To develop a biosimilar of an advanced biologic, scientists conduct an in-depth analysis of the originator product and steadily isolate the critical quality attributes (CQAs) that define the safety and efficacy of the active ingredient. The measured ranges for the originator’s CQAs form the basis for establishing comparability criteria for the biosimilar product. The process continues by selecting and engineering an appropriate cell line that will express a protein that can match those CQAs as closely as possible. All these steps happen before manufacturing can even begin. Once identified, the selected cell line is turned over to our process development teams who use state-of-the-art cell culture and purification technologies to design the best, safest, and most robust process to consistently manufacture the final product. Then, and only then, can manufacturing begin — a process that requires highly specialized scientists and technicians and highly intricate and sophisticated technologies.
Since all biosimilars are made from living cells, their inherent complexity requires years of development and testing. What’s more, biosimilars of advanced biologics are tens of thousands of times more complex than small molecule generic medicines and hundreds of times more complex than first-generation biosimilars, like the ones of insulin or growth hormone therapies.1 Each step of the manufacturing process can modify the product, and the process requires controlling hundreds of input parameters that can each impact the safety and efficacy of the final product. This manufacturing complexity can lead to a high degree of variability — variability that in producing its originator biologics, Biogen has learned to isolate and control throughout the manufacturing process. Our understanding of this complexity has allowed us to develop extensive statistical models and process controls to evolve and improve every step of the manufacturing process for producing both our originator biologics and biosimilars of advanced biologics. The precision, care, and rigor that we bring to the manufacturing process define the quality, safety, and efficacy of the final product.
1. Schellekens, H. The first biosimilar epoetin: but how similar is it? Clin J Am Soc Nephrol. 2008;3(1):174-178