Peak Integration of Electropherograms in GMP and Research Labs: Navigating Increased Scrutiny Amid Data Integrity Audits and Inspections.

Abstract

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.