主题：【原创】【第二届网络原创作品】PROCESS VALIDATION IN MANUFACTURING OF BIOPHARMACEUTICALS的翻译

Preface
Process validation continues to be a topic of much debate and confusion for biopharmaceutical manufacturers. It is usually perceived as a regulatory requirement and good business practice, since it can prevent failed batches when based on science and risk assessments. This book provides insights into the key aspects and current practices of process validation.
工艺验证一直是生物制药企业争论和困惑的话题。因为它基于科学和风险评估可以预防不合格批，通常被理解为法规需要和良好的商业规范。本书提供了关键方面的深刻见解和现行工艺验证规范。
Chapter 1 addresses some of the current process validation concerns. In Chapter 2, the use of a risk assessment method (failure modes and effect analysis [FMEA]) is presented as a means to prioritize process parameters for further process characterization prior to validation. FMEA provides a logical approach that can aid in establishing critical parameters and ensure process robustness. Specific examples on the use of FMEA will aid readers to establish this method in their own organizations.
第一章指出了一些现行工艺验证的难点。第二章中使用风险评估（FMEA）作为早于验证的为工艺特性鉴定区分工艺参数的方法。FMEA提供了逻辑性的途径来帮助制订关键参数和确保工艺的耐用性。使用FMEA的具体例子将帮助读者在自己的组织中制订该方法。
Process characterization is a prerequisite for process validation. In Chapter 3, a description of how to carry out thorough and consistent process characterization is presented. “Precharacterizaion” studies, which are used to help define the scope of the actual experimental characterization work, are also discussed. The discussions on timing of process characterization, needed resources, and a stepwise approach provide valuable insights. The importance of scale-down in process characterization is also addressed.
工艺特性鉴定是工艺验证的先决条件，在第三章中，出现了描述如何进行彻底的和连续的工艺特性鉴定。也讨论了用来帮助定义实际试验特性工作范围的预特性鉴定研究。该工艺特性鉴定的时期，需要的资源和渐近式方法的讨论提供了有价值的观点。也提到了规模缩小在工艺特性鉴定中的重要性。
Accurately scaling down to mimic manufacturing processes is essential in several aspects of process validation. Chapter 4 provides further guidance and strategies for scaling down unit operations, including chromatography, chemical modification reactions, ultrafiltration, and microfiltration. In addition to general scale-down principles and parameters, the authors address specific problems and present some examples.
精确的规模缩小到模拟生产工艺在工艺验证中若干方面都是必不可少的。第四章对规模缩小的单元操作，包括色谱，化学改变反应，超滤和微孔过滤提供了进一步的指南和战略。还有通用的规模缩小原则和参数，作者提到了具体的问题和存在的一些例子。
Prior to establishing a process that can be validated, it is essential to consider potential risks from adventitious agents, which include viruses, bacteria, fungi, mycoplasma, and transmissible spongiform encephalopathies. The potential sources of these agents and testing programs for them are described in Chapter 5. Examples of contamination events in biopharmaceutical manufacturing are presented. Bioburden assessment and sterility issues are also addressed, and a summary table describes adventitious agents, recommended tests, and stages at which to perform testing.
先制订工艺才能验证，必须考虑从试剂中存在的外源性污染的风险如，病毒，细菌，真菌，支原体和可遗传的海绵状脑病。这些污染的潜在的源头和其检测程序在第五章中描述。生物药品制造中的污染事件的例子是存在的。生物负载评价和无菌问题也提到了，并且汇总表描述了外源性污染，建议的检测和在何阶段进行检测。
In Chapter 6, the life span of both chromatography and filtration media is addressed. There are discussions on the various factors that influence life span, along with experimental approaches for validation. The use of small-scale models for validation is discussed. The application of concurrent validation to provide life span data, an approach gaining more acceptance lately, is also discussed in this chapter.
在第六章中，提到了色谱和过滤介质的使用寿命。对于除了验证的实验性的方法之外的各种不同的影响使用寿命的因子进行讨论。小规模验证模型的使用也进行了讨论。同步验证提供使用寿命数据的验证的应用，近来获得更多认同的方法也在本章中进行了讨论

