Transgenic plants are increasingly considered a competing system for producing high-value recombinant proteins for biomedical and industrial purposes at affordable costs (1). Researchers have shown that molecular farming (or biopharming) is a secure technology that is capable of rendering valuable recombinant proteins free of toxins and animal pathogens in a relatively short time (2,3,4,5,6). Scientists have also demonstrated that most recombinant antibodies produced in plants maintain their functional properties (substantial bioequivalence) as well as do those produced in mammalian cell…
Manufacturing
Design of Experiments for Fed-Batch Process Development in Shaken Cultures
When designing a recombinant protein production process, a high number of parallel cultivations must be carried out. That task is typically performed using batch cultures in shake flasks or microwell plates, in which fermentation conditions are not monitored. To overcome that limitation, we combined the SensorDish Reader and Shake Flask Reader systems (from PreSens) with an enzymatic glucose delivery system (EnBase technology from BioSilta Oy) for Escherichia coli cultivations. Our objective was to determine whether SensorDish reader cultures would yield…
Outsourcing Facility Safety for Biomanufacturing
As the life-science industry increasingly outsources noncore functions, some companies are finding that managing the expanding web of safety and environmental requirements associated with various functions is, in turn, growing vastly more complex. As multiple third parties handle numerous noncore activities, the risk — and headaches — of monitoring them effectively is a growing challenge by any standard. At first glance, the lowest-risk solution for many organizations may seem to be managing associated safety programs with in-house personnel and programs.…
Accounting for the Donnan Effect in Diafiltration Optimization for High-Concentration UFDF Applications
The biopharmaceutical industry is targeting high-concentration protein formulations to enable subcutaneous administrations. Such administration can provide better patient convenience than intravenous administration. One challenge associated with high-concentration formulations is increased electrostatic interaction between proteins and excipients. That is a result of increased protein-charge density at high protein concentrations. Such interactions can create an offset between excipient levels in final products and diafiltration buffers in ultrafiltration processes. The effect of such electrostatic interactions in a membrane process is known as the…
Analysis By Size and Charge
An early BPI Lab article addressed the power of liquid chromatographic separations for biopharmaceutical laboratory use (1). Such techniques separate biomolecules based on a number of different properties: size, solubility, hydrophobicity/-philicity, binding affinity. The next most powerful means of separation — and thus high-resolution identification — of nucleic acids and proteins/peptides is based primarily on electrostatic properties: electrophoresis. Although it doesn’t really work in a process or preparative setting, it is a fundamental technique in modern biopharmaceutical laboratories, where it…
A Sustainable, Single-Use Facility for Monoclonal Antibody Production
Pierre Fabre, the second largest independent pharmaceutical group in France, recently opened a new facility to expand its monoclonal antibody (MAb) production for clinical supply. The Antibody Biotechnology Unit (ABU) facility was designed to provide needed flexibility for adapting to various process and capacity changes, so it includes state-of-the-art single-use technologies. The facility was also built with sustainability in mind to minimize the company’s environmental footprint. The company integrated this plant into an existing antibody research and development (R&D) center,…
A Global Joint Venture Strategy for Biosimilars Development
In April 2013, biopharmaceutical company Pfenex (San Diego, CA) announced a joint venture with biologics manufacturer Stelis Biopharma, Inc. (“Stelis”), earlier known as Agila Biotech, (a wholly owned subsidiary of Strides Arcolab Limited (Bangalore, India) for the commercial development of six biosimilars. The companies will also leverage technology and global development expertise from GE Healthcare Life Sciences (Uppsala, Sweden) and Bio-XCell Malaysia (Nusajaya, Malaysia). Such international, multicompany collaboration strategies have become a growing trend in the highly competitive biosimilars industry.…
Cost-Effectiveness and Robustness Evaluation for Biomanufacturing
As the biotech sector has matured, it has come under increasing economic and regulatory pressures for continuous improvement in both drug development and manufacturing. As a result, assessing the value potential of alternative strategies has become critical to decision-making in areas such as bioprocess and facility design, capacity sourcing, and portfolio selection. Related decisions typically involve large cash expenditures and thus have a direct bearing on the feasibility of business units and whole companies. Figure 1: () Making such decisions…
How to Hit a Moving Target
Although multiple factors can compromise the drug-like properties of biological molecules, we are still at a very early stage in learning how to assess them. This is despite — or perhaps more correctly, because of — the pharmaceutical industry’s accelerating drive to develop biological molecules as therapeutic agents. And I say “we” because this applies not only to the biopharmaceutical industry itself and the analytical instrument companies that serve it, but also those charged with regulating it. We are all…
Enabling Technologies
We hear a great deal lately about the maturation of the biopharmaceutical industry — and much advancement over the past decade or so has been in business models, financing, and product pipelines. Meanwhile, regulators around the world have become more well versed in the subject matter and have adjusted their approaches to and expectations from the industry. However, the practical side of developing, characterizing, and manufacturing biotherapeutic products cannot be overlooked — nor its importance overstated. Many technological…