Evaluating the inter and intra batch variability of protein aggregation behaviour using Taylor dispersion analysis...

Area of Science:

• Biopharmaceuticals
• Analytical Chemistry
• Protein Science

Background:

• Biosimilar pharmaceuticals require rigorous characterization to ensure similarity to originator products.
• Assessing lot-to-lot variability and higher-order structures is crucial for biosimilar approval.
• Existing analytical methods may have limitations in detecting subtle protein variations.

Purpose of the Study:

• To explore Taylor dispersion analysis (TDA) as a sensitive technique for evaluating batch-to-batch variability in biopharmaceuticals.
• To compare TDA with dynamic light scattering (DLS) for analyzing protein aggregation and higher-order structures.
• To investigate the correlation between protein purity and physical behavior under stress conditions.

Main Methods:

• Taylor dispersion analysis (TDA) was used to study batch-to-batch variations in bovine serum albumin (BSA).
• Dynamic light scattering (DLS) was employed as a comparative analytical technique.
• Protein samples were subjected to heat shocking to assess unfolding and aggregation.

Main Results:

• TDA revealed inter- and intra-batch differences in BSA, demonstrating its sensitivity to variations.
• TDA effectively monitored the stability and reversibility of protein aggregates.
• A correlation was observed between protein purity and reduced aggregation after heat stress.
• TDA identified low levels of aggregates missed by DLS, highlighting its enhanced sensitivity.

Conclusions:

• Taylor dispersion analysis (TDA) is a highly sensitive technique for studying higher-order protein states and aggregation.
• TDA is suitable for evaluating detailed batch-to-batch variability and process-induced physical changes in biopharmaceuticals and biosimilars.
• The sensitivity of TDA to subtle changes is critical for ensuring the safety and efficacy of biosimilar products.