不同微生物對消毒劑的抗性也各不相同。它們的順序從大到小的排列如下：

化學(xué)消毒劑按他們的化學(xué)型分類。其中包括醛，醇，鹵素，過氧化物，季胺類化合物，和酚類化合物。

抗微生物化學(xué)試劑可分為三類：殺菌劑，消毒劑和殺孢子劑。這里列出的是通常與每個類別相關(guān)聯(lián)的試劑類型。

由于蒸發(fā)快、殘留低的特點，消毒已被帶入APA的物品時應(yīng)使用醇類（即異丙醇和乙醇）化學(xué)試劑。除非與材料存在相容性問題，應(yīng)使用70％異丙醇（IPA）代替70％乙醇（ EtOH），因為異丙醇的殺菌作用被認為比乙醇稍大。雖然醇類對活細胞具有相對較好的殺菌活性，但醇類的快速揮發(fā)顯著降低了其效力。醇類殺菌劑對孢子無效。

酚類和季銨化合物對活細胞具有廣譜殺菌活性。這些化學(xué)物質(zhì)典型特征會帶來表面殘留。緊隨它們的使用應(yīng)清除該部分殘留，例如通過異丙醇擦拭清除。

次氯酸鈉（漂白劑）和過氧化氫/過氧乙酸化合物是廣泛使用的殺孢子劑。過氧化氫也可用于（通常在6％濃度）提供對霉菌和一些孢子形式微生物提供抗菌活性。過氧化物比醇類抗菌活性更高，分解后形成水和氧氣，不產(chǎn)生留殘。當(dāng)消毒程序要求清除孢子類微生物時應(yīng)采用化學(xué)殺孢子劑。不幸的是，除過氧化氫外這些化學(xué)品均有一定殘留。

New suppliers and new antimicrobial chemical agents for use in the disinfection program should be qualified prior to use following established procedures. A satisfactory audit, qualification testing, and a clearly defined
Certificate of Analysis (CoA) are important aspects to be considered as part of the qualification. If changes occur in the agent\'s formulation, packaging, or manufacturing site, an evaluation should be performed to determine if requalification is required.

用于消毒程序的新的供應(yīng)商和新的殺菌化學(xué)試劑應(yīng)在使用前根據(jù)建立的程序進行確認。令人滿意的審計、確認測試和清楚定義的檢驗報告（ COA）被認為是確認中的重要部分。如果試劑的配方、包裝或生產(chǎn)場所有所變更，則應(yīng)進行評估以確定是否需要重新確認。

When choosing a new antimicrobial chemical agent from a supplier, evaluate the supplier\'s:
在從一個供應(yīng)商處選擇一個新的殺菌化學(xué)試劑時，要評估供應(yīng)商的：

• Product literature/technical data
  產(chǎn)品文字/技術(shù)數(shù)據(jù)

• Material safety information
  物料安全信息

• Material compatibility
  物料相容性

• Compatibility information
  相容性信息

• Storage conditions
  存貯條件

• Packaging presentations
  包裝

• Expiring dating
  有效期

• Disposal requirements
  處理要求

• Efficacy data
  有效性數(shù)據(jù)

• Sterility and sterilization information (if the product is provided sterile)
  無菌和滅菌信息（如果產(chǎn)品是作為無菌產(chǎn)品）

In evaluating supplier information related to the efficacy of an antimicrobial chemical agent, it is important to understand the testing methodology and standards used. These often vary depending on where the agent was registered and the claims made regarding its use. 
在評估關(guān)于殺菌化學(xué)試劑有效性的供應(yīng)商信息時，了解所用的測試方法和標準非常重要。這些通常根據(jù)試劑注冊地不同，以及關(guān)于其用途的聲明而有差異。

Depending on the specific use of the antimicrobial chemical agent and experience with the specific supplier, an audit may need to be performed. Extra attention should be given to the following during an audit:

根據(jù)殺菌化學(xué)試劑的特定用途和特定供應(yīng)商的經(jīng)驗，可能需要進行審計。在審計中需要注意以下方面：

Environmental control and cleaning of the manufacturing or packaging area and equipment used to manufacture the antimicrobial chemical agent.
用于生產(chǎn)殺菌化學(xué)試劑的生產(chǎn)或包裝區(qū)域和設(shè)備的環(huán)境控制和清潔

Control and disinfection or sterilization of the antimicrobial chemical agent packaging containers.
殺菌化學(xué)試劑包裝容器的控制和消毒或滅菌

