Two major challenges associated with optimizing biomanufacturing operations remain unresolved. The first is variability: how to understand and improve manufacturing with significant variation in process times throughout all unit operations. The second is complexity: modern biomanufacturing facilities are complex and interconnected, with piping segments, transfer panels, and valve arrays, as well as water for injection (WFI) and other shared resource constraints. That complexity is becoming even greater with the need for process standardization and processing of higher (and…
Author Archives: Rick Johnston
An Industry Perspective on Quality By Design
The US FDA’s quality by design (QbD) initiative and associated ICH Q8, Q9, and Q10 guidance documents are increasingly embraced by the biopharmaceutical manufacturing industry for ensuring consistent product quality and lower costs of development and manufacturing. One critical problem the industry faces involves understanding how to implement QbD and determine the benefit of such projects — which require the work of many groups across quality, manufacturing sciences, and engineering departments. Here we present the results from a survey of…
Modeling Perfusion Processes in Biopharmaceutical Production
Perfusion processes are considered more difficult to model than batch-based fermentation processes because up to a third of a perfusion-based campaign is spent outside “steady-state†production mode. Variabilities in cell density, titer, and harvest rate (HR) during ramp-up necessitate planning and explicit modeling of variabilities in these processes and their subsequent downstream operations. Longer continuous fermentation times require more rigorous attention to risk than do batch-based systems. A flexible purification platform must respond to changing fermentation conditions. Here…
The Dinosaurs Reborn: Evaluating Stainless Steel and Disposables in Large-Scale Biomanufacturing
Although a number of biomanufacturers have adopted disposable technologies for small-scale process design, there has been considerable debate over the role of single-use systems in large-scale biopharmaceutical manufacturing— particularly in retrofitting facilities. Some experts have gone so far as to suggest that large-scale stainless steel fermentors are “dinosaurs,†with their large capacities, long installation lead times, and low flexibility. I advocate a systematic approach to look holistically at possible retrofit technologies in existing (stainless steel) facilities, with particular…