制药用水和蒸汽系统指南.docx

1、制药用水和蒸汽系统指南A GUIDE FOR NEW FACILITIES 为新型设施准备的指南VOLUME 4: WATER AND STEAM GUIDE卷4：水和蒸汽系统的指导原则EXECUTIVE SUMMARY执行概况 DECEMBER 20002000年12月 A DOCUMENT DEVELOPED IN PARTNERSHIP WITH FDA 本文件由下列单位与FDA合作编写ISPE PHARMACEUTICAL ENGINEERING GUIDE/ISPE制药工程指南FOREWORD /序For many years, the pharmaceutical industry

2、 has experienced increases in the cost of new facilities. These increases in cost have been driven in part by uncertainty about the requirements for regulatory compliance. Some significant areas of concern are validation, particularly related to automation systems, and the trend to validate back to

3、source utilities. The absence of a consistent and widely accepted interpretation of some regulatory requirements has led to one-upmanship. This practice of building increasingly technically advanced facilities has led to increased cost, longer lead times and, in some cases, delays in bringing new pr

4、oducts to market.长年以来，制药行业在购进的大量新设施方面的支出一直持续增长。造成这些支出的部分原因是法规符合力度的要求的无常。验证是得到重点关注的方面之一，特别是与自动化系统、回溯验证源效用的趋势、建筑和HVAC有关的内容。一致且得到广泛接受的法规要求的欠缺造就了突出的情况：对技术先进的设施的追求导致成本的剧增、交货与订货之间所需时间的延长、以及，在某些情况下，可导致新产品上市的延期。 In May 1994, engineering representatives from the pharmaceutical industry engaged in a discussio

5、n with the International Society for Pharmaceutical Engineering (ISPE) and the Food and Drug Administration (FDA). As a result of that discussion in November 1994, ISPE began work on 10 facility engineering Guides, now known as the Baseline Pharmaceutical Engineering Guides. The first, “Bulk Pharmac

6、eutical Chemicals,” was published in June 1996. The second, “Oral Solid Dosage Forms,” was published in February 1998. The third, “Sterile Manufacturing Facilities,” was published in February 1999. This is the fourth such Guide, covering Pharmaceutical Water and Steam Systems. Each Engineering Guide

7、 was created by, and is owned solely by ISPE. FDA provided comments on this and previous Guides, and many of their suggestions have been incorporated.1994年5月，制药行业的技术代表与国际制药工程协会（ISPE）和美国食品与药品监督管理局（FDA）召开了讨论会。讨论的结果是从1994年11月起，ISPE开始致力于10本设施工程学指南的编写，这10本指南也就是现在为大家所熟知的Baseline制药工程指南。1996年6月出版的指南的第一卷的内容是

8、关于批量药用化学品（BPC）的，第2本，“口服固体制剂”出版于1998年2月；第3本，“无菌生产设施”出版于1999年2月。本指南是这个系列的第4卷，介绍的是制药用水和蒸汽系统的内容。每本指南都由ISPE编写，其版权归ISPE独家拥有。FDA对这本指南和本系列之前出版的指南的编写都给予了宝贵意见，这些意见很多都已经整合入本系列丛书中。 As with the BPC Guide, OSD and Sterile Guide, the Water and Steam Guide has been sponsored by ISPEs Pharmaceutical Advisory Council

9、, made up of senior pharmaceutical engineering executives from owner companies, and ISPE senior management. Overall planning, direction and technical guidance in the preparation of the Water and Steam Guide was provided by a Steering Committee most of whom were involved in the BPC Guide. The Water a

10、nd Steam Guide itself was produced by a Task Team of individuals who expended a great deal of their own time in its preparation and development.与BPC指南、OSD和无菌指南相同，这本水和蒸汽系统指南也得到了ISPE的药品咨询委员会的赞助；该委员会的成员由企业自身的制药工程高中级资深管理人员、FDA和ISPE管理高层组成。指导委员会为调试和合格确认指南的编写提供整体规划、方向的定位和技术指导；该委员会主要由参与BPC指南编写的人员组成。水和蒸汽系统指南

