PDA发布《数据完整性检查应对指南》

PDA在其2018年5月/ 6月PDA 制药科学与技术期刊上发表了题为《PDA 讨论要点：文档/数据管理与控制以及数据可靠性为准备检查的最佳实践（PDA Points to Consider: Best Practices for Document/Data Management and Control and Preparing for Data Integrity Inspections）》的文章，该文章包括对11个数据完整性相关的问题的解答，如下：

Question 1: Copies of GMP Records

疑问1：GMP记录的拷贝

Context: On a daily basis, there are many valid reasons why a firm may wish to make copies of GMP records, including records that contain a lot number, batch-specific data, test results, or other data. For example, firms may make a copy of a batch record to provide to a Technical Services group to conduct an investigation. Especially in light of recent 483 observations that highlight documents with batch information found in a shredder, it is unclear under what conditions it is permissible to treat copies of GMP records as uncontrolled, non-GMP records. Requiring that the issuance, management, and destruction of all of these documents be controlled by the Quality Unit imposes an unnecessary burden on industry. The key is for firms to be able to show how they assure that an original record is the original record and that the data in the record satisfy ALCOA principles.

背景：在日常的工作中，公司有很多正当理由解释为什么他们需要拷贝GMP记录。这些记录中有批号、批数据、测试结果或其他数据。例如，公司为技术服务团队提供一份批记录的扫描件以供他们进行调查。特别是最近的483缺陷信中，在碎纸机中发现了包含批次信息的文件问题较为突出，在何种条件下按照非受控、非GMP记录的方式来处理这些GMP复印件的拷贝并不清楚。如要求这些文件由质量部发放、管理和销毁则对行业强加负担。关键是公司要能够证明他们如何能保证原始记录就是原始得记录并且记录中的数据符合ALCOA原则。

Issue: Is a copy of a GMP record (e.g. printout of the raw data or photocopy/scan of a paper original record) itself considered a GMP document?

问题：可以认为GMP拷贝件（例如原始数据的打印件或一份纸质原始记录的照片/扫描件）本身就是GMP文件吗？

Clarification: As long as firms have full control over original GMP documents and the original GMP document is retained as required by the firm’s procedure, copies can be created and destroyed as needed. A copy of a GMP record need only be retained if additional GMP information (e.g., raw data) is recorded on the document copy. As a part of maintaining control over GMP records, it is advisable to make sure that copies can be readily distinguished from originals (e.g., copies are stamped as “copy” and/or originals are stamped as “original”).

解释：只要公司对原始GMP文件有完全的控制权且原始GMP文件按照公司既定的制度进行保存，那么就可以按需制作或销毁拷贝件。只有在GMP文件的拷贝件上记录了额外的GMP信息（例如原始数据），那么这种拷贝件才需要保存。作为对GMP记录维持控制的一部分，最好确保拷贝件可以非常容易和原件区分开来（例如在拷贝件上印上“拷贝章”和/或在原件上印上“原件”章）。

Question 2: Documents not traditionally considered GMP records 

疑问2：传统上不认为是GMP文件的文件

Context: In recent 483s, we have observed that documents not traditionally considered GMP records (e.g., e-mails and other communications) become the object of scrutiny and observations. A working definition of what the agency currently views as a GMP record for such things as e-mail, supervisor schedule, etc. would be helpful for industry. Firms communicate informally about production and quality-related activities on a continuing basis in order to facilitate operations. An e-mail regarding batch release may be essentially the written equivalent of a phone call from one colleague to another stating that a batch has been released. Requiring formal controls around all of these documents, or requiring that such documents cannot be printed and discarded/destroyed/shredded at will, creates a large burden on firms and their quality units.

背景：在最近的483缺陷信中，我们发现传统上不认为是GMP文件的文件（例如电子邮件和其他通讯件）正成为检查对象并被列为缺陷项。那么对当前监管机构对于何种文件如电子邮件、生产计划等认为为GMP文件合适的定义，将会对行业有所帮助。公司经常为便于工作进行一些生产和质量相关活动的非正式沟通。一封关于批放行的邮件可能本质上相当于一名员工打电话给另外一名员工通知批次已放行的书面记录。如要求对所有这些文件进行正式的控制或要求这些文件不能被随意打印和丢弃/销毁/粉碎，将会对公司和他们的质量部门造成沉重的负担。

Issue: Are e-mails or other papers that contain batch-related information such as product name, lot number, or test results considered GMP records if local procedures are clear on what is the system of record?

