Monday, February 27, 2012

Medical News:New Process Could Ease Isotope Crunch - in Radiology, Nuclear Medicine from MedPage Today

Medical News:New Process Could Ease Isotope Crunch - in Radiology, Nuclear Medicine from MedPage Today:

New Process Could Ease Isotope Crunch

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The solution to a looming shortage of the medical isotope technetium-99 may lie in the basements of many hospitals, according to Canadian scientists.

The answer: cyclotrons.

Researchers associated with Vancouver'sTRIUMF nuclear physics research center say machines that are widely used to make other imaging isotopes can be modified to make technetium-99, the substance at the heart of the isotope crisis.

The process is relatively simple to implement and can produce commercial quantities of technetium-99 at a reasonable cost, they said. Best of all, it uses equipment that is a lot cheaper than a nuclear reactor, currently needed to make the isotope.

"We don't think there are any show-stoppers here at all," said Tom Ruth, PhD, who is principal investigator for the two-year, $6-million project.

"We've demonstrated it all works and it's feasible and within the economic realm of being competitive," he told MedPage Today.

But there remain a few hurdles that still need to be cleared, according to Robert Atcher, PhD, of the University of New Mexico in Albuquerque, who is past president of SNM and chairman of the molecular imaging society's isotope committee.

Among them are regulatory issues, he told MedPage Today, such as does the technetium-99 produced by the cyclotrons meet medical safety standards, and does the production process itself meet nuclear safety guidelines?

Atcher pointed out that cyclotron production may work well in the Canadian health system but he's not convinced it's suitable for the U.S.

Isotope Insufficiency

If one possible solution to the isotope crunch lies in Canada, the root of the problem is also there.

Canada's aging NRU reactor in Chalk River, Ont., is the main source of technetium-99 in North America. It has been in and out of service for the past several years, and the Canadian government says it will get out of the medical isotope business entirely by 2016.

That's a problem because technetium-99 is used in about 85% of all medical imaging procedures, and the remaining facilities that produce it -- reactors in the Netherlands, Belgium, France, Australia, and South Africa -- are unlikely to be able to take up the slack left by the Canadian shutdown.

The reactors don't actually make technetium-99. Instead they make molybdenum-99, a radioactive substance that decays into technetium-99.

The molybdenum-99 is packed into "generators" and distributed to hospitals, where nuclear medicine specialists can draw off the technetium-99 as needed for about a week.

The cyclotron process is more direct, Ruth said. For between three and six hours, the machine sends a stream of high-energy protons at a target of molybdenum-100, a nonradioactive isotope of the element, converting some of its atoms to technetium-99.

At the end of that time, a half-hour chemical processing step removes technetium-99 from the target and it's ready to be used in imaging procedures, he said. Unlike nuclear reactors, the machines that are needed are in wide use.

The downside is that the technetium-99 has a half-life of only about six hours, meaning it can't be stored for a long time or shipped long distances, Atcher said.

In Canada, where a large fraction of the population lives in urban centers, that may not matter, he said, as a dozen cyclotrons could probably handle the country's needs.

But in the U.S., the distance factor might mean that rural areas would be left out, Atcher said.

As well, the short half-life might make it more difficult to get technetium-99 on an emergency basis -- at night, for instance, or on weekends -- where specialists currently can simply draw off a little more from their generators.

"You can't equal the convenience of the generator," Ruth conceded. "That's why they've lasted so long."

So some generator production will probably continue, but the cyclotron process is "a piece of the puzzle," he said.

The researchers made a point of using machines similar to those now in use. In particular, of the three machines they modified to make the substance, two were 16 MeV machines made by GE, which are in common use around the world.

At least in Canada, one of the regulatory hurdles -- establishing nuclear safety -- is under way, Ruth said. The Canadian Nuclear Safety Commission, the equivalent of the U.S. Nuclear Regulatory Commission, was involved in and approved the modifications to the test machines.

The second hurdle, establishing medical safety, will require clinical trials. Ruth said he and his colleagues hope to have a phase I study running this fall to show that their isotope is both safe and efficacious.

