歐盟GMP無菌新附錄解讀——影響性評估
歐盟GMP無菌新附錄解讀——影響性評估
發布日期：2017-03-15 18:11
附錄1第四章人員(yuán)章節，與前一(yī)版本的主要變化分(fēn)類解讀的摘譯如下(xià)：
Chapter 4 contains 16 clauses, compared with 10 from the 2007 version. Only 4 clauses are brand new, with others previously located in different sections of Annex.新的附錄1第四章有16條，2007版隻有10條。這16條中(zhōng)有4條是全新的。 以下(xià)爲本文中(zhōng)的術語解釋：
Brand New – clauses which do not have any significant correlation to an existing clause from the 2007 version of Annex 1. Each clause is categorized for potential impact individually.全新的——與附件1的2007版本中(zhōng)的現有條款沒有任何相關性的條款。每個條款分(fēn)别針對潛在的影響進行分(fēn)類。
Negligible Change – clauses that will not, or are unlikely to, require action to ensure compliance. These may be exact or near copies of previous clauses, or they may be reworded clauses where the intent has not changed.輕微的變化——可能不需要采取行動來确保合規的條款。可能是和前一(yī)版本條款的同樣的條款，或是意思沒有改變但重新進行描述的條款。
Minor Change – clauses which are likely only to affect a small number of manufacturers and require only a relatively small effort to become compliant.微小(xiǎo)變化——可能隻影響少數生(shēng)産企業的條款，隻需要相對較小(xiǎo)的努力就可以符合規定。
Moderate Change – Still a relatively small number of affected manufacturers, but requiring greater effort for compliance.中(zhōng)等變化——隻有相對較少的生(shēng)産企業受到影響，需要很多的努力以達到合規。
Significant Change – Even with the significant changes, there will be some manufacturers whose practices already align with the new clauses. These changes will be significant because the number of manufacturers currently non-compliant is notably higher than for other changes, and/or the effort to ddress compliance is likely to be substantial compared with other changes.重大(dà)變化——即使有重大(dà)變化，也會有一(yī)些生(shēng)産企業的做法已經與新的條款保持一(yī)緻。這些變化将是非常重要的，因爲目前不合規的生(shēng)産企業數量明顯高于其他的變化，并且/或者與其他變化相比，需要達到合規的難度更大(dà)。
Brand New Clauses in Chapter 4第四章中(zhōng)全新的條款
| Draft草案序号 | Subject内容 | Potential impact潛在影響 |
| 4.1 | Manufacturers required to have sufficient and appropriate qualified/ experienced personnel 生(shēng)産企業需要有足夠和合适的合格/有經驗的人員(yuán) | None – has long been an inherent requirement of the basic GMP principles (clause 2.1). This clause references sterile manufacturing and testing (arguably unnecessarily)無影響 - 長期以來一(yī)直是基本GMP原則的内在要求（條款2.1）。本條款引用了無菌生(shēng)産和測試。 |
| 4.4 | Detailed description of gowning and aseptic practice qualification, and ongoing monitoring. Significantly, requires Grade A operators to be monitored on every exit 更衣和無菌操作确認的詳細描述，以及持續的監控。需要重視的是，要求A級操作人員(yuán)每次離(lí)開(kāi)均需要進行檢測。 | Moderate – like that most organisations both qualify operators and monitor Grade A personnel on every exit. However, neither are uniformly global practices and both require considerable resource to implement and maintain.中(zhōng)等 - 大(dà)多數企業都對操作員(yuán)工(gōng)進行資(zī)格确認，并對每個出A級的人員(yuán)進行取樣檢測。然而，兩者均不是世界統一(yī)的操作，所以需要相當多的資(zī)源來實施和維持。 |
| 4.5 | Rules for disqualification of cleanroom personnel 取消潔淨室人員(yuán)權限的規定 | Moderate – likely that most organisations have disqualification rules, but they may not be fully consistent with this clause.中(zhōng)等 - 大(dà)多數企業可能有取消權限的規定，但可能與本條款不完全一(yī)緻。 |
| 4.6 | Establishment of procedures for non-qualified personnel entering cleanrooms 建立沒有接受過相應培訓和授權人員(yuán)進入潔淨室的程序 | Minor – likely that most organisations have such procedures, but some may not.輕微 - 大(dà)多數企業可能都有這樣的程序，少部分(fēn)可能沒有。 |
第四章中(zhōng)輕微改變
| Draft草案序号 | 2007 | Subject内容 | Explanation of “Negligible Change” Status“輕微的變化”的解釋 |
| 4.7 | 38 | Operator health conditions and checking 操作人員(yuán)的健康情況和健康檢查 | Almost exact copy. Some word usage clarified. Requirement for health checks changed from “desirable” to “should be performed”. 基本是完全照搬2007版，一(yī)些用詞更明确。健康檢查的要求從“理想”變成“應該執行” |
| 4.8 | 39 | Entry to sterile facilities after high risk activities 進行過高風險操作後進入無菌室 | Further defined the scope of high risk activities, but almost the same statement. 更進一(yī)步明确了高風險操作的範圍，描述幾乎相同。 |
| 4.11 | 42 | Cleanroom clothing type, quality and use 潔淨服的類型、質量和使用 | Exact copy 完全一(yī)緻 |
| Draft草案序号 | 2007 | Subject内容 | Change改變 | Explanation of “Minor Change” Status“微小(xiǎo)變化”的解釋 |