问题：如果公司文件明确规定哪些属于记录系统，那么含有批相关的信息，如产品名称、批号或测试结果的邮件或其他纸质文件是否被认为是GMP记录？

Clarification: Whether a document is considered a GMP record depends on whether it is generated to satisfy a GMP requirement (see Data Integrity and Compliance with CGMP, Guidance for Industry, April 2016 draft, “When generated to satisfy a CGMP requirement, all data become a CGMP record.”) For example, if e-mail is used as a record of batch release, it is a GMP document. If e-mail is used to communicate that a batch has been released, but the system of record for batch release is not e-mail, then the e-mail is not a GMP record. Similarly, drafts of risk assessments, investigation reports, etc. are not cGMP records until they have been reviewed and finalized. If companies use e-mails for GMP purposes, it is advisable to have a controlled process, governed by an SOP.

解释：一份文件是否被认为是GMP记录，取决于这份文件的生成是否符合GMP要求（见数据可靠性和cGMP合规性行业指南，2016年4月草案，“当所有数据的生成满足GMP要求时，那么该记录就是cGMP记录”）。例如如果电子邮件作为批放行的记录，那么它就是GMP记录。如果电子邮件只是用来通知批已放行并且批放行的记录系统并不是电子邮件，那么这个电子邮件就不是GMP记录。类似的，草稿版风险评估和调查报告等。这些记录都不是GMP记录，除非经过审核和定稿。如果公司将电子邮件用于GMP用途，最好有相应的控制程序，通过SOP来管理。

Question 3: Personal Diaries 

疑问3：私人笔记

Context: It is common for employees to use personal diaries or paper to record notes for themselves for non-GMP purposes e.g. to-do list, training notes, personnel information. These notes are not considered to be GMP records by industry in general. Turning these notes into GMP records may in fact deter individuals from writing down information that is useful for effective time management or reinforcing one’s own learning.

背景：员工用私人笔记或者纸张来记录一些非GMP的东西，例如工作安排、培训注释、人员信息等。这些记录通常在行业内不认为是GMP记录。如果要求将这些记录转为GMP记录事实上反而可能会妨碍他们写下对时间有效管理或加强自身学习有用的信息。

Issue: What types of entries/information can be recorded in a personal diary without it being considered GMP record?

问题：何种条目/信息可以记录到私人笔记中并且不会被认为是GMP记录？

Clarification: If notes and diaries are used as personal and informal means of recording and are not the system of record for execution or documentation of GMP activities, then they are not considered to be GMP records. These informal recordings in personal notebooks might include to-do lists, training notes, coaching ideas, personnel information, etc.). Firms may want to consider controlling and spot checking personal notebooks to ensure that they are being used only for non-GMP information. Firms may also want to train employees on what is and is not proper for recording in personal notebooks.

解释：如果注释和笔记用于私人以及非正式的记录，并且不属于执行或记录GMP活动记录系统，那么它们就不会被认为是GMP记录。这些记录在私人笔记本上的非正式的记录可能包括工作计划、培训注释、执教思想、个人信息等。公司可以考虑控制和抽查这些私人笔记本以保证它们的确只被用于非GMP用途。公司同样可以培训员工关于什么可以以及什么不适合记录在私人笔记本上。

Question 4: Drafts of GMP documents 疑问4：

GMP文档的草稿件

Context: Firms generate many drafts of CGMP documents. It would be onerous and confusing to require that all of those documents be retained.

背景：公司会产生很多cGMP文档的草稿件。令人感到迷惑的是这些文档是否都需要存档，如果是的话工作量会非常繁重。

Issue: Are firms required to retain drafts of CGMP documents, such as reports of risk assessments, investigations, and validation?

问题：GMP文档的草稿件是否需要存档，例如风险评估报告、调查报告以及验证报告？

Clarification: Once a final GMP document of record is created, drafts and documents used in the creation of the document of record no longer need to be retained. This includes documents and drafts used or created in the course of conducting an investigation. The final document is the document of record. GMP Change Control processes come into effect once a GMP document is formally approved. As a part of maintaining control over GMP documents, it is advisable to make sure that drafts can be readily distinguished from final documents (e.g., they are stamped as “draft”).

