Growth in biopharmaceuticals is creating an unprecedented increase in demand for cell culture products. Cell culture techniques have been used in biological sciences for more than 50 years; however, cell culture applied to production systems has been around for only half that time. The cell culture industry, which began in the late 1980s from the utilization of recombinant DNA technology and cell hybridization, is, today, a major underpinning of the biopharmaceutical market.
Media, sera, and reagents are the fuel that powers these cell culture manufacturing engines, and suppliers are beginning to see sales ramping up accordingly. According to Kalorama’s Cell Culture: The World Market for Media, Sera, and Reagents, the market for these products is growing at an annual rate in excess of 12% and headed for more than $2.6 billion in 2011.
Changing Market Drivers
At the same time that demand for these products is increasing, the demand is also changing. Traditional sera products are stagnant, and, increasingly, researchers and process engineers are demanding products with more rigid controls over ingredients. The emergence of serum-free media and chemically defined media shows the increasing trend toward stringent component control, which has characterized the past few years of product development.
However, more change is on the horizon. Biomedical research at the basic levels will become a major driver of innovation for the cell culture market. Biomedical research and bioprocessing have a wide range of supply needs, including high-quality media and reagents for fermentation and cell culture. In cell biology research, cell screening technology has proved to be important in finding high-producing cell lines, and research is now focused on how to predict growth characteristics of cells at an earlier stage. Progress in the future will come from processes, such as metabolic engineering, that will aid in improving cell lines, which will continue to be a main focal point of research.
Stem Cell Research
Along these same lines, stem cell research will also add to the robust growth of the cell culture market. The growing use and diverse applications of stem cells are having a significant impact on the media market, as companies work to understand how best to optimize and influence their growth. For stem cell applications, serum-free media that lack growth factors, cytokines, or artificial stimulators of proliferation will play an increasingly important role.
The expected growth in the stem cell market provides a tremendous growth opportunity. Kalorama estimates that stem cell research accounted for nearly $1 billion million in expenditures last year, 10% of which was allocated to consumables, and about 5% of the consumable allocation was spent on media and other cell culture supplies. In addition, media and serum used in stem cell research are priced higher than similar, non-stem cell products.
Multiple licensing agreements and acquisitions have been made in the cell culture market by numerous companies in order to secure a foothold in the stem cell supply market .
Another important driver of the cell culture market will be the production of seasonal influenza vaccines, as well as pandemic vaccine candidates. The next generation of seasonal influenza and pandemic vaccines will be produced by cell culture-based technology. This trend bodes well for the continued growth of the cell culture market.
The traditional method of manufacturing influenza vaccines has been through egg-based technology. However, due to the sheer quantity of vaccines that may be needed in the future, both for seasonal influenza and pandemic influenza, there is a move away from egg-based systems. Cell-based vaccine production dramatically reduces the possibility for contamination and promises to be a more reliable, flexible, and expandable platform than egg-based methods.
While both methods could produce an equally effective vaccine against a virus, egg-based production is physically limited by the availability of specialized eggs and alone may not be able to meet the accelerated demands of a global influenza pandemic. Cell-based technology offers many benefits over egg-based production, including scalability, production risk mitigation (In the case of an avian flu pandemic, egg-producing flocks could decline, jeopardizing vaccine production capabilities.), speed of development (manufacturers are able to bypass the steps needed to adapt the virus strains to grow in eggs), and hypoallergenicity.
The U.S. government has been encouraging manufacturers to develop cell-based flu vaccine methods in recent years. The National Institute of Allergy and Infectious Diseases (NIAID) supports a research program to advance the development of cell culture technologies to improve and modernize the production of influenza vaccines. Between fiscal years 1998 and 2005, NIAID’s support for research for cell culture technology totaled approximately $35 million, according to the Department of Health and Human Services (HHS).
In addition, in March 2005 the HHS awarded a five-year contract to Sanofi Pasteur for $97 million to develop cell-based influenza vaccine technology, with the goal of obtaining the FDA license for a vaccine. In September 2006, Sanofi Pasteur announced that it had completed a clinical trial of its cell culture-based seasonal influenza vaccine and demonstrated the production-scale potential of a cell line in a successful bioreactor run of 20,000 L.
In October 2005, Chiron initiated a Phase I/II study of an investigational cell culture–derived influenza vaccine in the U.S. The company has also completed enrollment of a second Phase III study of a influenza cell culture vaccine in Europe. In July 2006, Novartis reported that it plans to build a new plant to make cell-culture-based influenza vaccines. The plant could begin production as early as 2011 and be ready for full production as early as 2012.
On the downside, a threat to the future of the cell culture market is the production of biopharmaceuticals in transgenic animals and plants. Transgenic domestic animals and plants as a manufacturing method for biopharmaceuticals has the potential to improve scalability and yield of cell culture and fermentation systems, which would reduce the cost of producing biopharmaceuticals dramatically. Additionally, when compared to the facilities and chemicals required for cell culture production, capital investment required for animal and plant production facilities is relatively low.
In recent years, the number of proteins developed and the types of transgenic platforms used for production have increased significantly. The EMEA approved the first transgenically produced biopharmaceutical in August 2006. The European Commission granted market authorization to ATryn, GTC Biotherapeutics’ (www.gtcbiotherapeutics.com) recombinant form of human antithrombin, for the prophylaxis of venous thromboembolism in surgery of patients with congenital antithrombin deficiency.
However, the obstacles to full realization of these transgenic technologies in the near term are legion, and the cell culture industry also appears to have multiple avenues of development to pursue and challenges to meet. For now, it looks like cell culture has plenty of time before being replaced by tobacco plants and herds of goats.