Challenges in Developing an Infrastructure Strategy

The idea of “thinking globally, but manufacturing locally” to each market is relatively new to the biopharmaceutical industry. As I mentioned in Chapter 2, vaccine makers are more familiar with the concept already. But many technological and economic factors are making other companies aware of this option. Offshoring clinical trials has been of great interest in the pharmaceutical industry for years now. Is it more cost-effective to make clinical materials “here” and ship them “there”— or to make them where they’ll be used? Can you maintain proper control over product and process, not to mention intellectual property and regulatory compliance? As with any other business strategy, these are not ventures to be taken lightly. There are pitfalls to avoid and rough waters to navigate along the way — and this kind of globalization may not be the way to go for some. For others, however, it could provide solutions to some very daunting challenges standing in the way of their success.

Recently Novozymes Biopharma’s UK vice president Peter Rosholm wrote about the biopharmaceutical industry’s future, pointing straight to India and China. “There will be a huge demand for biopharmaceuticals in these two economies. It’s important that biopharm manufacturers continue to invest in developing countries as these will provide the best ROIs” (1). Rosholm cautioned that an increase in biogeneric competition will be concurrent, “and we will have the same trends that we see occurring in the pharmaceutical industry at the moment.” For example, Dr. Reddy’s is already an international powerhouse in generic pharmaceuticals, and the Indian company is openly delving into biologics as well.

Some biosimilars will be made exclusively by new companies for their own local markets, as suggested by a deal announced in November 2009 between Malaysian companies Inno Bio Ventures and CCM Duopharma Biotech. Epoeitin will be their first product. “Our main focus is to provide affordable therapeutics to Malaysians,” commented Mohd Nazlee Kamal, group managing director of Inno Bio Ventures, at the public signing of their agreement (2). “We are glad that CCMD is also championing this cause with us.” In South Korea, meanwhile, Celltrion offers contract manufacturing services while working on its own biosimilar MAbs — and it’s far from being the only Asian company putting that kind of business model to the test (3).

Home-grown biotech in some new markets may present US and European companies with attractive partnerships in lieu of building or even outsourcing to the developing world. Might licensing arrangements be a way to stave off generic competition?

Training and Expertise

One of the first questions our reviewers asked when BPI started getting article submissions from new biotech manufacturing locales was, “Is it GMP?” With most of our previous editorial experience being confined to the United States and Europe, we wondered how to present something from Tunisia, for example (4). But several made it through our peer review process just fine, and we learned a valuable lesson. It was time to recognize that the biopharmaceutical “world” was truly becoming “global.” For example, even the biennial meeting of the European Society for Animal Cell Technology (ESACT), an event you might expect to be purely European in nature, attracts presenters and attendees from all over the world.

Bioprocess engineers at Inno Biologics in Malaysia connect a flexible hose to a bioreactor in preparation for culture harvesting. ()

For many years, of course, science and engineering departments at universities across the United States and Europe have welcomed brilliant students from the developing world. Consequently, biopharmaceutical companies are no strangers to non-European surnames. Just scan the author listings in any issue of BioProcess International. But something has changed in recent years: Many of these Western-educated scientists and bioprocess engineers are returning to their native countries — in particular, to India and China. Government incentives such as China’s “100 Talents” program have encouraged them to return, and burgeoning biotech hubs such as Singapore, Hyderabad, and Shanghai have job openings for them to fill. Indeed, the powerful pull of family and home soil are not to be underestimated.

What this means for companies considering whether to build, buy, license, or outsource manufacturing in areas with emerging markets is that the question of bioprocess expertise and familiarity with good manufacturing practices is increasingly moot. As time goes on, that situation will inevitably continue to improve. Training and operations are less an issue of capability and more simply one of culture and communications. And companies such as Pacific Bridge (www.pacificbridge.com) are ready to provide assistance with recruitment and other issues.

Social and Cultural Barriers

Business culture complicates matters when two different companies merge or partner together or when one hires the services of the other, even when people in different states work for the same company. Ask any of your New York colleagues about the people they’ve worked with in California, for example — or either’s view of those they’ve done business with in Texas — and vice versa. Consider your own experiences in mergers and acquisitions. Expand these “culture clashes” to include people in Spain, France, and the United Kingdom, and you’re already facing some challenges. Go beyond the Western world, and the situation may become truly daunting.

