A 級(jí)：高風(fēng)險(xiǎn)操作區(qū)，如灌裝區(qū)、膠塞加料盤、敞口的安瓿和西林瓶、無菌對(duì)接。通常情況下，該條件下應(yīng)設(shè)有局部單向流保護(hù)，例如層流操作臺(tái)或隔離器。整個(gè) A 級(jí)區(qū)域的單向流的維護(hù)應(yīng)被證明或驗(yàn)證。應(yīng)通過設(shè)施、設(shè)備、工藝及過程的設(shè)計(jì)來最小化操作人員進(jìn)入 A 級(jí)區(qū)的直接干涉活動(dòng)（例如在沒有限制系統(tǒng)和手套箱技術(shù)的保護(hù)下）的次數(shù)。
Grade B area: For aseptic preparation and filling, this is the background cleanroom for the Grade A zone (where it is not an isolator). When transfer holes are used to transfer filled, closed products to an adjacent cleanrooms of a lower grade, airflow visualization studies should demonstrate that air does not ingress from the lower grade cleanrooms to the Grade B. Pressure differentials should be continuously monitored. Cleanrooms of lower grade than Grade B can be considered where isolator technology is used (refer to paragraph 4.22).
B級(jí)：對(duì)于無菌配制和灌裝等高風(fēng)險(xiǎn)操作， B 級(jí)區(qū)是 A 級(jí)潔凈區(qū)所處的背景潔凈室。當(dāng)使用傳遞孔來進(jìn)行傳遞灌封密閉產(chǎn)品至相鄰的低級(jí)別房間時(shí)，此處的氣流流行試驗(yàn)應(yīng)該證明低級(jí)別房間的空氣不會(huì)倒灌至 B 級(jí)別的房間。此處的壓差需要連續(xù)監(jiān)測(cè)。如果使用了隔離器技術(shù)，可以考慮比 B 更低級(jí)別（參照條款 4.22）。
Grade C and D area: These are cleanrooms used for carrying out less critical stages in the manufacture of aseptically filled sterile products but can be used for the preparation /filling of terminally sterilized products. (See section 8 for the specific details on terminal sterilization activities).
C級(jí)和D級(jí)：指用于執(zhí)行無菌填充產(chǎn)品生產(chǎn)過程不太關(guān)鍵的操作步驟的潔凈區(qū)， 但可用于制備/灌裝最終滅菌產(chǎn)品。（有關(guān)最終滅菌活動(dòng)的詳細(xì)信息，請(qǐng)參見第 8 節(jié)）。
In cleanrooms, all exposed surfaces should be smooth, impervious and unbroken in order to minimize the shedding or accumulation of particulates or micro-organisms and to permit the repeated application of cleaning, disinfectant and sporicidal agents where used.
潔凈室內(nèi)，所有暴露的表面應(yīng)光滑、無滲漏且無破損以盡可能降低微?；蛭⑸锏拿撀浠蚍e聚，并可耐受清洗劑、消毒劑和殺孢子劑的重復(fù)使用。
在密閉的隔離操作器或手套箱內(nèi)，可使用單向流或較低的風(fēng)速。
B級(jí)：指無菌配制和灌裝等高風(fēng)險(xiǎn)操作A級(jí)區(qū)所處的背景區(qū)域。
C級(jí)和D級(jí)：指生產(chǎn)無菌藥品過程中重要程度較低的潔凈操作區(qū)。
潔凈室和區(qū)域內(nèi)的氣流流形應(yīng)進(jìn)行可視化研究，以證明從低等級(jí)區(qū)域到較高等級(jí)區(qū)域沒有倒灌，并且空氣不會(huì)從較不潔凈的區(qū)域（例如地板）或經(jīng)過操作員或設(shè)備將污染傳遞至高級(jí)別的區(qū)域。其他需要證明氣流流型的區(qū)域應(yīng)通過風(fēng)險(xiǎn)評(píng)估來進(jìn)行。氣流流型的研究應(yīng)在動(dòng)態(tài)和靜態(tài)條件下進(jìn)行。記錄氣流流型的視頻應(yīng)保存。當(dāng)建立設(shè)施的環(huán)境監(jiān)測(cè)計(jì)劃時(shí)，應(yīng)考慮氣流可視化研究的結(jié)果。
氣閘的設(shè)計(jì)和使用應(yīng)能提供物理隔離以最大限度地降低不同區(qū)域的微生物和微粒污染，并為物料和人員在不同級(jí)別之間的移動(dòng)提供通道。如果可能，用于人流的氣閘間應(yīng)當(dāng)與用于物流的氣閘間分開。如果不能實(shí)現(xiàn)，應(yīng)該考慮按時(shí)間分別執(zhí)行人流、物流的程序。氣閘應(yīng)能被經(jīng)過濾的空氣有效地吹掃來確保潔凈級(jí)別的維持。氣閘的最后階段在靜態(tài)狀態(tài)下應(yīng)與其通向的潔凈室的潔凈度相同（活性和非活性顆粒）。進(jìn)入和離開 B 級(jí)潔凈室的更衣室期望獨(dú)立設(shè)置。在不可行的情況下，應(yīng)考慮按程序?qū)⒒顒?dòng)（進(jìn)/出）基于時(shí)間的分隔。如果 CCS（污染控制策略） 指出交叉污染的風(fēng)險(xiǎn)很高，則應(yīng)考慮進(jìn)入和離開生產(chǎn)區(qū)域的單獨(dú)更衣室。氣閘的設(shè)計(jì)應(yīng)如下：
