Department of Clinical Immunology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 9132, USA.
J Immunol Methods. 2011 Jan 5;363(2):104-19. doi: 10.1016/j.jim.2010.07.004. Epub 2010 Jul 22.
Flow cytometry is a powerful and flexible analytical tool used during all stages of drug development. While substantial effort is invested in development and validation of analytical methods, instrument validation is often neglected. Flow cytometers are evolving at a pace that surpasses the protracted timeline of drug discovery and development. Therefore, it becomes fundamentally important to the success of the study to document the validated state of the flow cytometer and verify data integrity at the time of study conduct. It is important to bear in mind that validation strategies are critical components of the entire process involved in bringing new therapeutic options to the medical community; drugs which eventually manifest as successful new treatments for those individuals afflicted with disease. Formal industry guidance is provided through Good Laboratory Practices [GLP], which require validation of all computerized systems and equipment used to support pre-clinical studies for regulatory submissions. Key elements of instrument validation processes have been delineated through guidance documents published by regulatory agencies and industry working groups to support the rigorous compliance needs of GLP. However, most testing to support drug development is conducted in less strict regulatory environments. Such comprehensive validation efforts may not be appropriate for laboratories supporting early discovery or basic research, however, laboratories involved in regulated stages of development, such as pre-clinical and clinical phases, should consider these recommendations. This paper presents a consensus methodological approach that the authors have used successfully to ensure data integrity in flow cytometric studies conducted during drug development.
流式细胞术是一种在药物开发的所有阶段都非常强大且灵活的分析工具。虽然在分析方法的开发和验证方面投入了大量精力，但仪器验证往往被忽视。流式细胞仪的发展速度超过了药物发现和开发的漫长时间线。因此，在研究进行时记录经过验证的流式细胞仪状态并验证数据完整性对于研究的成功至关重要。需要牢记的是，验证策略是将新的治疗选择带给医疗社区的整个过程的关键组成部分；这些药物最终为那些患有疾病的人提供了成功的新治疗方法。正式的行业指南通过良好实验室规范 [GLP] 提供，要求对用于支持监管提交的临床前研究的所有计算机系统和设备进行验证。通过监管机构和行业工作组发布的指导文件，已经确定了仪器验证过程的关键要素，以支持 GLP 的严格合规需求。然而，大多数支持药物开发的测试都是在监管环境不太严格的情况下进行的。这种全面的验证工作可能不适合支持早期发现或基础研究的实验室，但参与监管开发阶段的实验室，如临床前和临床阶段，应考虑这些建议。本文提出了一种共识方法学方法，作者已成功地使用该方法来确保药物开发过程中进行的流式细胞术研究的数据完整性。