Differences in leadership are strongly influenced by local culture. Some cultural attitudes expect greater distance between managers and employees than in the United States, with its “teamwork” mantra. Some cultures are more formal; some are less formal. Some are more punctual; some less. In China, business is traditionally considered less important than academics and scholarship, whereas in the United States the opposite is generally true. Attitudes toward time off vary widely even among countries on both sides of the north Atlantic; add Japan, South Africa, Russia, Malaysia, India, and others into the mix, and the resulting charted data would look like a shotgun blast. All these differences cannot be simply dismissed by setting a global company policy and expecting it to be followed.

Cultural differences can manifest in legal ways — e.g., intellectual property laws and religious holidays — and in not-so-legal ways such as counterfeiting, piracy, and terrorism. To many people in the biotech industry, these are perhaps the most worrisome aspects of offshoring. As the World Health Organization (WHO) and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) make progress on bringing the regulatory requirements of different countries into some kind of harmony, international patent authorities are working toward a similar goal. Any company that’s considering doing business in another country is well advised, however, to begin with due diligence in all these areas. Consultants such as Strategic Manufacturing Worldwide (www.smwbiotech.com) can provide expertise in project management across cultural divides. Other consultants and advisors can help talk you through the intricacies of import and export regulations, as discussed in S. Revelle Gwyn’s article in this special issue.

Language, Time, and Travel

Communication, as has been pointed out in many an article on contract manufacturing in BioProcess International and elsewhere, is key to success in an outsourcing arrangement. It’s also key to working across borders but within the same company — or to keep other kinds of partnerships strong. As illustrated by many a case study, it’s hard enough to get your point across when the person on the other end of the phone (or email) is across town. But when he’s on the other side of the world, simple logistics can make projects even more difficult.

Language barriers are not to be taken lightly. English may have become the default “language of science” for much of the world, but that doesn’t mean everyone speaks it with the same comfort, fluency, or even dialect. At BPI, we have to be particularly aware of industry jargon and colorful idioms that can be tossed about in conference presentations (and the articles that are adapted from them) as well as general conversation. When your audience is as far-flung as ours, the excuse that “everyone knows what that means” doesn’t always apply.

As Boston translation service Language Connections (www. languageconnections.com) puts it, “To ensure compliance with manufacturing regulations, employees must have a clear understanding of the procedures that they are expected to perform” (5). So all manufacturing standard operating procedures (SOPs) must be translated into the language that’s generally spoken where they’ll be put into practice. And documents for regulatory submission need to be translated back into English. “Translation is not always as straightforward as one might expect, however; well-qualified translators familiar with biopharmaceutical manufacturing terminology are needed to avoid potential pitfalls.” Managers should visit with well-trained native interpreters. “If the language barrier is not addressed, numerous problems can arise, including production delays, unexpected changes in manufacturing SOPs, and noncompliance with CGMPs. Ultimately, all these factors directly affect the quality of the product being manufactured.” In one case, for example, a simple phrase like “place gasket face up” caused unexpected confusion in Puerto Rico (6). But which part is the “face” of a gasket? InSpanish, a more detailed description of how it should fit into place was necessary instead.

DSM BIOLEGICS AND AUSTRALIAN GOVERNMENTS WILL BUILD A CMO FACILITY IN BRISBANE

In May 2010, DSM Biologics announced that it was entering into a partnership with the Queensland state government and the national government of Australia to design, build, and operate the country’s first major mammalian biopharmaceutical manufacturing facility in Brisbane, Queensland. The >70,000-ft² facility will offer mammalian process development and GMP clinical and commercial manufacturing services.

DSM Biologics’ president Karen King commented, “This offering will be an important continuation and expansion of the services we currently provide out of our facility in Groningen, The Netherlands.” Services at the new site will support all mammalian cell lines and process technologies, including standard CHO-based systems and the PER.C6 cell-line technology (to which DSM has coexclusive licensing rights for proteins and MAbs with Dutch biotech company Crucell). It will be located within Queensland’s Translational Research Institute.

The Australian governments will provide full funding for the facility as part of the Queensland 10-year Biotechnology Strategic Plan. DSM will provide technological expertise to design and set up the facility and its proprietary technologies in operations. Biotechnology is growing in Australia, with >400 companies currently engaged in development activities and an estimated $60 million Australian in annual CMO activity fees exported out of the country because of its lack of a local CMO.

