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An Integrated Risk Assessment for Analytical Instruments and Computerized Laboratory Systems（I） 对于分析型仪器和实验室计算机化系统的完整性风险评估 A risk assessment is presented for determining the amount of qualification and validation work required to show that instruments and computerized laboratory systems are fit for their intended purpose. 提出风险评估，以确定确认和验证工作量，以表明仪器和实验室计算机化系统适合其预期目的。  Risk management is one of the new requirements for the pharmaceutical industry following the publication of the Food and Drug Administration's (FDA) 'Good Manufacturing Practices (GMPs) for the 21st Century'(1) and the International Conference on Harmonization (ICH) Q9 on Quality Risk Management (2). How much qualification and validation work is required in connection with a regulated task is dependent on a justified and documented risk assessment. The United States Pharmacopeia (USP) General Chapter <1058> (3) on analytical instrument qualification (AIQ) has an implicit risk assessment in that it classifies instrumentation used in a regulated laboratory into one of three groups: A, B, or C. The chapter defines the criteria for each group, but leaves it to individuals to decide how to operate the classification in their own laboratories. 风险管理是继FDA 21世纪GMPs（1）和ICH Q9质量风险管理（2）之后对制药行业的一项新要求之一。与监管任务相关的确认和验证的工作量取决于合理的和有记录的风险评估。美国药典（USP）第1058章（3）关于分析仪器确认（AIQ）有一个隐含的风险评估，它将受监管实验室中使用的仪器分类为A、B或C三个组中的一个。本章为每个组定义了标准，但是留给个人决定如何在他们自己的实验室中操作分类。  Software is pervasive throughout the instruments and systems in groups B and C, as acknowledged by <1058> (3). From a software perspective, Good Automated Manufacturing Practice (GAMP) 5 Good Practice Guide (GPG) for Validation of Laboratory Computerized Systems(4) is widely recognized within the industry and by regulators, but it is not consistent with some of the elements of USP<1058>. The USP general chapter is currently under revision and ideally the revised version will be fully compatibility with the GAMP 5 guidelines and good practice guides (4–6). In the meantime, however, users are left with a question: Do I follow USP<1058> or GAMP 5? We shall answer this question here. 正如<1058>(3)所承认的，软件在B组和C组的仪器和系统中是普遍存在的。从软件的角度来看，良好的自动化生产实践（GAMP）5良好实践指南（GPG）用于验证实验室计算机系统（4）在业界和监管者中被广泛认可，但它与USP＜1058＞的某些元素不一致。USP总则目前正在修订中，理想情况下，修订版本将与GAMP 5指南和良好实践指南（4-6）完全兼容。然而同时，给使用者留下一个问题，我该遵循USP<1058> 还是 GAMP 5？我们将在这里回答这个问题。 In November 2010, there was an American Association of Pharmaceutical Scientists (AAPS) meeting in New Orleans, Louisiana, where the status of <1058> was debated. That same month Bob published some of his thoughts about the advantages and disadvantages of that general chapter (7). The advantages consisted of the classification of instruments and systems, which was also its greatest disadvantage, as it was too simplistic. Simply saying that an instrument fit into group B ignored the possibility that there were in-built calculations that needed to be verified because of 21 CFR 211.68(b) requirements (8) or that some instruments enable users to build their own programs. Furthermore, the approach to software for group C systems was naïve as it placed the responsibility for validation on the supplier rather than the user. Chapter <1058> also referenced the FDA guidance for industry entitled General Principles of Software Validation (9), which was written primarily for medical devices; the configuration and customization of software is not mentioned there. 2010年11月，美国药物科学家协会（AAPS）在路易斯安那州新奥尔良召开会议，对<1058>的地位进行辩论。同月，Bob发表了一些关于总则（7）利弊的看法。优点包括仪器和系统的分类，这也是其最大的缺点，因为它过于简单。简单地说，适合B组的仪器忽略了由于21CFR 211.68(b)要求(8)而需要验证的内置计算或者一些仪器使得用户能够构建他们自己的程序的可能性。此外，针对C组系统的软件方法是幼稚的，因为它将验证责任置于供应商而不是用户。第<1058>章还参考了FDA关于工业的指南，标题为“软件验证的一般原则（9）”，该指南主要是针对医疗设备编写的，其中没有提到软件的配置和自定义。 