与电子表格使用相关的合规性问题汇总-基于FDA警告信整理

时间

2017年1月13日

FACTA Farmaceutici

You stored original data in an “unofficial” and uncontrolled electronic spreadsheet on a shared computer network drive.
In response to this letter:
Comprehensively evaluate test samples performed by other analysts from January to September,2014, when the unofficial spreadsheet was in use.

Evaluate the extent of uncontrolled spreadsheets at your facility.

检查发现该公司存在使用共享网络盘中的”非正式”及不受控的电子表格存储原始数据的情况。
FDA要求：
1）综合评估使用过非官方电子表格期间内测试的样品；

2）评估不受控电子表格的使用及影响程度。

2016年8月25日

Pan Drugs Limited

For example, the computer in your quality unit area did not have controls to restrict access and prevent unauthorized changes to data files and folders. All employees had access to your Annual Product Review (APR) spreadsheet. The desktop computer containing the APR was not locked.

质量部门中的计算机没有进行控制以限制访问并防止未经授权的更改数据文件和文件夹。例如所有员工都能访问该公司的年度产品回顾（APR）电子表格。

2016年8月3日

Ropack, Inc.

Failure to validate computer software for its intended use according to an established protocol when computers or automated data processing systems are used as part of production or the quality system, as required by 21 CFR 820.70(i). For example, your firm was utilizing an uncontrolled spreadsheet to track equipment requalification due dates.

计算机软件作为产品质量体系的一部分，未按照21 CFR 820.70（i）的要求依据既定方案进行验证。例如该公司使用了一个未受控的电子表格跟踪设备的再确认日期。

2015年12月18日

Virbac Corporation

Your Complaint SOP states that QA shall maintain the customer complaint report files. Your firm’s QA unit maintains a separate Excel spreadsheet for those complaints that come directly into the Bridgeton QA unit. You have no centralized system for tracking all your complaints. The use of Excel requires many management controls to prevent data alteration, and Excel does not have an audit trail to identify data changes.

该公司 QA部门使用一个单独的Excel表格而非集中式的系统来维护那些直接发到Bridgeton QA部门的投诉。FDA认为使用Excel需要很多管理控制措施来防止数据修改，并且Excel自身没有审计追踪功能来识别数据变更。

2015年10月22日

Sandoz International GmbH

Two uncontrolled Excel spreadsheets were used to record discrepancies and certain in-process drug quality data.

使用两个不受控的Excel电子表格记录偏差和某些药品中控质量数据。

2014年7月21日

Med-Mizer, Inc.

Also, your firm tracks complaint data on a spreadsheet that contains free form text fields that are not standardized, resulting in an inability to adequately trend the data. For example, when using complaint data from January 1, 2011 to February 19, 2014 to trend for “Description of Failure” for “6090,” fourteen complaints are shown. However, the spreadsheet contains several different descriptions of the same part failure that when totaled resulted in a total count of forty complaints related to the inline coupler, part #6090.”

该公司跟踪投诉数据的电子表格，其中包含自由形式的文本字段，这不规范，导致了数据分析中出现问题。例如，一个管理投诉数据的电子表格，因对同一问题”描述失败”包含几种不同的描述，导致使用表格内部公式计算”描述为失败”问题总数时，将原本的14统计为了40。

2013年9月27日

Aarti Drug Limited

Additionally, at the Aarti Drug Limited facility (FEI 3009688205), the investigator noticed that the use of the Excel® spreadsheets in analytical calculations are neither controlled nor protected from modifications or deletion. The investigator noticed that the calculation for residual solvent for XXX uses an Excel spreadsheet that has not been qualified. We are concerned about the data generated by your QC laboratory from non-qualified and uncontrolled Excel spreadsheets.

该公司未对用于分析计算的Excel电子表格进行控制和保护，电子表格可被修改和删除。表格未经验证（例如XXX品种的溶剂残留计算表格non-qualified）。FDA对该公司QC实验室使用未经验证及不受控制的电子表格产生的数据表示担心。

2012年6月13日

Compañía Internacional de Comercio

Specific violations observed during the inspection include, but are not limited, to the following: Your firm has not established appropriate controls designed to assure that laboratory records include all data secured in the course of each test, including graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific component, drug product container, closure, in-process material, or drug product, and lot tested . Specifically, the inspection revealed that your firm has not established written procedures to control and account for electronically generated worksheets used by analysts to record analytical test results. Analysts in your QC laboratory print an uncontrolled number of worksheets from computers throughout the QC laboratory without supervision.

