Manufacturing

Optimizing Vaccine Supply Chains Through Quality Management in Manufacturing

The recent product recalls of PedvaxHib and Comvax vaccine batches are a reminder that the control of vaccine manufacturing processes is of the highest importance. This rings especially true because the target population for these two products is children under the age of five. The Hib vaccine guards against meningitis and other serious infections caused by the bacterium Haemophilus influenzae. In this particular recall, type b vaccine was tested and determined to be free of contaminating microorganisms before being released…

Modeling Flow Distribution in Large-Scale Chromatographic Columns with Computational Fluid Dynamics

Column chromatography remains a key unit operation in downstream processing of biopharmaceuticals. For most commercial processes, two to three chromatography steps are used to remove process-and product-related proteins, DNA and adventitious agents. As the biopharmaceutical industry has increased its product offerings and related demands, downstream processes have fast become a bottleneck (1, 2). Many commercial and clinical processes include a number of cycles on one or more chromatography steps to process the harvest from a single production batch. PRODUCT FOCUS:…

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.…

Biomanufacturing Capacity Use Showed Solid Performance in 2007

It appears that it will take more than just the subprime mortgage crisis to put a dent in biopharmaceutical manufacturing. Based on results of our latest annual report, capacity use in 2007 remained essentially steady for mammalian cell culture: at nearly two-thirds, 63.3% compared with 63.9% the year before (1). Capacity use represents the percentage of an industry’s production capacity that is actually in use. It measures how effectively manufacturers and industries are making use of their fixed assets. This…

The Emerging Generation of Chromatography Tools for Virus Purification

Chromatography media and methods have evolved continuously since their introduction a half century ago. Traditional methods use columns packed with porous particles. They still dominate chromatography applications in the field of virus purification, but the past 20 years have witnessed the ascendance of alternative supports, namely membranes and monoliths. These newer media exploit the familiar surface chemistries — ion exchange, hydrophobic interaction, and affinity — but they use unique architectures that offer compelling performance features. The Architecture of Chromatography Media…

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…

Manufacturing Patient-Specific Cell Therapy Products

Several cellular therapies are currently progressing through clinical development with the potential to address unmet medical needs affecting millions of patients. As cell-based therapeutics receive regulatory approval and reach the market, the primary challenge will quickly become manufacturing such products in sufficient volume to meet demand. Aastrom Biosciences has developed tissue-repair cell (TRC) technology for use in autologous, patient-specific cellular therapy (PSCT) and is conducting late-stage clinical trials both in the United States and Europe. TRCs are derived from a…

Probing Thermal Stability of MAbs By Intrinsic Tryptophan Fluorescence

In the arsenal of biophysical techniques available for rapidly monitoring the stability of protein formulations, spectroscopic techniques have some convincing advantages over others (1, 2). The main advantages to using methods such as circular dichroism (CD), infrared spectroscopy (IR) and fluorescence spectroscopy are their extremely high sensitivity (favorable signal-to-noise ratios), freedom from sample interactions with column resins or extrinsic probes (noninvasive techniques), and coverage of an extremely broad protein concentration range — from pM to mM (3, 4). To reduce…

Reconsidering the Supply Chain

An emerging challenge for biotech companies is understanding the bigger picture: How should manufacturing facilities be configured to link together process technologies? Should plants be highly flexible or focus on process standardization? How would a disruptive new technology affect current supply chains, and how could it be implemented? Meeting the challenge requires a complete and detailed understanding of supply chains. Much current focus in process development is on improving operations, with limited consideration to how improvements affect “big picture” variables.…

Validation of Adventitious Virus Removal By Virus Filtration

Regulatory bodies around the world expect downstream purification processes to demonstrate robust clearance of model adventitious viruses in time for execution of phase 3 clinical trials and product licensure (1,2,3). Model viruses selected for these studies should represent a diversity of viral physicochemical properties, and the clearance methods applied should include orthogonal mechanisms such as clearance based on size alongside chemical inactivation. Virus filtration is a critical unit operation used in numerous purification processes of monoclonal antibodies (MAbs), recombinant proteins,…