Protein Particulates and Biosimilar Development: Analytical Tools and Therapeutic Implications

Abstract

Particulate content of parenteral products represents one of the major challenges during the development and commercialisation of safe biotherapeutics. Indeed, the presence of particles is one the top 10 reasons for product recalls. The risk of immunogenicity and adverse clinical reactions in patients has resulted in subvisible particles becoming one of the major focus topics for regulatory agencies. The US FDA has issued several guidance documents in the recent past on subvisible particles, immunogenicity, quality and technical aspects of biosimilars. These guidance documents make the characterization of subvisible and submicron particles relevant and important for both novel biotherapeutics and biosimilar therapeutics. Significant advances have been made in analytical technologies, improving the detection, quantification, and characterisation of particles from the nm range up to 100 μm plus. With this improvement in analytical tools, there is an increasing expectation from regulatory agencies for sponsors to provide more robust subvisible particle characterisation along with risk assessment. Understanding the particulate content of biotherapeutics provides a unique challenge in the Biopharmaceutical industry. Although regulatory requirements for biotherapeutics filing, demand compliance with USP <788>, recent instances have demonstrated the serious consequences of performing only limited particle characterization. Characterizing the subvisible and submicron particles in biosimilars is extremely critical from an immunogenicity and safety perspective. In the coming years, characterization of subvisible particles will continue to play a crucial role in biosimilar development and approval.