Global Demands Require Technical Innovation In Biopharm Manufacturing

By Clare Jones, Ph. D.

Scientific advances and socioeconomic trends are rapidly changing the global biopharmaceutical development and bioproduction scene, offering new opportunities and challenges to pharmas, biotechs, and their suppliers. Perhaps the biggest change in recent years has been the globalization of the pharma marketplace. According to Chuck Kummeth, president, Lab Consumables Division, Thermo Fisher Scientific, “While North America and Europe remain strong and still constitute much of the demand, the emergence of new markets in China, India, the Middle East, and Latin America have led companies like ours to invest in facilities and collaborations in these rapidly developing countries.” Increasingly, a focus on the development of local manufacturing facilities, rather than relying on costly exports, is an objective which will allow pharmas and biotechs to meet the healthcare needs of their populations. Moreover, there is an increasing drive for innovation through R&D, rather than generics, a global trend which, as Kummeth explains, “Is supported by a developing trend towards the production of regionally relevant medications.” Biologics are also becoming more important. A recent Scientia forecast predicted that biologics will grow more than 8% in sales — more than $178 billion by 2014. This will be maintained by a continued surge in technical advances that make the manufacture of vaccines and monoclonal antibodies, for example, increasingly efficient.

At the same time, the increasing complexity of the production of biologics is driving more investment. As second-generation biologics such as monoclonal antibodies replace first-generation therapeutic proteins, there is also an increased demand for more advanced in vitro cell culture techniques with ever-growing capacities. Such sophisticated systems for mammalian cell production also require specially trained personnel, making outsourcing an extremely viable option. As part of a strategy to penetrate new markets and reduce costs, outsourcing has grown dramatically in the last year or so, and it has been reported that CMOs will, by 2012, have grown their mammalian cell culture production capacity by more than 90% over 2008 levels.

Investment Drives Innovation In Emerging Markets
Governments across Asia are investing heavily in infrastructure and healthcare to provide better access to medical care and improve drug availability. This, in turn, has stimulated regional and local demand for medicines that are compliant with local regulations and suitable for export. This strategic focus is stimulating change in biopharmaceutical development and production, and it is no surprise that the countries that have traditionally had a strong focus on biogenerics are today implementing strong R&D programs for the development of biologics. India, for example, has adopted changes to its patent regime, which has encouraged many vaccine companies to initiate programs aimed at developing innovative products for locally relevant diseases such as Japanese encephalitis and cholera.

In fact, the governments of many Asian countries now have biologics firmly on the agenda. For instance, Taiwan recently launched a comprehensive “biotech takeoff” package, aimed at commercializing its country’s innovation efforts, with money available for any company that can access the global market with its products. In Malaysia, companies with a strong R&D offering (homegrown or foreign) qualify for a comprehensive range of government benefits; and in China, an increased presence of multinationals and new government policies have contributed to a long-term strategy for the production of proprietary medicines for export. Furthermore, last year the Chinese government announced a plan to invest $125 billion in healthcare reform, further supporting recent predictions that China will become by 2015 the second largest pharmaceutical market after the United States. Variants on this model fit other countries such as Japan, where the focus is still predominantly on generics, but where the government has stated that new drugs must make up 30% of the market by 2012.

The Collaborative Approach
The future growth of chemically synthesized drugs is looking negligible at best. As such, companies across the globe are reaching out to research-based partners to further drive innovation within R&D with the hope of adding proprietary drugs and biologics to the current generic offering. For global pharma, local collaborations and partnerships will alleviate some degree of risk, but on a regional level, they can open up the market for local companies and CROs and facilitate funding for research institutions to drive longer-term innovation. In just one of many examples, Pfizer, Merck, and Eli Lilly have recently set up the Asian Cancer Research Group to drive research for cancers that are more common in Asian populations. This is an instance of a growing trend in precompetitive collaboration and will help big pharma get a foothold in the Asian markets.

According to a recent survey of collaborations, 27% of companies had a South-South collaboration but 53% had a North-South collaboration (south = a term applied to developing markets, north = a term applied to developed markets), and multiple partnerships were seen as the way forward, with an average of three collaborations reported per company. These included supply agreements, licensing deals, and some R&D partnerships, and most were formed with the aim of accessing each other’s markets. In R&D, vaccines were a particularly important area. For instance, Bio-Manguinhos (Rio de Janeiro) is working with Havana’s Finlay Institute on a new meningitis vaccine to address an outbreak in Africa. In another example, Inno Biologics, which is Malaysia’s first CMO, has established a strategic manufacturing partnership with Boehringer Ingelheim (BI) and is BI’s first partner in Asia. Local collaborations are important as well. In India, Dr. Reddy’s Labs and Nicolas Piramel are among the many Indian firms sponsoring research at the Indian Institute of Science.

But, what does this mean at the development level? Well, technology providers are continuing to invest in their R&D efforts to meet the needs of the sophisticated cell culture systems being put in place, as well as the requirements of local markets. Local collaborations are enabling regional-specific input into product development, and that will drive innovation and benefit the global marketplace. Expanding on this, Kummeth notes, “This collaborative approach with local industry is essential for pharma and suppliers alike. We are building credibility and trust with the local scientific community and listening to the specific application needs of the customer. Furthermore, we are partnering with users to provide good application support.” Kummeth further highlights the investment that manufacturers of products for bioproduction are making in Asia. “The recent expansion of the Thermo Fisher production facilities in Shanghai follows the opening of a site in Beijing dedicated to the hydration of cell culture media and a joint venture in Lanzhou, China, for the collection, processing, and selling of serum into local markets.”

From Upstream R&D To Downstream Production
Technical advances at all stages of the process are driving the development and production of biopharmaceuticals. Perhaps the most significant are streamlined expression technology, platform technologies, automation, and the increasing switch from stainless steel to single-use bioprocessing equipment. Indeed, the latter is proving particularly well-suited to the requirements of local manufacture. Single-use technology reduces capital investment costs and time to start-up, and as noted by David Radspinner, Ph.D., director of global marketing and customer applications, bioprocess production at Thermo Fisher Scientific, “The single-use market is predicted to grow 8% to 10% annually within an overall 8% to 14% predicted increase in biomanufacturing.” Single-use also allows for flexibility in bioproduction. Moreover, improvements in cell technology have led to increased titres of monoclonal antibodies, which open up the prospect of using single-use bioreactors to meet market demand. Automation and increased throughput in operations like cell line productivity screening and process development have also made upstream operations more efficient. Platform technologies where similar process steps — including host cell line and expression vector optimization and purification are adopted for all products in a class — are also contributing greatly to bioproduction efficiency. Kummeth adds, “The provision of high-quality cell culture platforms and containment systems that are specifically developed to facilitate easy scale-up and commercialization of bioproduction processes are key.”

About The Author
Clare Jones, Ph.D., is a senior account manager at Alto Marketing, a company dedicated to scientific communications for the healthcare, pharma, and biotech industries. Her background includes research at the Institute for Biomedical Research, University of Birmingham, United Kingdom, where she received her Ph.D. in immunology.