[技术] 灭菌验证确认需考虑的10件事

AutoclaveValidation / Qualification is mandatory for all machines used for biologicalsterilization, in the biomedical and pharmaceutical industries. Sterilizationcan be accomplished by either physical or chemical means. The principalphysical means is autoclaving; other physical methods include boiling and dryheat.

灭菌器验证/确认对于所有用于生物灭菌、生物医学和制药行业的设备都是强制的，灭菌可以通过物理或者化学的方式，主要物理方式就是高压灭菌法，其他物理方法包括沸腾和干热。

Chemicalsused for sterilization include the gases ethylene oxide and formaldehyde, andliquids such asglutaraldehyde . Of all these sterilants, autoclaving is thefastest and most reliable, which is why the regulators always scrutinizeautoclave validation / Qualification activities. Here are 10 items to considerwhen qualifying autoclaves.

采用化学物质进行灭菌的包括气体环氧乙烷和甲醛，液体如戊二醛。所有这些消毒剂，其中高压灭菌法是最快最可靠的，这也是为什么监管机构总是会仔细审查高压灭菌器验证/确认活性，这里有10条注意事项需在高压灭菌柜确认中考虑的问题。

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• Testingof Steam for Porous Product Sterilization Before commencing temperature testingthe correct conditions must be satisfied. The first condition for sterilizationof porous product is saturated steam quality. The ideal for steam sterilizationis dry saturated steam and entrained water (dryness fraction ≥ 97%). Thelargest heat transfer occurs when the steam is at boundary conditions. If thesteam is dry or contains gas then it cannot condense and its effectiveness isreduced.
  在对多孔产品蒸汽灭菌测试开始前必须满足正确的测试条件。首要条件是灭菌产品的饱和蒸汽质量。理想状态下的灭菌蒸汽是干燥饱和蒸汽和携带水（干燥度≥97%）。最大的热传递放生在蒸汽临界条件。如果蒸汽干燥或则含有气体，它将无法凝结导致效率降低。
  
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• EquipmentUsed for Testing The equipment used must support 21 CFR Part 11 and must be ofadequate accuracy. Testing with equipment that is not appropriate can be amajor problem so also buy from a trusted vendor. As a small temperature rangeis required for accuracy (A few degrees) the accuracy of the equipment is veryimportant for the overall measuring chain.
  用于测试的设备必须能够满足21CFR第11部分的要求，必须足够精准。测试用设备不合适也可能是一个重大问题，因此，需从值得信赖的供应商处购买。作为小温度范围准确度要求（几度）,设备的整体测量链条的准确性是非常重要的。
  
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• SystemDescription of Autoclave The first impression is very important when thequalification of critical equipment such as an autoclave is at stake. A gooddescription of the system in a protocol shows that you understand how theprocess works and which critical points you need to keep under control. Thisdescription must contain the programs that are used, how they work, how many,where the control probes are located and what regulates this process.
  在关键设备如高压灭菌器的确认中的系统描述作为第一印象是非常重要的。优秀的描述可以看出你对设备的了解和设备所有关键点都是可控的。这些描述必须包含使用的所有程序，设备怎么工作，多少控制探头位于设备那个位置，如何调节整个程序。
  
  
• OperatingInstructions, Calibration and Maintenance Before the temperature is tested itmust be checked whether the operating instruction are valid, whether theinstruments are calibrated and what was changed in the system since the lastqualification occurred. Operating Instructions must include parameters ofsterilization, the scheme item and position of the control probes in thechamber. The emphasis is on the calibration of instruments because small errorsin temperature can affect the Fo value to a great extent.
  使用说明书、校验和维护温度测试之前必须确认和检查操作指令是否有效。是否设备经过校准和系统从上次到现在经过了维护。使用说明书必须包括灭菌参数，计划项目和温度探头在前提中的位置。而重点是仪器的校准，因为微小的温度错误将导致很大程度上F0值的影响。
  