GAMP Good Practice Guide for Laboratory Systems Updated 实验室系统更新的GAMP实践指南 The publication of the first edition of the GAMP Good Practice Guide for Validation of Laboratory Computerized Systems (5) had some problems. However, in the recently published second edition (6), the good practice guide was aligned with GAMP 5 (4) and was updated to be risk-based (as reflected in the new title). Collaboration with us during the writing enabled both the good practice guide and the new draft of USP<1058> (11) to be more closely aligned and have a unified approach to qualification and validation of instruments and computerized laboratory systems. (The GAMP GPG uses the term laboratory computerized system in contrast to the more common term of computerized laboratory system;however the two terms are equivalent.) We have a paper soon to be published that maps the two approaches and shows that they are very similar despite some differences in terminology (12). 第一版GAMP《实验室计算机系统验证良好实践指南》（5）的出版存在一些问题。然而，在最近出版的第二版(6)中，良好实践指南与GAMP 5(4)一致，并被更新为基于风险的(如新标题所示)。在撰写过程中与我们的合作使得良好实践指南和USP<1058>(11)的新草案能够更加紧密地结合在一起，并且对仪器和计算机化实验室系统的确认和验证具有统一的方法。（GAMP GPG使用术语实验室计算机化系统，与更常见的术语计算机化实验室系统相比；然而，这两个术语是等价的。）我们即将发表一篇论文，对这两种方法进行映射，并表明尽管在术语上有一些差异，但它们非常相似（12）。 Progress Updating USP <1058> USP <1058>更新的过程 The original basis of USP<1058> was the 2004 AAPS white paper 'Analytical Instrument Qualification,' which focused on a risk-based approach to AIQ by classifying apparatus, instruments, and systems depending on the laboratory's intended use. The definition of the intended use is the key part of the process, because the same item could be classified in any of the three groups depending on its use. Intended use is also an essential part of our risk assessment presented in this column. USP<1058>最初的基础是2004年AAPS的白皮书“分析仪器确认”，该白皮书聚焦于通过根据实验室的预期用途对设备、仪器和系统进行分类来对AIQ进行基于风险的方法。对预期用途的定义是处理的关键部分，因为根据他的用途相同的项目可以被分进三组中的任何一组。预期用途也是我们在这栏中提出的风险评估的至关重要的部分。 However, the current weakness of the overall risk-based approach is the way in which software is assessed. Software is pervasive in group B instruments and group C systems. Chapter <1058> currently references the FDA guidance document, General Principles of Software Validation (9). This guidance was written primarily for medical device software, which is neither configured (modified to the business process by vendor supplied tools) nor customized (writing software macros or modules that are integrated with the application). Given that many analytical instruments and systems are configured or customized, this guidance does not fit well in a regulated GxP laboratory environment. 然而，当前基于风险的总体方法的缺点是评估软件的方式。软件在B组仪器和C组系统中是普遍存在的。<1058>章当前参考FDA指南文件《软件验证的一般原则》（9）。本指南主要是针对医疗设备软件编写的，既没有配置（由供应商提供的工具修改到业务流程），也没有定制（编写与应用程序集成的软件宏或模块）。鉴于许多分析仪器和系统是配置或定制的，本指南不适用于受管制的GxP实验室环境。 In January 2012, we published a stimulus to the revision process in the on-line version of Pharmacopeial Forum(13), in which we proposed an update forUSP<1058>.In our proposal, instrument qualification was integrated with computerized system validation rather than being two separate activities. This would provide regulated laboratories with the opportunity to reduce the amount of work and avoid potential duplication. In this publication, we included a risk-assessment flow chart for determining the amount of work to perform to qualify analytical instruments and, where appropriate, validate the software functions and applications. From the comments received, we updated the flow chart. We present it here as a simplified method for classifying the apparatus, instruments, and systems in your laboratory. 2012年1月，我们在药典论坛（13）（此处指的是PF,USP---译者注）的在线版中发布了对修订过程的刺激，我们在其中提出了USP<1058>的更新。