清洁验证可接受限度(中英文版)(PDA TR 49内容节选3)
FDA清洁验证检查指南(中英文对照)
FDA清洁验证检查指南（中英文对嬉）清洗过程验证检查指南GUIDE TOINSPECTIONS VALIDATION OF CLEANINGPROCESSES请注意：本指南是检查官和其他FDA人员的参考材料。
本指南不受FDA约束,并没有赋予任何人任何权利、特权、收益或豁免权。
I•介绍L INTRODUCTION自从机构文件，包括原料药化学制剂检查指南和生物制剂检查指南，大体上提到该清洗问题以来，就出现了关于清洗过程验证的大量讨论。
这些机构文件清晰的建立了要验证的清洗过程需要达到的要求。
本指南是为了通过讨论实际操作是可接受的（或不可接受的），来建立检查要求的一致性和统一性。
同时，对清洗验证需要了解的是，像其他过程验证一样，可能有不止一种方法来对过程进行验证。
最后，任何验证过程的测试就是指科学数据是否显示出系统与要求相符和产生的结果是否符合预先定义的参数指标。
本指南只适用于化学残留物的设备清洗。
II•背景对于FDA来说,要求设备在使用前进行清洗并不新奇o1963GMP 法规倍B分133.4）中指出"设备S应该按照清洁和有序的方式进行维K在1978 CGMP法规中也包含了非常相似的有关设备清洗的护***o童节（211.6刀。
当然,清洁设备的主要理由是防止药品被污染或掺假。
在历史上，FDA检查官寻找由于对设备不当的清洗和维护和/或不良的灰尘控制系统而带来的总体不卫生情况。
而且，从历史上来说，FDA对非青霉素药品中的青霉素污染或药品中的活性激素或荷尔蒙交叉污染更加关注。
有很多药品在过去十年中被撤回就是因为实际的或潜在的青霉素的交叉污染。
导致FDA对由于不满足要求的过程导致交叉污染的可能性的进—步关注的案例是，1988年对成品药消胆胺树脂USP的撤回。
用于生产成品的原料药被生产农用杀虫剂中产生的中间体和降解物污染。
本案例中的交叉污染被认为是由于回收溶剂的重新使用。
回收溶剂由于缺乏对溶剂桶的重新使用的控制而被污染。
APIC 201405原料药厂清洁验证指南：4.0可接受标准
APIC 201405原料药厂清洁验证指南：4.0可接受标准（上）（中英文）注：本文件是由CEFIC 的APIC内的清洗验证工作组制定。
CEFIC: 欧洲化学工业委员会(cefic,europeanchemicalindustrycouncil)4.0 Acceptance Criteria 可接受标准4.1. Introduction 概述Companies must demonstrate during validation that the cleaning procedure routinely employed for a piece of equipment limits potential carryover to an acceptable level. That limit established must be calculated based on sound scientific rational.公司在验证时要证明各设备日常所用的清洁程序能将带入下一产品的潜在残留限制在一个可以接受的水平。
所建立的限度必须进行科学合理的计算。
This section provides practical guidance as to how those acceptance criteria can be calculated. It is important that companies evaluate all cases individually. There may be specific instances where the product mix in the equipment requires further consideration.本部分提供实用的指南，指导如何计算这些可接受标准。
公司对各案进行各案评估是非常重要的。
有时还需要考虑产品从哪步开始混入设备中。
The acceptance criteria preferably should be based on the Acceptable Daily Exposure (ADE) calculations whenever this data is available. The Acceptable Daily Exposure defines a limit at which a patient may be exposed every day for a lifetime with acceptable risks related to adverse health effects. Calculations of Acceptable Daily Exposures of API’s and intermediates are usually done with involvement of industrial hygienists and toxicologists, who review all available toxicology and clinical data to set the limits. The justification of the calculation should be documented.如果可以获得可接受日暴露（ADE）值，最好依据其计算可接受标准。
中英文 PDA TR 无菌生产设施的清洁消毒程序原理
14.8 Aspects of a Disinfection Program 14.9 Assessment of Understanding and Qualification 15.0 CONDUCTING INVESTIGATIONS RELATED TO CLEANING AND DISINFECTION 16.0 CONCLUSION 17.0 APPENDIX I: HISTORY OF DISINFECTION 17.1 Disinfecting Technologies ofthe Past 17.2 Disinfecting Technologies in the Age of Chemistry 17.3 Discovering Microorganisms as a Basis of Disease 17.4 Microbiological Contamination Control Today 18.0 APPENDIX II: REGISTRATION OF SANITIZERS, DISINFECTANTS AND SPORICIDES 19.0 APPENDIX III: OVERVIEW OF THE U.S. ENVIRONMENTAL PROTECTION AGENCY 20.0 APPENDIX IV: OVERVIEW OF THE EU BIOCIDAL REGULATIONS
