FAQs regarding Cross Contamination
1. Is it acceptable to refer to scientific papers for the Contamination Control Risk Assessment in addition to the general guidelines?
除了通用指南之外，在污染控制風(fēng)險評估中參考科學(xué)論文是否可以接受？
Yes. Both WHO and EMA in the EU GMP Guideline Part 3 QRM principles (ICH Q9) encourage the industry to include scientific data from literature after evaluation of being applicable to the specific case as well as toxicological evaluations from external sources in risk assessments, particularly for setting health-based exposure limits (HBELs) to decide which level of segregation is needed to avoid cross-contamination.
是的。世界衛(wèi)生組織（WHO）以及歐盟藥品生產(chǎn)質(zhì)量管理規(guī)范（GMP）指南第 3 部分質(zhì)量風(fēng)險管理（QRM）原則（國際人用藥品注冊技術(shù)協(xié)調(diào)會 Q9）都鼓勵制藥行業(yè)在評估文獻(xiàn)中的科學(xué)數(shù)據(jù)對特定案例的適用性后，將其納入風(fēng)險評估，同時也鼓勵納入來自外部的毒理學(xué)評估數(shù)據(jù)，尤其是在設(shè)定基于健康的暴露限值（HBEL）以確定需要何種程度的隔離措施來避免交叉污染時。
2. How and to what extent should surfaces that do not come into contact with the product be taken into account when considering the measures in avoiding cross contamination?
2.在考慮避免交叉污染的措施時，對于不與產(chǎn)品接觸的表面，應(yīng)如何以及在何種程度上加以考量？
Surfaces such as walls, floors, equipment exteriors and HVAC systems may be involved in cross contamination and should therefore be evaluated in a cross contamination control strategy. However, for cleaning validation EMA Annex 15 explicitly requires consideration of product contact surfaces.
墻壁、地板、設(shè)備外表面以及暖通空調(diào)系統(tǒng)等表面可能會參與到交叉污染中，因此應(yīng)在交叉污染控制策略中對其進(jìn)行評估。然而，對于清潔驗證，歐盟藥品管理局（EMA）附錄 15 明確要求考慮與產(chǎn)品接觸的表面。
3. Is a roughness of 0.8 µm a general requirement for good cleanability? Can you say a roughness of e.g. 1.6 is half as good?
3.表面粗糙度 0.8 µm是否是良好可清潔性的通用要求？是否可以說粗糙度為 1.6 µm（例如）的可清潔性是其一半？
Yes and no. 0.8 µm Ra is the widely accepted limit for cleanable GMP-grade stainless steel surfaces and can be considered as industrial standard. Cleanability is not linear; a surface of 1.6 µm is not "half as clean" - but it may trap significantly more residue. Also, cleanability is heavily dependent on the types of residues.
是也不是。0.8 µm的算術(shù)平均粗糙度（Ra）是可清潔的 GMP 級不銹鋼表面廣泛接受的限值，可被視為工業(yè)標(biāo)準(zhǔn)。可清潔性并非線性相關(guān) —— 粗糙度為 1.6 µm的表面并非 “清潔能力減半”，但其可能截留的殘留物會顯著增多。此外，可清潔性在很大程度上取決于殘留物的類型。
4. For OSD production in a shared facility: when is a clean corridor principle acceptable without an airlock for each production room and when is an airlock typically required?
4.對于共享設(shè)施中的口服固體制劑（OSD）生產(chǎn)：在什么情況下，不為每個生產(chǎn)房間設(shè)置氣閘而采用潔凈走廊原則是可接受的？在什么情況下通常需要設(shè)置氣閘？
Only under strict conditions. The clean corridor concept is acceptable if:
僅在嚴(yán)格條件下可行。清潔走廊概念可接受的情況如下：
clear unidirectional flow of personnel and materials exists
differential pressures are maintained
robust cleaning and containment (if applicable) are demonstrated
人流和物流嚴(yán)格單向
維持壓差
證明有可靠的清潔和密閉措施（如適用）
For potent APIs or highly sensitizing agents, dedicated airlocks are typically required per EU GMP Annex 3, PIC/S and ISPE Baseline® Guide for OSD.
對于高活性原料藥（APIs）或高致敏性物質(zhì)，根據(jù)歐盟 GMP 附錄 3、PIC/S（藥品檢查合作計劃）以及 ISPE（國際制藥工程協(xié)會）《口服固體制劑基準(zhǔn)指南》，通常需要為每個生產(chǎn)房間設(shè)置專用氣閘。
5. Which parameters does a "state of the art" cleaning verification measure?
5.一項 “優(yōu)秀” 的清潔驗證會測量哪些參數(shù)？
Typically:
通常包括：
Total organic carbon (TOC)
Specific active ingredient (API) residues
Bioburden / endotoxins (if applicable)
Conductivity/pH for cleaning agent residues
Visual inspection
總有機(jī)碳（TOC）
特定活性成分（API）殘留
生物負(fù)載 / 內(nèi)毒素（如適用）清潔劑殘留的電導(dǎo)率 /pH 值
目視檢查
6. How often does the periodical cleaning validation verification have to be performed?
6.定期清潔驗證確認(rèn)應(yīng)多久進(jìn)行一次？
According to a risk-based schedule. EU GMP Annex 15 and PIC/S PE009 recommend periodic requalification of cleaning processes. The frequency must be justified (e.g. every 1-3 years) and triggered by changes in:
根據(jù)基于風(fēng)險的計劃執(zhí)行。歐盟 GMP 附錄 15 和 PIC/S PE009 建議對清潔工藝進(jìn)行定期再確認(rèn)。頻率應(yīng)有合理依據(jù)（如每 1-3 年一次），并在以下情況發(fā)生變更時觸發(fā)：
product type
cleaning SOP
equipment
campaign duration
deviations or failures
產(chǎn)品類型
清潔標(biāo)準(zhǔn)操作程序
設(shè)備
活動持續(xù)時間
偏差或故障
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