Various types of viral vectors are being employed extensively as gene therapeutics to treat cancer and genetic diseases. Among the viruses that have been produced for human clinical trials (i.e. retrovirus, adenovirus, poxvirus, adeno-associated virus, and herpesvirus vectors) adenoviruses exhibit the lowest pathogenicity yet still infect an extensive range of cell types with high efficiency. These key characteristics make recombinant adenoviruses efficient gene-delivery vehicles and excellent research tools. However, the time-consuming and complex processes of generation, amplification, purification, and quality testing associated with production of recombinant adenoviruses make it difficult for many researchers to utilize these vectors. This is particularly true with respect to cell culture optimization and the virus propagation protocols employed in vector production. In this regard, the development of innovative cell culture techniques has become vital for optimizing vector production for gene therapy…
BioProcessing Journal Posts
Conventional medical technologies to address tissue and organ dysfunction have resulted in a host of approaches, largely device-based. Examples include maintenance dialysis for renal dysfunction, use of pacemakers, stents, oxygenators, and valves to neutralize the effects of cardiovascular dysfunction, and replacement of large joints with mechanical substitutes. Advances in transplantation science have led to increasing success in replacing diseased kidneys, livers, hearts, pancreata, and lungs. There are, however, significant and severe limitations to these conventional therapies, most notably the demand by a growing and aging population. There is a well-recognized limitation in the supply of tissues and organs. In the year 2000, for example, 77,000 people were awaiting organ transplants, while only 23,000 were performed. High tech medicine is costly; U.S. healthcare expenditures as a percent of gross domestic product are expected to reach 16.7% by 2007…
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…
Within the United States, greater than 90% of the available transfusible blood products are collected, processed, and distributed by regional blood centers. The remaining blood products are collected by hospital-based blood banks and are usually provided only to patients in the collecting facility. The “region” in which a blood center offers services (i.e., collecting blood from volunteer donors and providing blood components to healthcare facilities), is usually an arbitrarily and independently defined group of contiguous counties surrounding a major metropolitan area. However, the borders of the region can be elastic and easily altered by gaining or losing access to donor groups or customers. It is not uncommon for a geographic area to be simultaneously “claimed” by neighboring competing blood centers. America’s Blood Centers (ABC) is a not-for-profit trade organization that provides services and advocacy for independent not-for-profit regional blood centers. ABC’s seventy-five members collect approximately 45% of the country’s blood products…
Foreign substances, such as disease-causing viruses and other infectious agents are recognized by the body’s immune system as invaders. Parts of the spectrum of our defenses are antibodies that bind these antigens and direct their destruction by other elements of the immune system. Antibodies have two very useful characteristics. First, they are extremely specific; that is, each antibody binds to one particular antigen. Second, the body retains the memory of encounters with antigens, enabling it to reproduce an antibody response to a later attack by that that same agent or disease. These properties make it possible to develop vaccines. It is the first trait of antibodies, their specificity, which makes monoclonal antibody (MAb) technology so valuable. Not only can antibodies be used therapeutically, to protect against disease, they also can help diagnose a wide variety of illnesses and can detect the presence of infectious agents (including biological threat agent). The use of MAbs specific for biological warfare agents in fielded assays requires maintaining a high-quality and economical supply of these reagents…
With the advent of whole cell-based therapeutics has come a growing standardized quality control and quality assurance of the processes employed for developing and manufacturing cellular materials, similar to the controls over traditional drugs and biologicals. Cellular therapeutics present unique process and quality control challenges due to the innate complexities of living cells, making it important to use whole cell assays to provide detailed pictures of the status and consistency of cell preparations that will be used to treat patients. This article illustrates how a cellular assay from Guava Technologies addresses these issues…