The biopharmaceutical manufacturing sector is rapidly gearing up production capacity to satisfy the steadily escalating global demand for complex biologics to combat a number of treatable illnesses. Frequently, the biotherapeutics in demand are too complicated to be chemically synthesized and thus are beyond the reach of traditional pharmaceutical approaches. To effectively address this issue, these products must be developed and produced using viable and robust biological systems…
Category: <span>Manufacturing</span>
The modern age of blood transfusion began after the Second World War, as detailed in Douglas Starr’s book, Blood: An Epic History of Medicine and Commerce. During the war, it became apparent that early and aggressive medical treatment utilizing whole blood or plasma could increase the chances of survival for military personnel wounded in combat. In the United States, a national program to encourage blood donation was created to provide the needed blood, which was then shipped as whole blood or plasma to war zones. After the war, physicians were eager to apply surgical advances developed on and off the battlefield to the care of the general population. Because these advances relied on blood transfusion, for the public to realize their benefit, adequate supplies of whole blood and blood components needed to be available to hospitals across the country. This was often not the case…
Xcyte Therapies has recently introduced a bioreactor-based process for the GMP manufacture of autologous activated T cells, Xcellerated T Cells™, for clinical trials. Using a single customized disposable 20-L Cellbag™ with a working volume of 10 L on a customized Wave Bioreactor platform (Wave Biotech, Bridgewater, NJ), the Xcellerate™ III Process has supplanted the 60-L static Xcellerate II Process that used 60 bags cultured in a standard incubator. Compared to the Xcellerate II™ Process, the Xcellerate III Process significantly reduces the overall labor, the number of culture containers, bag spikes, and sterile connections required, as well as reducing the process volume and the cost of goods, while more than quadrupling the final cell density and doubling the facility capacity. These process improvements are achieved without compromising final product composition or quality…
On January 31, 2003, FDA under the leadership of Commissioner Dr. Mark McClellan, issued a report entitled “Improving Innovation in Medical Technology: Beyond 2002.” One of the goals described in this report is to “speed potentially important emerging technologies to the market by reducing regulatory uncertainty and increasing the predictability of product development.” The technology areas of cell therapy and gene therapy were specifically identified. This article highlights some of the challenges for manufacturers and regulators of these products and describes ongoing efforts at FDA — as well as opportunities to partner with FDA — to improve the product development process for cell therapy and gene therapy products…
A clinical-scale manufacturing process has been developed for the ex vivo expansion of autologous cytolytic T lymphocytes (CTLs) directed against cells infected with the hepatitis B virus (HBV). The process is based on the Rapid Expansion Method (REM) technology originally developed at the Fred Hutchinson Cancer Research Center in Seattle, WA by Greenberg and Riddell. Preparations are underway to initiate a company-sponsored Phase I clinical trial in which REM will be used to expand rare autologous HBV-specific CTLs that will then be infused to patients chronically infected with HBV. Earlier studies have shown that such patients mount only a weak CTL response to HBV. Chronic hepatitis B can lead to severe liver damage such as cirrhosis and hepatocellular carcinoma. By infusing clinical-scale quantities of autologous HBV-specific CTLs into chronic HBV patients, it may be possible to boost the immune system so that it can control the viral infection…
Contract manufacturing of recombinant protein drugs and vaccines, as well as other biopharmaceuticals, has been the focus of considerable interest during the past decade. Fueled by a strong clinical development pipeline, primary manufacturing of biopharmaceuticals on a contract basis has attracted multinational industrial concerns willing to invest on the promise of potentially higher returns than are experienced in the production of traditional small molecule drugs. Biopharmaceutical contract manufacturers have made significant contributions to the development and subsequent commercialization of a few highly successful products. However, despite strong growth, consistent profitability has been elusive. The market has changed overr the past decade as customer projects progressed from process development through market launch. Now that several preeminent market players have successfully made the difficult transition from clinical to commercial supplier, what has been learned and how is the market expected to evolve over the next five years?…
Bioreactor productivities are highly dependent on the process used to cultivate mammalian cells. These productivities directly affect the manufacturing plant capacity, and thereby the economics of production of monoclonal antibodies (MAbs). Historically, companies have chosen bioreactor process strategies that emphasize simplicity of scale-up at the expense of productivity, and conducted manufacturing using well-characterized and relatively straightforward batch processes. Such processes have successfully produced small or moderate quantities (ranging from ~100 g to ~ 1 kg per lot) of the desired antibody. Given the anticipated demand for large-scale quantities of MAbs (and the high stakes for the companies investing in these new biological entities), it is worthwhile to revisit these past selection strategies and see if — and under what conditions — they remain optimal today…
The revolution in biotechnology has led to 133 biotechnology-derived medicines being approved by 2001 with sales of $22 billion. This is less than 10 percent of today’s total pharmaceutical market, but it is a rapidly growing sector. Biologics are predicted to grow to nearly $50 billion by 2008. Marketed biopharmaceuticals include several blockbuster products with multibillion-dollar sales. In recent years, biotechnology-derived therapies represented 10 percent to 20 percent of all new approved molecular entities and hundreds more are in development, including nearly 200 proteins in late-stage trials. Microbial and mammalian expression systems are typically used to produce biotherapeutic proteins (many companies are also working on transgenic expression systems). Microbial cultures (typically, Escherichia coli or yeast) are used to produce smaller, less-complex proteins or those where specific modifications, especially glycosolation, are not required…
In the past, most large construction projects used a system called design-bid-build. Now, pharmaceutical companies planning cleanrooms have begun using an improved system, design-build, which can save millions of dollars and cut months from construction schedules. Design-build also can provide better quality end results than design-bid-build…
Long-term growth of the biopharmaceutical industry is increasingly relying on outsourcing to overcome the current capacity constraints, especially for monoclonal antibody production. Companies are often reluctant to commit to building multimillion dollar manufacturing facilities for potential products with no guarantee of approval. Therefore to offset risks, companies will enter into contract manufacturing arrangements…