The technetium-99 they produce, he said, is identical structurally to the substance produced by molybdenum-99 generators. But the cyclotron process also introduces some other technetium isotopes -- less than 1%, the researchers calculated -- and those might have some unforeseen toxicity.

Ruth said Health Canada, the government department that has equivalent safety jurisdiction to that of the FDA, has also been aware of the research from the beginning.

Technetium Tussles

Another issue is cost, Atcher said. Given that the Canadian reactor is going out of business, there was pressure in Canada to find other sources of isotopes, even if they cost more.

But whether the U.S. market would pay more is another question, he said.

Ruth told MedPage Today he thinks the cost per dose will not be much higher, as least according to his group's preliminary calculations. But complicating the picture are the subsidies that underlie the current price of technetium-99.

All of the reactors in the business, including Chalk River, are primarily research machines that get substantial support from their respective governments -- in essence, a subsidy for the isotope business.

But there is currently a push to use molybdenum-99 made in reactors that use low-enriched uranium, unlike the highly enriched uranium used in current machines.

Those facilities may not get similar support, so that the cost of generators would rise, Ruth said.

The U.S. Department of Energy has been supporting efforts to develop a domestic source of isotopes. Two groups had been trying to develop a reactor-based technology, but one of those --led by General Electric -- has recently dropped the project.

As well, there are two projects based in Wisconsin that do not use reactors. Madison-basedNorthStar Medical Radioisotopes is hoping to have commercial production of molybdenum generators this year, while Middleton-based Phoenix Nuclear Labs is also developing a production process.

Because of that work, Atcher said he is more optimistic that the isotope market can become more stable than it has been.

"But when we have a hard deadline of 2016, you always wonder what can go wrong in terms of technical development," he added.

Bench to Bedside

Technical development aside, it's also important to get products from the lab to the clinic, Ruth said. His group has done the scientific spadework and is now trying to find commercial partners to make and distribute cyclotron-produced technetium-99.

Ottawa-based Nordion, the current commercial intermediary between the Chalk River reactor and the clinic, said it's discussing the issue with TRIUMF.

In a statement, the company said it considers the cyclotron process to be something that would supplement reactor-based production.

For clinicians, Ruth said, the key question is reliability -- can they depend on having enough isotope? That is a matter of how the cyclotrons are distributed and what other demands are placed on them.

For example, the machine they tested in Vancouver could probably supply the needs of the Greater Vancouver Area, with a population of about 2.1 million.

That device, at the B.C. Cancer Agency, has other functions, Ruth said, but a similar machine dedicated to making technetium-99 could probably serve all of the people in the province, some 3.5 million.

Similar calculations would have to be made anywhere the process is used, he said.

On the other hand, clinicians are used to some isotopes with a short half-life, such as fluorine-18, so that the distribution channels should not be a major issue.

"We think we've dotted all the i's and crossed all the t's," he said.

But "time will tell," Atcher noted.

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Monday, February 20, 2012

Three snapshots of Chinese innovation - McKinsey Quarterly - Strategy - Innovation

Three snapshots of Chinese innovation - McKinsey Quarterly - Strategy - Innovation

Three snapshots of Chinese innovation

Chinese innovation is evolving in diverse ways and at an uneven pace across a range of different industries. Presented here are ground-level views from three of them: automobiles, semiconductors, and pharmaceuticals.

General Motors and its Chinese joint-venture partners sold more cars in 2010 in China (2.35 million units) than in the United States (around 2.2 million units). In an edited version of an interview with McKinsey’s Glenn Leibowitz and Erik Roth, GM China president Kevin Wale explains the importance of team-based innovation efforts in China and describes GM’s rapidly growing Advanced Technical Center in Shanghai. He also observes that innovation in China’s auto industry is more about commercialization models than technical achievements.

While automotive innovation has had years to take hold, innovation on the leading edge of the semiconductor business remains nascent. But barriers that once held back local chip makers now appear to be eroding. This means global players will face some tough trade-offs in the years ahead. The challenge: how to participate in China’s growth—which may well require joint ventures with domestic players—without sacrificing valuable intellectual property. McKinsey’s Bob Dvorak, Sri Kaza, and Nick Santhanam describe this dilemma and present a few ideas for multinational companies trying to overcome it.