21.0 APPENDIX V: EPA-RELATED SAFETY LABELING INFORMATION
22.0 APPENDIX VI: AOAC PROTOCOL TESTING FOR DISINFECTANT REGISTRATION 23.0 APPENDIX VII: EN TESTS FOR DISINFECTION EFFICACY 24.0 APPENDIX VIII: LARGE-SCALE GASSING OR FOGGING OF CLEAN ROOMS
清洁验证之分析方法-下(中英文版)(PDA TR 49内容节选7 )
清洁验证之分析方法-下(中英文版)（PDA TR 49内容节选7）6.5 Analytical Method Validation6.5 分析方法验证This section focuses on analytical method validation for “chemical” residues.这部分关注化学残留的分析方法验证Typically, endotoxin methods are compendia methods and do not require formal validation but require a confirmation for their application of use or suitability.内毒素方法是药典方法，不需要正式的验证，但需要使用或者适用性确认。
Microbiological methods that are approved microbiology laboratory methods do not require additional method validation.被微生物学实验室方法批准的微生物方法不需要额外的方法验证。
6.5.1 General Principles6.5.1 基本原则Since one key part of cleaning validation is setting residue limits and then measuring (using an analytical method) the actual residues left on surfaces after cleaning, it is critical that the analytical method be appropriately validated.因为清洁验证主要的一部分是设定残留限度，然后测量(使用分析方法)清洁后表面的实际残留。
清洁验证精选全文
清洁确认：每次清洁时，按批准的清洁方法进行清洁并取样检测，直到达到预期的结果为止。
二、10版GMP的要求（附录：确认与验证）
二、10版GMP的要求（附录：确认与验证）
二、10版GMP的要求（附录：确认与验证）
二、10版GMP的要求（附录：确认与验证）
NOEL：无明显作用水平
方法一、基于最低日治疗剂量的1/1000 Based on Drug Active Dose
公式：PAD T29
L---公用设备允许残留总量，mg MTDDprevious---清洁前产品最低日治疗剂量A活性成分，mg LDDnext-----清洁后要生产的产品B制剂的最大日治疗剂量，mg MBSnext------清洁后要生产的产品B制剂的最小批量，kg
原因分析
日常监控
再验证
变更管理
否
是
否
是
是
三、清洁验证策略（思路、方法）
三、清洁验证策略
清洁规程制定
三、清洁验证策略
清洁规程制定
三、清洁验证策略
G
2、设备分组： 设备分组要求组内设备相似，并且清洁工艺相同。在清洁验证中，设备分组是一种将需清洁验证的设备合理分组，避免多余测试的有效方法
验证部 2019.6.27
GMP清洁验证法规解读？ 清洁验证和清洁确认区别，适用范围？ 清洁验证策略-目标残留物的选择？ 接受标准计算？ 取样方法和取样点选择？ 清洁验证方法学验证（取样方法和检验方法） 清洗验证状态的维护？ 规范清洁验证方案编写？ 清洁验证中常见问题分析讨论？
培训内容简介
EMA（欧洲药品管理局）清洁验证
FDA TR29清洁验证
清洁验证之分析方法-上(中英文版)(PDA TR 49内容节选6 )
清洁验证之分析方法-上(中英文版)（PDA TR 49内容节选6）6.0 Analytical Methods分析方法It is essential to a cleaning validation program that the appropriate analytical methods are utilized.一个清洁验证程序使用适当的分析方法是非常必要的。
Analytical methods must be appropriate in that they can adequately detect the residue(s) of concern.分析方法必须适当，能充分检测到相关残留物。
It is also important to understand what can be concluded from the analytical result (e.g., was the productnot removed or was the cleaning agent not removed?).对能从分析结果中推断出什么的理解也是非常重要的（比如：产品没有被去除或清洗剂没有被去除？）。
The results of testing will determine if the cleaning validation cycle is acceptable or if it needs to beredeveloped.检测结果将决定清洁验证周期是否接受或者是否需要重新开发。
Thus, it is important to have confidence in the results.因此，对结果的信任是非常重要的。
This section discusses how to select the appropriate assay methods, detailed information on theapplicability and use of nonspecific assays and microbial test methods,and assay method validation.本部分讨论怎样选择合适的分析方法及其适用性的详细信息，非特定分析和微生物测试方法的使用，和分析方法验证。
生物制品清洁验证考虑要点(中英文版)(PDA TR49 节选1)
