This article documents the progress, current state, and projected future trends in titer and yield as industrial and technological benchmarks for commercial-scale biopharmaceutical manufacture. Biopharmaceutical product commercial-scale manufacturing (bioprocessing) was benchmarked by tracking titers and yields over time, from the 1980s to the present, and further out ten years. This study compiled commercial-scale titer and yield data for a set of 39 major biopharmaceuticals, nearly all mammalian-expressed proteins, particularly, monoclonal antibody products. This included extensive searches of many potential data sources, including contacting knowledgeable bioprocessing professionals. In the 1980s and early 1990s, average titers at commercial scale started out at < 0.5 g/L. The current average reported commercial-scale titer is 2.56 g/L. We also confirmed that the manufacture of commercial products has, over the years, undergone repeated cycles of technical production upgrades, with titers and yields increasing incrementally, even for the oldest products. BioPlan estimates that ?3 g/L is now the industry standard titer for new bioprocesses being developed, with ?7 g/L now presumed to be the general industry top-end titer level that, while not unusual, is not often achieved. In terms of yields, we found a 70% yield to be the current industry average yield, not the often-cited 75%. Improvements in downstream purification technologies (e.g., as demonstrated by higher yields) have been fewer and adopted more slowly than upstream production.
BioProcessing Journal Posts
This study assessed a novel statistical approach using space-filling designs (SFDs) and self-validating ensemble modeling (SVEM) machine learning to efficiently identify key process factors using recombinant adeno-associated virus type 9 (rAAV9) gene therapy manufacturing as a case study. Based on risk assessment of parameters that may impact rAAV9 production, we have evaluated six process parameters using 24-run SFDs generated by the JMP statistical software. SFDs are a new class of design of experiment (DoE) created with the objective of covering the entire design space as completely as possible; this in turn allows more accurate modeling of complex response surface behavior typically found in bioprocesses.
The price per patient for protein-based and monoclonal antibody (mAb) therapies runs into thousands of dollars per patient each year. These therapies cost considerably more to manufacture than small molecules. Hence, if mammalian or insect cell lines expressing high protein titres can be selected and optimized for protein expression using microscale bioreactor models early in development, then manufacturing costs can be reduced significantly…
For the ongoing 2014 Ebola virus outbreak, all viable options and technologies need to be evaluated as potential countermeasures to address this emerging biological threat. Novavax, Inc. has a rapid, practical vaccine development and manufacturing platform with the capability to deliver clinical trial material and, ultimately, commercial doses in response to novel infectious disease agents. This report describes the application of our platform technology for the successful generation, manufacture, and release of a clinical batch of Zaire ebolavirus glycoprotein nanoparticle vaccine three months from project initiation…
This paper describes how a biopharmaceutical product development effort can be structured to identify, understand, and plan activities and goals required to efficiently and rapidly deliver new products and therapies to patients. Although the paper focuses on manufacturing, the approach can be used for all aspects of pharmaceutical product development from establishing an intellectual property position, developing a comprehensive manufacturing plan, to creating a marketing program…
The gram-negative bacterium, Escherichia coli, has a long history in the world of laboratory and industrial processes due to its ease of manipulation and well-understood genome. It is widely cultured under aerobic conditions. High cell density cultivation of E. coli is a powerful technique for the production of recombinant proteins. Indeed, 30% of the FDA-approved biopharmaceuticals on the market are produced in E. coli. An Escherichia coli fermentation run conducted using the Eppendorf BioFlo® 320 bioprocess control station achieved high cell density at 12 hours, as determined by a maximum optical density (OD600) measurement of 215.2. The weights of dry and wet cells were also measured…
The purification of PHB-01 plantibody derived from tobacco leaves imposed difficulties when the plantibody solid-liquid extraction design was performed. Thus, our study focused on assessing a combination of an aqueous two-phase extraction (ATPE) procedure and affinity chromatography for solving some of the issues in plantibody purification. This was done using a complete factorial redesign, different polyethylene glycol (PEG)/K2PO4 proportions, and pH values in each partitioning variant.
Sea lice are the most problematic marine pathogens the salmon industry has to deal with, significantly affecting Europe and America. The worst offenders are genera: Pseudocaligus, Caligus, and Lepeophtheirus. Over €305 million in losses are estimated. Recent results have suggested that subolesin/akirin/myosin32 are good candidate antigens for the control of arthropod infestations such as sea lice. The aim of this study was to design and optimize the purification step of MY32/Ls protein to obtain the active pharmaceutical ingredient against sea lice. Non-chromatographic purification strategies were employed, based on published works, to establish rupture, washing, solubilization, and refolding conditions…