Finally, Steve Yang, head of R&D for Asia and emerging markets for the global drugmaker AstraZeneca, articulates some key differences between pharma development in China and Western markets. The starting point: different disease prevalence (gastric and liver cancer, for example, are more prevalent in China). In an edited version of an interview with McKinsey’s Jeremy Teo, Yang describes new models of innovation that could emerge from China, as well as the long-term commitment to talent development that will be needed for AstraZeneca’s Chinese research center to reach its innovative potential.

AUTOMOTIVE INNOVATION IN CHINA: THE VIEW FROM GENERAL MOTORS

Kevin Wale is the managing director of GM China, which he has led since 2005.

car photo

Innovation through commercialization

There’s probably more innovation in going to market and in thinking about new business opportunities than there is in technical innovation. Technical innovation is lagging behind the rest of the world in maturity. The country is trying to get there as quickly as it can but doesn’t have the deep graduate research capability that the rest of the world has.

What China does better than any place else in the world is to innovate by commercialization, as opposed to constant research and perfecting the theory, like the West. When the Chinese get an idea, they test it in the marketplace. They’re happy to do three to four rounds of commercialization to get an idea right, whereas in the West companies spend the same amount of time on research, testing, and validation before trying to take products to market. The electric vehicle is a good example. The Chinese view is that it’s not going to be perfect, and they’re not trying to make it perfect from day one. They’ve got a few more series of improvements to go, and they’ll work on them in parallel with finding out what the customer really likes and adapting to that. That’s an innovative way of doing innovation, something that the rest of the world is struggling to understand. In our business in China, if we don’t innovate through or with commercialization, we’re going to lag behind our competitors.

The power of teamwork

We’re trying to set up a small unit that is designed to focus on what some people call “innovation,” but what I call “predator versus prey.” Everyone’s coming after us, and we want to stay the predator. The only way to do that is by having people who are focused on who is doing what to us and where the opportunities are.

We find the deployment of small task teams is by far the best approach to drive these innovative ideas. Take OnStar,1 for instance, which was actually quite innovative for this market. The way we did it was well ahead of others. These systems are released by code, and they’re now up to OnStar 8. We deployed the absolute latest and went straight to 8; we didn’t start at 1. It was a calculated risk that we could make a business model that could benefit from this technology and cover the significant cost and technical support required to support that. Being out there, it feels like you’re in the Wild West. Four to five of you are in a team. You don’t have a lot support, but a lot of responsibility.

In our joint ventures, we’re happy to take innovation from suppliers any day of the week. We encourage suppliers to come up with new ideas. We have a lot of local technology in our cars. Our people wanted to lead and they worked with suppliers to develop new ways of doing things. Lighting systems and infotainment are pretty much at the cutting edge of what’s available.

R&D and advanced design centers in China

We wanted to take advantage of some of the great talent that’s going to be coming out of the universities. They’re going to be coming out in droves. They’re not at the advanced graduate stage, simply because they don’t have the mentors in the system, but they will be coming out, and there’s plenty of good talent now that we can staff.

We also want to do research and applied development that is close to the biggest market in the world. It really is very easy to ignore the realities of life when you don’t confront them every day. So we want to make sure that we have activity in the market, with people who speak the language, understand the culture, and confront that culture every day. The first building that’s going up is a battery lab. With the electric vehicle, there will be a lot of suppliers, a lot of government support; the rules will be different, and the applications will be different. We want to be here, where we will be learning that every day and reacting to it every day. It’s the same research capability we have in Detroit, but we’re able to do the work here and frame it around real local knowledge.

We also will have an advanced design center here for the same reason. It’s hard to imagine doing advanced design without taking into account the influence of the largest and fastest-growing market in the world. So we’re putting in a starting point where we will have the basis for future creativity in the country.

The leader of our R&D is a local Chinese who has worked in R&D in China and has excellent connections with the local universities. We also have excellent connections with universities, and we run multiple projects through a program called “PACE”2 and through cooperative development. That will be the starting ground for recruiting.

Also, we’re offering more internships than we normally do because we want to take the best young technical talent. Initially, we will supplement them with skilled researchers from the rest of the world, primarily the United States. But at the end of the day, we will use local skilled talent. We don’t see a problem for the size of what we’re doing here. It’s a big site, but it’s not a big number of people at a particular time—probably 300 people to start with—among all those areas: design, advanced research, powertrain engineering.

