歐盟GMP無菌新附錄解讀——影響性評估

發布日期：2017-03-15 18:11
Chapter 4 – Personnel第四章：人員
2017年12月29日歐盟發布的附錄1草案的第4章，與2007年附錄1中的“人員”部分相比，有較大的變化。新修改的條款在大部分都是根據行業先進的實踐做法，很大程度上改進了2007版附錄中不明確的條款。
附錄1第四章人員章節，與前一版本的主要變化分類解讀的摘譯如下：
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版只有10條。這16條中有4條是全新的。 以下為本文中的術語解釋：
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版本中的現有條款沒有任何相關性的條款。每個條款分別針對潛在的影響進行分類。
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確保合規的條款?？赡苁呛颓耙话姹緱l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.微小變化——可能只影響少數生產企業的條款，只需要相對較小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.中等變化——只有相對較少的生產企業受到影響，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.重大變化——即使有重大變化，也會有一些生產企業的做法已經與新的條款保持一致。這些變化將是非常重要的，因為目前不合規的生產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。
 Brand New Clauses in Chapter 4第四章中全新的條款
Draft草案序號Subject內容Potential  impact潛在影響
4.1Manufacturers  required to have sufficient and appropriate qualified/ experienced personnel
生產企業需要有足夠和合適的合格/有經驗的人員		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 - 長期以來一直是基本GMP原則的內在要求（條款2.1）。本條款引用了無菌生產和測試。
4.4Detailed  description of gowning and aseptic practice qualification, and ongoing  monitoring. Significantly, requires Grade A operators to be monitored on  every exit
更衣和無菌操作確認的詳細描述，以及持續的監控。需要重視的是，要求A級操作人員每次離開均需要進行檢測。		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.中等 - 大多數企業都對操作員工進行資格確認，并對每個出A級的人員進行取樣檢測。然而，兩者均不是世界統一的操作，所以需要相當多的資源來實施和維持。
4.5Rules for  disqualification of cleanroom personnel
取消潔凈室人員權限的規定		Moderate – likely  that most organisations have disqualification rules, but they may not be  fully consistent with this clause.中等 - 大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致。
4.6Establishment  of procedures for non-qualified personnel entering cleanrooms
建立沒有接受過相應培訓和授權人員進入潔凈室的程序		Minor – likely  that most organisations have such procedures, but some may not.輕微 - 大多數企業可能都有這樣的程序，少部分可能沒有。
Clauses with Negligible Change in Chapter 4
第四章中輕微改變
Draft草案序號2007Subject內容Explanation of  “Negligible Change” Status“輕微的變化”的解釋
4.738Operator  health conditions and checking
操作人員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，一些用詞更明確。健康檢查的要求從“理想”變成“應該執行”
4.839Entry to  sterile facilities after high risk activities
進行過高風險操作后進入無菌室		Further  defined the scope of high risk activities, but almost the same statement.
更進一步明確了高風險操作的范圍，描述幾乎相同。
4.1142Cleanroom  clothing type, quality and use
潔凈服的類型、質量和使用		Exact copy
完全一致
  Clauses with Minor Change in Chapter 4第四章中的微小改變
Draft草案序號2007Subject內容Change改變Explanation   of “Minor Change” Status“微小變化”的解釋
4.236Number of  personnel in cleanrooms
潔凈室人員數量		Expanded to  reference QRM for determination, document in CCS and validate. Additional  emphasis on importance for aseptic processing
擴展引用QRM進行確定，在CCS中記錄并驗證。更重視無菌加工的重要性		Commonly  already done, may prompt QRM and validation for some.
通常已經執行，可能有一些需要加強QRM和驗證
4.940Personal items  in clean areas
潔凈區私人物品		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話，或者是否允許將公司電話作為低級別清潔區域（例如D級）的通信設備進行控制，尚不清楚。
4.1673Operator  behavior in cleanrooms
操作人員在潔凈室的活動		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
在對操作員干擾有爭議時，檢查人員可以借助氣流可視化研究
 Clauses with Moderate Change in Chapter 4第四章中的中等改變 
Draft草案序號2007Subject內容Change改變Explanation of “Moderate Change” Status“中等變化”的解釋
4.337Training of all personnel involved in correct  manufacture of sterile products
需要培訓所有無菌操作相關人員		Adds qualification and assessment as an expectation and  expands some definitions of roles
增加期望目標“確認和評估”，擴展了一些角色的具體定義		Qualification and assessment of cleaning, maintenance  and monitoring staff may not be universal.
對于清潔人員，維修人員和監測人員的確認和評估可能不普遍。
The concept of assessment may be open to some  interpretation
評估的概念展開進行解釋
4.1344Outdoor  clothing and facility clothing
個人外衣和潔凈室工作服		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，很多情況下可能需要對更衣要求進行改變。
4.1444Grade 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.
無菌眼罩過去未被強制執行，之前只有口罩和手套要求如此頻繁的進行更換
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，但也會有一些公司不得不改變更衣程序。
4.1545Washing and  sterilization of clean room garments
潔凈服的清洗和滅菌		Almost  verbatim version of previous clause, but adds requirement to check integrity  after washing, prior to sterilization
幾乎照搬上一版本，但增加了在滅菌前清洗后需要檢查完整性		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
作為強制性的GMP要求，這將需要通過外包洗衣或者在內部進行程序化
Clauses with Significant Change in Chapter 4
第四章中的重大改變
Draft草案序號2007Subject內容Change改變Explanation of  “Significant Change” Status
 “重大變化”的解釋
4.1041Handwashing,  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)
在滅菌檢查之后，增加對服裝外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?，F在，它是強制性的，將需要更詳細的程序，并需要有證明文件證明已經完成
4.1243Gowning  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：
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.
大多數公司已經做到了（a），但是可能達不到（b）?？赡苄枰獙贸绦蚝?或組件進行一些調整。（c）項在大多數國家不太可能成為問題，但在亞洲使用消毒鞋的做法很常見，需要修改。