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1. 無(wú)菌工藝模擬的目的

9.34 Periodic verification of the effectiveness of the controls in place for aseptic processing should include a process simulation test using a sterile nutrient media and/or surrogate in place of the product. Selection of an appropriate nutrient media should be made based on the ability of the media and/or surrogate to imitate product characteristics at all processing stages. Where processing stages may indirectly impact the viability of any introduced microbial contamination, (e.g. sterile aseptically produced semi-solids, powders, solid materials, microspheres, liposomes and other formulations where product is cooled or heated or lyophilized), alternative procedures that represent the operations as closely as possible can be developed and justified. Where surrogate materials, such as buffers, are used in parts of the process simulation, the surrogate material should not inhibit the growth of any potential contamination.

對(duì)無(wú)菌工藝的控制措施有效性的定期確認(rèn)，應(yīng)該包括一個(gè)使用無(wú)菌營(yíng)養(yǎng)培養(yǎng)基和/或安慰劑的工藝模擬試驗(yàn)。根據(jù)培養(yǎng)基和/或安慰劑在所有工藝階段模仿產(chǎn)品特性的能力，應(yīng)選擇適當(dāng)?shù)臓I(yíng)養(yǎng)培養(yǎng)基。如果加工階段可能間接影響任何引入的微生物污染的生存能力（例如無(wú)菌生產(chǎn)的半固體、粉末、固體材料、微球、脂質(zhì)體和其他制劑，其中產(chǎn)品被冷卻、加熱或凍干），應(yīng)盡可能地開(kāi)發(fā)并證明能夠代表操作的可替代程序。如在工藝模擬的某些地方使用替代品，如緩沖液，其不應(yīng)抑制任何潛在微生物污染的生長(zhǎng)。

2. 無(wú)菌工藝模擬的要求

9.40 Process simulation tests should be performed as part of the initial validation, with at least three consecutive satisfactory simulation tests that cover all working shifts that the aseptic process may occur in, and after any significant modification to operational practices, facilities, services or equipment (e.g. modification to the HVAC system, equipment, major facility shut down, changes to process, number of shifts and numbers of personnel etc.).

工藝模擬試驗(yàn)應(yīng)該執(zhí)行首次驗(yàn)證，每班應(yīng)有至少三個(gè)連續(xù)符合要求的、涵蓋所有無(wú)菌工藝中可能發(fā)生的換班的模擬試驗(yàn), 還包括操作、設(shè)施、服務(wù)或設(shè)備（如 HVAC 系統(tǒng)調(diào)整、設(shè)備、主要設(shè)施關(guān)閉、工藝變更、班次數(shù)和人員數(shù)量等）。

3.再驗(yàn)證要求

9.40 Normally, process simulation tests (periodic revalidation) should be repeated twice a year (approximately every six months) for each aseptic process, each filling line and each shift. Each operator should participate in at least one successful APS annually. Consideration should be given to performing an APS after the last batch prior to shut down, before long periods of inactivity or before decommissioning or relocation of a line.

對(duì)于每一種無(wú)菌工藝和灌裝線，工藝模擬試驗(yàn)(周期性再驗(yàn)證) 通常一年應(yīng)該被重復(fù)兩次(大約每六個(gè)月)，每個(gè)班次操作人員至少要每年參加。當(dāng)生產(chǎn)線長(zhǎng)期不使用、或者在停用或移位前，應(yīng)該考慮在最后一個(gè)生產(chǎn)批次后進(jìn)行一次無(wú)菌工藝模擬試驗(yàn)。

9.51 An aseptic process or filling should be subject to a repeat of the initial validation when:

在以下情況下，無(wú)菌過(guò)程或灌裝應(yīng)重復(fù)初始驗(yàn)證:

i. The specific aseptic process has not been in operation for an extended period of time.

特定的無(wú)菌生產(chǎn)工藝長(zhǎng)時(shí)間未生產(chǎn)。

ii. There is a change to the process, equipment, procedures or environment that has the potential to affect the aseptic process or an addition of new product containers or container-closure combinations.

工藝、設(shè)備、程序或環(huán)境變更有可能影響無(wú)菌工藝，或采用新的產(chǎn)品容器或密封件組合。