Best Practices for Performing Analytical and Functional Biosimilarity Assessment of Recombinant Monoclonal Antibody Biosimilars

Biotherapeutic products have revolutionized the diagnosis and treatment of numerous complex to manage diseases, such as cancer, autoimmune disorders, and infectious diseases. When compared with small molecules (pharmaceuticals), this class of therapeutic agents has proven to be more effective and, in general, have fewer side effects. However, they are more expensive (typically 10-1000 times more) and this limits their global affordability and accessibility. This realization has driven the rise of biosimilars, which are products that have been deemed to be highly similar to a reference product that has been already approved in the regulatory jurisdiction under consideration. A key element in receiving approval for a biosimilar product is for the manufacturer to successfully demonstrate its biosimilarity, an exercise comprising extensive characterization using a gamut of orthogonal, high-resolution analytical and functional tools. Once biosimilarity has been demonstrated, the extent of clinical evaluation that the manufacturer has to perform is significantly curtailed. In this white paper, we discuss various challenges that a manufacturer faces when performing these biosimilarity exercises for monoclonal antibody (mAb) products. Particular attention has been paid to the impact of excipients on these assessments. Using multiple case studies, we elucidate the impact of the removal of these excipients on product stability as well as the impact of their presence on the outcome from any of the analytical and functional tools that are commonly used in these biosimilarity assessments. We also offer best practices for the manufacturers of biosimilars to overcome the challenges associated with the presence of excipients in mAb formulations. Finally, we discuss the number of batches, the development of acceptance criteria and the importance of orthogonal methods in the demonstration of biosimilarity using examples from regulatory filings and guidances.