Accelerating biotherapeutic development

Significance of the topic

Monoclonal antibodies, biosimilars, antibody–drug conjugates and emerging nucleic acid–based therapies present extraordinary analytical challenges due to their size, microheterogeneity and propensity for post-translational modifications. Reliable characterization of these complex molecules is essential to ensure safety, efficacy and regulatory compliance throughout development, manufacturing and storage.

Objectives and study overview

This overview delineates a suite of fit-for-purpose analytical workflows designed to support every stage of biotherapeutic development. From high-throughput screening in early discovery to robust routine methods in quality control, the aim is to accelerate timelines while delivering comprehensive molecular insights.

Methodology and instrumentation

• High-Resolution Accurate Mass (HRAM) spectrometers: Orbitrap Exploris 240/480, Orbitrap Ascend Tribrid, Q Exactive UHMR and Astral platforms
• Ultra-High Performance Liquid Chromatography (UHPLC): Vanquish series including standard, Duo and Neo configurations
• Specialized separation columns and chemistries: MAbPac SEC-1, CX-1 pH gradient kits, DNAPac RP
• Ion exchange and size exclusion chromatography for native and intact protein analysis
• Automated sample preparation: SMART Digest, Pierce Fab kit, KingFisher duo systems
• Ion chromatography (ICS-6000) with HPAE-PAD for glycan profiling
• Charge Aerosol Detection (CAD) for lipid nanoparticle composition
• Software suite: BioPharma Finder, Chromeleon, Proteome Discoverer and enterprise data platforms

Main results and discussion

Integrated workflows achieve high throughput and sensitivity, enabling detection and quantitation of low-abundance variants. Intact and native MS workflows provide rapid assessment of molecular weight, glycoform distribution and aggregate levels. Subunit and peptide mapping workflows deliver detailed sequence coverage, PTM mapping and disulfide bond analysis. HDX-MS reveals conformational dynamics, while glycan, gene therapy vector and oligonucleotide methods enable precise profiling of critical quality attributes.

Benefits and practical applications

• Accelerated decision making through rich, information-dense datasets
• Cost savings by early detection of heterogeneity and process deviations
• Reproducible, GMP-ready methods ensuring regulatory alignment
• Seamless scale-up from R&D to QC laboratories
• Unified software environment for streamlined data analysis and traceability

Future trends and possibilities

As biologic modalities evolve, analytical demands will intensify. Advances in ion mobility, real-time AI-driven data processing and single-cell proteomics are anticipated. Further automation and integration of multi-attribute and multi-omics platforms will deepen quality-by-design insights and support continuous process verification.

Conclusion

A holistic portfolio combining advanced MS, UHPLC, tailored sample prep and unified informatics provides a robust foundation for biotherapeutic development. Leveraging these fit-for-purpose tools accelerates time-to-market, ensures product quality and meets stringent regulatory requirements.