Tangential flow filtration (TFF) is widely used in biopharmaceutical processing for protein purification – a common application for TFF is ultrafiltration for concentration/diafiltration of proteins. In this type of application, the product protein is retained (concentrated) within the feed side of the ultrafiltration membrane, while the buffer components and other small impurities (smaller than the membrane pore size) freely pass through the membrane into the permeate side. Several scholarly articles are available in literature which discuss the ultrafiltration application as well as its optimization strategies. Another category of application where TFF finds significant use is in the clarification of cell culture bioreactor and microbial fermenter feed solutions using microfiltration membranes. In some of these microfiltration TFF applications (e.g., mammalian cell culture clarification), the product (protein) freely passes through the microfiltration membrane and is recovered on the permeate side, while the contaminating impurities (cells, cell debris, colloids) are retained on the feed side of the membrane. In certain other microfiltration TFF applications (allantoic fluid clarification in egg-based flu process), the product (flu virus) may get concentrated on the feed side of the microfiltration membrane (similar to an ultrafiltration step), while the contaminating impurities (ovalbumin, etc.) may get removed into the permeate side…
Tag: <span>bioreactor</span>
Traditionally, the Six Sigma framework has underpinned quality improvement and assurance in biopharmaceutical manufacturing process management. This paper proposes a neural network (NN) approach to vaccine yield classification and compares it to an existing multiple linear regression approach. As part of the Six Sigma process, this paper shows how a data mining framework can be used to extract further value and insight from the data gathered during the manufacturing process, and how insights into yield classification can be used in the quality improvement process.
Viable cell density (VCD), the quantitative assessment of living cells, is commonly determined by laborious and inaccurate off-line cell counting methods. Single-function in situ probes have been developed using various technologies including optical density, radio frequency and dielectric permittivity. Optical density measurements predict total biomass but are sensitive to cell debris accumulation and inherent media turbidity. Near-infrared (NIR) has the advantage of being able to measure many key analytes in the cell culture simultaneously. NIR has been used to acquire real-time measurements of glucose, glutamine, glutamate, and media nutrients such as amino acids and metabolites (e.g., lactate and ammonia). NIR probes can be sterilized in place, and real-time measurements can be acquired throughout the mammalian cell culture processes…
Mass transfer is one of the most crucial parameters during scale-up in cell culture, and may cause variations in specific yields. At the cellular level, all the cells require proper supplementation of essential nutrient sources: nitrogen, oxygen, and carbon. The ability of cells to grow, maintain viability, and provide high specific productivity depends on the proper distribution of these nutrients. The latter depends on proper mass transfer to supply oxygen, carbon, and nitrogen through agitation and aeration, along with other micronutrients…
In the last few years, we have seen many biotech products approved by FDA. These products have gained public awareness because of their ability to treat several debilitating diseases with very minimal side effects, and thereby impact the quality of life for many people. As a result, the biotech industry is constantly in the news for its successes and programs to develop new therapeutics for many unmet medical needs. Immunomedics, Inc., a New Jersey biotechnology company, recently completed an expansion project that included new bioreactor manufacturing suites and support laboratories. Building on the company’s existing headquarters site and fully integrating the new capacity into the existing operational facility, the project spanned two years and was completed in 2003…
Neurodegenerative diseases such as Parkinson’s disease and multiple sclerosis, along with injuries such as stroke affect millions of individuals worldwide and costs healthcare systems billions of dollars each year in North America alone. The diseases result from the death of specific cell types within the central nervous system. Current treatment efforts have focused primarily on alleviating symptoms using pharmaceuticals. However, recent advances in our understanding of these conditions, coupled with advances in biology, genomics, transplantation, and biochemical engineering are making cell therapy (the transplantation of viable cells to replace dead cells) more attractive as a potential avenue of treatment…
Single-use, disposable components offer many advantages in the manufacturing of biologics. They are clean and ready to use when supplied, which obviates the need for sterilization and decreases the requirement for services such as water for irrigation (WFI) systems and steam generators. Disposable components are not used for subsequent operations, eliminating the chance of cross contamination between process runs. Long lead times for equipment installation can be avoided because the need for stainless steel equipment is reduced or eliminated. Systems are less complex, therefore engineering requirements are also reduced. There is no need for clean-in-place (CIP) or steam-in-place (SIP) operations, along with the associated piping, valves, controls, or pressure rating of vessels. Moreover, the use of disposable components reduces the complexity of validation…
Within the biopharmaceutical industry, mammalian cell culture is extensively used to manufacture a various biopharmaceutics uncluding antibodies, interferons, hormones, crythropoietin, clotting factors, immunoadhesins, and vaccines. The market for monoclonal antibodies (MAbs) alone is expected to grow 30% a year and reach sales of nearly $6.5 billion in 2004. The vast majority of these biotherapeutics are secreted glycoproteins obtained from mammalian cell lines such as: Chinese hamster ovary (CHO), human embryonic kidney 293 (HEK-293 or 293). NS0, and baby hamster kidney (BHK). As is the goal with most commercial products, biotechnologists strive to generate these valuable proteins in the highest yields possible in order to utilize mammalian bioreactor facilities efficiently…