• Documentation and review of antimicrobial chemical agent production processing activities.
  殺菌化學(xué)試劑生產(chǎn)處理活動的文件記錄和審核

• For aseptically filled agents, the environmental monitoring (EM) program data, including alert and action levels, trending, corrective actions taken, and the use of neutralizing agents for the EM media used.
  對于無菌灌裝試劑，環(huán)境監(jiān)測（ EM）程序數(shù)據(jù)，包括警戒限和行動限、趨勢、所采取的糾正措施以及所用EM培養(yǎng)基的中和劑使用

• For agents labeled as sterile, sterility testing data and qualification of the sterilization process.
  對于標識為無菌的試劑，無菌測試數(shù)據(jù)和無菌工藝確認

• Water systems and the quality of water used in the manufacturing process.
  水系統(tǒng)和工藝用水的質(zhì)量

• Package or container integrity studies.
  包裝或容器完整性研究

• For double- and triple-bagged containers, disinfection of filled container and overwrapping integrity.
  對于雙層或三層袋裝容器，灌裝容器消毒和外包裝完整性

• For double- and triple-bagged containers where a claim of sterility is made for inner bags, qualification of the sterilization process used.
  對于雙層和三層袋裝容器，如果內(nèi)袋有無菌聲明，所用的滅菌過程的確認

• Handling and storage of finished product containers or work in progress.
  成品容器或中間產(chǎn)品的處理和存貯

• Study results to support label claim of agent.
  支持試劑標簽聲明的研究結(jié)果

• Documentation related to regulatory approval of agent.
  與試劑法規(guī)批準有關(guān)的文件記錄

• Change control: customer notification of ingredient changes or process changes that would affect the finished product—for example, wrapping, irradiation, and sterilization.
  變更控制：會影響成品，例如，包裝、輻射和滅菌，的成分變更或工藝變更時對客戶的通知
  

Qualification testing of a new antimicrobial chemical agent should include both laboratory and insitu testing. Chemical analysis of the actives and microbial efficacy testing should be performed.
對一個新的抗菌化學(xué)試劑的確認測試應(yīng)包括化驗室和現(xiàn)場測試。要進行活性化學(xué)分析以及微生物有效性測試。

Chemical analysis of the actives may be provided by the vendor or, alternatively, performed in-house or by a qualified contract laboratory using the vendor\'s method. Microbial efficacy testing, whether in suspension or in
carrier studies, should be performed in-house or by a qualified contract testing laboratory.
活性化學(xué)分析可以由供應(yīng)商提供，或者內(nèi)部測試，或由一個經(jīng)過確認的合同化驗室使用供應(yīng)商的方法進行測試。微生物有效性試驗，如果是在混懸液中或在載體研究中，應(yīng)內(nèi)部進行測試，或由經(jīng)過確認的第三方化驗室進行測試。

The antimicrobials chemical agents used for testing should be close to or beyond their stated in-use expiration date (this should take into account a ready to use and/or a use dilution prepared from a concentrate expiry). Testing should be done in replicate on multiple lots of the antimicrobial chemical agent where applicable. It should be noted that significant registration testing on multiple lots of the agent is performed by the company registering the product to ensure product consistency between lots and stability throughout the stated shelf life.
用于測試的抗菌化學(xué)試劑應(yīng)鄰近或超出其使用有效期（這里要考慮直接使用和/或稀釋使用時濃縮液的有效期）。如果可以的話，應(yīng)對多個批次進行平行測試。要注意的是對多批試劑的重要的注冊測試是由注冊公司來進行的，以確保產(chǎn)品不同批次之間的一致性，以及其所聲明的整個貨架期的穩(wěn)定性。

Additional qualification may be performed if changes in product formulation or packaging or site investigations deem it necessary. Information supporting the qualification includes the following seven areas:
如果生產(chǎn)配方或包裝進行了變更，或現(xiàn)場調(diào)查認為必要時，可能需要進行再次確認。支持確認的信息包括以下七個方面：