在我们看来，仪器确认是与计算机化 验证是一体的，不是两个分离的活动。这样给监管实验室提供了减少工作量和避免潜在重复的机会。在本次出版物中，我们包含了一个风险评估流程图，用于确定执行分析仪器确认的数量，并在适当的时候验证软件功能和应用。根据收到的评论，我们更新了流程图。我们在这里把它作为一种简化的方法来分类你们实验室的设备、仪器和系统。   风险评估方法 为什么需要一个完整的风险评估方法？ Why an Integrated Risk Assessment Approach? 为什么需要一个完整的风险评估方法？ The basic risk assessment model in <1058> is the classification of any item used in a laboratory into group A, B, or C based on a definition of intended use. This is generally a sound approach, because apparatus (group A), instruments (B), or systems (C) are easily classified. However, there is a weakness in that the level of granularity currently offered by <1058> is insufficient to classify the variety and permutations of instruments (B) and systems (C) used in combination with software in the laboratory today. <1058>中基础的风险评估模板是根据定义预期用途将实验室中使用的任一物件分为A/B/C三组。这是常用的方法，因为设备（A组），仪器（B组）或者系统（C组）很容易被分类。然而，有一个缺点是，由<1058>提供的分类水平不足以对目前实验室中结合软件使用的仪器(B)和系统(C)的种类和排列进行分类。 Therefore the risk assessment presented in this column is to provide a means of 因此，本栏的风险评估致力于提供一种方式：1. Unambiguously differentiating between apparatus (group A) and instruments (group B) based on functionality. 1、基于功能明确区分设备（组A）和仪器（组B）。2. Linking software elements with the various types of instrument (group B) and systems (group C) as current instrumentation is more complex that the simplistic use of groups B and C in the current version of USP<1058>. This will identify subgroups within groups B and C. 2、将软件元素与各种类型的仪器（B组）和系统（C组）连接起来作为当前仪器要比当前版本USP<1058>中简单使用B组和C组要复杂得多。这将标识出B组和C组的子组。
References参考 (1) US Food and Drug Administration, Guidance for Industry: Good Manufacturing Practices for the 21st Century (FDA, Rockville, Maryland, 2002). (2) International Conference on Harmonization, ICH Q9, Quality Risk Management (ICH, Geneva, Switzerland, 2008). (3) General Chapter <1058> 'Analytical Instrument Qualification' inUnited States Pharmacopeia 36 –National Formulary 31 (United States Pharmacopeial Convention, Rockville, Maryland, 2012). (4) ISPE, Good Automated Manufacturing Practice (GAMP) Guide, version 5 (International Society of Pharmaceutical Engineering, Tampa, Florida, 2008). (5) ISPE, GAMP Good Practice Guide Validation of Laboratory Computerized Systems, 1st Edition (International Society of Pharmaceutical Engineering, Tampa, Florida, 2005). (6) ISPE, GAMP Good Practice Guide: A Risk Based Validation of Laboratory Computerized Systems, 2nd Edition (International Society of Pharmaceutical Engineering, Tampa, Florida, 2012). (7) R.D. McDowall, Spectroscopy 25 (11), 24–29 (2010). (8) Current Good Manufacturing Practice Regulations for Finished Pharmaceutical Goods, in 21 CFR 211.68(b) (U.S. Government Printing Office, Washington, DC, 2008). (9) US Food and Drug Administration, Guidance for Industry, General Principles of Software Validation (FDA, Rockville, Maryland, 2002). (10) R.D. McDowall, Spectroscopy 26 (12), 14–17 (2012). (11) Proposed revision to United States Pharmacopeia <1058> Analytical Instrument Qualification in United States Pharmacopeia(United States Pharmacopeial Convention, Rockville, Maryland, 2013). (12) L. Schuessler, M.E. Newton, P. Smith, C. Burgess, and R.D. McDowall, Pharm. Tech., in press. (13) C. Burgess and R.D. McDowall, Pharmacopeial Forum 38 (1), 2012. (14) Computer Validation Initiative Committee of the Society of Quality Assurance, Computer Risk Assessment (Society of Quality Assurance, Charlottesville, Virginia, circa 1997). (15) ISPE, GAMP Good Practice Guide, A Risk Based Approach to Compliant Electronic Records and Signatures, (International Society of Pharmaceutical Engineering, Tampa, Florida, 2005). (16) R.D. McDowall, Quality Assurance Journal 12, 64–78 (2009). |
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