检查中发现该企业没有建立适当的控制措施以保证实验室记录被合适地标识或归属至所属对象，这不符合21 CFR 211.194（a）（4）的要求。
具体地，该公司没有制定书面程序来控制和说明分析人员用以记录测试结果的电子表格。分析人员在QC实验室的电脑上未受监督地打印了数量不受控制的电子表格。

2011年5月16日

Aubrey Inc.

Failure to validate software used as part of production or the quality system for its intended use according to an established protocol, as required by 21 CFR 820.70(I). For example, your firm did not validate use of an Excel spreadsheet used to calculate the Moisture Vapor Transmission Rate (MVTR) per test procedure XXX Revision B.

计算机软件（例如用于计算MVTR的Excel电子表格），作为产品质量体系的一部分，未按照21 CFR 820.70（i）的要求依据既定方案进行验证。

2010年10月12日

Advanced Testing Laboratory, Inc.

We observed 8 of 9 worksheets where one or more tabs with formula cells were not locked. These worksheets were used for analyzing raw data from drug component and product samples, including XXX. Your firm’s SOP 100-G-0110, “Creation and Use of Templates,” stated that cells, in which data is entered, must be locked within their electronic template.
In your response, your firm states that you will enforce the existing procedure by reviewing the current inventory of electronic data files and disposing of non-compliant spreadsheets. In addition, you will retrain analysts on the current procedure. Your response, however, is inadequate because you do not assess whether the raw data results, generated using unlocked templates, are valid.

该公司用于分析原料药及制剂样品原始数据的大多数（9个中的8个）电子表格中，均存在一个或多个带公式单元格未被锁定的情况，而这与法规要求及该公司的SOP均不符。
在该公司对483的答复中，承诺将加强对现有程序的执行、梳理现有表格并处理不合规表格、同时将对分析人员进行重新培训。但FDA认为其答复是不够的，因为没有对使用未锁定表格处理的原始数据结果进行有效性评估。

2010年6月10日

Medefil, Incorporated

Your firm has no procedures for controlling laboratory worksheets including changes to worksheets, issuance of laboratory worksheets, and reconciliation of laboratory worksheets. The worksheet “Internal Communication - Batch Release Information” by the warehouse, which is used to identify released product, was created after XXX documented release of finished product for Heparin I.V. Flush Syringes and Normal Saline I.V. Flush Syringes prior to obtaining media fill results. This sheet is used to communicate batch release information to warehouse operations. Use of this sheet is not documented in any Medefil procedure nor is control over this sheet documented.

该公司没有实验室电子表格的控制（发行、变更、一致性控制等）程序。
例如仓库用于识别放行产品的某工作表，它的使用既没有在任何的程序中记录，也没有在工作表本身的记录文件中收到控制。

2010年4月20日

Capricorn Pharma, Inc.

Your firm has failed to exercise appropriate controls over computer or related systems to assure that changes in master production and control records, or other records, are instituted only by authorized personnel [21 C.F.R § 211.68(b)].
Your firm’s laboratory analysts have the ability to access and modify the formulas in the Excel spreadsheets used to calculate assay results for Guaifenesin and XXX drug products. Due to this unrestricted access, there is no assurance that the formulas in the Excel preadsheets are accurate and valid.

该公司未能对计算机或相关系统实施适当的控制，以确保主生产和控制记录或其他记录的变更仅由授权人员实施。
例如该公司的实验室分析人员能访问和修改用于计算检测结果的Excel电子表格中的公式。由于这种不受限制的访问，Excel电子表格的准确性和有效性得不到保障。

2009年10月5日

Phoenix Bio-Tech Corporation

Failure to validate computer software for its intended use according to an established protocol when computers or automated data processing systems are used as part of production or the quality system, as required by 21 CFR 820.70(i).
We have reviewed your responses and have concluded that they are inadequate because a copy of your revised procedures and the Excel spreadsheet validation protocols/procedures and reports were not provided. It is unclear how you plan to document quality system records that were previously documented in the (b)(4) system.

