PDA数据完整性工作组对于11个问题的建议

恨我不成钢

根据其自身经验，通过广泛的企业调查，在AAM和PBOA支持下，PDA识别出了当前与数据管理和控制有关的一些问题。这些问题曾被FDA检查频繁指出或导致FDA法规措施。PDA数据完整性工作组此次选择了11个问题来进行说明，其中包括有在各种情形下的最佳规范建议。此文件的目的是通过分享PDA成员的专业知识与对当前最佳规范的理解帮助企业澄清这些问题，帮助工厂更好地实现合规。

1-6题的内容说明在这里：「PDA思考：GMP迎检，非GMP内容你也准备好了么？」

Question 7: Use of shredders

碎纸机的使用

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

背景：并没有GMP要求禁止在工厂内摆放或使用碎纸机。但是，根据最近关于碎纸机和碎纸的缺陷，如果有更多关于碎纸机和文件管理的指南将会很有帮助。

Issue:   What restrictions pertain to the placementand use of shredders?

问题：碎纸机的放置和使用有哪些限制？

Clarification: There are no restrictions on theplacement of shredders in a facility. However, due to the risk of unauthorizedshredding of GMP records, it is recommended that firms prohibit shredders orother means of potential unauthorized document destruction in areas where GMP functionsare performed. This especially includes those areas that create raw data,including production, warehouse, and laboratory areas, where the risk is moreacute. It is acceptable to have shredders in areas that do not generate GMPrecords and/or documents, although procedural controls are advisable. Thesedepartments can include HR, finance, and other management areas.

说明：在工厂内放置碎纸机并无限制。但是，鉴于未经授权即行销毁GMP记录的风险，建议公司禁止在执行GMP职能的区域内放置碎纸机或其它可能未经授权即行销毁文件的方式。这尤其包括那些创建原始数据的区域，包括生产、仓库和化验室区域，这些地方风险尤其敏感。在不生成GMP记录和/或文件的地区配置碎纸机则是可以接受的，当然还是建议设置有程序管理。这些部门可以包括HR、财务和其它管理区域。

With respectto use of shredders, non-GMP records can be destroyed through whatever means afirm decides, including shredding (as long as such destruction does not violatecorporate document retention policies). GMP records can be destroyed only whenthey have passed their retention period or if a true copy is being retained inplace of original records.

关于碎纸机的使用，非GMP记录可以通过公司决定的任何方式销毁，包括碎掉（只要此种销毁不会违反公司文件保存原则）。GMP记录只有在超过其保存期后方可销毁，或者是真实副本替代原件记录保存后方可销毁。

For purposesof preserving confidentiality, firms may choose to provide secure bins fordocuments that require destruction in areas where there are not shredders. Ifthose bins are in or near a GMP area, it is recommended that firms createprocedures defining how destruction is accomplished. For example, Quality Unitreview of bin contents may be appropriate in certain circumstances, such asduring an audit or in cases of suspicion of inappropriate document or datamanagement.

为保密起见，公司可以选择为没有碎纸机的区域内需要销毁的文件提供安全箱。如果这些箱子放置在GMP区域内或附近，建议公司创建程序来定义如何完成销毁。例如，质量部门可以在特定情形下检查箱内资料，如在审计期间或如果怀疑文件或数据管理不恰当时。

In a Researchand Development department, there may be GMP and non-GMP studies. It isadvisable to create procedures and controls to prevent unauthorized destructionof GMP records in R&D.

在研发部门，可能有GMP研究和非GMP研究。建议创建程序和控制以防止未经授权地销毁了研发中的GMP记录。

Similarly,there are no restrictions on placement of correction fluid (e.g., Wite-Out) andsticky notes such as Post-It Notes, but it is advisable to prohibit them in GMPareas.

类似地，修正液（例如修正笔）和便利贴（如报事贴）的放置亦无限制，但建议在GMP区域禁止其使用。

Question 8: Retention of closed circuit television(CCTV)
问题8：闭路电视（CCTV）的保存

Context: 背景

Firms areunclear what is required for retention of closed circuit television (CCTV) footage.

公司不太清楚闭路电视（CCTV）录像的保存要求。

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

问：公司需要保存CCTV录像多久？

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 retentionpolicies. In general, there is not a GMP requirement to use CCTV. If CCTVfootage is serving a GMP purpose, such as for batch release, then the footageshould be retained as GMP documentation because it is part of the raw datasupporting the disposition of the batch. It is not a GMP requirement to recordaseptic process simulation/media fills, nor is retention of such videosrequired, unless the video is used as the primary documentation of a GMPoperation (activity) that is not documented by other means (such as significantactivities that are not documented on the batch record or control records forthe process simulation batch). Please note, however, that it is a cGMPexpectation to make a video of a smoke study validation. This video is the rawdata supporting the qualification of a controlled environment, and the videoshould be retained as a GMP record. Aspects of local data privacy requirementsalso need to be considered in defining local procedures.

