Recombinant DNA-transduced cellular products encounter the product development and regulatory issues of both gene therapy and cellular therapy products. The characterization of recombinant DNA-transduced cellular products remains highly challenging for both sponsors and regulatory agencies. The regulatory concerns and product testing for such cellular products are similar to those for all biologicals. These concerns include the demonstration of product safety, identity, purity, and potency; the control of the manufacturing process to ensure the consistency of product manufacturing under a proper quality control program; and the demonstration of reproducibility and consistency of product lots by means of defined product lot release testing criteria…
BioProcessing Journal Posts
Biopharmaceuticals are predicted to become the main driving force of the pharmaceutical market in the near future. Other than blockbuster products such as erythropoietin, an increasing number of approved recombinant therapeutic proteins are based on antibody technology (e.g., fusion proteins or monoclonal antibodies [MAbs]). In contrast to relatively simple products produced in Escherichia coli bacteria (e.g., insulin), proteins which require complex posttranslational modifications such as glycosylation have to be produced in eukaryotic cells. In this context, production systems have been dominated by mammalian cell culture. Nevertheless, alternative eukaryotic expression technologies based on yeast, insect cells, transgenic animals, or transgenic plants are under development. Plants are a particularly promising alternative to mammalian cell culture because of their excellent safety aspects and estimated cost-efficient upstream/cultivation processes. In addition, plants are well known for their ability to express biologically functional monoclonal antibodies. In comparison to the seed plants most widely used for transgenic protein expression — tobacco, corn, and rice — mosses provide unique, beneficial features…
Psoriasis is a chronic, inflammatory disease of the skin that is estimated to affect 2-3% of the U.S. population. The estimated annual outlay for treating the disease has ranged from $1.6 billion to $3.2 billion, and the cost to individuals with the disease is far higher than the monetary costs. Psoriasis is characterized by excessive keratinocyte proliferation, leading to a significant thickening of the epidermis, expansion of epidermal rete pegs into papillary dermal space and abnormalities in the differentiation process. Clinically, one sees red, raised, scaly lesions that can occur over any part of the body. The etiology of the disease is complex and not well understood. T-cells are almost certainly involved in the initiation and maintenance of psoriatic lesions. Although the triggering event is immunological, alterations in keratinocyte function also appear to be important to the overall pathophysiology…
Many precautions are taken in a typical research lab to ensure the integrity of biological specimens. Temperature, storage, and personnel access, among others, are all tightly controlled, and codified into standard operating procedures (SOPs), if not almost biblical law. And no wonder — companies have millions invested in biotech solutions whose progress is often measured in years and decades. Scientists have their life’s work on the line. So, it is with some surprise that the diligence most companies exercise during the research and development process is not always maintained during specimen transport. Every time a specimen leaves the lab, be it for further analytical testing or investigational purposes, it runs a heightened risk of contamination, especially from fluctuating temperatures. Ensuring that this does not happen should be the responsibility and concern of everyone with a stake in a biological product’s success…
The aim in process filtrations is to purify the liquid preparation by removing particulate impurities while obtaining as large a throughput as possible under practical conditions. The rate of flow should be expeditious enough to meet time constraints when necessary. This places a focus on the applied differential pressure level that motivates the liquid flow. A balance must be sought. Higher differential pressures increase the flow rates but may decrease throughputs by compaction of the filter cake. Also, higher applied pressures may minimize the adsorptive retention of particles. Deciding which is the proper filter involves small-scale filtration trials. The choice of the filter having been made, its size, in terms of the area necessary for the processing of the production batch, is arrived at by extrapolations from the small-scale tests that were performed…
In the last few years, we have seen many biotech products approved by FDA. These products have gained public awareness because of their ability to treat several debilitating diseases with very minimal side effects, and thereby impact the quality of life for many people. As a result, the biotech industry is constantly in the news for its successes and programs to develop new therapeutics for many unmet medical needs. Immunomedics, Inc., a New Jersey biotechnology company, recently completed an expansion project that included new bioreactor manufacturing suites and support laboratories. Building on the company’s existing headquarters site and fully integrating the new capacity into the existing operational facility, the project spanned two years and was completed in 2003…
In today’s aggressive biopharmaceutical market, many drug discovery organizations, including both big pharmaceutical companies and small technology start-up companies, are outsourcing the development and manufacturing of their biopharmaceuticals to specialized contract manufacturing organizations (CMOs). Outsourced biopharmaceuticals range from those in early phase production to products that are well advanced down the development pipeline. As a result, there has been an expansion of CMOs that specialize in all aspects of biopharmaceutical manufacture, from process invention and development, through small-scale GMP production, to process validation and large-scale manufacture. The CMOs provide R&D services, quality function, and state-of-the-art good manufacturing practice (GMP) facilities needed for the production of biopharmaceutics. Using CMOs for biopharmaceutical process development and manufacture provides major cost savings by dispensing with the need to invest in experienced personnel and expensive manufacturing facilities…
Baculovirus, particularly AcMNPV (Autographa californica multiple nucleocapsids polyhedrosis virus), is widely used for heterologous protein expression. There are several shortcomings in the current practice of preserving and scaling up baculovirus: 1) extracellular baculovirus stocks, routinely prepared in large volumes and stored at 4º C, are often unstable; 2) laborious and time-consuming steps to amplify and titer the baculovirus stocks are often necessary, and generally recommended, for achieving consistent viral infection and protein expression; 3) once prepared, the baculovirus is suspended and stored in conditioned medium. Given the complex, undefined, and unstable nature of the spent media components, including proteases and nucleases, protein expression tends to vary even when steps are taken to titer the virus stock and adjust the amount of stock used for infection. Here, we will report a new method for preserving and scaling up baculoviruses that: 1) provides a new form of viral stock more stable than the traditional, extracellular stock; 2) eliminates the need for virus amplification and retitering; 3) drastically reduces the turn-around time and resources required for scale-up; and 4) improves yield and consistency in protein expression.