Analytical tools for the characterization of protein identity and structure are fundamental to many fields of biochemical research. For the development of protein biopharmaceuticals, it is particularly important to measure modifications of the structure that may affect safety and efficacy. This application requires the analysis of large numbers of samples during process development. Small quantities of modifications must be detected in samples that are in the presence of more abundant native protein. Many kinds of analytical techniques are applied to this problem including peptide mapping, bioassays, liquid chromatography, spectroscopy, and so on. One of the most attractive tools is mass spectrometry, since essentially any change in the molecule is accompanied by a change in molecular weight. With the recent advent of readily accessible mass spectrometers capable of routine exact mass measurement, it is appropriate to consider the detailed requirements for this application…
BioProcessing Journal Posts
The biologics market, although difficult to estimate, is currently thought to be in excess of $20 billion. In recent years, the growth in the novel therapeutics market has continued to exceed all but the most optimistic of expectations. The number of products in early stage trials may already be over 1,000, with an estimated 40 or so additional products in the process of finally being released to the market. The biologics market is led by relatively few “blockbuster” drugs, but the breadth of novel products continues to expand. This has resulted in exciting times for clinicians but has resulted in concern related to the bottleneck of production capacities for these drugs, as well as the pressure from healthcare agencies to reduce the cost of goods…
In today’s biopharmaceutical pipeline, monoclonal antibodies are a predominant modality for a broad range of clinical indications, including inflammatory disorders, oncology, and infectious diseases. More than two dozen antibody-based products are commercially available. In 2004, six of the 12 new biopharmaceutics that gained approval in the United States and Europe were antibody-based products. Most antibody therapies require high doses over a long period of time, which requires large amounts of purified product per patient. Therefore, manufacturing capacity to meet the demands of antibody production is a real challenge. It is desirable to have highly productive and consistent manufacturing processes. In addition, speed to market is critical to deliver health benefits to patients quickly and to achieve business success…
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…
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…