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Guest Commentary: Bioproduction goes global
Biopharmaceuticals, including monoclonal antibodies and vaccines, make up an increasingly large proportion of drugs on the market and in the development pipeline.
These are exciting times for those involved in R&D and scale-up manufacturing as the market evolves toward an increasing global model with an expanding host of new opportunities. According to a recent report and survey of biomanufacturing capacity and production1, outsourcing of bioproduction has increased dramatically in the last two years. Companies polled list the United States as their preferred outsourcing destination, followed by India, Singapore, Ireland, Germany, the U.K. and China.
Previously, the choice of an outsourcing location was driven mainly by the desire to cut costs. That's still true in many cases, particularly in difficult economic times. But now more than ever before, companies are driven by the desire to penetrate new and emerging markets, particularly in China, India, the Middle East and Latin America.
The biopharmaceutical marketplace is now truly a global one. Therefore, companies today are investing in facilities and collaborations in "the South" (the umbrella term often given to less developed countries). Increasingly, these countries want to develop local manufacturing facilities, rather than relying on costly exports, to meet the healthcare needs of their populations. They are also increasingly focused on innovative offerings rather than generics.
At the same time, biosimilars can offer pharma companies many new opportunities. Biologic drugs, like monoclonal antibodies, are notoriously expensive. Now that the patents of so many key biotech drugs have expired—or soon will—the prospect of manufacturing a "generic" (biosimilar) or even better (biobetter) version looks increasingly attractive for companies that have the know-how and technology transfer capabilities.
Companies wishing to set up a facility in a less-developed country may benefit from government initiatives, for there are few such countries that do not have biotech high up on their development agendas, although the extent to which plans have actually been put into practice varies widely. Governments across Asia, for instance, are investing heavily in infrastructure and healthcare to provide better access to medical care and improve drug availability. These developments have done a great deal to stimulate regional and local demand for better supplies of medicines, particularly vaccines. Strategies for developing innovative and cheaper therapeutics that are compliant with local and export regulations are a focus on both a national and global level.
Of particular interest is how countries such as India, with a traditionally strong focus on generics, are strategically aligning toward innovation. India already has a strong pharmaceutical sector, and there are further opportunities to develop new drugs and biosimilars. Changes to the national patent organization have also steered many vaccine companies into programs aimed at innovative products for locally relevant diseases such as encephalitis and cholera in Japan. Meanwhile, in Malaysia, home-grown or foreign companies with strong R&D now qualify for a comprehensive range of government benefits2.
Additionally, China is fast emerging as a global biotech "hotspot." With an increased presence of multinationals and new government policies and pressures, the market is fundamentally moving from one that is dominated by the production of generic drugs to one with a long-term strategy for the development of innovative medicines able to compete in the global marketplace. The forecasted growth in this market is so strong that China is predicted to become the second-largest pharmaceutical market after the United States by 20153.
Therefore, technology developers and suppliers in the United States and Europe have been watching carefully and noting how this growth and investment will stimulate change in terms of the location of biopharmaceutical production. In order to meet the demand of the growing number of local bioproduction facilities, there has been a strong focus, specifically on output in the APAC region, on the localization and consistency of supply.
Success in such endeavors requires a strong focus on R&D and bioproduction manufacturing. Fortunately, the R&D aspirations are also better realized, thanks to technical advances driving both the development and production of biopharmaceuticals at all stages. The most significant of these advances are streamlined expression technology, automation, the adoption of platform technologies and the increasing switch from stainless steel to single-use bioprocessing equipment4.
Also underway is a move from media-based serum to chemically-defined media and a general shift toward making all components used in the biotech industry animal- and protein-free wherever possible.
Improvements in media and expression vectors have led to a dramatic increase in monoclonal antibody titers over the last decade. These days, yields of 10 grams per liter are not unusual. Moreover, R&D has led to structural changes in antibody molecules that have made them more potent.