Personnel airlocks: Areas of increasing cleanliness used for entry of personnel (e.g. from Grade D to Grade C to Grade B). In general hand washing facilities should be provided only in the first stage of the changing room and not be present in changing rooms directly accessing Grade B cleanrooms.
人流氣閘室：人員進(jìn)入更高級(jí)別潔凈度的區(qū)域（例如，從D 級(jí)到 C 級(jí)到 B 級(jí)）。通常來講，洗手設(shè)施只能在更衣室的第一階段提供， 并且直接進(jìn)入 B 級(jí)別的更衣室不能有洗手設(shè)施。
Material airlocks: used for materials and equipment transfer.Only materials and equipment that have been included on an approved list, developed during validation of the transfer process, should be allowed to be transferred into the Grade A zone or Grade B cleanroom via an airlock or pass-through hatch. Equipment and materials (intended for use in the Grade A zone) should be protected when transiting through the Grade B cleanroom. Any unapproved items that require transfer should be pre-approved as an exception. Appropriate risk assessment and mitigation measures should be applied and recorded as per the manufacturer’s CCS and should include a specific disinfection and monitoring programme approved by quality assurance.
物流氣閘：用于物料和設(shè)備的傳遞，只有包含在確認(rèn)列表部分中并且經(jīng)過傳遞驗(yàn)證的的物料和設(shè)備方可通過氣鎖或通道轉(zhuǎn)移進(jìn) A/B 級(jí)區(qū)域；當(dāng)在 A級(jí)區(qū)使用的設(shè)備、 物料從 B 級(jí)區(qū)轉(zhuǎn)移時(shí)， 應(yīng)該被保護(hù)起來。任何未經(jīng)批準(zhǔn)的物料需要轉(zhuǎn)移都屬于需要預(yù)先批準(zhǔn)的異常情況。應(yīng)根據(jù)生產(chǎn)商污染控制策略進(jìn)行適當(dāng)?shù)娘L(fēng)險(xiǎn)評(píng)估和降低措施，并予以記錄，應(yīng)包含由質(zhì)量保證部門批準(zhǔn)的特定的消毒和監(jiān)測(cè)程序。
Pass-through hatches should be designed to protect the higher grade environment, for example by effective flushing with an active filtered air supply.The movement of material or equipment from lower grade or unclassified area to higher grade clean areas should be subject to cleaning and disinfection commensurate with the risk and in line with the CCS.
傳遞窗的設(shè)計(jì)應(yīng)能保護(hù)較高等級(jí)的環(huán)境，例如通過使用主動(dòng)過濾的空氣進(jìn)行有效風(fēng)淋。將物料從低級(jí)別或未定級(jí)區(qū)域移至更高等級(jí)的潔凈區(qū)域時(shí)，應(yīng)進(jìn)行與其風(fēng)險(xiǎn)相稱清潔和消毒并符合 CCS（污染控制策略）。
Both sets of doors for pass-throughs and airlocks (for material and personnel) should not be opened simultaneously. For airlocks leading to a Grade A zone and Grade B areas, an interlocking system should be used. For airlocks leading to Grade C and D cleanrooms, a visual and/or audible warning system should be operated as a minimum. Where required to maintain zone segregation, a time delay between the closing and opening of interlocked doors should be established.