Integration with global product development

I’d say with a fair degree of confidence that we integrate our Chinese operations fully into our global operations better than anyone else in the world. If we’re working on a global program, we’ll be doing serious work down the road the same way as they’re doing it in the United States or Germany.

Our engineering centers two years ago introduced the subcompact Chevrolet Sail, which was completely designed here. The low-cost passenger vehicle was difficult to provide out of a global solution because we were trying to cater to too many global needs. That opened the opportunity for the Sail. We were able to focus on addressing a solution that wasn’t going to come out of a global package.

The latest Buick GL8 minivan was introduced here and was done pretty quickly through capability that is built here in China, using a combination of on-the-job mentoring, coaching, and expert assistance from overseas, as well as a very structured development process from our global team. The GL8 is an old GM architecture that no one else wanted, but it’s a terrific product for China. It has turned into an unbelievably good-looking and highly desirable car. I can’t tell you how many senior executives and CEOs ring me up trying to speed up their provision of the GL8.

The Baojun brand is a lower-priced sedan aimed at consumers who live outside of China’s major markets. It’s just a massive opportunity in China, and the ability to meet the income needs and transportation needs of that group of people was never going to be met by GM in a traditional sense.

For the full version of this interview, seeInnovating in China’s automotive market: An interview with GM China’s president.”

SEMICONDUCTORS: A NEW SOURCE OF CHINESE INNOVATION?

Bob Dvorak is a director in McKinsey’s Silicon Valley office, where Sri Kaza and Nick Santhanam are principals.

semiconductor factory photo

The semiconductor industry is a powerful example of the tension surrounding China’s potential for innovation. The country’s leaders understand the important role silicon plays in product innovation,3 so for two decades they have sought to create a more potent domestic semiconductor industry—with mixed results. China purchases 33 percent of the world’s chips ($100 billion worth), using them both in products sold domestically and in exports. But most of the Chinese industry competes in commoditized areas such as chip assembly and testing, and Chinese semiconductor companies hold 4 percent or less of the most prized segments of the global value chain in chip design and manufacturing.

This article highlights four obstacles that have kept the country in check, the potential for their impact to diminish, and the resulting challenge for global producers that have been reluctant to share key elements of intellectual property (IP) with Chinese players.

Shifting winds

Structural changes in the industry and the marketplace, coupled with new industrial policies that promote next-generation technologies and technology transfers from abroad, are combining to weaken the barriers that have held China back.

Chips designed for China’s needs

Chinese players have exerted little influence on semiconductor design, technology standards, or chip selection for major product categories such as mobile phones, laptop computers, and LCD televisions. Most decisions about design and functionality come from global champions and reflect the preferences of consumers in Europe, Japan, and the United States.

But that dynamic is shifting, along with the rising economic power of China’s middle class, with its increasingly diverse needs. Some Chinese companies are now moving to the forefront of a “built in China, for China” movement. Their clout is likely to mean that more semiconductor platforms will be designed locally. Consider the fact that in 2010, Chinese consumers purchased 19 percent of all PCs sold throughout the world, 18 percent of the LCD TVs, 14 percent of the mobile phones, and 26 percent of the automobiles (all by unit volume).

China’s manufacturers, meanwhile, are leveraging this domestic scale to sell in global markets: Lenovo now ranks second in global PC sales and ZTE fourth in the manufacture of handsets. Huawei ranks among the top three world players in all segments of telecom equipment.

Export controls lose their bite

The home governments of leading semiconductor manufacturers have long banned the sale of leading-edge manufacturing technology to China. Current controls by Taiwan and the United States, for example, bar the export of equipment used to make chips below the 65-nanometer threshold.4 As a result, Chinese manufacturers are at least two generations behind the highest-performing 32-nanometer chips.

Market changes, however, are eroding the impact of these bans. Leading-edge semiconductors represent only 14 percent of global demand—half the market share of 2003—as fewer devices require the highest levels of processing power.5 That’s particularly true of devices favored by China’s new consumers, whose purchases often involve entry-level mobile phones and TVs. The result: a more level playing field for China’s players, some of which can now use manufacturing processes that are two generations behind to mass-produce chips that represent sizable markets (for example, analog integrated circuits and microcontrollers).