澄清 ：非GMP用途的CCTV录像，如安保录像，应依据适用的公司程序和保存政策进行处理。一般来说，并无使用CCTV的GMP要求。如果CCTV录像用于GMP用途，如用作批放行，则该录像应作为GMP文件保存，因为它是支持批处置的原数据的一部分。记录无菌工艺模拟/培养基灌装并非GMP要求，保存此类录像亦非GMP要求，但当录像用作GMP操作（活动）的基础文件记录，并且没有其它方法记录（如批模拟批次的批记录或检验记录上未记录的重大活动）时除外。请注意，无论如何，CGMP都要求对烟雾试验验证录制录像。该录像是支持受控环境确认的原始数据，并且该录像要作为GMP记录保存。在定义内部程序时，也需要考虑内部数据隐私方面的要求。

Question 9: Data capture capabilities
问题9：数据捕获能力

Context: 背景

Many pieces ofproduction and laboratory equipment have extensive data capture capabilities.Firms are unclear whether they can disable unnecessary functions and/or rely onalternate recordkeeping systems.

许多生产设备和化验室设备均具备广泛的数据采集能力。公司并不清楚他们是否能关闭不需要的功能和/或依赖于替代的记录保存系统。

Issue: If a piece of production orlaboratory equipment has electronic data storage capability, is a firm requiredto utilize that capability?

问：如果一台生产设备或化验室设备有具电子数据存贮能力，公司是否必须使用这种能力？

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 electronicdocumentation system in place that meets GMP requirements. Please note,however, that if electronic raw data is dynamic, then a fixed/static paper orelectronic record may not constitute a complete copy of the original recordbecause that record may be missing GMP-required data that is captured in theelectronic system. Also, if there is an electronic audit trail, it should notbe turned off in favor of a manual audit trail as a manual audit trail isnecessarily less robust than an automatic one.

澄清：如果生产设备或化验室设备采集的是GMP所要求的数据，则必须使用，具备有可靠且完整的其它纸质或电子文件记录系统且符合GMP要求者除外。请注意，无论如何，如果电子原始数据是动态的，则固定/静态纸质或电子记录可能并无法构成一份完整的原始记录副本，因为该记录可能会遗失采集在电子系统中的GMP所需数据。还有，如果存在电子审计追踪，则不应因为喜欢手动审计追踪而将其关闭，因为手动审计追踪肯定不如自动审计追踪更稳健。

If anautomated data capture system is disabled, it is advisable to document a goodfaith rationale for disabling the system. Firms should be prepared to defendthe rationale during inspection if necessary, including evidence that all datarequired by cGMP is captured and retained by alternate system(s) as applicable.

如果一个自动化数据采集系统被关闭，则建议记录下关闭此系统的理由。公司应做好准备必要时在检查期间为自己的理由抗辩，包括证明所有CGMP要求的数据均已被采集，并由替代系统保存（适用时）的证据。

If anelectronic data capture system is not disabled and is not utilized for GMPpurposes, firms’ procedures should clearly identify what system is used as thesource of raw data and what system is not. It is also recommended that firmsreview the non-disabled system’s data as a part of their procedures. The reasonfor this is that any data that is captured may be inspected by FDA and could bethe basis for concerns about data integrity, for example in the case ofdiscrepancies between data in the two different systems.

如果电子数据捕获系统并未关闭，并且未作为GMP用途，公司的程序应清楚识别哪个系统被用作原始数据的来源，哪个系统没有。还建议公司审核未关闭的系统中的数据，并将该审核作为其程序的一部分。这么做的原因是所有采集的数据可能会被FDA检查，并且可能成为数据完整性关切的基础，例如，当2个不同系统内的数据存在差异时。

Question 10: Quality Plans
问题10：质量计划

Context: 背景

Firms may bereluctant to create and document quality plans (documentation of their goalsand timelines for quality system improvement) for fear of that plan being usedas the source of 483 observations.

公司可能不愿意创建并记录质量计划（其质量体系改进目标和时间表的文件记录），因为害怕该计划被作为483缺陷的源头。

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

问：如果一个公司订有质量计划，FDA检查人员是否会将该计划作为483缺陷的基础？

Clarification:If a firm has a quality plan, an investigator may assess the sufficiency ofthat plan and whether the plan is being fully and timely executed. The factthat a firm has a reasonable quality plan in place may not prevent observationsbut 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 executingthe plan may be viewed by a regulator as a positive indicator of the firm’sstatus. Using a firm’s quality plan as a roadmap for negative observationscould create a disincentive to creation of such plans. Regulators oftenencourage 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.

澄清：如果一个公司订有质量计划，检查人员可能会评估该计划的充分性，以及该计划是否有全面及时执行。公司订有一份合理的质量计划的事实可能并不能防止出现缺陷，但可以作为公司具备自我认同以及解决问题的意愿的证据。公司计划的充分性，以及公司在执行计划上取得的进展，在监管人员看来可能是公司状态的良性指标。使用一个公司的质量计划作为不良缺陷的蓝图可能会抑制创建此类计划的活动。如果公司发现数据完整性缺陷，监管人员常常会鼓励公司主动合规，而不是等待这些问题成为检查的一部分。

Question 11: Questioning investigator actions in the field
问题11：质疑检查人员的现场行为

Context: 背景

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

FDA的现场检查人员之间有着很大差异，而检查也可能以多种不同方式展开。如果公司认为某检查人员行为不恰当或正在检查非GMP记录、文件或设施，却没有理由，有些公司不太确定该要怎么办。

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

问：如果公司相信FDA的检查人员行为不恰当，或正在检查非GMP记录、文件或设施却没有明显的理由，公司应如何做？

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 adulteratedor misbranded or otherwise prohibited by the FD&C Act. The only explicitlimits on FDA’s inspectional authority are that it does not extend to financialdata, sales data other than shipment data, pricing data, personnel data (otherthan data as to qualification of technical and professional personnelperforming functions subject to inspection), and research data that is beyondthe scope of FDA requirements. (See FD&C Act 704.)