| 4.2 | 36 | Number of personnel in cleanrooms 潔淨室人員(yuán)數量 | Expanded to reference QRM for determination, document in CCS and validate. Additional emphasis on importance for aseptic processing 擴展引用QRM進行确定，在CCS中(zhōng)記錄并驗證。更重視無菌加工(gōng)的重要性 | Commonly already done, may prompt QRM and validation for some. 通常已經執行，可能有一(yī)些需要加強QRM和驗證 |
| 4.9 | 40 | Personal items in clean areas 潔淨區私人物(wù)品 | The previous list has been expanded to include “other personal items such as mobile phones” 之前的清單增加了“其他私人物(wù)品例如手機” | Lack of clarity over whether mobile phones should be prohibited altogether, or whether controlled use of company phones as communication devices in lower level clean areas (e.g. Grade D) may still be permitted. 對于是否應該全面禁止使用移動電(diàn)話(huà)，或者是否允許将公司電(diàn)話(huà)作爲低級别清潔區域（例如D級）的通信設備進行控制，尚不清楚。 |
| 4.16 | 73 | Operator behavior in cleanrooms 操作人員(yuán)在潔淨室的活動 | Adds statement regarding the potential to change air currents 增加關于潛在的對氣流的改變的說明 | Enables inspectors to seek airflow visualization studies where there is contention on operator intervention 在對操作員(yuán)幹擾有争議時，檢查人員(yuán)可以借助氣流可視化研究 |
| Draft草案序号 | 2007 | Subject内容 | Change改變 | Explanation of “Moderate Change” Status“中(zhōng)等變化”的解釋 |
| 4.3 | 37 | Training of all personnel involved in correct manufacture of sterile products 需要培訓所有無菌操作相關人員(yuán) | Adds qualification and assessment as an expectation and expands some definitions of roles 增加期望目标“确認和評估”，擴展了一(yī)些角色的具體(tǐ)定義 | Qualification and assessment of cleaning, maintenance and monitoring staff may not be universal. 對于清潔人員(yuán)，維修人員(yuán)和監測人員(yuán)的确認和評估可能不普遍。 The concept of assessment may be open to some interpretation 評估的概念展開(kāi)進行解釋 |
| 4.13 | 44 | Outdoor clothing and facility clothing 個人外(wài)衣和潔淨室工(gōng)作服 | Adds recommendation for dedicated socks prior to entry to Grade C 增加在進入C級之前穿專用襪子的建議 | This is not universal practice and may require changes to gowning requirements in many cases 這不是普遍的做法，很多情況下(xià)可能需要對更衣要求進行改變。 |
| 4.14 | 44 | Grade A/B garments A/B級服裝 | Adds requirement for sterile eyewear and garment change at least every work session 增加需要無菌眼罩，至少每班進行更衣 | Sterile eyewear has not been mandated in the past. Previously only masks and gloves were mandated for such frequent change. 無菌眼罩過去(qù)未被強制執行，之前隻有口罩和手套要求如此頻(pín)繁的進行更換 While many companies currently conform with the new requirement, there will be some organisations that have to make changes to gowning procedures. 雖然很多公司目前都符合新的要求，但也會有一(yī)些公司不得不改變更衣程序。 |
| 4.15 | 45 | Washing and sterilization of clean room garments 潔淨服的清洗和滅菌 | Almost verbatim version of previous clause, but adds requirement to check integrity after washing, prior to sterilization 幾乎照搬上一(yī)版本，但增加了在滅菌前清洗後需要檢查完整性 | As a mandated GMP requirement, this will need to be proceduralised, either by the outsourced laundry, or internally, if the washing is done in-house 作爲強制性的GMP要求，這将需要通過外(wài)包洗衣或者在内部進行程序化 |
第四章中(zhōng)的重大(dà)改變
| Draft草案序号 | 2007 | Subject内容 | Change改變 | Explanation of “Significant Change” Status “重大(dà)變化”的解釋 |
| 4.10 | 41 | Handwashing, changing and managing garments 洗手和管理服裝的改變 | Adds requirement for visual inspection of garments for cleanliness and integrity (on top of sterilization check) 在滅菌檢查之後，增加對服裝外(wài)觀清潔和完整性的要求 | Many organisations do cleanliness/integrity checks in a cursory or informal way. Now that it is mandated, will require more detailed procedures and arguably documented confirmation that it has been done 許多公司以粗略或非正式的方式進行清潔/完整性檢查。現在，它是強制性的，将需要更詳細的程序，并需要有證明文件證明已經完成 |
| 4.12 | 43 | Gowning requirements for all classified areas 所有控制區域的更衣要求 | Practically no change for C or D. C級和D級基本無變化。 A/B is changed in that: A/B級的改變如下(xià)： a)Sterile eyewear is mandated 強制要求佩戴無菌眼罩 b)Eyewear and masks shall cover all facial skin 眼罩和口罩必須遮住所有面部皮膚 c)Footwear must be sterilized (disinfection no longer sufficient) 鞋套必須是滅菌的（僅消毒是不夠的） | Most organisations already do (a), but even those who do may not meet (b). Some adjustment to application and/or components may be required. Item (c) is unlikely to be an issue in most countries, but the practice of using disinfected footwear is common in Asia, and will require modification. 大(dà)多數公司已經做到了（a），但是可能達不到（b）。可能需要對應用程序和/或組件進行一(yī)些調整。（c）項在大(dà)多數國家不太可能成爲問題，但在亞洲使用消毒鞋的做法很常見，需要修改。 |