Upstream Development

The Need for a New Process

Surveying BPI readers’ experiences SANJA GJENERO (WWW.SXC.HU) Better, faster, safer: The current drug-development “paradigm” emerging from the FDA is pushing for innovations that reduce process inefficiency and cost. The plethora of new risk-based methodologies include tools being developed as process-analytical-technology (PAT) tools within the encircling parameters of a process design space. All this parallels (and drives) some predictions that the biotechnology industry has seen the last of its blockbuster models, as predictive genomic tools enable personalized approaches to therapeutic development.…

Shrinking the Costs of Bioprocess Development

Process development for large-scale bioproduction is generally more labor-intensive, time-consuming, and expensive than for comparable nonbiological processes because of the large number of individual processes and potential variables involved. To ensure the future commercial viability of biological manufacturing processes and prevent bottlenecks, it is essential to accelerate development of both upstream and downstream processing, as well as to improve process analytics. This not only reduces time and cost factors involved in design of robust bioprocessing protocols, but also reduces the…

Creation of a Well Characterized Small Scale Model for High-Throughput Process Development

    Streamlining process development has been the focus of the biotechnology industry over the past several years. To be financially viable in the current market, a company has to be competitive in all three of the following areas: quality, speed, and price (1). Attaining any two of the three attributes at a time is no longer sufficient. With new tools and technologies along with improved understanding of the cell-culture process, doing high-quality process development while reducing both cycle time…

Maintaining Product Titer While Replacing Undefined Components in a CHO Culture System

    Proteins, hydrolysates, and lysates of plant or yeast origin are commonly used in cell culture media for large-scale manufacturing processes for human biotherapeutics. Lot-to-lot variability in the composition of such constituents is well established and can affect multiple biological performance indicators. Our goal was to replace an undefined, protein-containing medium with a chemically defined medium (meaning the chemical structure and concentration for each component in a formulation is known). Such a formulation should be free of protein and…

Development and Qualification of a Generic IgG Quantification Assay Using Surface Plasmon Resonance

Fast, precise, and accurate quantification technologies are indispensable for efficient process development in applications such as IgG production in a GXP environment. Based on surface plasmon resonance (SPR) technology, the Biacore C system from GE Healthcare (www.biacore.com) is an alternative technology for IgG quantification that has benefits over traditional methods. Assay development is simplified and accelerated due to real-time detection. Assay hands-on time is reduced, and sample throughput can be increased using automation and efficient data evaluation with regulatory-compliant software.…

Real-Time Bioreactor Monitoring of Osmolality and pH Using Near-Infrared Spectroscopy

Osmolality and pH are important cell culture process parameters, key elements that are often examined and optimized to improve the productivity of cell-culture–based bioprocesses. Osmolality affects cell viability and growth by regulating the transport of water and nutrients through cell membranes and pH maintains the isotonicity of a culture. To monitor these parameters in cell culture, samples are typically withdrawn and passed through a multifunction analyzer as the BioProfile 400 instrument from NOVA Biomedical (www.novabiomedical.com). Withdrawing samples during a bioreactor…

Novel Excipients Prevent Aggregation in Manufacturing and Formulation of Protein and Peptide Therapeutics

Protein and peptide therapeutics may undergo numerous physical and chemical changes during manufacturing, shipping, storage, and administration that can adversely alter drug potency and safety. Earlier concerns focused upon denaturation (unfolding), oxidation, and deamidation of certain key aminoacyl residues. Recently, aggregation has emerged as a key issue underlying multiple deleterious effects for peptide- or protein-based therapeutics, including loss of efficacy, altered pharmacokinetics, reduced stability and product shelf life, and induction of unwanted immunogenicity. As a result, the US FDA and…

The Genesis of New Production Tools for Biotechnology Manufacturers

The biotechnology industry has from the start been characterized by its dependence on innovation. New therapeutics, new indications, new technologies — and the continual drive toward new approaches for optimizing processes — all contribute to getting novel products to the market (and to patients) efficiently and cost-effectively. Most of the technical literature reports on development processes for the therapeutic products themselves. But one element largely ignored forms an essential foundation to the work of the biotechnology industry: How are products…

The Next Generation of Biologicals and Their Production Systems

Combined advances in molecular biology, cell biology, and genomics have led to a wealth of new information about cellular processes. A growing understanding of the fundamentals of cell biology is now being translated into products that use an approach to exert a biological effect that is different from that of most biologicals currently on the market. To date, most biological products consist of highly purified proteins with a specific activity that alleviates or stops the symptoms of a certain condition.…

Cellular Therapy Success Through Integrated Automation

Cell therapies are being developed for a rapidly expanding range of indications. Genzyme Corporation has a treatment of cartilage in joints in long-term follow-up stage (Genzyme Corporation, www.genzyme.com). Cell Therapies are being investigated successfully in applications to treat infectious diseases such as AIDS, repair spinal cord injuries, strengthen immune systems, and treat neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and epilepsy. Positive results have been reported in treating arteriosclerosis and other cardiovascular diseases, congenital defects, breast reconstruction, and liver…