Affinity Ligand Technology
Affinity ligand technology is also being applied by a new company, Purely Proteins (Cambridge, U.K.), which will supply proteins on any scale to accelerate drug discovery. "We want to be able to provide all the proteins in the proteome," said David Bailey, Ph.D., Purely Proteins' CEO.
Specific sectors within bioprocessing also have their own unique challenges. Paul Kemp, Ph.D., CEO of Intercytex (Manchester, U.K.), described how in tissue engineering, with living products, scaling out must replace scaling up. Intercytex has several products in the area of wound healing and hair replacement in clinical trials.
"One unanticipated issue and hidden cost is shipping and packaging, because of the limited shelf life of the product. Manufacturing a living product is challenging because the process is the product," said Dr Kemp.
John Birch, Ph.D., CSO from Lonza (Slough, U.K.) pointed out that monoclonal antibodies are the fastest growing category of biopharmaceuticals, and manufacturing involves facing key issues relating to volume, demand, and speed of production.
"So far, there have probably been more opportunities for process improvement in upstream processing," he said. "I expect attention to shift toward downstream improvements as our upstream processes get better. We need to use all that stainless steel more effectively."
In upstream operations, cell screening technology has been important to find the all-too-rare high-producing cell lines, and there is a focus on how to predict growth characteristics of cell lines at an earlier stage.
"Improving host cell lines is going to be hugely important going forward," notes Dr. Birch, adding that selecting variants, such as CHO cells that will go into suspension or those with anti-apoptotic characteristics can be very fruitful (apoptosis is a natural form of cell death).
There are also the first attempts at metabolic engineering. "Progress in the future will come from improving cell lines. CHOs in suspension have 40 times the productivity of ordinary CHO cells," he said. "The increasing volume of demand is a real driver for improving these processes."
It is also worth looking into other production systems for biologics. Dr. Birch said that while mammalian cell culture will continue to dominate, it is not impossible that there'll be a shift toward bacterial production in future.
E. coli or fungi might be used to produce monoclonal antibodies, because it may be possible to engineer the relevant glycosylation pathways into these production cells. This would eliminate the problem of biologics from microbial production systems not having the proper glycosylation pattern needed to make them clinically active.
In the future, biopharmaceuticals might even be designed as much for their ease of manufacture as for their therapeutic potential. Genomic and proteomic tools ought to help in this respect by increasing our knowledge of cell physiology.
Bioprocessing has a wide range of supply needs, including high quality media for fermentation and cell culture. HyClone, a long-established media producer from Logan, UT, recently opened an expanded facility in Cramlington (near Newcastle) to help meet the needs of the growing bioprocessing community in the U.K. and elsewhere in Europe.
The company is part of the Perbio Science organization of U.K. and Belgium which, in turn, has become a part of Fisher Scientific, which wants to increase its footprint in biomanufacturing. HyClone Europe manufactures sterile liquid products and disposable bioprocessing containers.
"We respond to the way the industry is goingit is all about disposables and animal-derived component-free media," said Mike Bell, director of operations at Cramlington.
The new facility has four production suites dedicated to sterile animal-derived and animal-derived component-free media dry powdered media, and disposable bioprocess containers. There is also a new 2,300 L/hour water-for-injection system.
Segregation of animal and non-animal media in separate suites is a "key design feature" of the new facility according to Bell. The 2,500-m2 facility is a four-fold increase on previous capacity and will cater to the increased requirements as biologicals come through to market.
The disposable bags with tubes and connectors are made of five layers of medical grade plastic film and can be used at all stages of production. HyClone aims to be a one-stop shop with its single-use containers, media, and chromatography buffers.
One of HyClone's customers is Avecia Biotechnology, a sponsor of BioProcess U.K. The company provides custom manufacture of microbial and mammalian-based therapeutics. The company's new Advanced Biologics Centre (ABC 5000) is a twin 5,000-L production facility for microbial fermentation to meet customers' needs as they move rapidly toward making approved products.
This complements the original 1,000-L facility which has been dedicated to early-phase manufacturing. "We support customers through the whole development journey," comments Kevin Cox, vp for biotechnology at Avecia.
Recently, the company became involved in the production of defense vaccines against anthrax and plague for the U.S. government, switching the company to drug development as well as contract manufacturing. Avecia won a $9 million contract from the NIH, followed by a $72 million contract in 2003 for Phase II for the anthrax project. The contract for plague vaccine is worth $51 million.
The anthrax vaccine raises antibodies that target the antigen that otherwise allows the bacterium's "lethal factor" and "edema factor" into the host cell. The company has a lot of IP around this project, and the product is being made for both pre- and post-exposure use. The plague vaccine is based on a similar principle and Phase I trials are about to start.