The new biologics manufacturing facility should be commissioned and operational in 2013. BioPharmaceuticals Australia (BPA) is responsible for the overall initiative. BPA’s CEO David Hughes said, “We were impressed with the experience, expertise and technologies of DSM Biologics. Their vision of the biologics plant of the future matches ours, and Australia’s first facility will have state-of-the-art capabilities.”

Often overlooked when it comes to communication are time and travel. Working closely with colleagues in the Middle East, Asia, Latin America, or Africa can mean being separated from them by 12 or more time zones. Americans who are used to immediate answers to their questions must learn patience when no one’s on the other end of the phone because it’s the middle of the night at the manufacturing plant. Thank goodness for email (and text/voice messaging)! But what if production in China has to be shut down until someone in Europe can be reached?

With airfares and associated surcharges going up, hotel rates seemingly incapable of dropping in response to the recession, and security issues complicating matters, business attitudes toward travel have been changing over the past couple years. But business travelers are still filling up those increasingly tight-fitting airline seats. Everyone knows how much face-to-face meetings help business relationships — whether within or between companies. We editors look forward to the couple times a year we can get together — at BIO’s annual convention and our own conference, for example — with BPI’s publisher and sales staff, even though it often takes flying from our small Oregon city to the east coast to make it happen.

Imagine if doing so meant flying from Massachusetts to Malaysia, from Austria to Australia, or from to Shanghai to San Antonio. Of course it’s not impossible; every day some 50,000–70,000 commercial airline f lights crisscross the skies of the world. But such trips can be ordeals even before adding interruptions from misbehaving volcanoes into the mix. That said, it’s been business as usual for people in many other industries since the era of the Concorde. Like many other caveats mentioned here, this is something to keep in mind when considering a cross-border relationship or offshore manufacturing — but it’s certainly no reason to dismiss them completely.

About the Author

Author Details
Cheryl Scott is senior technical editor of BioProcess International.

REFERENCES

1.) Rosholm, P. 2009.Biopharmaceuticals: What Does the Future Hold? Life Science Leader.

2.) Inno Bio Ventures and CCM Duopharma Biotech to Target Local Market with Biosimilars.

3.) 2005.Made in Asia: Innovative Automation Strategies for Asia’s Emerging Biopharmaceutical Manufacturing Hub Next Gen. Pharmaceut..

4.) Kallel, H, and DM Fathallah. 2003. Producing an Anti-ß2 Integrin MAb By a Hybridoma Cell Line in a 2-Liter Stirred-Tank Bioreactor. BioProcess Int. 1:54-59.

5.) White Paper 2008. Biopharmaceutical Manufacturing and Offshoring in Puerto Rico — Linguistic and Cultural Challenges, Language Connections, Boston.

6.) Jones, AC. 2004. Translating SOPs in a Pharmaceutical Manufacturing Environment. Accurapid www.accurapid.com/journal/28biomeda.html 8.

7.) Brooks, K. 2008.CRO Asia Pacif ic Expansion: Risk and RewardContract Pharma.

8.) Champion, H. 2009.Assuring Quality in the Global Supply Chain: Measuring Risk in SourcingContract Pharma.

9.) Davis, K. 2008. Biopharmaceutical Manufacturing: The Challenge of Global Regulatory Compliance. Pharmaceut. Technol. 32.

10.) Finnegan, S, and K. Pinto. 2007. Offshoring to Asia. BioProcess Int. 5:S52-56.

11.) Kermani, F. 2009.The Middle East: Pharma’s New FrontierContract Pharma.

12.) Lee, ZJ, and XL. Ji. 2009. Creating an Effective Strategy for Offshoring to China. BioProcess Int. 7:14-19.

13.) Li, S, and S. Wheelwright. 2008. Partnering with a CMO in China. BioProcess Int. 6:S20-S23.

14.) Strauss, M, and J. Novak. 2009. Selection and Oversight of Domestic and International CMOs. BioProcess Int. 7:24-31.

15.) Subramaniam, KV. 2009.Biopharmaceutical Contract Manufacturing Scenario in IndiaBioSpectrum Asia Resource Guide:66.

16.) Symonds, DS, and JW. Frazier. 2007.Leveraging Strengths in Competitive API Markets: A Provider’s Perspective on Asian PartnershipContract Pharma.

17.) Wolff, E. 2009.Chemical Facility Anti-Terrorism Standards: Recent Changes in Securit y Affect Pharma FacilitiesContract Pharma.