氣閘和傳遞窗兩端的門不得被同時(shí)打開。通向 A 級(jí)區(qū)和 B 級(jí)區(qū)的氣閘應(yīng)使用互鎖系統(tǒng)，并能防止有超過一扇的門被同時(shí)打開；對(duì)于通向 C 級(jí)區(qū)與 D 級(jí)區(qū)的互鎖，應(yīng)至少有一個(gè)可視和/或可聽的報(bào)警系統(tǒng)運(yùn)行。當(dāng)需要維持區(qū)域隔離時(shí)，應(yīng)建立互鎖門開關(guān)時(shí)間的延遲（即互鎖門關(guān)閉只有需要隔一段時(shí)間才能重新打開）。
Cleanrooms should be supplied with a filtered air supply that maintains a positive pressure and/or an airflow relative to the background environment of a lower grade under all operational conditions and should flush the area effectively. Adjacent rooms of different grades should have pressure differentials of a minimum of 10 pascals (guidance value). Particular attention should be paid to the protection of the critical zone. The recommendations regarding air supplies and pressures may need to be modified where it is necessary to contain certain materials (e.g. pathogenic, highly toxic or radioactive products or live viral or bacterial materials). The modification may include positively or negatively pressurized airlocks that prevent the hazardous material from contaminating surrounding areas. Decontamination of facilities (e.g. the cleanrooms and the heating, ventilation, and air conditioning (HVAC) systems) and the treatment of air leaving a clean area, may be necessary for some operations. Where containment requires air to flow into a critical zone, the source of the air should be from an area of the same grade.
潔凈室應(yīng)提供經(jīng)過過濾的空氣，該空氣供應(yīng)在所有操作條件下均相對(duì)于較低等級(jí)的背景環(huán)境保持正壓和/或氣流， 并能有效沖洗該區(qū)域。不同潔凈級(jí)別的相鄰房間之間應(yīng)維持至少 10 帕（指導(dǎo)值）的壓差。應(yīng)特別注意對(duì)風(fēng)險(xiǎn)級(jí)別最高的區(qū)域的保護(hù)，如包括一些物料， 如致病性的、高毒性、放射性或活病毒或細(xì)菌物料或產(chǎn)品，與送風(fēng)和壓差相關(guān)的建議可能需要調(diào)整， 調(diào)整可包括正壓或負(fù)壓氣閘，以防止有害物質(zhì)污染周圍區(qū)域。設(shè)施凈化，如潔凈室和空調(diào)系統(tǒng)，以及在某些操作時(shí)對(duì)排出潔凈區(qū)的空氣的處理可能是有必要的。如果防止外泄需要空氣流入關(guān)鍵區(qū)域，則空氣來源應(yīng)來自相同等級(jí)的區(qū)域。
Indicators of pressure differences should be fitted between cleanrooms and/or isolators. Set-points and the criticality of pressure differentials should be documented within the CCS. Pressure differentials identified as critical should be continuously monitored and recorded. A warning system should be in place to instantly indicate and warn operators of any failure in the air supply or reduction of pressure differentials (below set limits for those identified as critical). The warning signal should not be overridden without assessment and a procedure should be available to outline the steps to be taken when a warning signal is given. Where alarm delays are set, these should be assessed and justified within the CCS. Other pressure differentials should be monitored and recorded at regular intervals.
