As pharmaceutical and biopharmaceutical companies become more global in nature with products that have the potential to reach into the worldwide marketplace, a special understanding is needed of the requirements that are specific to varying geographical areas. Specifically, the regions for worldwide pharmaceutical distribution can be broken into America, Europe, and Asia-Pacific, with each region presenting its own regulation and technical challenges. There are many issues that are common among these regions, but each region’s focus may be different. Typically, an issue arises in one region and then migrates to another as people become aware of the issues and concerns. For example, the use of prefilled syringe systems in Europe and Asia has migrated to the American marketplace, amounting to a more significant volume…
BioProcessing Journal Posts
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 “flexible generic purification scheme” approach has been adopted to develop a robust manufacturing process that allows the application of similar operational conditions to different monoclonal antibody molecules…
Biopharmaceutical manufacturers are constantly seeking new ways to lower production costs, while simultaneously increasing cost effectiveness without sacrificing quality. The U.S. biotech industry has grown from $8 billion in 1992 to $30 billion in 2002. As productivity in biopharmaceutical manufacturing has increased, pressures to contain costs have mounted in the healthcare industry, coupled with increased demands by investors, which results in increased cost containment pressures on the industry as a whole. Some biotechnology products need to be produced in large quantities (hundreds of kilograms per year) to meet both current and expected demand. This requires significant manufacturing capacity, and makes the types of incremental process improvements commonly sought in chemical pharmaceutical processing an attractive proposition for biopharmaceutical manufacturing…
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…
Since the mid-1970’s, when Kohler and Milstein first discovered the process by which myeloma cells and splenocytes could be fused to produce monoclonal antibodies (MAbs), a whole new world of important therapeutic, prophylactic and diagnostic products has opened up, bringing in huge benefits for patients and manufacturers. The total sales of therapeutic MAbs reached more than $13 billion in 2005. Sixteen of the 18 FDA-approved MAbs came to the market after 1997, and over 150 are currently in clinical development, suggesting their increasing medical importance and the remarkable, recent advancements in development technology…
A number of antibody drugs are currently in clinical development and 22 antibodies (including five diagnostic antibodies) have received FDA market approval in the last decade. A number of different technologies are now being used successfully to isolate potent therapeutic antibodies with minimal immunogenicity and improved safety. These include chimerisation (mouse/human antibodies), humanisation (complementarity-determining region [CDR] grafting), transgenic mice, phage display, ribosome display, and other emerging technologies. The phage and ribosome display technologies used at Cambridge Antibody Technology (CAT) are based on the physical linkage of gene to gene product which enables the recovery and enrichment of genetic material encoding the selected antibody…
A program for control of biopharmaceutical raw materials is a critical quality system that helps assure patient safety and contributes to product quality. The systems for testing and acceptance must be scientifically based, and meet global regulatory requirements and standards. When a new raw material is sourced, it is important to quickly establish the quality profiles for the supplier and the raw material. Among the numerous challenges that confront a company attempting to establish an effective, compliant, raw materials program, this paper will address the following: • Challenges in sourcing and tracing raw materials that are suitable for use in human therapeutics • Challenges and obstacles in qualifying suppliers • Special challenges faced by a firm that has outsourced its manufacturing and/or quality control (QC) testing…