June 2008

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…

Reviewing the Real Costs of GMP Compliance

Readers of our February 2008 article “Construction and Start-Up Costs for Biomanufacturing Plants: Canadian Case Studies in the Cost of Regulatory Compliance” may have noticed something missing (1). Two somethings, in fact: First, biographical information for coauthor Agnès Coquet was not listed at the end of the article. She is manager of analytical development for Debiovision Inc. of Montreal, Quebec, in Canada; 1-514-842-9976, ext. 104; acoquet@debiopharm. ca. Second, “Table 1” was called out on the fourth page of the article…

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…

at the 2008 BIO International Convention

Come join the staff of BioProcess International at the Biotechnology Industry Organization’s 2008 International Convention in San Diego, 17–20 June. As organizers of the BioProcess Product Focus Zone in the BIO Exhibition Hall, we will look forward to seeing you at our Booth #2438. Not only will you have a chance to visit with our exhibitors, but attendance is free at the zone’s Process Theater. There, for the second year in a row, a number of industry experts and exhibitors…

Products, Services, and Literature

Pilot-Scale Fermentation Product: 19.5-L and 40-L sterilizable-in-place fermentors Application: Bacterial, yeast, or fungal cultures Features: BioFlo 510 is an intermediate-sized CGMP-compliant modular fermentor design for easy addition or removal of components as requirements change. The compact system offers control of =32 process loops from a touchscreen interface, with multiple analog inputs and outputs provided for connection of =14 external devices. The controller enables trend-graphing of eight process parameters simultaneously, stores multiple batch recipes, and can be used with optional SCADA…

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,…

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…

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…

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…

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…