Chapter 7 begins with an overview of filtration validation and a discussion of validation that can be performed in scaled-down studies as well as those aspects that require manufacturing scale. Next is a section on the validation of sterilizing-grade filters. Subsequent sections address validation of filters used for clarification and virus removal filters. Details of tangential-flow filter validation are presented. Also included are descriptions of specific validation issues in clarification of bacterial cell harvest and lysate clarification, mammalian cell clarification, and protein concentration and diafiltration. Cleaning validation for reusable membranes is also discussed.
第七章伊始是过滤验证的概述和可以进行规模缩小研究和那些需要生产规模方面验证的讨论。然后是除菌级滤器验证的章节，随后的章节提到了用来分离（纯化）和除病毒的滤器验证。也提到了切向流滤器的验证的细节。当然也含有详尽的细菌细胞捕获分离和溶菌液分离、哺乳动物细胞分离和蛋白质浓缩和渗滤验证问题的描述。也讨论了可再生膜的清洁验证。

It has been said that without assays, you have nothing. In Chapter 8, analytical test methods are discussed with a special focus on well-characterized biological and biotechnological products. Appropriate methods for testing raw materials and in-process samples during the various manufacturing steps are addressed. The authors also discuss Process Analytical Technology (PAT), which is being driven by the FDA as a means to better control processes. Another section of this chapter presents methods used for product characterization, release, and stability testing. Also included are the ever-problematic potency assay and strategies for choosing a quality-control testing scheme. Other topics discussed are the use of assays for demonstrating comparability, assay validation, dealing with out-of-specification (OOS) results, and assay revalidation.
曾有人说过没有分析，你就没有任何东西。在第八章中讨论了具体的基于已很好定性了的生物和生物技术产品的分析测试方法。提到了适当的检测原料和各种不同的生产步骤中中控样品的方法。作者也讨论了FDA正在推动的作为更好控制工艺的一种手段的PAT技术。其他该章的小节有进行产品特征化、放行、稳定性测试的方法。也包括了一直有争议的效价测定和选择质量控制测试计划的战略。其他讨论的话题是使用分析（数据）来显示可比性，分析方法验证，如何处理OOS结果和分析方法再验证。

In Chapter 9, the reader is provided with a regulatory perspective on facility design and validation issues. Written by two ex-FDAers, this chapter provides details on the regulatory requirements and the information that should be provided in a license application. Also presented are the requirements for cell inoculum suites and areas intended for fermentation/harvest, purification, and bulk filtration. In addition, support areas, such as those used for preparation of media and buffers, and the use of closed systems to reduce environmental classifications are discussed. There are extensive sections on utilities, cleaning, and environmental monitoring. Multiproduct facility issues are addressed. In the section on facility inspections, the authors provide insight into the current focus of inspections.
在第九章，给读者提供了关于厂房设施设计和验证实施的法规远景。由两个前FDA官员撰写，本正解提供了法规要求和注册时应提供的信息的详细内容也提到了细胞接种房和用来发酵/捕获，纯化和批量过滤的区域的要求。另外，如那些用来制备培养基和缓冲液和用密闭系统来减少环境级别的辅助区域也进行了讨论。有大量的关于公用系统，清洁和环境监测的小节。也提到了生产多种产品的厂房设施的问题。在关于厂房设施检查的小节中，作者提供了现行检查关注的焦点的深刻见解。

Chapter 10 discusses the importance of taking a risk-based approach toward computerized system compliance and how it adds value to the product and process that is commensurate with cost. It is concluded that a sound computer system validation (CSV) program encourages the introduction of new and exciting technologies with the ultimate promise of safer, more effective, and more affordable medicines.
第十章讨论了使用计算机系统来进行基于风险管理的方法的重要性和它如何使产品增值和工艺与消耗相称。它推断一个健全的计算机系统验证计划能促进新生和激动人心的科技的引入，从而最终保证更安全，更高效和价格更合理的药品。