计算机软件（含Excel等自动数据处理系统），作为产品质量体系的一部分，未按照21 CFR 820.70（i）的要求依据既定方案进行验证。
因该公司未提供修订程序和Excel电子表格验证方案/程序和报告的相关资料。FDA评估认为其对483答复不够充分。

2009年4月27日

Hill Dermaceuticals, Inc.

Your laboratory records did not include a record of all calculations performed in connection with laboratory tests as required by 21 CFR § 211.194(a)(5). For example, laboratory notebook #7, page 49, documents the assay results, but not the calculations performed in Test number DSFS D-13 and Test number TG 521 for the analysis of XXX, lot #HI7908. The notebook does not document reference to the spreadsheet calculation used to generate the results. In addition, the assay results generated by the spreadsheet were not verified for accuracy. Your response dated February 16, 2009, states that you have established procedures to ensure that calculations of method validation studies are recorded. The Records Management SOP, Section 5.7.4.7, states that the procedures shall define what and how data is to be recorded in respective logbooks. However, this SOP omits instructions to include in the notebook the reference to the spreadsheet calculation used to generate the results, as well as the raw data and calculations. In addition, you continued to release products based on assay results generated by the spreadsheet that have not been verified for accuracy.

记录本仅记录了检验结果，没有记录计算过程，而且没有引用执行计算生成结果的电子表格。此外，用电子表格计算产生的检验结果没有验证其准确性。
该公司在对483的答复中声明已建立程序用于确保方法验证研究的计算被记录，其记录管理SOP规定了什么样的数据应怎样被记录在各自的日志中。
但检察官认为该公司的回复忽略了483中的指示，其SOP未规定在记录本中引用用于计算的电子表格（含原始数据及计算）。此外，在未验证准确性的情况下，该公司继续使用电子表格计算检验结果用于产品放行。

2007年5月17日

Quantimetrix Corporation

Software used as part of the production quality system was not validated for its intended use according to an established protocol . Specifically, Spreadsheets intended to check for outliers and calculate mean, SC, % CV, value assignments for finished devices.

用于检查异常值，计算平均值、SC、%CV等的电子表格，作为产品质量体系的一部分，未按照21 CFR 820.70（i）的要求依据既定方案进行验证。

2007年5月9日

TOSOH AIA, Inc

the method for tracking (i .e . Microsoft Excel) the number of samples placed in the incubator was unauthenticated.

用于恒温箱中样品数量管理的方法（如微软Excel）未经验证。

2006年1月17日

National Genetics Institute

There are no data to demonstrate that the quality control/quality assurance spreadsheets used for tracking and trending various quality metrics have been properly validated (installation qualification, operational qualification, and performance qualification) and are performing as intended.

没有数据证明用于跟踪和监控各种质量指标的QC/QA电子表格已被正确地验证（IQ，OQ，PQ），不能证明电子表格的运行状况符合预期。

2003年12月23日

Eldon Biologicals A/S

Failure to establish and maintain adequate procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a) and (b). For-example:
b. Microsoft 2000 Excel spreadsheet software used manufacturing has not been validated for the purpose of generating a worksheet for formulation of reagents. No documentation was found to establish or verify corrections made to the program.
Failure to validate computer software for its intended use according to an established protocol, as required by 21 CFR 820.70(i). For example; the Microsoft 2000 Excel spreadsheet software program was not validated for formulation of reagents and was seen to give incorrect data

1）该公司未按照21 CFR 820.70（i）的要求根据既定的方案验证Excel电子表格软件（该表格用于生产中制定试剂配方表），并且发现有错误数据。
2）检查中未发现就上述问题建立或确认改正措施的文件。说明该公司未能按21 CFR 820.100（a）和（b）的要求建立和保持实施CAPA的适当的程序。

2001年7月10日

EP MedSystems

Your firm failed to validate several computer databases that are used for quality functions including your Access database, your XXX software, and your MS Excel spreadsheet program as required by 21 CFR 820.70(i).

该公司未按照21 CFR 820.70（i）的要求验证用于质量功能的几个计算机数据库、XXX软件及微软Excel电子表格程序。