  

• ProcedureOne of the most common mistakes is inaccurate testing procedures. The testprocedure must be unambiguous and accurate and must not leave the possibilityfor different interpretations. Ambiguous: Put the thermocouple in a glassbottle. Unambiguous: Put the thermocouple in a glass bottle at the contact between the bottom of the bottle and the side of the bottle (This is the most criticalplace to collect condensate). Related: Train Your Staff on Risk Based EquipmentQualification.
  过程的一个最常见错误是不准确的测试程序。这个测试程序必须明确和准确，不得产生不同的解释。模棱两可：热电偶放置于玻璃瓶中。明确：把热电偶放置于玻璃瓶的底部和边缘之间（这个是收集冷凝最关键的地方）。相关：培训你的员工基于风险的设备确认
  
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• LoadThe most common objections are about loads. That they are not sufficientlydescribed and that regular production does not reflect the qualified load beingused. This can be avoided by item photographing and releasing the same patternsin the protocol and work instructions. This will avoid the arbitraryinterpretation of descriptive configuration. Although sometimes this may seemtrite the differences in the temperature profiles of the solution and airfilters can be great. Pay special attention to the worst case loads and explainthe rationale (mostly filter and silicone hose).
  负载最常见的问题是关于装载。描述不充分，导致生产不能将确认过的装载使用到实际生产中。可以采用拍照和方案中装载模式作对比。这个将避免描述性问题的任意解释，尽管有时温度分布和空气过滤器似乎已经是老生常谈的问题。特别注意最坏情况的装载解释（主要是过滤器和硅胶管。）
  
  

• The Position of the Thermocouples The position of the thermocouples must beunambiguous and precise to avoid different interpretations by individuals thatperform tests or inspections. You do not want to enter into a debate aboutwhere the thermocouple is positioned. Of course, the critical areas must becovered, and this must be explained in the rationale. When sterilizing liquidloads studies must be done to define coldest and warmest point for min and maxload.
  热电偶位置，热电偶位置必须明确和准确，以避免执行过程不同的解释。不要进入讨论热点偶位置。当然关键区域必须被覆盖到，这个必须在基本原理解释到，当灭菌液体装载验证中必须对最大和最小装载进行测试以确定最冷和最热点。
  
  
• AcceptanceCriteria in the Heat Penetration Tests Since there are differences in thestandards (e.g. PDA Technical Report and EN 285) it would be best if alleligibility criteria are taken into account. Special emphasis should be onequilibration time and temperature because it is a requirement for a good Fo.
  热穿头测试的接受标准，法规之间的差异性（如PDA技术报告和EN285）,最好考虑到所有合格标准是最好的。特别强调应该在平衡时间和温度，因为他要求一个好的F0值。
  
  

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• DeviationsDeviations cannot be forgotten as they may be encountered regularly throughoutthe qualification process. A robust deviation management process should existas they may impact the quality of the product. Good handling of deviations helpus to improve our qualification, though they are often viewed negatively andnot as a mechanism for process improvement.
  偏差。偏差不能被遗忘，因为他们可能在整个确认过程经常遇到。一个有效的偏差管理过程应该存在，因为他们可能会影响产品的质量。良好的偏差处理程序帮助我们关键我们的确认，尽管他们常常被认为是负面和作为过程改进的一种机制。
  
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• ReportsThe report should be accurate as it eliminates the use of data from theprotocol and the ability to find errors in them. The report should contain thetime and the date of tests, parameters, results related to temperature, BIresults, positions of thermocouples, Fo and comparison of results from initialand previous qualification in order to see in which direction the process ismoving.
  报告。报告的数据应该准备，因为他们消除了方案中使用的数据和发现错误的能力。报告应该包含时间和日期，参数，温度结果，BI结果，热电偶位置，F0和最初的对比结果，确定工艺偏移的趋势
  
  

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