• Description of packaging, label, and container type
  包裝、標簽和容器類型描述

• Description of ingredients and concentrations
  成分和濃度描述

• Lot or batch number
  批號

• Efficacy testing results
  有效性測試結(jié)果

• Irradiation or other sterilization verification certification
  輻射或其它滅菌確認認證

• Safety data sheet information
  

  安全數(shù)據(jù)信息表

• Disposal information
  處理信息
  

Efficacy Testing 

有效性測試

The demonstration of antimicrobial chemical agents to provide their respective kills is a function of the concentration of microorganisms present, the type of microorganisms, the choice of agent, the concentration of the agent, the porosity or texture of the surface to be cleaned, the method of application, and the contact time.Routinely, the agent used should be effective against the normal microbial vegetative flora recovered from the facility. Many efficacy testing guidelines, such as the Association of Official Analytical Chemist (AOAC), suggest high microorganism inoculum levels requiring longer contact times to destroy the population of cells . As the normal clean room bioburden level is very low, the inoculum levels for testing would ideally depict levels seen in the controlled area. As this would not be practical in a test environment ahigher inoculum level should be used and should not exceed 105. The antimicrobial chemical agent used within the industry can be broken into three general areas: sanitizers, disinfectants, and sporicides.
抗菌化學(xué)試劑殺滅效果是被殺滅微生物濃度、微生物類型、試劑選擇、試劑濃度、要清潔的表面的孔隙度或質(zhì)地、所使用的方法以及接觸時長的函數(shù)。一般來說，所用的試劑應(yīng)對從設(shè)施中回收到的常規(guī)微生物植物群落有效。許多有效性測試指南，例如美國分析化學(xué)家協(xié)會（ AOAC），建議高濃度微生物接種需要更長的接觸時長以摧毀細胞群。由于常規(guī)潔凈間生物負載水平非常之低，測試的接種水平理想地描述了受控區(qū)域所見水平。由于這種情況在測試環(huán)境中不現(xiàn)實，需要使用更高的接種水平，應(yīng)超出105。行業(yè)內(nèi)所用的抗菌化學(xué)試劑可以分為三個常規(guī)區(qū)域：滅菌劑、消毒劑和殺孢子劑。

Sanitizers 

滅菌劑

Sanitizers provide minimal reduction in thirty seconds to ten minutes and are often used for low levels of vegetative microorganisms. The type of sanitizer will dictate the appropriate contact time required. Alcohol is an example of a commonly used sanitizer.
殺菌劑提供在30秒到10分鐘最小減少量，通常用于低水平的植物性微生物。滅菌劑的類型決定了所需適當(dāng)?shù)慕佑|時長。乙醇是常用的滅菌劑的例子。

Disinfectants

 消毒劑

Disinfectants exhibit a higher level of efficacy than sanitizers, and their kill is dependent on the inoculums and the contact time. Disinfectants will typically kill vegetative microorganisms with the exception of spore-forming microorganisms. Examples include quaternary ammonium compounds and phenolics.
消毒劑比滅菌劑具有更高的有效性，其殺滅性與接種水平和接觸時長無關(guān)。消毒劑一般會殺滅植物性微生物，孢子形態(tài)除外。消毒劑例子包括季胺鹽和酚醛物。

Sporicides 

殺孢子劑

Sporicides provide up to a total kill depending on the inoculums and the wet contact time and will kill bacterial spore formers as well as mold. Products commonly used today include bleach, hydrogen peroxide, and a mixture of hydrogen peroxide and peracetic acid.
殺孢子劑提供全面殺滅性，其殺滅能力與接種水平、濕潤接觸時長有關(guān)，能殺滅細菌孢子形態(tài)以及霉菌。現(xiàn)今常用產(chǎn)品包括漂白劑、過氧化氫、過氧化氫和過氧乙酸混合物。

In general, contact or dry times in qualification studies should not exceed 120 seconds for alcohols (70% isopropanol and 70% denatured ethanol) and 10 minutes for disinfectants and sporicides. Longer contact times may be required based on the specific chemical agents used.
一般來說，在確認研究中接觸時長或干燥時長，乙醇（ 70%異丙醇，和70%變性乙醇）應(yīng)超過120秒鐘，消毒劑和殺孢子劑應(yīng)超過10分鐘。如果所用的是特定的化學(xué)試劑，可能需要更長的接觸時長。

Methods to demonstrate efficacy include in-suspension and surface carrier (coupon) studies. In general, a total of three antimicrobial chemical agents (sanitizer, disinfectant, or sporicide) are all that would be qualified within the typical biopharmaceutical or pharmaceutical facility. While historically it was thought that a wide array of disinfectants were required to minimize the buildup of facilityresistant microorganisms, this is no longer a widely
held belief.
證明有效性的方法包括懸浮液和表面載體（樣本）研究。一般來說，三種抗菌化學(xué)試劑（殺菌劑、消毒劑或殺孢子劑）的總合都要在典型的生物藥品或藥品設(shè)施里進行確認。歷史上曾經(jīng)有過想法需要寬范圍的消毒劑來最大程度減少設(shè)施耐藥菌的累積，但現(xiàn)在這種想法已不再廣泛流行了。