Vertical Integration of Disposables in Biopharmaceutical Drug Substance Manufacturing

level: interMediAte S ingle-use (disposable) technologies are gaining significant traction in biopharmaceutical manufacturing due to reductions in capital investment for plant construction, lower requirements for cleaning and sterilization, and the advantages of eliminating crosscontamination during multiproduct manufacturing (1–4). In the early days of disposables, single-use (SU) systems were used only in specific unit operations (5–6). Recently, however, options have become more widely available throughout drug-substance manufacturing (7–10). Companies now focus on selecting the right SU technology from an array of options and integrating those choices into production processes. KBI Biopharma operates an endto-end current good manufacturing practice (CGMP) manufacturing facility for biologics derived from mammalian cell culture up to the 2,000-L scale. That experience has given us a unique vantage point into disposables. Here we sample the diversity of SU technologies available for each unit operation in a biomanufacturing process and highlight some key considerations for integrating them. One remaining concern has to do with scaling up a cell culture process to achieve comparable performance at different scales, so we illustrate a successful scale-up using disposable bioreactors.