Reordering China’s high-tech zones

China’s industrial planners made missteps in early efforts to incubate a semiconductor industry. Rather than concentrate investments and incentives in one geographic area, as the Taiwanese did with Hsinchu Science Park, government officials dispersed their bets, financing fabrication sites in 19 cities. This fragmentation hindered the establishment of a vibrant semiconductor ecosystem with clusters of manufacturing prowess and design talent.

China has corrected its course, however, and now is concentrating more investment in a smaller number of cities—for instance, Chengdu, Dalian, and Shanghai. These centers have a stronger base of expertise, as well as a critical mass of manufacturers and suppliers. They are attracting investment from global leaders and developing more broadly based value chains in areas such as wireless communications systems.

A new regime for technology transfer

Foreign players own most of the IP across the semiconductor value chain, and the lion’s share of revenue streams for the design of semiconductors and the processes used to manufacture them goes to non-Chinese companies. While the Chinese have found ways to acquire or piece together IP to build a strong position in many industries, the challenge in semiconductors is uniquely difficult because of the complexity of chip design and manufacturing and the high level of materials science that is required.

China, however, has one of world’s best-funded and ambitious tech industry policies, and acquiring semiconductor know-how and IP remains a high priority. Increasing China’s chances for success is a new, two-pronged initiative that will increase the pressure on global companies to share their IP with Chinese partners. The first part involves stepped-up investments and new policy directives that will advance large, next-generation technology platforms such as cloud computing, the Internet of Things,6 and hybrid electric vehicles. These three markets represent tens of billions of dollars in opportunities for global and domestic semiconductor companies. The second part sets targets for indigenous innovation, with the goal of reducing dependence on foreign technologies to 30 percent, from the current 50 percent. Government purchases of products and services, from mobile phones to cloud-computing networks, will favor products that incorporate high levels of domestically developed technology.

Strategic choices for global players

For global semiconductor players, the dilemma is clear: how to participate in what will probably be the world’s most dynamic technology growth environment while safeguarding core IP and know-how. These companies must remember that China seeks to use transferred IP and manufacturing methods to create its own champions that can compete with global countries around the world, not just in the local market.

The experience of high-speed rail players provides a cautionary tale. Global companies were encouraged to form partnerships with Chinese ones to develop a national high-speed network. Some foreign companies favored a relatively restrictive sharing of IP, but a classic prisoner’s dilemma7 scenario played out: the attractiveness of market access gave global players a powerful incentive to ditch hard-line positions. In the end, industry partnerships were formed on less restrictive terms. Within three years, Chinese companies had absorbed key elements of the core technology, and since 2007 they have won nearly $20 billion in new rail contracts.

Global semiconductor players thus will need to be clear about the terms of engagement with potential partners. China’s complex fabric of national, provincial, and local policy makers and companies creates a considerable opportunity for customized strategies. Forming ventures with strictly delineated IP transfer terms is the obvious solution. Global leaders such as GE (in rural health care) and ABB (in electric motors and power transmission) are exploring alternatives.

One option is for foreign companies to launch indigenous R&D centers with Chinese universities and institutes and to focus these facilities on developing technologies for unproven but promising next-generation domestic markets. Multinationals that participate in such ventures align themselves with China’s goals while they contain IP risks to markets that are still evolving. Another approach is to focus on local product development in partnership with downstream players such as auto manufacturers. This strategy helps multinationals meet local-technology requirements and provides for more active risk management.

This is an edited version of an article that originally appeared in the inaugural issue of McKinsey on Semiconductors (September 2011), available on the McKinsey & Company Web site.

PHARMACEUTICAL INNOVATION: ASTRAZENECA’S EXPERIENCE IN CHINA

Steve Yang is vice president and head of R&D for Asia and emerging markets at AstraZeneca, which he joined in January 2011.