解释：一旦最终的GMP文档记录定稿，这些文档定稿过程中的草稿件和文档就不在需要留存，包括调查过程中使用或产生的草稿件和文档。定稿的文档则是正式的记录。当一份GMP文档得到正式批准后，GMP变更控制程序即开始生效。作为GMP文档维持控制的一部分，最好确保那些草稿件可以和最终的文档易于区分（例如在草稿件上盖上“草稿”章）。

Question 5: Emails as GMP records 

疑问5：邮件作为GMP记录

Context: Firms use e-mail for a variety of GMP and non-GMP purposes. It is unclear to many firms which uses constitute GMP uses and whether a firm’s entire e-mail system becomes a GMP system due to its use.

背景：公司通常都会在GMP和非GMP的活动中使用电子邮件。许多公司都不清楚哪些用途属于GMP用途以及公司是否因需要为电子邮件的用途而将整个电子邮件系统变成GMP系统。

Issue: Are e-mails considered to be GMP records?

问题：电子邮件是否被认为是GMP记录？

Clarification: Whether e-mails are GMP records depends on whether they are being used to communicate GMP actions or content or capture GMP decision-making. For example, if e-mail is used as the system of record for batch release, then those e-mails are GMP records, and local procedures should be clear on what is the system of record. If e-mail is used to communicate that a batch has been dispositioned, but that decision is formally captured elsewhere in accordance with the firm’s SOPs, then the e-mail is not a GMP record. Similarly, if e-mail is used as the official system for escalation of quality issues per a firm’s SOPs, then those e-mails are GMP records. If e-mail is used for informational purposes to note that there has been an escalation, and there is a separate system of record for escalations, then the e-mail is not a GMP record. The use of e-mail in GMP process(es) should be well-described in the relevant SOP(s). 

解释：电子邮件是否是GMP记录取决于他们是否是用于GMP活动或内容的沟通还是用于记录GMP决策。例如，如果电子邮件用于批放行的记录系统，那么这些邮件就属于GMP记录。公司需要有程序清晰规定记录系统是什么。如果电子邮件只是用来通知产品已经被处理，而正式的决定是按照SOP在别处记录，那么这种电子邮件就不是GMP记录。类似地，如果按照公司SOP，电子邮件作为质量问题升级的正式系统，那么那些电子邮件就是GMP记录。而如果电子邮件只是用于信息参考，说明下发生了问题升级并且有独立的系统来记录这次问题升级，那么这种电子邮件就不属于GMP记录。用于GMP用途的电子邮件需要在相关的SOP中进行详细的描述。

To create a GMP record that is separate from the e-mail system, and to avoid an e-mail system being used as a GMP system of record, a firm may wish to consider printing, signing/initialing, and dating all of the relevant e-mails that constitute a GMP record. All of this should be done in accordance with a written SOP.

为建立一个独立于电子邮件系统的GMP记录以及为避免电子邮件系统用于GMP记录系统，公司可以考虑对所有GMP记录相关的电子邮件进行打印、签名/简签以及签日期。这些工作都需要按照书面的SOP进行。

Question 6: Business records that are not GMP records 

疑问6：不属于GMP记录的业务记录

Context: Recent inspections have delved into business records that are not GMP records, such as footage from security cameras, drafts of GMP documents such as investigations, uncontrolled document copies, and security key card access systems. FDA may choose to inspect these items and may even use them as a means of finding GMP violations. However, the fact that records may be inspected should not mean that these items are GMP records. Otherwise, it would create an enormous burden on the Quality Unit to review and control new kinds of records.

背景：最近的检查开始关注不属于GMP记录的业务记录，例如安全录像影像、GMP文件草稿，例如调查、非受控的文件拷贝件以及安全密匙卡访问系统。FDA可能选择检查这些项目且甚至可能把他们作为GMP违规定论的一种方式。然而，尽管这些记录被检查，但并不是意味着它们属于GMP记录。否则质量部门需要审核和控制这些记录，这会造成巨大的负担。

Issue: If non-GMP records, such as footage from security cameras, drafts of GMP documents such as investigations, uncontrolled document copies, and security key card access systems are inspected, does that mean that they are considered to be GMP records?

