February 2012

About halfway through our first decade in publication, we became well acquainted with a new buzzword phrase in the biopharmaceutical industry: downstream bottleneck ( 1 ). This followed on the heels of a manufacturing capacity crunch that had been forecast shortly before BPI made its debut. Thanks to herculean efforts by upstream process and cell line engineers, that crunch didn’t pan out. In its place, however, high-titer production moved the pressure downstream. Now separation and purification engineers were tasked with handling concentrated feed streams, hard-to-purify proteins, and new contaminant profiles as culture media transitioned from serum-based to chemically defined ingredients. Meanwhile, a few high-profile incidents of adverse events in patients were focusing regulatory, public, and industry attention on the subject of viral safety. BPI acknowledged its importance in a dedicated supplement late in 2005. Editorial advisor Hazel Aranha urged a risk-based approach ( 2 ), following an FDA qual...

Single-use bioprocessing equipment has become well-accepted technology in a relatively short time. Disposable devices and components have created market niches and new segments that continue to evolve. In this dynamic environment, it is difficult to measure acceptance or assess market growth. Here we project the world market for cell culture single-use systems (SUS) as well as problems affecting that market, including adoption for commercial manufacture. This is based on our 10-year analysis of the industry, with data from our eighth annual survey report on biomanufacturing ( 1 ). Complex SUS devices with unique attributes continue to emerge. The first single-use bioreactors — Wave rocker platforms (now from GE Healthcare) — entered the market just about 10 years ago. The disposable-bioreactor market remains dynamic, with new entrants and variants continually being tested as alternatives to stainless steel for commercial applications. Single-use technologies (SUTs) now make up a large percentage of small-...

The Asia–Pacific region is a vast geographic area with a loose definition — covering East Asia, Southeast Asia, and Oceania. It includes a variety of cultures and races and is home to both developed and developing countries. Depending on the definitions of the region, the gross domestic product (GDP) varies from $500 per capita in East Timor to $41,500 in Australia, and the populations climb from a mere 55,500 in Australian Samoa to a vast 1.3 billion in China ( 1 ). Lower costs for drug development and manufacturing have been the traditional driver for taking European and US companies into developing countries in the Asia– Pacific. The region boasts lower labor costs and an educated workforce — including Western-trained scientists returning home — and a huge population of potential patients and controls for clinical trials (often treatment-naïve, and non-Caucasian). By contrast, many trials in the West enroll only Caucasian patients, which do not provide advantages to patients of Asian origin living in E...

Lentiviral vectors are important tools for gene transfer because of their ability to transduce a number of cell types without the need for host cells to be dividing ( 1 , 2 ). As a result, investigators are using them as gene delivery vehicles in clinical applications ( 3 , 4 , 5 , 6 ). Although these vectors are used routinely in many research laboratories, large-scale production using current good manufacturing practice (CGMP) methods comes with a set of challenges that must be considered as more clinical trials using lentiviral vectors receive regulatory approval ( 7 ). One important consideration in designing a CGMP-compatible process is the need to have a manufacturing protocol that produces consistent lentivirus for multiple CGMP productions. Several methods are commonly used to transfect cells with lentiviruses: e.g., lipofection, electroporation, and calcium phosphate transfection. The selected method must consistently produce high-titer virus. Although several laboratories have produced stable p...

Host-cell proteins (HCPs) are bioprocess-related impurities that may be present in intermediate or final biopharmaceutical products such as recombinant monoclonal antibodies (MAbs). Although the potential clinical and genetic effects of HCPs are largely unknown, studies have shown that HCPs may cause immune responses and adverse reactions in patients when present at sufficient high levels ( 1 , 2 , 3 ). Consequently, US Food and Drug Administration (FDA) and European Commission regulations require that the level of HCP in a bioproduct be quantitatively measured during manufacturing and before approval for therapeutic use ( 1 , 2 ). The safe level of residual HCP is suggested as <100 parts per million (ppm) or below detectable levels using a highly sensitive analytical method ( 1 , 2 , 3 , 4 ). For such reasons, detection and evaluation of HCPs are critical parameters for the development of robust and consistent bioprocesses for protein-based biologics. PRODUCT FOCUS : PROTEINS, ANTIBODIES PROCESS FOCUS :...

Assurance of sterility throughout drug manufacturing is paramount to patient safety. Drug products must be free of contamination from microbes, particulates, and chemicals. To that end, we see continued and increased regulatory scrutiny, with adoption of US Food and Drug Administration (FDA) and European Medicines Agency (EMA) standards outside the United States and the European Union. To consistently make microbe-free products, drug manufacturers must implement robust, validated processes that include sterilizing filtration. Sterilizing-grade filtration is used in a number of manufacturing process steps. In final fill operations, a sterile filtrate is necessary, so validation under worst-case conditions is required. For example, a high titer of a small organism may be used with the maximum allowed filtration time and maximum pressure. During intermediate operations, sterilizing-grade performance is highly desirable to keep a low microbial contamination risk and serve as insurance against potential in-pro...

Biosensing Product: SpectroSens optical microchips Applications: Environmental monitoring and antibody detection Features: By using light to measure change, optical biosensors from Stratophase bring precision, flexibility, and cost-effectiveness to real-time monitoring and diagnostics. The SpectroSens microchip biodetector is coated with specific antibodies that bind with high specificity and affinity to biological targets. When a given toxin, bacteria, antibody, or virus is present in a sample, it binds and triggers a positive detection. One disposable microchip can be used to test multiple samples simultaneously or several biological targets within a single sample. Online application notes describe how to use the technology for biohazard agent detection, antigens (using ovalbumin as a model), and antibodies (using IgG as a model), among other applications. Contact Stratophase www.stratophase.com Contract Fill and Finish Service: Formulation and filling Applications: Parenteral products Features:

More therapeutic candidates are nearing approval, and the many classes of oligonucleotide therapeutics in development are creating great excitement. The peptide pipeline is vital, with candidates that could be blockbusters. To tap into this market and get the best information to move your program forward, there is no better place to meet than at TIDES. Manufacturers face tremendous pressure to keep drug costs down with uncertainty about regulatory expectations for analytics and GMP manufacturing issues. The industry needs to know about regulatory changes as well as risks to supply-chain integrity. This conference can help you learn how to proceed. Learn lessons from peers who have been through the development process so that you can move your manufacturing process program forward efficiently. Hear about the latest technologies that can help you save time, reduce costs, and increase yields. Meet potential collaborators and business partners in the best networking forum for the oligonucleotide and peptide m...