Since the 1980s launch of the first recombinant-DNA–sourced protein insulin, the 1990s introduction of interferons and interleukins, and the first commercial approval of MAbs around the turn of the century, the therapeutic protein market has shown a very healthy growth of 15–19% (Figure 1). Between 1980 and 2004, about 300 antibodies and 400 other recombinant proteins entered clinical trials, totaling about 750 products (1). Figure 1: () A survey of biopharmaceutical production technologies in 2005 shows that Chinese hamster ovary…
Sunday, June 1, 2008 Daily Archives
Effect-Based Compliance
Regulatory compliance is a competitive team activity that creates real value reflected in the bottom-line accounting of company profitability. Champions earn freedom to operate for their companies; losers are enjoined, have products seized, and/or are prosecuted for their (mis)deeds. The players and fans use FDA form 483s and warning letters as metrics for measuring relative standing. The operational paradigm is that “employees” tend to define competitors in the context of a company’s market. In the regulatory game, competitors are less…
Vendor Voice: A New Paradigm for Bacterial Strain Engineering
From rapidly obtaining sufficient amounts of active protein in early stage development to cost effectively producing kilogram and even metric ton quantities for commercial supply, protein expression is critical at every stage of biopharmaceutical drug development. Having a high-performance protein expression platform across all stages is invaluable for the speed and success of protein and vaccine development. Historically, biopharmaceutical researchers and process development scientists have used Escherichia coli in their laboratories to generate small quantities of protein. If target expression…
A Review of Therapeutic Protein Expression By Mammalian Cells
During the past five years, many biopharmaceuticals have found their way into clinical trials and commercial production (1–4). So far, about 60 million patients worldwide have benefited from these new drugs. The market for biopharmaceuticals was estimated at US$33 billion in 2004 and projected to reach US$70 billion by the end of the decade. During the period 2003–2006, regulators in Europe and the United States approved 32 biopharmaceuticals for human use, including hormones and growth factors, therapeutic enzymes, vaccines, and…
From Pandemics to Bioterrorism
On 28 March 2008, BioProcess International hosted a panel discussion at the annual INTERPHEX conference (26–28 March 2008 in Philadelphia, PA), titled “From Pandemics to Bioterrorism: The Role of Bio-Manufacturing in Global Healthcare.” The discussion format grew out of a series of conversations over several months involving the panel members, INTERPHEX organizers, and BPI’s editor in chief (all participants are listed on the previous page). The group started with the premise that the biotechnology industry has a vital role to…
Expression of a Fab Fragment in CHO and Pichia pastoris
Mammalian cell expression systems are currently essential for production of glycosylated biopharmaceuticals such as monoclonal antibodies or molecules requiring even more complex glycan structures. Various host cell and vector systems aimed at improving expression levels and quality have been established (1, 2). Development of biopharmaceutical product candidates from genes to clinical trials should be based on technology platforms that will require no major changes in the entire development chain, including manufacturing once a product candidate has successfully progressed through phase…
Determining the Effect of Raw Materials on Manufacturing-Scale Cell-Culture Performance
Large-scale cell culture production processes routinely involve multicomponent cell culture media formulations including both chemically defined raw materials and complex raw materials such as hydrolysates (1). Even minor variations in the compositions of either can lead to variability in protein productivity or product quality. That often persists despite the use of a raw material lot-blending strategy at large scales to “average out” raw material trends. And a raw material lot-blending strategy can makes it more difficult to identify which single…
Probing Thermal Stability of MAbs By Intrinsic Tryptophan Fluorescence
In the arsenal of biophysical techniques available for rapidly monitoring the stability of protein formulations, spectroscopic techniques have some convincing advantages over others (1, 2). The main advantages to using methods such as circular dichroism (CD), infrared spectroscopy (IR) and fluorescence spectroscopy are their extremely high sensitivity (favorable signal-to-noise ratios), freedom from sample interactions with column resins or extrinsic probes (noninvasive techniques), and coverage of an extremely broad protein concentration range — from pM to mM (3, 4). To reduce…
Carbohydrates and Their Analysis, Part Three
A large proportion of the therapeutic biotechnology products already in the market or under development are glycoproteins. Therapeutic glycoproteins are produced as recombinant products in cell culture systems, which raises the importance of understanding the biosynthetic events described in the previous installments of this three-part article. Lack of control in a bioprocess could easily change glycosylation patterns by distorting the activities taking place in the Golgi apparatus. Disruption of the delicate balance among substrate availability, optimum pH for specific activities,…
A Bioreactor System Based on a Novel Oxygen Transfer Method
Bioreactor technologies for mammalian cell culture may seem quite sophisticated (1). In fact, efficient mammalian cell culture is simple and requires just two major elements: mixing and oxygen (O2) transfer. Traditional methods for mixing use an impellor, and the classical O2 transfer method features a sparging stone that expels air bubbles to increase the O2 transfer surface area in contact with a culture medium. Mammalian cells are sensitive to shear forces and also to the toxicity of pure or enriched…