of a single test material (either liquid or solid) throughout the entire simulation which may introduce significant differences in the simulation and in how contamination might occur when pared to the routine production process. 通常會(huì)要求在整個(gè)模擬測(cè)試中使用單個(gè)測(cè)試材料（或液體或固體），和傳統(tǒng)的生產(chǎn)工藝相比，這有可能引起明顯的差異和污染。 Disadvantages 缺點(diǎn) ? If contamination is detected the identification and correction of sources is more difficult than in a unit operation simulation. 如果發(fā)現(xiàn)污染，污染源的識(shí)別和糾正比一系列單元操作模擬更加困難。 Advantages 優(yōu)勢(shì) ? The simulation may be able to follow the process more closely than a series of smaller simulations. 相比一系列的小型模擬測(cè)試，該 模擬測(cè)試更加貼近下列工藝。 應(yīng)當(dāng)承認(rèn)，決定進(jìn)行整體模擬或分步模擬方法于對(duì)微生物生長(zhǎng)介質(zhì)或其他材料在模擬中的使用是獨(dú)立的。如果一個(gè)無菌 BPC生產(chǎn)中所使用的所有操作單元都以適當(dāng)?shù)姆绞竭M(jìn)行評(píng)估，那么分段模擬方法作為一個(gè)全面的、在一次單獨(dú)模擬中涉所有操作單元的測(cè)試是非常合適的。無菌原料工藝的總生產(chǎn)工藝一般由一系列的單元工藝構(gòu)成。但修改需要注意不改變模擬結(jié)果以及相關(guān)慣例操作。 Risk assessment approaches such as hazard analysis and critical control point (HACCP), failure effects mode analysis (FEMA) or fault tree analysis (FTA) may be used to determine appropriate ，例如 HACCP、 FEMA或 FTA可以用于確定合適的挑戰(zhàn)。 In the development of protocols or procedures used for the definition of process simulation tests, the use of worst case challenges such as those described above is an essential element of a wellfounded program. 在建議用于定義工藝模擬試驗(yàn)的方案 或過程時(shí)，一個(gè)有良好根據(jù)的程序會(huì)使用上面提到的“最差條件”的挑戰(zhàn)。 The conduct of a process simulation for a sterile bulk typically includes activities and manipulations that are specific for its execution. 對(duì)于無菌原料的工藝模擬的進(jìn)行通常包括大量特定的活動(dòng)和操作。 ? performing a process simulation test after pletion of the last lot in a production campaign。 設(shè)備消毒的完成與開始模擬之間時(shí)間間隔過長(zhǎng) ? using a growth promoting medium or placebo material in the process simulation test rather than an inhibitory material。 使用人員數(shù)超過灌裝工藝所需。使用的原料、設(shè)備、器具等在滅菌后于無菌工藝區(qū)保留時(shí)間超出期限。 Process simulation tests readily lend themselves to worst case challenges. Some of t