生物制品清洁验证考虑要点（中英文版）(PDA TR49 节选1) 1.0 Introduction 介绍Cleaning validation plays an important role in reducing the possibility of product contamination from biopharmaceutical m a n u f a c t ur i n g equipment. It demonstrates that the cleaning process adequately and consistently removes product residues, process residues and environmental contaminants f r o m the cleaned eq u i p m e n t / s y s t e m , so that this eq u i p m e n t / s y s t e m can be safely used for t h e m a n u f a c t ur e of defined subsequent products (which may be the same or a different product). As used in this Technical Report, “product” may be a drug product, bulk active, intermediate, o r another type of f o rmu l a t i on .If “drug product” is intended, that terminology will be utilized. While cleaning validation for biotechnology m a n u f a c t ur i n g has many of the same elements as for o t h e r pharmaceutical manufacturing, there are enough differences such that a separate Technical Report focusing on biotechnology cleaning validation is appropriate.清洁验证在生物制药生产设备降低产品污染方面扮演了一个重要的角色。
FDA清洁过程验证的指导(英译)
一般要求：FDA专家已经为各种设备写了SOP细化清洁过程。
如果一个产品的不同批次有相同的清洁过程，产品变换时用不同的清洁过程。
我们希望这些不同的细节能被写下来。
同样，如果一个过程用于清洗水溶性残留，另一个过程用于清洗非水溶性残留，这些过程应该被写下来，并且要判断这个过程是否实施。
散装的药品决定了特定装备的特定化学生产过程，很难从设备上清洗的残留物和胶状残留。
流体干燥床是另一个常用于特定产品的难以清洗的设备的例子。
任何清洗过程中的残留（溶剂等）要从设备上清洁FDA专家要求有一个清洗过程的书面流程要被验证FDA专家当可接受的验证和重复验证被要求时，希望验证过程确认谁为过程负责，并推进验证研究FDA 专家要求准备在确认样品过程和包括这些方法的敏感性在内的分析方法的每一个生产系统中或单一设备在样品生产过程中的在进一步研究中写下验证参数。
FDA专家要求对应于参数和结果研究文件的验证研究。
FDA专家希望有被经理推进的和标明了是否清洁过程被验证的最后的验证报告。
数据应该支持残留物已经被降到一个“可接受的程度”的结论。
清洁验证的评估第一步聚焦于验证过程的目标，一些企业已经在发展这些目标时失败了。
在看到企业使用清洁过程的特殊样品和实验过程没有真正的评价在评价清洁过程时一些问题要被提出。
例如：一个设备或系统在何时变干净？需要用手清洁吗？是用手还是用溶剂清洗干净？主要的清洗过程一批到一批，一个产品到一个产品很显然吗？这些问题的答案对于检查很重要对于要决定过程的有效性的清洁过程的评估时很重要。
对于分辨提高有效措施何公司资源的结果的步骤这些答案也有帮助。
决定每个设备的清洗过程号。
一个设备或系统有一个清洁过程，然而这将依靠生产的品种，和是否同一产品的批次之间（在一个大的时间段或不同产品的批次间清除干净了。
当清洁过程在同一产品的不同批次间（在大的过程中的不同批量的同一中间体）最严格需要为达到一个标准，设备的“明显清洁”。
这些批次间的清洁不需要验证。
APIC-清洁验证指南(英文)
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20 20 22 23 26
7.0
7.1 7.2
DETERMINATION OF THE AMOUNT OF RESIDUE
Introduction Validation Requirements
30
3ion Guidance
7.3 7.4
Sampling Methods Analytical Methods
4
Cleaning Validation Guidance
Example 1: Product A will be cleaned out. The product has a standard daily dose of 10 mg and the batch size is 200 kg. The next product B has standard a daily dose of 250 mg and the batch size is 50 kg. Both A and B are administrated orally and SF is set to 1000. Calculate the MACO for A in B! 10 (mg) x 50 000 000 (mg) -----------------------------------1000 x 250 (mg)
3.0 Scope
Five specific areas are addressed in this Guidance document, namely:
• • • • •
Acceptance Criteria Levels of Cleaning Bracketing and Worst Case Rating Determination of the amount of residue Cleaning Validation Protocol
清洁验证之取样方法（PDATR49内容节选5中英文版）
清洁验证之取样方法（PDATR49内容节选5中英文版）清洁验证之取样方法（PDA TR 49内容节选5 中英文版）5.0 Sampling Methods 取样方法It is essential to a cleaning validation program that the appropriate sampling techniques are utilized.Sampling must be conducted with techniques appropriate for the equipment surfaces and for the natureof the study, including the analytical methods used. This section discusses types of sampling methods,sampling recovery validation studies, and the training and qualification of samplers.在清洁消毒验证中采用适当的取样技术是必要的。