问题：如果这些非GMP记录，如全录像镜头、GMP文档例如调查的草案、非受控的文件拷贝件以及安全密匙卡访问系统受到检查，是否意味着它们被认为是GMP记录？

Clarification: No. When generated to satisfy a CGMP requirement, all data become a CGMP record. But the fact that a non-GMP record may be subject to inspection or may be the source of an inspectional observation pertaining to a GMP issue does not turn it into a GMP record. However, if a system is intended to provide documented evidence of a GMP function or GMP result then it is a GMP system. For example, if a key card entry system is used beyond employee exit and entry and is used as a log to monitor time spent in an aseptic core for purposes of media fill compliance, then it is being used for GMP purposes and should be clearly defined as such by local procedure. However, if such a system is evaluated on an occasional retrospective basis as part of a GMP investigation to ensure that an employee did not over-stay in the aseptic core, then that does not mean it should be considered a GMP system. Of course, any documentation from that system that is part of an investigation should be kept (in paper or electronic form) as a part of the investigation.

解释：不。只有当所有数据的产生完全符合cGMP要求时，它们才会被认为是cGMP记录。但事实上非GMP记录也可能会受到监管机构的检查或成为检查时提出的GMP相关的缺陷，但这并不会使它们成为GMP记录。然而如果一个系统用于为GMP活动或GMP结果提供书面的证据，那么它就是GMP系统。例如密匙卡访问系统用于记录员工的退出和进入并且作为无菌核心区域进行的培养基灌装所花时间是否合规的监控记录，那么它就是作为GMP用途在使用并且必须在公司制度中明确规定。然而，如果这个系统只是偶尔在某个GMP调查中进行审核评估以确保员工没有在无菌核心区域逗留太久，那么这个系统就不应该是GMP系统。当然从这个系统得到的任何文档都可以作为调查的一部分并应留存（可以是纸质或电子格式）。

Question 7: Use of shredders 

疑问7：碎纸机的使用

Context: There is no GMP requirement prohibiting the placement or use of shredders in a facility. However, in light of recent observations relating to shredders and shredding, more guidance on shredders and document management would be helpful.

背景：没有任何GMP要求禁止在工厂摆放或使用碎纸机。但是根据最近和碎纸机以及粉碎相关的缺陷项，更多的碎纸机和文档管理的指南会带来更多的帮助。

Issue: What restrictions pertain to the placement and use of shredders?

问题：碎纸机摆放和使用相关的限制有哪些？

Clarification: There are no restrictions on the placement of shredders in a facility. However, due to the risk of unauthorized shredding of GMP records, it is recommended that firms prohibit shredders or other means of potential unauthorized document destruction in areas where GMP functions are performed. This especially includes those areas that create raw data, including production, warehouse, and laboratory areas, where the risk is more acute. It is acceptable to have shredders in areas that do not generate GMP records and/or documents, although procedural controls are advisable. These departments can include HR, finance, and other management areas. With respect to use of shredders, non-GMP records can be destroyed through whatever means a firm decides, including shredding (as long as such destruction does not violate corporate document retention policies). GMP records can be destroyed only when they have passed their retention period or if a true copy is being retained in place of original records. For purposes of preserving confidentiality, firms may choose to provide secure bins for documents that require destruction in areas where there are not shredders. If those bins are in or near a GMP area, it is recommended that firms create procedures defining how destruction is accomplished. For example, Quality Unit review of bin contents may be appropriate in certain circumstances, such as during an audit or in cases of suspicion of inappropriate document or data management. In a Research and Development department, there may be GMP and non-GMP studies. It is advisable to create procedures and controls to prevent unauthorized destruction of GMP records in R&D. Similarly, there are no restrictions on placement of correction fluid (e.g., Wite-Out) and sticky notes such as Post-It Notes, but it is advisable to prohibit them in GMP areas.

