Breaking ground at the new site is the latest sign that Novartis is leading the pack in the cell-based flu vaccine race, following the June approval of its cell-based flu shot Optaflu in the EU. The facility is expected to be able to produce 50 million doses of seasonal trivalent flu vaccine, and up to 150m doses of monovalent vaccine supplemented with company's adjuvant technology in the event of a pandemic outbreak. This capacity at the Holly Springs, North Carolina, site is greater than at any other Novartis vaccine manufacturing plant, all of which use traditional egg-based vaccine production techniques. Ground was broken at the site on Thursday, with completion expected in 2009 and initial vaccine production kicking off in 2011. Full capacity should be achieved "very quickly thereafter," but will also depend on market demand for seasonal vaccine, a company spokesperson told in-PharmaTechnologist.com. The company's investment in the Holly Springs site is due to hit $600m (€443m), funded in part by a 2006 multi-million-dollar grant from the US Department of Health and Human Services (HHS) to support the development of cell culture-derived flu vaccines. The HHS's aim is to be able to domestically produce 600 million doses of flu vaccine within six months of a pandemic outbreak declaration - a quarter of which could come from the Novartis facility. Optaflu was the first cell-based flu vaccine to gain approval in the EU and is due to be submitted for regulatory review in the US next year. The vaccine is currently manufactured in Novartis' facilities in Marburg, Germany, and should be available in Germany and Austria for the 2007/8 flu season. Production of Optaflu will be transferred to the Holly Springs facility once it becomes operational in a few years' time, though in-PharmaTechnologist.com was told that other production facilities should be safe, with no closures currently foreseen as a result of the new production site. Novartis has a research license from French firm Vivalis to study its avian embryonic stem cell lines for potential vaccine and therapeutic protein development, but also has its own proprietary cell line derived from MDCK cells. According to Novartis, virus cultivation using the company's proprietary cell line offers the possibility of more robust virus proliferation along with development of a vaccine seed strain that matches the original 'wild' virus more closely. Earlier this year Novartis was also awarded an additional grant from the HHS to bring its vaccine adjuvant technology to the US. The adjuvant, MF-59, is currently used in Novartis' pandemic flu vaccine Focetria, recently granted approval in the EU. The proprietary MF-59 adjuvant can be used to stretch supplies of vaccine, as it allows smaller quantities of viral antigens to be used in each dose compared to un-adjuvanted vaccines. Regulators worldwide have thrown their weight behind technologies that could help combat the shortfall in global vaccine production capacity, and the associated potential crisis in the event of a flu pandemic. Many firms have invested in researching dose-sparing measures such as the use of adjuvants, as well as shunning the traditional yet cumbersome egg-based manufacturing techniques. Cell-based systems have come to the fore as the potential future of vaccine manufacture, promising to slash the time it takes to produce vaccine batches, increase the number of strains that can be incorporated into vaccines, and do away with the reliance on the availability of chicken eggs. A wake-up call to the industry came during the 2004/5 flu season when contamination at a manufacturing site operated by Chiron, now part of Novartis, threatened half of the entire US flu vaccine supply. The episode alerted regulators and vaccine manufacturers to the shortcomings of current production methods, and kick-started the drive for alternatives with renewed vigour. With World Health Organization concerns that global vaccine manufacturing capacity is simply not up to the job should a flu pandemic strike, the race has been on to develop more efficient production methods and safeguard public health. With Novartis' Holly Springs facility representing the very first move into full-scale, dedicated cell culture-based vaccine manufacture in the US, the company appears to be leading the pack in this new era of vaccine production.