The system, which was developed by Percivia, a DSM Biologics and Crucell joint venture, uses the former's XD technology to significantly boost the growing density of the latter's PER.C6 cell line that has been modified to express the antibody in question. Percivia's CEO Marco Cacciuttolo said that: "This new achievement surpasses all other reported titre levels to date with any mammalian system and demonstrates the robustness and power of the PER.C6 platform." He added that the firm is "particularly enthused with the user-friendliness of the system."
Marcel Lubben, vice president of business development at DSM Biologics added: "We are extremely pleased with this achievement. This milestone coincides with our commitment to provide the most inherently robust manufacturing platform and ensure the utmost product quality for protein manufacturing." A recent Business Insights report predicted that the contract bio-manufacturing market, which was worth about $2.5bn in 2006, will expand by around 5 per cent a year through to 2011. The study estimated that the developmental pipelines of pharmaceutical firms' contain around 500 candidate protein drugs and a further 50 protein-based medications that have entered clinical trials.
In addition, the current global market for proteins and monoclonal antibodies is worth between $50bn and $60bn and is estimated to grow to $200bn by 2020, according to a Reuters report. Previously, DSM predicted that Percivia has sales opportunities of more than $200m annually. Focus on purification steps
Oya Yavuz, Crucell's director of corporate communications and investor relations told in-PharmaTechnologist.com that the breakthrough is significant because "using [currently available] mammalian cell expression systems, the average yield is around 2-4 grams per litre, with notable cases at over 8 grams per litre in fed-batch mode of operation. In fact, PER.C6 cells have also reached 8 grams per litre using chemically defined media in a fed-batch mode of operation." Yavuz added: "this is a significant advantage of using the XD process, as it is possible to maintain a high cell viability throughout the entire duration of the culture, as opposed to fed-batch where viability steadily declines over the culture run. This property of the XD process allows for consistent quality of product at any stage of the culture as the cells are maintained at the same and most efficient metabolism during the entire culture."
After exceeding 20g/L target yield, Percivia's current focus is "to further develop the product recovery and purification steps to make the exceedingly high yields upstream translate in practical and concrete advantages to the entire industry when it comes to produce complex biologicals using small and efficient unit operations," she said. Yavuz also said that while protein expression using CHO and myeloma cells, complex vector systems such as GS (glutamine synthetase), and emerging fungal expression systems provide alternatives, the PER.C6 platform is the only human cell line-based technology and the only one with a dedicated set of experts to provide technical support to the licensees.
She added that to date, 30 manufacturing firms around the world have licensed the PER.C6 platform for protein production.