Chapter 10 discusses the importance of taking a risk-based approach toward computerized system compliance and how it adds value to the product and process that is commensurate with cost.
第十章讨论了使用计算机系统来进行基于风险管理的方法的重要性和它如何使产品增值和工艺与消耗相称。
这句是什么样的句式呢？compliance这个词在句中是什么位置？
It is concluded that a sound computer system validation (CSV) program encourages the introduction of new and exciting technologies with the ultimate promise of safer, more effective, and more affordable medicines.
It is concluded 翻译为它推断，有点直接了。

原文由 何当奇(redanqi) 发表:
Chapter 10 discusses the importance of taking a risk-based approach toward computerized system compliance and how it adds value to the product and process that is commensurate with cost.
第十章讨论了使用计算机系统来进行基于风险管理的方法的重要性和它如何使产品增值和工艺与消耗相称。
这句是什么样的句式呢？compliance这个词在句中是什么位置？
It is concluded that a sound computer system validation (CSV) program encourages the introduction of new and exciting technologies with the ultimate promise of safer, more effective, and more affordable medicines.
It is concluded 翻译为它推断，有点直接了。

你可以这样看

Chapter 10 |discusses| the importance of taking a risk-based approach toward computerized system compliance and| how it adds value to the product and |process that is commensurate with cost.

两个and中的三个内容是平行的，至于compliance，可以这样看 XX compliance，就是服从XX的要求，但是这里直译很拗口

关于直译的问题，想了很多，发现这样表示出来反而更清楚

In Chapters 11, 12, 13, and 14, many of the concepts described in the previous chapters are illustrated with case studies. First, we learn in Chapter 11 about process optimization and characterization studies for the purification of an E. coli-expressed protein product. Chapter 12 also addresses purification validation — in this case, for a therapeutic monoclonal antibody that is expressed and secreted by Chinese hamster ovary (CHO) cells. In Chapter 13, a matrix approach for process validation of a multivalent bacterial vaccine is described. Chapter 14 describes viral clearance validation studies for a product produced in a human cell line.
在11，12，13和14章中，在之前章节中已描述了的许多概念用案例研究加以描述。首先，我们在第11章中知道了关于大肠杆菌表达的蛋白产物的纯化工艺优化和特性研究。第十二章也指出了纯化验证——在这个案例中，是关于由中华仓鼠卵巢洗标表达和分泌的治疗性单克隆抗体产品。第十三章中，描述了用矩阵方法进行的多价细菌疫苗的工艺验证。第十四章中描述了由人体细胞株产生的一个产品的病毒清除验证研究

Guidelines to Process Validation
GAIL SOFER
CONTENTS
1.1 Introduction ..................................................................... 1
1.2 Current Validation Citations/Problems ......................... 2
1.3 Validation: Today and Tomorrow.................................... 7
1.3.1 Today ..................................................................... 7
1.3.2Tomorrow..............................................................8 References............................................................................... 10
1.1 INTRODUCTION
Much has already been written about process validation for biopharmaceuticals, and there are worldwide guidelines already established. Why, then, did we decide to produce yet another book on this topic? For starters, the guidelines addressing validation are usually purposefully broad to allow for the variability in products, manufacturing methods, analysis, clinical indications, patient populations, and doses for biopharmaceuticals. As a result, there is still much discussion related to validation approaches and specific issues that must be addressed to satisfy regulatory authorities and reproducibly produce safe and efficacious biopharmaceuticals. Furthermore, developing technologies, both analytical and manufacturing, can impact validation, and it is expected that sponsors of biopharmaceuticals will remain current with new developments.
关于生物制药的工艺验证已经有许多著作了，并且已经制订了全球化的指南，但是为什么我们任然决定出另一本关于这个话题的书呢？在开始时（对初学者？？），指南指出了验证通常有目的性的广泛的用于允许产品的变更，生产方法，分析，临床适应症，患者群和生物制药剂型。因此，仍然有很多与验证方法和为满足监管机构而必须指出的具体问题和重复产出安全和有效的生物药品的讨论。此外，分析和生产方面发展中的科技，都能影响验证，希望生物制药的赞助商将持续（支持）现在的新研究。

楼主的翻译很精彩
就是觉得在中文的组织上如果能够再中文化一点会更好