Biosimilar manufacturing and comparability

Because a biologic is defined by its process, a biosimilar developer starts from scratch: it builds a new CHO cell line expressing the same amino acid sequence, develops a process whose glycan pattern, charge variants, aggregates and potency fall within the range of many lots of the reference product, and runs analytical, pharmacokinetic and usually one comparative clinical trial. The EU approved the first biosimilar in 2006 and the first oncology antibody biosimilars in 2017; the FDA approved Zarxio (filgrastim, Sandoz) in 2015 as the first US biosimilar, Mvasi (bevacizumab, Amgen) and Ogivri (trastuzumab, Mylan and Biocon) in 2017, and Truxima (rituximab, Celltrion) in 2018. Several biosimilars of each now compete, made by Celltrion in Incheon, Samsung Bioepis, Amgen, Pfizer, Sandoz, Biocon in Bengaluru, Dr Reddy's and Intas among others.

Manufacturing is where the value lies: the same CHO culture, Protein A purification and fill-finish chain as the originator, run by companies competing on cost of goods, so biosimilar makers were early adopters of high-titre processes and single-use plants. Regulators police them with the same GMP inspections and with comparability rules (ICH Q5E) whenever a process changes. Uptake is high in Europe and rising in the United States; in low- and middle-income countries biosimilar trastuzumab is often the only affordable route to HER2-directed therapy.