解释：在工厂中并不限制摆放和使用碎纸机。但是，因为存在GMP记录会被粉碎的风险，建议公司禁止在GMP相关活动进行的地方摆放碎纸机或其他未经授权的文件销毁设施，特别是原始记录生成的区域，包括生产部、仓库和实验室区域，这些区域中存在的风险更为严重。可以在一些不产生GMP记录和/或文档的区域放置碎纸机，当然最好有控制程序。这些部门包括人力资源部、财务部和/或其他管理区域。对于碎纸机的使用，可以通过公司决定的任何方式销毁非GMP记录，包括粉碎（只要不违反公司的文档留存政策）。只有当GMP文档过儿保存有效期时，它们才可以被销毁，或者用真实副本取代原始记录。为保护机密，在没有碎纸机的区域公司可以选择提供安全文件箱来保存该区域需要销毁的记录。如果安全箱放在GMP区域或附近，建议公司建立相应的制度明确如何完成销毁。例如，某些情况如审计期间或怀疑文档或数据管理不当的情况下，质量部门审核安全文件箱内的文件可能比较合适。在研发部门，可能存在GMP和非GMP研究。明智的做法是制定相应的制度和控制措施防止研发部门内未经授权的GMP记录销毁行为。类似地，对于修正液（例如修正笔）和便签条（例如便利贴）的防止也没有任何限制，但是也建议在GMP区域禁止放置和使用。

Question 8: Retention of closed circuit television(CCTV) 

疑问8：监控录像（CCTV）的保存

Context: Firms are unclear what is required for retention of closed circuit television (CCTV) footage.

背景：公司不清楚对于闭路电视（CCTV）的留存有何要求。

Issue: For how long does a firm need to retain CCTV footage?

问题：公司需要保存CCTV影像多久？

Clarification: CCTV footage from cameras that do not serve a GMP purpose, such as security cameras, should be handled in accordance with applicable firm procedures and retention policies. In general, there is not a GMP requirement to use CCTV. If CCTV footage is serving a GMP purpose, such as for batch release, then the footage should be retained as GMP documentation because it is part of the raw data supporting the disposition of the batch. It is not a GMP requirement to record aseptic process simulation/media fills, nor is retention of such videos required, unless the video is used as the primary documentation of a GMP operation (activity) that is not documented by other means (such as significant activities that are not documented on the batch record or control records for the process simulation batch). Please note, however, that it is a cGMP expectation to make a video of a smoke study validation. This video is the raw data supporting the qualification of a controlled environment, and the video should be retained as a GMP record. Aspects of local data privacy requirements also need to be considered in defining local procedures.

解释：一些从摄像机中得到的CCTV影像并不是用于GMP用途，例如安全录像。这些影像应按照公司相应的制度和留存政策进行处理。一般来说，对于CCTV的使用并没有GMP要求。如果CCTV影像用于GMP用途，例如批的放行，那么这些影像应按照GMP文档进行留存，因为它们是支持批处置原始数据的一部分。对无菌工艺模拟/培养基灌装进行录像以及对这些录像的保存并不是GMP要求，除非录像被用作GMP操作（活动）的主要文件资料，而没有其他方式的记录（例如在工艺模拟批生产时，重要的活动并没有记录在批记录或控制记录中）。然而需要注意的是，cGMP期望对烟雾研究验证进行录像。这份录像是支持受控环境确认的原始数据并且该录像应按照GMP记录来保存。另外在制定公司制度时也需要考虑本地数据隐私需求。

Question 9: Data capture capabilities

疑问9：数据采集功能

Context: Many pieces of production and laboratory equipment have extensive data capture capabilities. Firms are unclear whether they can disable unnecessary functions and/or rely on alternate recordkeeping systems.

背景：需要生产和实验室设备均具备广泛的数据采集功能。公司不清楚他们是否可以关闭这些不需要的功能和/或依赖备用的记录保存系统。

Issue: If a piece of production or laboratory equipment has electronic data storage capability, is a firm required to utilize that capability?

