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.
Category: <span>Cell Lines</span>
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…
Stem cell-based regenerative medicine has great potential to advance the therapeutic treatment of human diseases. Among the various stem cell platforms, mesenchymal stem cells (MSCs) represent one of the most promising options. Currently, there are over 500 clinical trials based on MSCs registered at the NIH’s ClinicalTrials.gov website. Although successful expansion of MSCs in vitro has been well-established, higher-yield, billion-cell expansion of MSCs remains a bottleneck. In this study, we successfully demonstrated large-scale culture of human adipose-derived mesenchymal stem cells (AdMSCs) in an industrial, single-use vessel at 3.75 L scale.
Cells cultured in 2D can differ in terms of both physiology and cellular responses compared with cells in vivo. This has led to a surge in the popularity of using 3D culture techniques as mounting evidence suggests that culturing cells in 3D is more representative of the in vivo environment, even to the extent that the gene expression profiles of cells from 3D cultures more accurately reflect clinical expression profiles than those observed in 2D cultures. 3D culture offers the potential for more accurate models of drug delivery and efficacy, as well as numerous clinical and research applications, and is becoming increasingly capable of integrating into high-throughput activities. Spheroids, or sphere cultures, have become an especially exciting area of 3D in vitro culture due to their great potential for use in studies that investigate growth and function of both malignant and normal tissues. These sphere cultures have contributed considerably to our knowledge of cellular responses thanks to the accuracy with which they reflect the in vivo system.
Polysaccharide-based vaccines are widely used to protect against Streptococcus pneumoniae (S. pneumoniae) infections in infants and the elderly. However, their use is limited by strain specificity, which restricts both their geographical and economical utility. There is an urgent need for protein-based vaccines that are likely to provide broader, more economical protection against the global burden of pneumococcal disease. In this paper, we describe the pre-clinical development of a multi-subunit protein vaccine that can be manufactured efficiently and economically to meet this need. Genetically engineered Streptococcus pneumoniae TIGR4 B7.1 PlyD6 cell substrate was constructed to deliver non-toxic Ply.
The production of biopharmaceutical drugs typically involves a biological expression within a bacterial, yeast, or mammalian cell expansion system. Getting to the final product requires multiple purification steps, from primary clarification to the final formulation and sterile filtration. The aim of the initial purification steps is not to purify the stream perfectly but rather, to prepare the stream for finer and more specific purification steps further downstream. Apart from efficiently removing contaminants, the clarification stages also need to maintain high product recovery whilst being consistent and robust.