There is lots of buzz about China being the next hot place for global clinical trials. The numbers being bandied about suggest $2 billion in Chinese pharmaceutical research and development in 2008. That's expected to surge to $10 billion by 2010. The Chinese government just committed $1 billion toward jump-starting its biotech industry. So there is no doubt the potential for research in China is massive.
But judging by the 45th annual Drug Information Association (DIA) conference this year, the present level of industry-based activity in China is fraught with short-term issues.
That was especially evident in a session on training investigators in China. Sandra Garrett, executive chairman of Rockville, Maryland, contract research organization (CRO) Global Research Services, has been in China for a decade. She reminded DIA attendees that each of the states in China handles drug regulation with more regional autonomy than in the U.S. model. “Each [state] has a different set of objectives and a different target audience,” Garrett explains. There is a State Food and Drug Administration (SFDA), formed in 1998, but it oversees product manufacturing, trade and registration.
Another big problem? Minimal standardization of data. “The State Food and Drug Administration has not yet established guidelines for standardizing data transmission and data collection,” says Garrett. “In essence, for Western companies who are coming in to do research in the country, there are no standardization policies for the design of case report forms (CRF) or the collection of data, or how the data will ultimately be submitted to the agency in China for state regulatory approval.” Nor are there any defined processes for adverse event reporting in trials taking place in China.
The U.S. FDA has a presence in China, but it is small—just three offices set up in 2008, during “the Heparin fiasco,” says Garrett, referring to the Heparin recall after a contaminated, Chinese-manufactured batch of the blood thinner killed 81 people and caused severe allergic reactions in 785 people. The new FDA offices in China are primarily there for inspections, says Garrett.
As many ClinPage readers know, there's also a big issue around the start-up time for trials. Formal approval from the SFDA is required before conducting a trial; it can take between six months and a year to obtain. The good news is that an approval is valid for three years, allowing sponsors and CROs to plan ahead. Folks hoping to get started right away will be sorely disappointed.
As in any emerging clinical trial market, informed consent is an issue in China. Garrett observes that, ten years ago, when her CRO was setting up shop in Shanghai, she hired linguistics experts to translate its documents into Mandarin Chinese. The company was startled to learn the language had no equivalent terms for “to inform” or “to consent.” That lead to problems, she recalls. Now, patients considering a clinical trial must go through classes to ensure that they understand elementary issues related to consent.
“For those of you who think it's easy to fly across the world, open up your office and start to do clinical research ... you need to have a paradigm shift, because in fact that is not true—especially if you look at the concept of having to train on informed consent,” Garrett says.
Another issue: staffing. As in India, it will get worse before it gets better. Jenny Zhang, senior director of business development for the CRO Tigermed Consulting, pointed out that though the clinical trial market may be growing by 40 percent per year, the number of qualified workers in the field is only growing by about 20 percent.
“So there's a huge gap—in the CRO industry in particular. Most of the CROs in China have less than 10 years in operation; they face a huge turnover problem. Sponsors also face huge challenges in obtaining and retaining qualified staff,” says Zhang, who's president of the Association of Clinical Research Professionals' (ACRP) China chapter.
China joined the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) in March of 2008. Before that, the country had its own version of Good Clinical Practice (GCP) guidelines, which closely resembled ICH GCP, says Zhang. Those guidelines required that all sites participating in a trial be China GCP-certified. Since that was enacted six years ago, 325 institutions have gotten the permit. That's only a fraction of China's 18,000 hospitals and 1.9 million doctors.
Phase I studies, as in India, remain off limits unless the tested compound was originally developed in China. Phase II and III remain a virtually untapped market. So the lion's share of the projects to date have been in Phase IV.
As a result, most research in China need not comply with GCP. Chinese regulations do not allow drugs to be sold there unless they have already been approved elsewhere. But drugs must be tested in a Phase IV trial in China to reach its market. So most of the trials in China haven't been global research projects but needed to gain access the Chinese market.
Adding it all up, China's population of 1.3 billion virtually guarantees it will be a major research hub in the future. But the country still has work to do before a global clinical trials industry can flourish there.
—by Suz Redfearnd9A2t49mkex