问题：如果某台生产或实验室设备具有电子数据存储功能，公司是否必须使用这种功能？

Clarification: If production or laboratory equipment captures data that is required under GMPs, it must be used unless there is a reliable and complete alternate paper or electronic documentation system in place that meets GMP requirements. Please note, however, that if electronic raw data is dynamic, then a fixed/static paper or electronic record may not constitute a complete copy of the original record because that record may be missing GMP-required data that is captured in the electronic system. Also, if there is an electronic audit trail, it should not be turned off in favor of a manual audit trail as a manual audit trail is necessarily less robust than an automatic one. If an automated data capture system is disabled, it is advisable to document a good faith rationale for disabling the system. Firms should be prepared to defend the rationale during inspection if necessary, including evidence that all data required by cGMP is captured and retained by alternate system(s) as applicable. If an electronic data capture system is not disabled and is not utilized for GMP purposes, firms’ procedures should clearly identify what system is used as the source of raw data and what system is not. It is also recommended that firms review the non-disabled system’s data as a part of their procedures. The reason for this is that any data that is captured may be inspected by FDA and could be the basis for concerns about data integrity, for example in the case of discrepancies between data in the two different systems.

解释：如果生产或实验室设备采集的数据被用于GMP，那么这项功能必须被使用，除非另外有符合GMP要求且可靠和完整的替代纸质或电子文档系统。请注意如果电子原始数据是动态的，那么固定/静态的纸质或电子记录可能并不属于原始记录的完整拷贝，因为这种记录可能会丢失电子系统采集到的GMP数据。同样，如果系统具有电子审计追踪功能，则该功能不应被关闭以支持手动审计追踪，因为手动审计追踪必然没有自动审计追踪可靠。如果自动化数据采集系统被关闭，最好记录下关闭这个系统的合理理由。公司应准备好在检查期间如有必要的话详细阐明这个理由，包括所有GMP要求的数据都已经被采集的证据以及合适的话有另外备用的系统留存。如果某个电子数据采集系统没有被关闭并且没有用于GMP用途，公司应在其制度中清晰标明哪些是产生原始数据的系统，哪些不是产生原始数据的系统。建议公司在其制度中规定审核这些没有关闭系统的数据。这样做的原因是这些系统采集到的数据有可能受到FDA的检查并且可能会成为数据完整性缺陷。例如两台不同的系统中数据相互矛盾。

Question 10: Quality Plans

疑问10：质量计划

Context: Firms may be reluctant to create and document quality plans (documentation of their goals and timelines for quality system improvement) for fear of that plan being used as the source of 483 observations.

背景：因为担心质量计划可能会成为483缺陷的来源，公司可能会不愿意建立和记录质量计划（质量系统改进的目标和时间线）。

Issue: If a firm has a quality plan, will an FDA investigator use that plan as the basis for 483 observations?

问题：如果公司有质量计划，FDA检查员会不会在质量计划上提出483缺陷？

Clarification: If a firm has a quality plan, an investigator may assess the sufficiency of that plan and whether the plan is being fully and timely executed. The fact that a firm has a reasonable quality plan in place may not prevent observations but can be evidence of a firm’s willingness to selfidentify and address issues. The adequacy of the firm’s plan and the progress that the firm has made in executing the plan may be viewed by a regulator as a positive indicator of the firm’s status. Using a firm’s quality plan as a roadmap for negative observations could create a disincentive to creation of such plans. Regulators often encourage firms to proactively meet with them if the firm finds data integrity deficiencies, rather than waiting for those issues to be part of an inspection.

解释：如果公司有质量计划，检查员可能会评估计划的充分性以及计划是否被完整且及时地执行。事实上，如果公司的质量计划合理的话，尽管不会避免483的发出，但是可以作为公司自我认同以及解决问题决心的证据。公司计划的充分性和执行计划取得的进展可能会作为监管者视为公司主观积极的指标。将质量计划作为检查出负面问题的路标会阻碍计划的制定，而监管者通常鼓励公司如果发现数据完整性问题主动积极地去解决，而不是等到被检查出来。

Question 11: Questioning investigator actions in the field 

现场质询检查员的行为

Context: There is a diversity of FDA investigators in the field, and inspections can unfold in a variety of ways. Some firms are unsure of what to do if they perceive that an investigator is acting inappropriately or inspecting non-GMP records, documents, or facilities without cause.

背景：现场检查的FDA检查员不尽相同，而且检查可以以多种方式开展。一些公司不确定如果他们觉得检查员行为不当或者没有任何原因检查了非GMP下的记录、文件或厂房设施，他们应该怎么做。

Issue: If a firm believes that an FDA investigator is acting inappropriately or inspecting non-GMP records, documents or facilities without an apparent cause, what should the firm do?

