Biosimilars and Future Biotherapeutics

Manufacturing and Quality Control of Biosimilars

The manufacturing and quality control of biosimilars are central to ensuring their safety, efficacy, and similarity to reference biologics. Unlike small-molecule drugs, which are chemically synthesized and easily replicated, biosimilars are large, complex proteins produced using living cells, making their manufacturing process highly sensitive and technically demanding. The cornerstone of biosimilar development lies in the robust characterization of the reference biologic, followed by the careful design of a cell line and production process that can replicate the reference product’s structure and function as closely as possible. This involves extensive analytical studies to evaluate critical quality attributes (CQAs) such as protein folding, glycosylation patterns, charge variants, and impurity profiles. These attributes must remain within an acceptable range to demonstrate biosimilarity, and any differences must be scientifically justified as non-impactful on clinical performance. The Chemistry, Manufacturing, and Controls (CMC) requirements for biosimilars are rigorous and form a significant portion of the regulatory submission. The process begins with cell line development, where a stable and high-yielding expression system is selected and genetically engineered to produce the target protein. Following this, upstream and downstream processing steps—including fermentation, purification, filtration, and formulation—are optimized to ensure product consistency, scalability, and stability. Any change in process parameters, such as temperature, pH, or purification techniques, can lead to product heterogeneity, making process control critical.