Pharmaceutical lab photo

What’s different about China

There are many unique disease mechanisms in China. Gastric and liver cancers, for example, have high prevalence and, in many cases, could have different populations or different disease etiologies. That presents a white space on which R&D innovation can focus. We can use what we have learned in the West to understand this situation and to try to develop new medicines against those diseases. I hope that will open up new markets and help us meet unmet medical needs of patients in China and the rest of Asia.

Also very important is that China and, to some extent, India have shown the world the importance of conducting R&D with more resource efficiency, particularly by focusing on externalization. This could mean strategic outsourcing of certain R&D functions. It could also mean collaborating with academics or biotech companies, and that’s an area in which I believe China can offer tremendous potential not only for our local R&D operation but also for our global R&D.

Finally, there’s China’s urbanization. There are consequences to the migration to megacities with populations of more than 20 million. In these environments, people will increasingly have a more sedentary lifestyle. In such an environment, with high-density living, how do we continue to help people live a healthy lifestyle, prevent disease, and improve the quality of living? And the challenges and opportunities go beyond just inventing the next pill or vial for injection, to fundamentally thinking about what, with so many people living together, the best way is to prevent disease or at least slow down disease and some of the chronic disease progressions. That is something I don’t think the world has really tackled before. The scale of such innovation is where China can offer ground for experimentation.

Progress to date

We have made great progress and built a solid foundation. Our Innovation Center China was announced in 2006 as part of a $100 million investment we made in China, and it was launched in October 2007. During the four years since then, we have accumulated a lot of data, contributed to global oncology research in the area of biomarkers and translational science, and built credibility and a strong team locally. We are ready to expand our mission to become a drug discovery center, with a special focus on cancers prevalent in Asia, such as gastric and liver cancers.

But the journey has just started. If you use as a measure the time needed to develop a new drug, we still have a long way to go. It takes 10 to 15 years to take an idea all the way from a scientist’s hypothesis to products on the market. There is a Chinese saying that you may have a destiny, and that final destiny may be very bright, but the road that leads there is inevitably windy and full of challenges. That’s the case at both the strategic and operational levels. On a day-to-day basis, managing turnover and retaining and developing talent can be challenging, although in AstraZeneca R&D we are fortunate to have a turnover rate well below the industry average. Also, AstraZeneca is a multinational company, and the majority of our senior leaders, our resources, and our stakeholders are thousands of miles and many time zones away. Constantly gathering their support and commitment is very important.

Finally, we have seen a significant improvement in the IP environment. But, because of the rapid development of the legislative environment and the regulatory framework, there is a constant flow of amendments to policies on the IP law. In many cases, it took some time for the government, the legislature, and enforcement agencies, as well as industry, to understand fully what those new regulations meant. That’s just natural growing pains. In IP law, there has been a recent commitment reflecting the government’s increasing understanding of the importance of IP, but we hope to have more clarity around how those new laws will be interpreted and enforced.

The talent situation

There are a large number of scientists available, trained either overseas or locally. We have seen significant quality of talent both in the returnee population and in the locally educated population. There are disciplines—for example, chemistry and general biology—that tend to follow this trend. There are also disciplines that are highly specialized and require decades of training. In those areas, the talent, particularly those with experience, is in short supply. Examples would be toxicologists, pathologists, statisticians, and clinicians. That’s one dimension to look at: the technical competency of the talent.

The other dimension, given the fast growth of the markets, includes the leadership and management capabilities of the talent. In many cases, companies like ours need to ramp up our efforts quickly, so we are giving the scientists—particularly the scientific leaders—the mandate not only to do good science and to drive projects but also to become good leaders and good managers. If we use those criteria, the number of individuals who possess all these skills is smaller.

But in general, we are optimistic. From our own experience, we can recruit talent overseas and locally. And to support our portfolio, our mission, and, more important, the Innovation Center China, we have an excellent record in retaining and continuously developing those colleagues.

For the full version of this interview, seeInnovating in China’s pharma market: An interview with AstraZeneca’s head of R&D in Asia and emerging markets.”

About the Authors

Automotive innovation in China: The view from General Motors

Kevin Wale is the president and managing director of GM China, which he has led since 2005. This commentary is drawn from an interview with Glenn Leibowitz, an editor in McKinsey’s Taipei office, and Erik Roth, a principal in the Shanghai office.