Biologics are a diverse group of drug molecules dominated by monoclonal antibodies, proteins, and peptides of widely-varying sizes, but also include other advanced modalities such as gene therapies, nucleic acids, and conjugated therapies or vaccines. These modalities are targeting some of humanity’s greatest areas of unmet medical need, especially in cancer and autoimmune diseases. While their applications might be diverse, all require precise characterization to verify identity and stability properties, and to ensure a robust and safe drug product that behaves as intended in the patient.

Wyatt Technology’s suite of light scattering instruments of various types, integrated with existing, standard separation technologies, is designed to tackle the key production and quality control challenges across all biologic modalities.

The summary below outlines the main challenges faced by each modality and how advanced light scattering solutions can be applied to address them in various configurations.

Antibody and protein therapies
Proteins and monoclonal antibodies present challenges with aggregation, achieving purified solutions, assessing stability, and analyzing protein-protein interactions. Both of Wyatt’s two main light scattering technologies can be harnessed to address these challenges throughout the entire biologics development pipeline (figure 1). For example, multi-angle light scattering (MALS) can be used for absolute molecular weight and aggregation detection when combined with a size exclusion chromatography (SEC) column (SEC-MALS), whilst dynamic light scattering (DLS) can be used for size and stability assessment. Samples can be analyzed in either cuvettes or multi-well plates. Real-time MALS (RT-MALS) can be used to analyze molar mass and size during biomanufacturing.

Vaccines (including conjugates)
Vaccines based on viruses and virus-like particles, as well as on nucleic acids such as mRNA, present challenges with assessment of stability, size distribution and batch-to-batch consistency. Both MALS and DLS again find applications here, but also Electrophoretic Light Scattering (ELS) for particle size and charge stability assessment. DLS and ELS are especially useful for characterization of the lipid nanoparticles that encapsulate nucleic acids while field-flow fractionation with MALS can interrogate the entire mRNA + LNP complex even providing the encapsulation state.

Gene therapies
Gene therapies, whether based on viral or non-viral vectors, present challenges in size/concentration determination, aggregation, and payload integrity. FFF-MALS is often the technique of choice for detailed characterization of larger viral vectors such as lentivirus or exosomes, whilst SEC-MALS is more appropriate for smaller viral vectors such as adeno-associated virus (AAV). DLS is suitable for size assessment of all viral vectors in multi-well plates.

Peptides and nucleic acids
Peptides present challenges in their stability, aggregation, and conformational behavior. SEC-MALS can be used for the measurement of absolute molecular weight of peptides, without the need for standards, whilst DLS can be used for high-throughput screening for stability and self-association of both peptides and even unruly nucleic acids in multi-well plates.