问题：如果公司坚信FDA检查员行为不当或者检查了非GMP下的记录、文件或厂房设施而没有任何确切的理由，公司应该怎么做？

Clarification: The law defines FDA’s inspectional scope for a drug factory, warehouse, establishment, or lab as including “all things therein (including records, files, papers, processes, controls, and facilities) bearing on whether” drugs are adulterated or misbranded or otherwise prohibited by the FD&C Act. The only explicit limits on FDA’s inspectional authority are that it does not extend to financial data, sales data other than shipment data, pricing data, personnel data (other than data as to qualification of technical and professional personnel performing functions subject to inspection), and research data that is beyond the scope of FDA requirements. (See FD&C Act 704.)

解释：法律规定了FDA对制药厂、仓库、公司或实验室的检查范围包括了“其中所有的事情（包括记录、文件、纸张、工艺、控制以及厂房设施）只要”和掺假或是冒牌药或其他违反了食品药品和化妆品法案的行为有关。唯一明确的是FDA检查授权没有扩展到财务数据、销售数据以外的装运数据、定价数据、人事数据（除了技术和专业人员开展受检查业务资质有关的数据）以及超出了FDA要求的范围的研究数据（见FD&C Act 704）。

Firms should be aware, however, that FDA interprets its inspectional authority broadly. As FDA has stated, the law “authorizes FDA to conduct inspections at reasonable times, within reasonable limits, and in a reasonable manner. Although the [law] does not specifically define ‘reasonable,’ FDA has long maintained that the inspectional authority. . . ‘extends to what is reasonably necessary to achieve the objective of the inspection.’” (See Guidance for Industry, Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection (Oct. 2014). In 2012 the Food and Drug Administration Safety and Innovation Act (FDASIA), Public Law 112-144, was enacted. This law includes a provision that deems a drug to be “adulterated” if the drug “has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.” Under this law, drug manufacturers that delay, deny, limit, or refuse to permit entry or inspection are potentially subject to regulatory sanctions by FDA including Import Alert, Warning Letter, and Seizure.

然而，公司应意识到FDA的检查授权范围相当的广阔。正如FDA所称，法律“授权给FDA可以在任何合理的时间，任何合理的权限内以及以任何合理的方式开展检查。尽管【法律】没有详细定义‘合理’一词，但是FDA长期以来一直保持检查授权扩展至为实现检查目标任何必然合理的范围”（见行业指南-构成拖延、拒绝、限制或拒绝药物检查的情形，2014年10月）。在2012年，公众法律112-144，食品和药品监督管理局安全和创新方法（FDASIA）颁布。本法加入了一个条款,规定如果药物”在任何延误、拒绝或限制检查或拒绝进入或检查的工厂、仓库或公司和所有者,运营商或公司制造、加工、包装、或保存都被认为是掺假药。根据这项法律，延迟、拒绝、限制或拒绝进入或检查的药品生产商可能会受到FDA的监管处罚，包括进口警告、警告信和扣押。

One issue that arises is what FDA can inspect, such as whether FDA can inspect the firm’s e-mail system, phone messages, and individuals’ offices. It has also been reported that FDA investigators have requested information or data in a format other than that which is generally used or maintained by the firm, and informed the firm that it would be a refusal of inspection if the firm does not produce the requested information or data in that format.

那么要面对的一个问题是FDA可以检查什么，比如FDA是否可以检查公司的电子邮件系统、电话短信和个人办公室。据报道,FDA检查员要求提供公司通常使用或保存格式以外的信息或数据,并通知该公司如果公司不提供所请求格式,的信息或数据，这将被视为拒绝检查。

If a firm believes that an investigator is acting inappropriately or inspecting non-GMP records, documents, or facilities without an apparent cause, the first step is to raise that issue with the investigator. If the firm does not feel it can do so, or that effort is unsuccessful, the firm can contact the District Office at which the investigator works, the ORA ombudsman, or others in ORA or Center management to discuss the issue.

如果公司坚信检查员行为不当或检查了非GMP得记录、文档或厂房设施而没有合理的理由，第一步要做的是向检查员提出这个问题。如果公司感觉没办法这样做，或者尝试失败，公司可以联系检查员所在的地区办公室，ORA监察员或其他ORA或中心管理层讨论这个问题。