取样过程中涉及的技术方法应与设备表面和研究本质相适应，包括使用的分析方法。
这一部分讨论了取样方法的类型，验证取样回收研究以及取样人员的培训及资质。
5.1 Sampling Method Selection取样方法选择Selection of a sampling method depends on the nature of the equipment and the nature of the residue being measured. Sampling methods discussed here are direct surface sampling, swabbing, rinse watersampling and placebo sampling. It should be noted that while regulatory documents refer to swabbing as“direct” sampling and to rinse water sampling as “indirect” sampling, it is preferable and more descriptiveto refer to those sampling methods as “swab sampling” and “rinse sampling,” and reserve the t erm“direct sampling” for techniques such as the use of visual inspection.取样方法的选择取决于设备性质以及检测残留物的性质。
WHO清洁指南中英文
WHO 最新清洁验证指南中英文A p p en di x3C l e a ni n gva l i da t i on清洁验证T h et ex t o f t hi s a ppe n di x w as p r ev i o us l y p u bl i sh e d a s:本附录的文本以前以下列形式发表:■■A pp en di x3: C l e a n i n g va l i da t i on. In:W HO Ex pe r t C om m i t t e e o nS p ec i f i c at i on sf o r P h a rm a c e ut i c al P r epa r a t i on s, f o rt i et h re p o rt.G e n e va: W or l d H e al t h O r ga ni z at i on; 2006:An nex4 (W H OT e c hn i ca l R e po rtS e ri es,No. 937;附录3:清洁验证。
在:世界卫生组织药物制剂规范专家委员会第四十次报告。
日内瓦,世界卫生组织;2006:附件4(世卫组织技术报告系列，第937号;h t t ps://ww w.w ho.i nt/m ed i c i n e s/a re a s/qu a l i t y_s a f e t y/q u a l i t y_a s s u ra n c e/S u ppl e m e nt a ryG M P V a l i d a t i o n TR S937A nn ex4.p d f?ua=1).1.P ri n ci p l e原则1382.S c op e范围1383.G en e r al概述1394.C l e a ni n g v al i d at i o n p ro t o c ol s an d r ep o rt s清洁验证方案和报告1395.P e rs on n el人员1426.Eq ui p m ent设备1427.D et e r gen t s清洗剂1428.M i cr ob i ol o g y 微生物1439.S am pl i n g取样14310.A n al yt i c a l m et ho ds分析方法14511.E st abl i s hi n g a c ce p t abl e l i m i t s确定可接受标准1461.P ri n ci p l e原则1.1T he obj e ct i v es of go od m a nu f a ct u ri n g p r a ct i c es(G M P) i n cl ud e t h e pr e v en t i o n o f po s s i bl e c ont a m i n a t i o n a nd c ro ss-co nt am i n at i o n o f p h a rm a ce ut i c a l s t a rt i n g m a t e r i a l s a nd p ro du c t s.药品生产质量管理规范(GMP)的目标包括防止可能的污染和药物原料和产品的交叉污染。
清洁验证状态维护(PDA TR 49内容节选 中英文版)
清洁验证状态维护（PDA TR 49内容节选中英文版）8.0 maintenance of Validated state8.0 验证状态维护A key part of the validation life cycle for any system is maintenance of the validated state. This section deals with activities after the cleaning process has been designed and developed and after the formal validation protocols have been successfully executed. This is critical for cleaning validation, because a lapse in the validated state has the potential to adversely impact the quality, safety and purity of subsequent batches of the same or different products. The main tools for ensuring the continued maintenance of the validated state are change control, risk-based periodic monitoring and data trending review. Additionally, training and retraining are important areas of control for manual cleaning processes, as they are the primary mechanisms for controlling the cleaning cycle. In each of these three areas, knowledge of the design space (see Section 3.8) should be applied.验证状态维护是任何系统的验证生命周期的一个关键组成部分。
