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.

Verner Anderson
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Biopharmaceuticals, including monoclonal antibodies andvaccines, make up an increasingly large proportion of drugs on the market andin the development pipeline. 
Theseare exciting times for those involved in R&D and scale-up manufacturing asthe market evolves toward an increasing global model with an expanding host ofnew opportunities. According to a recent report and survey of biomanufacturingcapacity and production1, outsourcing of bioproduction has increaseddramatically in the last two years. Companies polled list the United States astheir preferred outsourcing destination, followed by India, Singapore, Ireland,Germany, the U.K. and China. 
Previously, the choice of an outsourcing location was drivenmainly 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.
Thebiopharmaceutical marketplace is now truly a global one. Therefore, companiestoday are investing in facilities and collaborations in "the South" (theumbrella term often given to less developed countries). Increasingly, thesecountries want to develop local manufacturing facilities, rather than relyingon costly exports, to meet the healthcare needs of their populations. They arealso increasingly focused on innovative offerings rather than generics.
At the same time, biosimilars can offer pharma companiesmany new opportunities. Biologic drugs, like monoclonal antibodies, arenotoriously expensive. Now that the patents of so many key biotech drugs haveexpired—or soon will—the prospect of manufacturing a "generic" (biosimilar) oreven better (biobetter) version looks increasingly attractive for companiesthat have the know-how and technology transfer capabilities.
Companies wishing to set up a facility in a less-developedcountry may benefit from government initiatives, for there are few suchcountries that do not have biotech high up on their development agendas,although the extent to which plans have actually been put into practice varieswidely. Governments across Asia, for instance, are investing heavily ininfrastructure and healthcare to provide better access to medical care andimprove drug availability. These developments have done a great deal tostimulate regional and local demand for better supplies of medicines, particularlyvaccines. Strategies for developing innovative and cheaper therapeutics thatare compliant with local and export regulations are a focus on both a nationaland global level.
Of particular interest is how countries such as India, witha traditionally strong focus on generics, are strategically aligning towardinnovation. India already has a strong pharmaceutical sector, and there arefurther opportunities to develop new drugs and biosimilars. Changes to thenational patent organization have also steered many vaccine companies intoprograms aimed at innovative products for locally relevant diseases such asencephalitis and cholera in Japan. Meanwhile, in Malaysia, home-grown orforeign companies with strong R&D now qualify for a comprehensive range ofgovernment benefits2.
Additionally, China is fast emerging as a global biotech"hotspot." With an increased presence of multinationals and new governmentpolicies and pressures, the market is fundamentally moving from one that isdominated by the production of generic drugs to one with a long-term strategyfor the development of innovative medicines able to compete in the globalmarketplace. The forecasted growth in this market is so strong that China ispredicted to become the second-largest pharmaceutical market after the UnitedStates by 20153.
Therefore, technology developers and suppliers in the UnitedStates and Europe have been watching carefully and noting how this growth andinvestment will stimulate change in terms of the location of biopharmaceuticalproduction. In order to meet the demand of the growing number of localbioproduction facilities, there has been a strong focus, specifically on outputin the APAC region, on the localization and consistency of supply.
Success in such endeavors requires a strong focus on R&Dand bioproduction manufacturing. Fortunately, the R&D aspirations are alsobetter realized, thanks to technical advances driving both the development andproduction of biopharmaceuticals at all stages. The most significant of theseadvances are streamlined expression technology, automation, the adoption ofplatform technologies and the increasing switch from stainless steel tosingle-use bioprocessing equipment4.
Also underway is a move frommedia-based serum to chemically-defined media and a general shift toward makingall components used in the biotech industry animal- and protein-free whereverpossible.
Improvements in media and expression vectors have led to adramatic increase in monoclonal antibody titers over the last decade. Thesedays, yields of 10 grams per liter are not unusual. Moreover, R&D has ledto structural changes in antibody molecules that have made them more potent.
Ten years ago, there was concern over whether companies, including contractmanufacturing organizations (CMOs), had enough capacity in terms of stainlesssteel fermentation equipment to meet demand for the large numbers oftherapeutic antibodies in the clinical pipeline. Increased titers and potencynow 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 a20,000-liter stainless steel fermenter.
