Tag: <span>chromatography</span>

Downstream processing is increasingly seen to be a capacity constraint for many biopharmaceutical manufacturing organizations. In our current study, nearly 75% of respondents reported that their facilities were experiencing some degree of capacity bottlenecks as a result of downstream processing. In comparison, 63.8% responded the same in the previous year. As the biopharmaceutical industry increases its focus on cost containment, product pricing, and healthcare reform, critical manufacturing operations have been pushed to center stage. Over the past few years, downstream processing, which includes complex operations such as filtration of final products and chromatography operations has become increasingly challenging, from budgetary and operational perspectives. As upstream operations continue to improve, the ability of current downstream facilities to handle the additional load has led to strains and constrictions. The industry is open to new solutions although few alternatives to current processes have been presented. A number of promising innovative technologies are on the horizon, but it will be a few years or more before they debut in clinical or commercial production operations….

Manufacturing

With the ­development of bacterial fermen­tation and ­mammalian cell culture as the sources for new recombinant products came a standardization of raw feed stocks. Therefore, manufacturers came to share the same types of problems. This standardization allowed a more systematic approach to process development divided into upstream (bacterial and yeast fermentation or mammalian cell culture) and downstream processing activities…

Manufacturing

Monoclonal antibodies and recombinant proteins have increased in importance and gained success as therapeutic agents in treating various diseases. Biomanufacturing of such a biopharmaceutical product by cell culture follows a main route. Upstream processing is strictly biology-driven, while on the other hand, purification is engineering driven. Fermentation is setting the pace. To some extent, that pace is a result of recent advances in cell culture, greatly increasing the densities of cells along with cell-related contaminants…

Manufacturing

In today’s biopharmaceutical pipeline, monoclonal antibodies are a predominant modality for a broad range of clinical indications, including inflammatory disorders, oncology, and infectious diseases. More than two dozen antibody-based products are commercially available. In 2004, six of the 12 new biopharmaceutics that gained approval in the United States and Europe were antibody-based products. Most antibody therapies require high doses over a long period of time, which requires large amounts of purified product per patient. Therefore, manufacturing capacity to meet the demands of antibody production is a real challenge. It is desirable to have highly productive and consistent manufacturing processes. In addition, speed to market is critical to deliver health benefits to patients quickly and to achieve business success…

Biologics Production Manufacturing

The diversity of the antibody-antigen interaction and our ability to manipulate this interaction has created an enormous potential for the discovery and development of IgG therapeutics and diagnostics. Along with the expanding clinical pipeline of antibody products, increasing efforts have been devoted to improving antibody production and purification procedures. In order to meet drug discovery needs with limited resources, the so called ‚Äúflexible generic purification scheme‚ÄĚ approach has been adopted to develop a robust manufacturing process that allows the application of similar operational conditions to different monoclonal antibody molecules‚Ķ

Biologics Production

Current expression technologies have enabled the production of thousands of recombinant proteins in diverse production hosts. Therapeutic recombinant proteins have been engineered for a variety of purposes including reduced antigenicity, longer half-life, simplified process development, and increased affinity. Protein engineering has relied on various high throughput methods (e.g., directed evolution, phage display) to identify candidate proteins with the desired therapeutic properties. The physiological and biochemical diversity of native and engineered proteins reflects on the abundance of production hosts, expression tools, and different approaches for protein purification. Notably, a key step in high-throughput protein production is purification, which is a bottleneck where large numbers of samples are involved. Universal purification methods that can be applied to virtually any protein, and that are amenable to automation, can be used to address this problem…

Biologics Production

The quantitative and qualitative analysis of proteins and their amino acid sequence composition is a critical operation in many research laboratories and operations. Much protein analysis is performed using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) or fluorescence detection. Although these methods are robust and widely used, certain issues limit their utility. For example, some proteins or peptides may have a poor UV response and can be difficult to detect. Direct comparisons of protein levels when quantitated directly by UV can also be problematic due to differences in extinction coefficients of various proteins…

Research

Poliovirus is a small (28-30 nm diameter) non-enveloped RNA virus belonging to the family Picornaviridae. The ability of poliovirus to cross the blood-brain barrier and its natural infectivity of central nervous system (CNS) tissue via the CD155 receptor, found exclusively in primates, has promoted the investigation of an attenuated poliovirus for the treatment of malignant gliomas. However, use of the virus in clinical testing is limited due to low yields obtained from conventional purification methodologies…

Biologics Production

With the advent of the first gene therapy product to market, the industry faces the challenge of mass-producing high-purity viral particles and plasmids. The concept of manufacturing therapeutic genes rather than therapeutic proteins as marketable products is still in its infancy. Although manufacturers of biopharmaceuticals have decades of experience in the purification of proteins, virus and plasmid products pose unique challenges that cannot be addressed without some modifications to traditional, protein-based approaches…

Biologics Production Cell & Gene Therapy Viral Vectors

The last 30 years have seen rapid and dramatic developments in recombinant DNA technology and the related biological sciences. In 1972, Paul Berg’s group used restriction enzymes to cut DNA in half and then used ligases to stick the pieces of the DNA back together. By doing this, they produced the first recombinant DNA. Within a year, the first genetically engineered bacterium existed. A little more than ten years later, recombinant human insulin was approved for diabetic patients and became the first recombinant healthcare product. Before the end of the 1980s, the first gene therapy trial had occurred. Today, a large number of recombinant proteins are used as marketed drugs and even more are in clinical trials targeting a wide range of diseases…

Biologics Production