澄清：法律将FDA对药品工厂、仓库、设施或实验室的检查范围定义为包括“其中所有事物（包括记录、文件、纸张、工艺、控制和设施），影响到是否”药品为掺假药或冒牌药或被FDCA禁止的其它情形。对FDA检查权限仅有的明确限制是不允许延伸至财务数据、销售数据（发货数据除外）、定价数据、个人数据（执行受检查职责的技术和专业人员资质相关数据除外），以及超出FDA要求范围的研发数据。（参见FD&C Act 704）

Firms shouldbe aware, however, that FDA interprets its inspectional authority broadly. AsFDA has stated, the law “authorizes FDA to conduct inspections at reasonabletimes, within reasonable limits, and in a reasonable manner. Although the [law]does not specifically define ‘reasonable,’ FDA has long maintained that theinspectional authority. . . ‘extends to what is reasonably necessary to achievethe objective of the inspection.’” (See Guidance for Industry, Circumstancesthat 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 tobe “adulterated” if the drug “has been manufactured, processed, packed, or held in anyfactory, warehouse, or establishment and the owner, operator, or agent of suchfactory, warehouse, or establishment delays, denies, or limits an inspection,or refuses to permit entry or inspection.” Under this law, drug manufacturers thatdelay, deny, limit, or refuse to permit entry or inspection are potentiallysubject to regulatory sanctions by FDA including Import Alert, Warning Letter,and Seizure

虽然如此，公司应明白FDA将其检查权限诠释的很广泛。正如FDA所声称的，法律“授权FDA在合理的时间在合理的限度内以及使用合理的方式执行检查。尽管【法律】并未明确定义何为‘合理’，但FDA长久以来一直保持其检查权威……‘扩展至为达成检查目标而必要的合理范围。’”（参见行业指南：构成拖延、否认、限制或拒绝药品检查的情形（2014年10月））。在2012年，FDA安全与创新法案（FDASIA）（公共法112-114）实施。该法包括有一项条款，如果一种药品“在任何工厂、仓库或设施中生产、加工、包装或保存，而该工厂、仓库或设施的业主、操作人员或代理拖延、否认、限制检查，或拒绝让检查人员进入或检查”，则该药品将被认定为“掺假”药品。依据此法律规定，拖延、否认、限制检查，或拒绝让检查人员进入或检查的药品生产商可能会受到FDA的法规制裁，包括进口禁令、警告信和没收。

One issue thatarises is what FDA can inspect, such as whether FDA can inspect the firm’se-mail system, phone messages, and individuals’ offices. It has also beenreported that FDA investigators have requested information or data in a formatother than that which is generally used or maintained by the firm, and informedthe firm that it would be a refusal of inspection if the firm does not producethe requested information or data in that format.

这引发出一个问题，就是FDA能检查什么，例如FDA是否能检查公司的电子邮件系统、电话短信和个人办公室。也曾有报道说FDA调查人员要求公司以其平时并不使用和保存的格式提供信息或数据，并且告知公司说如果公司不能按指定格式制作所索取的信息或数据即构成拒绝检查。

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

如果公司相信检查人员行为不恰当，或者正在检查非GMP记录、文件或设施，而没有明显的理由，由首先要向该检查人员提出此问题。如果公司并不认为可以这么做，或者是其努力并无成效，则公司可联系检查人员所工作的地区办公室、ORA巡视官（调查官员舞弊情况的政府官员），或其它ORA人员或中心管理人员讨论此问题。

Conclusion: 结论

PDAacknowledges that it may not be possible for a single firm or site to have ameaningful discussion of these issues in the context of an inspection orinspection response and is offering these best practices so that industry canproactively comply and properly prioritize its efforts to improve document managementand control and GMP in the most efficient and effective means possible. PDA acknowledgesthere are many more questions to be addressed and hopes that there can be anongoing dialogue between industry and regulators to facilitate answers.

PDA了解对于单个公司或场所来说，可能并无法在受检或检查回复情形下对这些问题进行有意义的讨论，因此提供这些最佳做法让企业可以主动合规，并以可能的最有效最高效的方式恰当地优先改进其文件管理和控制，以及GMP。PDA了解还有许多问题需要解决，并且希望在企业与监管人员之间能有持续的对话从而促进得出答案。

syhorchid

谢谢分享

云扬风轻

学习学习。

walker91

谢谢分享！

walker91

谢谢分享！

wamy425724

很有实际指导意义，谢谢！