11、的编写工作组的成员为这本书的编写和发展花费了大量私人时间。 Editors Disclaimer: /编辑的声明This Guide is meant to assist pharmaceutical manufacturers in the design and construction of new and renovated facilities that are required to comply with the requirements of the Food and Drug Administration (FDA). The International Society for

12、 Pharmaceutical Engineering (ISPE) cannot ensure, and does not warrant, that a facility built in accordance with this Guide will be acceptable to FDA.本指南旨在给药品生产者提供符合美国食品与药品监督管理局（FDA）要求的新设施的设计和构造方面的协助。国际制药工程协会（ISPE）并不为按照本指南要求建造的工厂通过FDA的检查提供担保和保证。This document is owned by ISPE. No reproduction of the

13、whole or any part of this document is to be made without the written authority of ISPE. 本文件的版权归ISPE所有。任何人不得在没有得到ISPE的授权信的情况下复制本文件的全部或部分内容。ACKNOWLEDGEMENTS /感谢CHAPTER WRITERS AND REVIEWERS /各章的编写人和审查人The following individuals took lead roles in the preparation of this document:以下人士在本文件的编写过程中发挥了带头作用：G

14、erald L. Geisler, Bristol-Myers Squibb Co. was Team Leader for the Pharmaceutical Water and Steam Guide. Moe Elmorsi , Boehringer Ingelheim, acted s the Guide mentor. Guides Steering Committee Chair Paul Lorenzo, (Retired)/ Paul DEramo, Johnson & Johnson The Core Team on the Pharmaceutical Water and

15、 Steam Guide comprised: Gerald L. Geisler, Bristol-Myers Squibb Co. Robert Myers, Kvaerner Jeff Biskup, Clark, Richardson & Biskup Bob Bader, Kinetics The Chapter Credits are as follows: Gerald Geisler, Bristol-Myers Squibb Co. Chapter 1: Introduction Brian Owens, H2O Pure, Inc. Gerald Geisler, Bris

16、tol-Myers Squibb Co. Chapter 2: Key Design Philosophies Brian Owens, Water Pure, Inc. Jeffrey Biskup, Clark, Richardson & Chapter 3: Water Options and Programming Biskup Maria Capote, Source Tech James C. Cox, Merck & Co. Gerald L. Geisler, Bristol-Myers Squibb Co. Ryan Schroeder, Clark, Richardson

17、& Biskup Sidney Brookes, DuPont Merck Pharmaceuticals Chapter 4: Source Feed Water Quality and Pretreatment ISPE BASELINE GUIDE WATER AND STEAM EXECUTIVE SUMMARY DECEMBER 2000 Michael Partow, Pfizer Inc. Andrew Zaske, Osmonics Gary Zoccalante, U. S. Filter Chapter 5: Final Treatment Non-Compendial a

18、nd Compendial Purified Water Sharif Disi, Meco Brian Owens, H2O Pure, Inc. Chapter 6: Final Treatment Compendial WFI Brian Owens, H2O Pure, Inc. Bob Bader, Kinetics Chapter 7: Pharmaceutical Steam Robert Myers, Kvaerner Gary Gray, East Group Bob Bader, Kinetics Randolph Brozek, Pfizer, Inc. James Co

19、x, Merck & Co Paul Skinner, Clark, Richardson & Biskup Gerald Geisler, Bristol-Myers Squibb Co. Chapter 8: Storage and Distribution Systems John Linder, CE & IC Debra Nahas, Eli Lilly & Co. Chapter 9: Instrumentation and Control John Fadool, Glaxo Wellcome Robert Myers, Kvaerner Manfred Septinus, Ro

20、che Carolina, Inc. Phil DeSantis, Fluor Daniel Chapter 10: Commissioning & Validation Dominick Smith, Regeneron Phil Desantis, Fluor Daniel Chapters 11 and 12: Appendices Sidney Brooks, DuPont Merk Pharmaceuticals James C. Cox, Merck & Co. Sharif Disi, Meco Brian Owens, Water Pure, Inc. Michael Part

21、ow, Pfizer Paul Skinner, Clark, Richardson & Biskup Gary P Zoccalante, U. S. Filter Pat H. Banes, Oakley Services Co. The above Guide Task Team worked on one or more chapters and volunteered countless hours to attend meetings, and review the many drafts, which were prepared over an eighteen-month pe