FDA清洁工艺验证指南中英文对照
FDA清洁工艺验证指南中英文对照FDA（Food and Drug Administration）是美国食品药品监督管理局的简称。
FDA的清洁工艺验证指南提供了有关如何验证食品加工设备和工艺的清洁性的指导，确保产品的安全。
下面是FDA清洁工艺验证指南的英文全文对照。
FDA Cleaning Process Validation GuideIntroduction简介This document provides guidance on how to validate the cleaning processes used in food processing equipment to ensure their cleanliness. Cleaning validation is an essential step in preventing cross-contamination and ensuring the production of safe products.本文提供了关于如何验证食品加工设备中使用的清洁程序以确保其清洁度的指导。
清洁工艺验证是防止交叉污染和确保生产安全产品的关键步骤。
General Principles基本原则1. Validation should be based on a scientific and risk-based approach, taking into account the specific characteristics of the equipment and the product being manufactured.验证应基于科学和风险评估的方法，考虑到设备和正在生产的产品的特殊特性。
2. The validation process should be well-documented and include clear objectives, acceptance criteria, and a description of the methods used.验证过程应有良好的记录，并包括明确的目标、准入标准和方法描述。
清洁验证可接受限度-下（中英文版）（PDATR49内容节选4）
清洁验证可接受限度-下（中英文版）（PDATR49内容节选4）清洁验证可接受限度-下（中英文版）（PDA TR 49内容节选4）4.2 limits for Cleaning agentsLimitsLimits for cleaning agents will also depend on the stage of manufacturing (formulation/fill vs. bulk activemanufacture). Typical cleaning processes for biotechnology involve either a caustic wash followed by aphosphoric acid step, or an alkaline detergent followed by an acidic detergent. Each of these situationswill be handled separately.4.2 清洁剂的限度清洁剂的限度也取决于生产的各个阶段（制剂/分装与原液生产）。
典型的生物制药清洁程序包括强碱清洗以及下一步的磷酸物的清洗，或者是碱性清洁剂以及随后的酸性清洁剂。
这些过程都是分开处理的。
4.2.1 limits for Commodity ChemicalsIf only commodity chemicals such as sodium hydroxide and phosphoric acid are used for cleaning, it iscommon practice to set limits for these indirectly as a conductivity value. Preferably, an acceptable levelof sodium hydroxide or phosphoric acid is established based on toxicity carryover calculations or based onthe effects on process parameters. The conductivity limit is then set at a level equivalent to thatconcentration at a specified temperature. It is typically the case that the conductivity limit established in this way is well above the conductivity limit for WFI at the same temperature. Therefore, limits are basedon either WFI specifications or on a slightly higher value (such as 5 μS/cm). The rationale for this is that itis more stringent than the “scientific” calculation allows.Furthermore, in many cases, phosphate ionsand/or sodium ions may be part of anysubsequently manufactured product. Therefore, carryover of smallamounts is not significant. It should also be noted that calculations based on toxicity of the commoditychemicals are extreme, since sodium hydroxide is not carried over into a final product as sodiumhydroxide, and phosphoric acid is not carried over into final product as phosphoric