Ten years ago, there was concern over whether companies, including contract manufacturing organizations (CMOs), had enough capacity in terms of stainless steel fermentation equipment to meet demand for the large numbers of therapeutic antibodies in the clinical pipeline. Increased titers and potency now open up the possibility of production of monoclonal antibodies in a large (1,000- or 2,000-liter) single-use bioreactor (SUB) instead of in a 20,000-liter stainless steel fermenter.
One of the main advantages of single-use or disposable bioprocess equipment is reduced capital costs over stainless steel. This could lower the barrier to entry into antibody manufacture in less developed countries, and indeed single-use is proving to be a truly disruptive technology. With plastic, there are none of the costs or inputs associated with clean-in-place or steam-in-place procedures, nor is there simultaneous need for these to be validated. There is also no potential for cross-contamination, which is a bonus for CMOs and other facilities involved in manufacturing multiple products.
Single-use is the key to quick, flexible set-up, allowing the emphasis on plant design to shift from the fixed facility to a simple, clean space. For these reasons, companies have been investing heavily in single-use technology and the market is showing significant annual growth.
Single-use bioreactors, from developmental-scale units to vessels that can produce commercial quantities, are just one class of an increasingly wide range of equipment. Fluid transfer systems, storage containers, filtration equipment and other parts are opening the door to the provision, by just a few leading suppliers, of integrated solutions in bioprocessing. Automated systems that incorporate technologies for growth, stacking, handling, moving and storing can today provide real workflow solutions. As a consequence, technology suppliers that can provide quality and innovation across a broad portfolio of bioproduction products will be in the strongest market position moving forward.
Meanwhile, increased efficiencies upstream have put pressure on downstream operations, including purification. The use of platform technologies may significantly aid integration and scale-up between the two, improving overall efficiency and ultimately yield. In a platform, similar process steps, including selection of host cell line, expression vector and purification strategy, are adopted for all products in a particular class. Filters, buffers, resins and raw materials are all standardized alongside the corresponding processes. So far, platform technologies have been applied mainly in monoclonal antibody manufacture. But there is no reason that they cannot be applied to other molecules. A platform technology has the advantage of allowing for better process understanding, which leads to a more robust and fully scalable process, aligning with the evolving demands of the regulatory agencies. If technical advances can make the bioproduction process more flexible and efficient, then global networks can develop and spread more rapidly.
With these new tools at companies' disposal, it is now easier to set up biotech R&D and production facilities anywhere in the world. But they are not the only factor. The other vital ingredient in making biopharmaceutical development truly global and able to meet populations' healthcare needs is intensive networking and multiple collaborations. Across the less developed world, companies are increasingly looking for research-based partners to facilitate development and further advance their product portfolios, with the hope of adding proprietary drugs to the current generic offering. From a developed nation perspective, there is undoubtedly a drive to form local collaborations and partnerships that will alleviate the risk for global pharma but, more important, can open up the market for local companies and contract research organizations and facilitate funding for research institutions.
Further innovation for the bioproduction market may be driven by local partnerships that will, in turn, reflect local demand. For example, China has different therapeutic goals and targets for vaccine development than North America, and it is predominantly focusing on chicken pox, rabies and hepatitis C. Although the development and production processes essentially remain the same, there are aspects of the associate technologies that are likely to evolve over time. For example, materials and coatings may be influenced by local and regional climatic factors such as temperature and humidity. Working at a local level not only to supply tried and tested technologies to the local markets, but to identify new routes of product development to meet region-specific demands, will be key to the bioproduction market moving forward.
In 2009, biopharmaceuticals accounted for 13 percent of pharmaceutical sales, and biotech drugs now make up 25 percent of the development pipeline5. It is only right that the whole world wants a share of the biotech revolution. It is up to us as technology innovators to look for the opportunities, wherever they arise, to make sure this happens.
Verner Andersen is vice president and general manager of Thermo Fisher Scientific Inc.'s Labware & Specialty Plastics business in Rochester, N.Y. Andersen has more than 30 years of industry experience. He attended Copenhagen University College of Engineering in Denmark, where he majored in Industrial Engineering.
1. Langer, E.S. "Biomanufacturing locally, thinking globally." BioProcess International, June 2010.