By contrast, technology innovations aimed at increasing yields and shortening development times can be very cost-effective, promising to reduce the need for large capital investments while getting the client into the clinic much faster. These innovations also provide a means of securing long-term relationships and continuing revenue streams through technology licensing agreements.
New cell line and expression technologies are a central focus of innovation efforts. Their biggest advantage is their ability to speed up process development by offering a flexible and well-characterized host system into which the client's protein can be engineered. Typically, the manufacturer's expertise with the cell line or host system means it can optimize and scale-up the system relatively quickly. In addition, with time and experience, the manufacturer is able to steadily improve the yields attainable with the system. In cell culture, raising yields from their historically low levels of less than 1 gram per liter to 1 to 2 grams per liter can dramatically alter the supply/demand balance for cell culture capacity.Lonza Biologics, with its proprietary glutamine synthetase (GS) gene expression system, was one of the first contract manufacturers to offer a proprietary expression system to accelerate development. According to company officials, continued development work has enabled them to push yields from well under 1 gram per liter to 1 to 3 grams per liter.
Now, more contract biomanufacturers are getting into the act. In 2002, DSM Biologics licensed the PER.C6 cell line from Crucell, including the rights to sub-license the technology to its biomanufacturing clients. The PER.C6 technology promises higher yields and faster development times for recombinant proteins and monoclonal antibodies made in cell culture. Since forming their alliance, the companies have announced 10 deals involving DSM biomanufacturing clients sub-licensing the PER.C6 technology.
According to DSM Biologics CEO Andre Bos, the Crucell alliance is part of DSM's strategy to become a top player in the contract biomanufacturing business. "We are seeking a big jump ahead in the biomanufacturing business," Bos said. DSM is moving carefully to expand its manufacturing capacity, having recently revised its Montreal expansion program to reconsider its tank scale and downstream processing requirements and make the facility more flexible.
In the microbial fermentation area, Dowpharma has been promoting its Pseudomonas fluorescens microbial expression technology. According to Dowpharma Business Director Nick Hyde, the technology promises better performance than other microbial systems, notably E. coli, including higher expression levels, no solid inclusion bodies, and better solubility and activity levels. The company's experience with the technology is extensive — Dowpharma's parent company, Dow Chemical, has been developing the system for 15 years and has used it for the manufacture of recombinant pesticide products and enzymes. Dowpharma offers development services for products incorporating the Pseudomonas fluorescens technology at its San Diego, CA, development facility and can scale up production at its Smithfield, RI, facility.
EQUIPMENT INNOVATION Not all technology innovation in the biomanufacturing industry is focused on cell lines and expression systems. Start-up biomanufacturer Xcellerex is pioneering new ways to exploit improvements in manufacturing and development equipment.
Xcellerex was founded in 2002 by former manufacturing managers from Millennium Pharmaceuticals. The company opened its laboratories in September 2003. Xcellerex is trying to revolutionize cell culture at both the development and commercial scales. In process development, it is adapting high throughput screening (HTS) technology, originally developed for drug discovery, to accelerate the development of robust manufacturing processes.
According to Xcellerex CEO and founder Parrish Galliher, HTS technology enables the company to test many more combinations of cell lines, media, and other inputs than can be tested in traditional development approaches. Very large experiments of 1,000 data points or more can be run using the HTS technology with fully instrumented microreactors, and process development times can be cut from 18 to 24 months to less than 12 months.