One of the main advantages of single-use or disposablebioprocess equipment is reduced capital costs over stainless steel. This couldlower the barrier to entry into antibody manufacture in less developedcountries, and indeed single-use is proving to be a truly disruptivetechnology. With plastic, there are none of the costs or inputs associated withclean-in-place or steam-in-place procedures, nor is there simultaneous need forthese to be validated. There is also no potential for cross-contamination,which is a bonus for CMOs and other facilities involved in manufacturingmultiple products.
Single-use is the key to quick, flexible set-up, allowingthe emphasis on plant design to shift from the fixed facility to a simple,clean space. For these reasons, companies have been investing heavily insingle-use technology and the market is showing significant annual growth. 
Single-use bioreactors, from developmental-scale units tovessels that can produce commercial quantities, are just one class of anincreasingly wide range of equipment. Fluid transfer systems, storagecontainers, filtration equipment and other parts are opening the door to theprovision, by just a few leading suppliers, of integrated solutions inbioprocessing. Automated systems that incorporate technologies for growth,stacking, handling, moving and storing can today provide real workflowsolutions. As a consequence, technology suppliers that can provide quality andinnovation across a broad portfolio of bioproduction products will be in thestrongest market position moving forward.
Meanwhile, increased efficiencies upstream have put pressureon downstream operations, including purification. The use of platformtechnologies may significantly aid integration and scale-up between the two,improving overall efficiency and ultimately yield. In a platform, similarprocess steps, including selection of host cell line, expression vector andpurification strategy, are adopted for all products in a particular class.Filters, buffers, resins and raw materials are all standardized alongside thecorresponding processes. So far, platform technologies have been applied mainlyin monoclonal antibody manufacture. But there is no reason that they cannot beapplied to other molecules. A platform technology has the advantage of allowingfor better process understanding, which leads to a more robust and fullyscalable process, aligning with the evolving demands of the regulatoryagencies. If technical advances can make the bioproduction process moreflexible and efficient, then global networks can develop and spread morerapidly.
With these new tools at companies' disposal, it is noweasier to set up biotech R&D and production facilities anywhere in theworld. But they are not the only factor. The other vital ingredient in makingbiopharmaceutical development truly global and able to meet populations'healthcare needs is intensive networking and multiple collaborations. Acrossthe less developed world, companies are increasingly looking for research-basedpartners to facilitate development and further advance their productportfolios, with the hope of adding proprietary drugs to the current genericoffering. From a developed nation perspective, there is undoubtedly a drive toform local collaborations and partnerships that will alleviate the risk forglobal pharma but, more important, can open up the market for local companiesand contract research organizations and facilitate funding for researchinstitutions.
Further innovation for the bioproduction market may bedriven by local partnerships that will, in turn, reflect local demand. Forexample, China has different therapeutic goals and targets for vaccinedevelopment than North America, and it is predominantly focusing on chickenpox, rabies and hepatitis C. Although the development and production processesessentially remain the same, there are aspects of the associate technologiesthat are likely to evolve over time. For example, materials and coatings may beinfluenced by local and regional climatic factors such as temperature andhumidity. Working at a local level not only to supply tried and testedtechnologies to the local markets, but to identify new routes of productdevelopment to meet region-specific demands, will be key to the bioproductionmarket moving forward.
In 2009, biopharmaceuticals accounted for 13 percent ofpharmaceutical sales, and biotech drugs now make up 25 percent of thedevelopment pipeline5. It is only right that the whole world wants ashare of the biotech revolution. It is up to us as technology innovators tolook for the opportunities, wherever they arise, to make sure this happens.
Verner Andersen is vice president and general manager ofThermo Fisher Scientific Inc.'s Labware & Specialty Plastics business inRochester, N.Y. Andersen has more than 30 years of industry experience. Heattended Copenhagen University College of Engineering in Denmark, where hemajored in Industrial Engineering.

1. Langer, E.S. "Biomanufacturing locally, thinkingglobally." BioProcess International,June 2010.

2. Aldridge, S. "Malaysia seeks biotech partners." NatureBiotechnology, April 2009.

3. "Nature ReviewsDrug Discovery," June 2010.
4. McLeod, L. "Advances in bioprocessing." BioProcessInternational, May 2009.
5. "Biopharmaceuticals Market Trends and Competition."Reportlinker, June 2010.

Verner Anderson

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