acid. If such chemicalswere carried over intact at high concentrations, process checks (such as a significant change in pH) wouldalso cause a non-conformance. Thus, the purpose is not to confirm compliance with WFI specifications,but rather to confirm low amounts of a cleaning agent. The rationale for allowing a conductivity limitslightly higher than the WFI limit is that the WFI limit applies to water in the recirculating WFI loop. Assoon as the water is taken out of that loop and passed through clean equipment (particularly throughspray devices where it can pick up carbon dioxide from the air), there is no expectation that it willnecessarily meet the WFI conductivity limit.4.2.1 市售化学试剂的限度如果只有市售化学试剂如氢氧化钠和磷酸用于清洁，那么通常的做法是用电导率的值为其设定间接的限度。
清洁验证-FDA 中英文
Validation of Cleaning Processes (7/93) 清洁工艺验证GUIDE TO INSPECTIONS VALIDATION OF CLEANING PROCESSES清洁工艺验证检查指南Note: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does no confer any rights, privileges, benefits, or immunities for or on any person(s).注：此指南是FDA 检查官和其工作人员的参考资料。
此文件不约束FDA，也不赋予任何人任何权利，特权，利益或豁免权。
I. Introduction 介绍Validation of cleaning procedures has generated considerable discussion since agency documents, including the Inspection Guide for Bulk Pharmaceutical Chemicals and the Biotechnology Inspection Guide, have briefly addressed this issue. These Agency documents clearly establish the expectation that cleaning procedures (processes) be validated.自从FDA的各文件，包括化学原料药检查指南和生物技术检查指南简单地提出了清洁验证这个话题之后，关于清洁工艺的验证已经引发了相当多的讨论。
这些官方的文件，都清楚地确定了对于清洁工艺需要被验证的期望。
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清洁验证可接受限度（中英文版）（PDA TR 49内容节选3）4.0 Acceptance Limits Cleaningvalidation is performed to demonstrate the effectiveness and consistency of a cleaningprocedure. The rationale for selecting limits for product residues, cleaning agents and microbialcontamination, as well as any other process components, should be logically based on the materials thatimpact the manufacturing process and the safety and purity of the product. The acceptable limits forcleaning manufacturing systems and component s should be “practical, achievable and verifiable.” (8)Limits for cleaning validation generally contain some measure related to the active protein (or othermajor component of interest), some measure related to the cleaning agent, some measure related tobioburden levels, some measure related to endotoxin levels, and a requirement that the equipment bevisually clean. In addition, if there are any specific toxicity concerns related to the active protein or otherprocess components (for example, cytotoxicity, al lergenicity, or reproductive hazards), the manufacturer’stoxicology or pharmacology groups may determine if a modification of limits is required, or whether theuse of dedicated equipment is needed.In the discussion that follows, issues for limits are considered based on the nature of the residue and onthe stage of manufacturing (e.g., bulk active vs. formulation/fill). Manufacturing stages include bulk activemanufacturing (all steps resulting in the bulk active drug substance) and formulation/ fill (formulation ofthe bulk active into a finished drug product and primary packaging of that drug product). Bulkmanufacturing is further divided into upstream process steps (all process steps through harvesting) anddownstream process steps (purification and following steps).4.0 可接受限度清洁验证的目的是为了证明清洁程序的高效性与一致性。
