Blanc Timothy, Wätzig Hermann, Sänger-van de Griend Cari
Technical Services/Manufacturing Science, Eli Lilly and Company, Branchburg, New Jersey, USA.
Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Braunschweig, Germany.
Electrophoresis. 2025 Jun;46(11-12):653-668. doi: 10.1002/elps.70002. Epub 2025 Jun 19.
Capillary electrophoresis (CE) often offers superior separation relative to chromatography for macromolecules like monoclonal antibodies (mAbs), a major pharmaceutical class. However, electropherogram baselines pose challenges that traditional chromatography algorithms cannot address, requiring complex integration processes. Integration in good manufacturing practice (GMP) laboratories is critically important and has become a focus of data integrity-centric regulatory inspections. Electropherogram integration challenges, the increased use of CE, data systems developed for chromatograms rather than electropherograms, and the increased regulatory scrutiny call for a resolution. This necessity also extends to R&D, clinical, and academic labs. This review examines authoritative sources such as pharmacopoeias, World Health Organization (WHO), Parenteral Drug Association (PDA), and scientific literature. However, none address electropherogram integration. These sources concur that companies should develop integration policies and SOPs. Training programs must ensure analysts are proficient in integration techniques and reviewers are appropriately qualified to assess integrations. Integration parameters must be captured, including slope sensitivity, smoothing factors, and timed events like peak start and stop and baseline correction. Analytical procedures (APs) should include illustrations that define proper integration. Although automatic integration is preferred for its efficiency and objectivity, it is not always accurate. Therefore, manual integration should be permitted under specific conditions, with all settings and iterations documented, justified, and reviewed. Industry collaboration is proposed to create practical integration guidelines specifically for CE.
对于单克隆抗体（mAb）等大分子而言，相对于色谱法，毛细管电泳（CE）通常能提供更优的分离效果，单克隆抗体是一类主要的药物。然而，电泳图谱基线带来了传统色谱算法无法解决的挑战，需要复杂的积分过程。在药品生产质量管理规范（GMP）实验室中进行积分至关重要，并且已成为以数据完整性为核心的监管检查的重点。电泳图谱积分挑战、CE使用的增加、为色谱图而非电泳图谱开发的数据系统以及日益严格的监管审查都需要得到解决。这种需求也延伸到了研发、临床和学术实验室。本综述考察了诸如药典、世界卫生组织（WHO）、肠外给药协会（PDA）等权威来源以及科学文献。然而，没有一个涉及电泳图谱积分。这些来源一致认为公司应制定积分政策和标准操作规程（SOP）。培训计划必须确保分析人员精通积分技术，并且审核人员具备适当资格来评估积分情况。必须记录积分参数，包括斜率灵敏度、平滑因子以及诸如峰起始和终止以及基线校正等定时事件。分析程序（AP）应包括定义正确积分的图示。尽管自动积分因其效率和客观性而更受青睐，但它并不总是准确的。因此，在特定条件下应允许手动积分，并记录、说明并审核所有设置和迭代情况。建议开展行业合作，专门为CE制定实用的积分指南。