22、riod.The following members of the Pharmaceutical Water and Steam Systems Task Team also worked on one or more of the chapters and reviewed drafts:Georgia Keresty, Ph.D., Bristol-Myers Squibb Paula Soteropoulis, Genzyme Corp. Alex Konopka, Eli Lilly & Co. John Trentacosti, Johnson & Johnson Carl Roe,

23、 Abbott Labs FDA Reviewers /FDA审查员We would like to thank the following FDA review team for their input to this Guide: Sharon Smith (Deputy Commissioner for External Affairs) Holston Joseph Phillips (Deputy Regional Food and Drug Director, Mid-Atlantic Region) Tracy Roberts (CDER, Office of Complianc

24、e) Robert (Atlanta National Expert) Coleman Richard (CDER, Office of Compliance) Friedman Nancy Rolli (Investigator, Drug Specialist, New Brunswick, NJ Inspection Post) 1. INTRODUCTION /绪论1.1 BACKGROUND /背景The design, construction, and validation (commissioning and qualification) of water and steam

25、systems for the pharmaceutical industry represent key opportunities for manufacturers, engineering professionals, and equipment suppliers. These systems are required to meet current Good Manufacturing Practice cGMP regulations while remaining in compliance with all other governing codes, laws, and r

26、egulations.FDA和其他注册机构在医药行业的水和蒸汽系统的设计、构造、验证（调试和合格确认）给生产者、工程专业人员和设备供应商提供了重要的商机。求这些设施不仅要达到现行的药品生产管理规范的要求，而且也要顺应其他管理条例、法律和规范。 The cost of bringing these systems on line is highly variable, owing to interpretation of regulatory requirements and overly conservative design approaches. This Guide is intende

27、d to offer a practical, consistent interpretation, while still allowing flexibility and innovation.法规要求的形形色色的解释，以及过度保守的设计方法，导致引进这些在线系统在花费上的极大差别。因此，本指南试图在允许灵活和创新的前提下，给出一种实用且一致的解释。This Guide was prepared by ISPE, with feedback from industry representatives from all areas and disciplines, and comments

28、provided by FDA. It reflects ISPEs current thinking related to engineering of new water and steam systems.在得到各个领域和学科的行业代表的反馈和FDA的意见的情况下，ISPE编写了这本指南。本书反映了ISPE在水和蒸汽的新型系统的工程方面的当前观点。 It is recognized that industry standards evolve, and this document reflects the understanding of them as of the publicati

29、on date.考虑到行业指南的不断变化与更新，需要指出的是，本指南反映的是截止出版日的行业标准和对这些标准的理解。1.2 SCOPE OF THIS GUIDE /指南的范围This Guide is intended for the design, construction, and operation of new water and steam systems. It is neither a standard nor a detailed design guide. The validation of water and steam systems, which comprises

30、commissioning and qualification activities, will not be discussed in-depth in this Guide, but is covered in the Commissioning and Qualification Baseline Guide.本指南适用于水和蒸汽的新型系统的设计、建造和操作，但这并不是一本标准或详细的设计指南。包括调试和合格确认活动的水和蒸汽系统的验证不是本指南深入讨论的问题；这些问题是调试和合格确认Baseline指南的阐述内容。The purpose of this Guide is to focu

31、s on engineering issues, and provide cost effective water and steam systems. Where non-engineering issues (e.g., microbiological topics) are covered, the information is included to stress the importance of such topics and the impact they have on water and steam system design. Such non-engineering to

32、pics, therefore, are not covered comprehensively, and specific advice from QA departments and technical experts must be sought where technical input is required.这本指南的重点是工程问题，其目的在于准备低本高效的水和蒸汽系统。指南中也提到了不属于工程问题的内容（如微生物），这是为了强调这些问题的重要性和这些问题对水和蒸汽系统设计的影响。当然，没有详细阐述这些不属于工程问题的内容；在要求给出技术内容的地方，必须咨询QA部门和技术专家。This Guide is intended primarily for regulatory compliance for the domestic United States (US) market, and follows US standards and references. European and other non-US stan