选择产品残留、清洁剂、微生物污染，以及其他任何工艺成分的限度，逻辑上应该基于物料对生产流程和产品的安全性和纯度的影响而定。
清洁生产系统和成分的可接受限度应该“切合实际、可达到、可证实”。
清洁验证的限度一般包含与活性蛋白（或者其他的主要物质成分）相关分析、与清洁剂相关的分析、与生物负载水平相关的分析、与内毒素水平相关的分析，以及设备目检清洁要求。
另外，如果存在任何与活性蛋白或者其他工艺组分相关的特别毒性物质（例如细胞毒性、变应原性、或者生殖危害物），那么生产商的毒理学或生理学团队就需要确定是否有必要改变限度，或者是否需要使用专用的设备。
在接下来的讨论中，限度的考虑应该基于自然残留和生产的各个阶段（例如，原液 vs.配制/分装）。
生产阶段包括主要原液生产（所有的步骤是为了获取活性药物）和配制/分装（将原液加入到成品的制剂以及药品物质的初级包装）。
原液的生产进一步分为上游生产步骤（收获药物前的所有步骤）和下游生产步骤（药物纯化以及后续步骤）。
4.1 key Issues in limits for activesBiotechnology cleaning processes often involvea change of the active molecule itself, which is commonlya protein. Proteinstypically are degraded to some extent by the cleaning processes commonly used inbiotechnology manufacturing. The most important mechanism for degradation is summarized below.In alkaline solutions, such as hot, aqueous solutions containing sodium or potassium hydroxide, proteinsmay hydrolyze to soluble oligomers or free amino acids. Ester groups on actives may be hydrolyzed to analcohol and a fatty acid. A common example of this is saponification of fats and oils to glycerol and fattyacid anions.Sodium hypochlorite is sometimes used inbiotechnology cleaning.Asacleaningagent,itisparticularly effectivein removing denatured protein residues from surfaces. It is a reactive oxidizer which will degrade proteinsin a more random manner to smaller fragments. A general concern with sodium hypochlorite use is its49 © Inc. 25xpossible deleterious effect on stainless steel components. Therefore, it is critical that the rinse cyclefollowing the use of sodium hypochlorite is adequate enough to remove any residual chloride ion beforeadding the subsequent acid wash.Proteins will hydrolyze at a high pH. The parameters of time and temperature have a significant influenceon protein hydrolysis. Therefore, the higher the temperature and pH, the more extensive proteinhydrolysis will occur. Because the protein is typically degraded into smaller fragments and thosefragments tend to be more polar, they are likely to be more water soluble and more readily removed fromequipment surfaces during the washing and rinsing processes. A second effect after protein exposure tohigh pH solutions is a possible irreversible, significant decrease of biological activity due to hydrolysis.4.1 活性物限度的关键问题生物技术的清洁过程经常涉及到活性分子本身的改变，因为这些活性物质通常是蛋白质。
在生物制品制造通常应用的清洁过程中，蛋白质都会在一定程度上发生降解。
下面就总结一下最主要的降解机制。
在碱性溶液中，尤其是高温，溶液中含有氢氧化钠和氢氧化钾，蛋白质就会水解成可溶的寡聚物或者自由氨基酸。
活性物质上的酯旨基团会水解为一个醇和一个脂肪酸，一个最为普遍的例子就是将脂肪和油脂转化为甘油和脂肪酸的皂化反应。
次氯酸钠有时会用于生物技术清洁，作为一种清洁剂，它能非常有效地从表面去除变性蛋白质残留。
它是一种活泼的氧化剂，它能够使蛋白质更随机地降解为更小的片段。
使用次氯酸钠时通常关注其对不锈钢成分的危害作用。
因此，关键的是，使用次氯酸钠后的漂洗循环能将氯离子残留冲洗干净，然后再进行酸清洁。