Maintaining Data Integrity: Understanding FDA ALCOA Guidance
在 2003 年关于实施其 21 CFR 第 11 部分数据完整性规则的指南中，FDA 使用首字母缩写 ALCOA，其中将良好的数据完整性实践定义为创建可归因于执行测试的技术人员的记录，这些记录是易读的，同时创建的，原始的并且准确的。
The FDA 21CFR part 11 ALCOA definition of complete, consistent and accurate data
可归属性（Attributable）
可归属性解释为，记录应包括电子“签名”，以将其与进行测量的仪器/人员联系起来，还应包括正在测试的水系统以及测试的日期和具体时间。这意味着用户通过登录到系统后进行电子签名。对电子签名格式的控制可以根据具体的站点来决定，并且通常由 IT 部门使用 Microsoft Active Directory 控件进行控制。理想情况下，应将在线仪器设定为遵循 Active Directory 控件，以确保根据特定站点的规则使用正确的电子签名格式。
清晰易读的记录（Legible records）
当然，记录必须清晰可辨，这意味着手写记录是不可接受的。FDA还建议，电子记录应该以开放的格式存储，并且可以以多种计算格式读取，以便在未来几年内可以访问和读取。FDA 推荐典型的格式，如 PDF、XML 或 SGML。
实时同步（Contemporaneous）
实时同步，这一词意味着样本被检测时应同时立即生成电子记录，这表示手工抄录纸质记录不是好的方式，并且整理纸质记录，然后手动转录在以后或日期变成电子格式也不是好的记录方式。
原始记录（Original）
实质上，每次将测试结果从一种形式转录到另一种形式都存在风险。即使将多个纸质记录扫描为电子格式，也存在重复或错过扫描的风险。因此，FDA 建议电子记录应为测试完成后创建的原始记录。显然，手动转录记录是风险最大的，有很大机率发生人为错误。
可归因记录（Attributable records）
最后一个在缩略词 ALCOA 中的 “A”。本质上，电子记录应该是准确的。这表明捕获这些电子记录的过程应当可靠，即应避免人工计算和人工输入数据，避免出现人为错误的机会。可归因是 ALCOA 中的 “A”。在线仪器生成的电子记录应包含将数据与用于测量的仪器以及测量时间和日期联系起来的信息。
我们的仪器专为方便 ALCOA 指导所设计。在此处了解详细信息：
QC Step |
Instrument |
Application |
Regulation |
A |
L |
C |
O |
A |
| Raw Material | ANATEL PAT700 | On-line Water for Injection (WFI), Purified Water (PW), Total Organic Carbon (TOC), Temperature and Conductivity | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for Alarm Trail, Audit Trail, Measurement Results | Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated | |
| QbD1200 | Grab-sample point of use testing for Water for Injection (WFI), Purified Water (PW) Total Organic Carbon (TOC) | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for Alarm Trail, Audit Trail, Measurement Results | Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated | ||
| LS 13 320 XR | Active Pharmaceutical Ingredient, Excipients | ISO 13320 | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for Alarm Trail, Audit Trail, Measurement Results | Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated | |
| Production | Vi-CELL BLU | Mammalian cell viability and concentration | USP <1046> | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for measurement Results | Secure data records stored and tracked at time of measurement | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated |
| Vi-CELL MetaFLEX | Mammalian cell bioreactor media health | Multi-level, Individual User Name and Password for all users | Legible reports can be printed or viewed on the instrument | Secure data records stored and tracked at time of measurement | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated |
||
| MET ONE 3400 | Routine environmental monitoring (air particulates) in sterile manufacturing cleanrooms |
EU GMP Annex 1, CGMP, ISO 14644-1 & -2 | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for Measurement Results including metadata | Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated | |
| MET ONE Facility Monitoring System | Sterile manufacturing cleanroom continuous air particulate monitoring | EU GMP Annex 1, CGMP, ISO 14644-2 | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for Alarm Trail, Audit Trail, Measurement Results | Secure data records stored in database at time of measurement | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated | |
| Final Product Testing | HIAC 9703+ | Final product sub-visible particulate counting in parenteral drug products |
USP <788> USP <789> |
Multi-level, individual User Name and Password for all users | Legible, secure PDF export for Alarm Trail, Audit Trail, Measurement Results |
Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated |
| Multisizer 4e | Final product visible particulate counting in parenteral drug products | USP <790> |
Multi-level, individual, user name and password for all users |
Legible secure PDF export for Audit Trail, Measurement Results | Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated |
*上述产品仅供工业与科研使用，不用于临床诊断
Products Designed for ALCOA Guidance
QC Step: Raw Material |
|||||||
Instrument |
Application |
Regulation |
A |
L |
C |
O |
A |
| ANATEL PAT700 TOC Analyzer | On-line Water for Injection (WFI), Purified Water (PW), Total Organic Carbon (TOC), Temperature and Conductivity | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for Alarm Trail, Audit Trail, Measurement Results | Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | Original electronic record created directly from the instrument | |
QC Step: Production |
|||||||
Instrument |
Application |
Regulation |
A |
L |
C |
O |
A |
| Vi-CELL BLU Cell Viability Analyzer | Mammalian cell viability and concentration | USP <1046> | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for measurement Results | Secure data records stored and tracked at time of measurement | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated |
| Vi-CELL MetaFLEX Bioprocessing Monitor | Mammalian cell bioreactor media health | Multi-level, Individual User Name and Password for all users | Legible reports can be printed or viewed on the instrument | Secure data records stored and tracked at time of measurement | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated |
|
| MET ONE 3400+ Air Particle Monitor | Routine environmental monitoring (air particulates) in sterile manufacturing cleanrooms |
EU GMP Annex 1, CGMP, ISO 14644-1 & -2 | Multi-level, Microsoft Active Directory Username and Password control creates unique electronic signatures for users | Legible secure PDF export for Measurement Results including metadata | Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated |
| MET ONE Facility Monitoring System | Sterile manufacturing cleanroom continuous air particulate monitoring | EU GMP Annex 1, CGMP, ISO 14644-2 | Multi-level, Individual User Name and Password for all users | Legible secure PDF export for Alarm Trail, Audit Trail, Measurement Results | Secure data records stored in database at time of measurement | Original electronic record created directly inside the counter | Your SOPs and sampling maps uploaded into the counter with version control. Completed records reviewed and approved for accuracy in the counter remotely via web-browser. No manual counter configuration or sample location entry. |
QC Step: Final Product Testing |
|||||||
Instrument |
Application |
Regulation |
A |
L |
C |
O |
A |
| HIAC 9703+ Liquid Particle Counter | Final product sub-visible particulate counting in parenteral drug products |
USP <788> USP <789> |
Multi-level, individual User Name and Password for all users | Legible, secure PDF export for Alarm Trail, Audit Trail, Measurement Results |
Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated |
| Multisizer 4e Coulter Counter | Final product visible particulate counting in parenteral drug products |
Multi-level, individual, user name and password for all users |
Legible secure PDF export for Audit Trail, Measurement Results | Secure PDF created on day of sample analysis | Original electronic record created directly from the instrument | SOP parameters pre-programed into the instrument and automated | |
*Pharmaceutical Online, An Analysis Of FDA FY2018 Drug GMP Warning Letters By Barbara Unger, Unger Consulting Inc., https://www.pharmaceuticalonline.com/doc/an-analysis-of-fda-fy-druggmp-warning-letters-0003, published February 1, 2019
Reflection paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials By GCP Inspectors Working Group https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/reflection-paper-expectations-electronic-source-datadata- transcribed-electronic-data-collection_en.pdf, published June 09, 2010