潔凈室和/或隔離器之間應(yīng)安裝壓差指示器。設(shè)定點(diǎn)和壓差的臨界值應(yīng)在 CCS（污染控制策略）文件化。被確定為關(guān)鍵壓差的應(yīng)得到連續(xù)監(jiān)測(cè)和記錄。應(yīng)建立警告系統(tǒng)以便立即向操作員指示并警告氣體供應(yīng)出現(xiàn)任何故障或壓差降低（低于確定為關(guān)鍵的限度值）。未經(jīng)評(píng)估，不得摒棄報(bào)警信號(hào)，并且應(yīng)提供程序概述發(fā)出警告信號(hào)時(shí)應(yīng)采取的步驟。如果設(shè)置了警報(bào)延遲，則應(yīng)在 CCS 內(nèi)對(duì)其進(jìn)行評(píng)估和證明。其他壓力差應(yīng)定期監(jiān)測(cè)和記錄。
氣鎖間兩側(cè)的門不應(yīng)同時(shí)打開?？刹捎眠B鎖系統(tǒng)或光學(xué)或（和）聲學(xué)的報(bào)警系統(tǒng)防止兩側(cè)的門同時(shí)打開。
在任何運(yùn)行狀態(tài)下，潔凈區(qū)通過適當(dāng)?shù)乃惋L(fēng)應(yīng)能確保對(duì)周圍低級(jí)別區(qū)的正壓，維持良好的氣流組織，保證有效的凈化能力。
當(dāng)使用或生產(chǎn)某些致病性、劇毒、放射性、活病毒、活細(xì)菌的物料或產(chǎn)品時(shí)，空調(diào)凈化系統(tǒng)的送風(fēng)和壓差應(yīng)作適當(dāng)調(diào)整以防止有害物質(zhì)外溢。必要時(shí)，生產(chǎn)操作的設(shè)備及該區(qū)域的排風(fēng)應(yīng)作去污染處理（如排風(fēng)口安裝過濾器）
應(yīng)設(shè)送風(fēng)機(jī)組故障的報(bào)警系統(tǒng)。應(yīng)在壓差十分重要的相鄰級(jí)別區(qū)之間安裝壓差表。壓差數(shù)據(jù)應(yīng)定期記錄或者歸入有關(guān)文擋中。
用于無菌工藝的 RABS 或開放隔離器的關(guān)鍵區(qū)域應(yīng)滿足 A 級(jí)區(qū)單向氣流要求。在氣流可能不是單向的封閉式隔離器系統(tǒng)中，應(yīng)提供 A 級(jí)條件，并應(yīng)證明在加工過程中為暴露的產(chǎn)品提供足夠的保護(hù)。RABS 和開放隔離器的設(shè)計(jì)，應(yīng)保證氣流從關(guān)鍵區(qū)域流向周邊區(qū)域(除非需要控制外泄，在這種情況下需要局部抽氣以防止污染物轉(zhuǎn)移到周圍的房間)。負(fù)壓隔離室應(yīng)僅在必須對(duì)產(chǎn)品進(jìn)行隔離的時(shí)候使用， 并采取風(fēng)險(xiǎn)控制措施以確保關(guān)鍵區(qū)域不受損害。
For RABS used for aseptic processing, the background environment should meet at least Grade B. The background environment for open isolators should meet Grade C or D, based on a risk assessment. Airflow studies should be performed to demonstrate the absence of air ingress during interventions, such as door openings.
對(duì)于 RABS，背景環(huán)境應(yīng)滿足 B 級(jí)區(qū)要求，根據(jù)風(fēng)險(xiǎn)評(píng)估，開放隔離器的背景環(huán)境應(yīng)達(dá)到C 級(jí)或 D 級(jí)。應(yīng)當(dāng)進(jìn)行氣流研究，以證明在干預(yù)過程中（例如門打開）沒有空氣進(jìn)入。
The background environment of a closed isolator should correspond to a minimum of Grade D. The disinfection/decontamination programme should be included as a key consideration when performing the risk assessment for the CCS of an isolator. Where additional process risks are identified, a higher grade of background should be considered. The decision as to the supporting background environment should be documented in the CCS.
封閉式隔離器的背景環(huán)境應(yīng)至少達(dá)到 D 級(jí)。在進(jìn)行隔離器 CCS 風(fēng)險(xiǎn)評(píng)估時(shí)，應(yīng)將消毒/凈化程序作為關(guān)鍵考慮因素。如果確定了其他過程風(fēng)險(xiǎn)，則應(yīng)考慮更高級(jí)別的背景。有關(guān)背景環(huán)境的決定應(yīng)記錄在 CCS中 。
物品進(jìn)出隔離操作器應(yīng)特別注意防止污染。
隔離操作器所處環(huán)境的級(jí)別取決于其設(shè)計(jì)及應(yīng)用。無菌生產(chǎn)的隔離操作器所處環(huán)境的級(jí)別至少應(yīng)為D級(jí)。
第十五條 隔離操作器只有經(jīng)過適當(dāng)?shù)尿?yàn)證后方可投入使用。驗(yàn)證時(shí)應(yīng)當(dāng)考慮隔離技術(shù)的所有關(guān)鍵因素，如隔離系統(tǒng)內(nèi)部和外部所處環(huán)境的空氣質(zhì)量、隔離操作器的消毒、傳遞操作以及隔離系統(tǒng)的完整性。
第十六條 隔離操作器和隔離用袖管或手套系統(tǒng)應(yīng)進(jìn)行常規(guī)監(jiān)測(cè)，包括經(jīng)常進(jìn)行必要的檢漏試驗(yàn)。
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