Partnering in CHINA

China is in the midst of a transformation from one of the world's top producers of generic medications to a leader in novel drug discovery. Companies like Eli Lilly, Novartis, and Bayer are investing heavily in R&D infrastructure.

(GETTY IMAGES)

Novartis alone-which said its 2008 sales rose 29%, boosted by its patent drugs-has so far invested 2.26 billion Yuan on infrastructure, marketing, and R&D facilities. This year Novartis is on track for the release of six new drugs in China, and by 2010 China is expected to be the fourth largest pharmaceutical market.

Add to this growth substantial new government investment into expanding health care access. According to China Daily,¹ the State Council has approved a long awaited draft plan of government investments in health care reform that will see the Chinese government commit $124.26 billion (850 billion Yuan) in the next three years to cover 90% of the population. The aim of the reform is to have the government bear the bulk of medical expenses for its people by 2011.

Global economics will only add to this double digit growth. Contrary to the rest of the world's credit condition, China banks are sitting on the highest amount of liquidity currently available. According to TheEconomist,² Chinese bank lending surged by 21% in the last year.

For small biotech and externally funded drug developers thirsting for cash and an inexpensive path to approval, Shanghai may be the path of least resistance.

According to Biospectrum,³ the pharma outsourcing industry in China has experienced over 35% year-to-year growth in the past few years. While the market growth and financial resources are very attractive, there are many challenges to face in this still emerging landscape.

Despite recent changes, pharmaceutical regulations in China are still burdensome and among the slowest to permit clinical trials. On average, it takes up to nine months from application for a trial to receive approval [http://www.cfs.gov.cn/cmsweb/webportal/W45649089/A64002920.html].

Therefore, a partner with extensive Chinese experience can be invaluable, offering advice as well as insight on the risks of a particular program.

Ticking timelines

The prolonged approval cycle coupled with the large number of less experienced investigator populations cause studies in China to lag behind parallel trials in more traditional markets. However, rapid project start up, as well as recruitment, more than make up for the initial delays.

These delays can also be overcome with proper investigator training and trial material distribution. Despite the mentioned issues, there are instances where trials in China catch up or outpace parallel research in the United States and Europe, where the recruitment cycles are slower.

Data and asset management

Strict regulations on the export of specimens and complete restriction of the export of genetic samples can impact the utilization of out-of-country support resources and increase the cost of technology transfers to multiple providers in the region. These complexities of exporting specimens restrict the ability to leverage labs outside of China during study sample peaks.

To overcome these limitations many local labs must outsource their biomarker and esoteric testing to specialty labs that do not have equivalent accreditation, certification or harmonization processes. It is therefore critical to evaluate any subcontractor arrangements to ensure the local specialty labs have the ability to support your development program.

As a byproduct of fast startup and recruitment, an onslaught of screening visits in a relatively short time causes a tidal wave of data, specimens, and screening samples potentially inundating available resources. These tsunamis of investigator data and laboratory samples can quickly overwhelm resources not accustomed to the environment.

Without well-established processes and a robust central lab protocol management system designed to handle these issues, the sheer volume could cause increases in scope, costs, and delays and impact study results.

A new landscape

To support the boom in drug development and help manage the complexities of clinical trials, service companies, CROs, and central labs have been establishing new facilities in China. However, these young investments will need time to mature and establish the experience pools needed to negotiate the complexities of this emerging and resource competitive landscape. Moreover, the competition is tight for access to the most experienced resources and researchers, and the complex regulatory affairs environment is a challenge.

It's clear, therefore, that partnering early with a regionally experienced company is crucial to success. China-based central labs often have detailed understanding of regulatory concerns and relationships with investigators that can assist in accelerating the application process and managing the recruitment of subjects effectively.

Best practices

Seasoned local staff can resolve issues quickly and in the local language. As mentioned earlier, the newcomers will need some time to develop the appropriate local experience pool. Staff in these new entities generally are junior and rely on direction from out-of-country management or resources. For major issues, the staff may require support from teams several time zones away.

Access to real-time lab metrics is a success factor for managing Chinese trials due to time zone difference with European- and U.S.-based sponsor companies. If access to safety reports and screening results are delayed, there is a resultant delay in response to issues contained in that data, which may impact the clinical trial.

Any weaknesses in training of Chinese investigators, communication with local transport and logistic providers, and cultural challenges will be reflected in these metrics. Formalizing a process to review, analyze, and course correct on a regular basis can protect program investments.

Establishing a strong relationship with a central lab partner early on can lead to a more efficient and effective use of study protocol design, appropriate assay choice, and biomarker selection and design, as well as provide insight on geographic considerations. In addition, tools and processes, from study set up to invoicing, can be customized with key input from the lab.

Other points to consider when selecting partner include:

• It is essential that an outsourcing partner is also well-versed in the GCP guidelines established by the SFDA.

• Cultural differences can pose challenges, so a partner that knows the country, culture, and the best way to navigate the local business climate will help save both time and money.

• Your outsourcing partner should have a demonstrated ability to attract and retain experienced, local, professional, and scientific staff.

Essential elements

While China is a unique and complex country, the formula for success can be put simply: early collaboration with a central lab partner with substantial experience in China.

With a financial and operationally vested interest in achieving the same goals set by the sponsor, a central lab with experience in China can offer insight to help maximize value from a trial as well as reduce direct and indirect costs associated with logistic and regulatory issues.

Renzo DiCarlo is vice president and general manager, MDS Pharma Services Global Central Lab, and Jenny Zhang* is general manager, Asia Pacific of MDS Pharma Services Global Central Lab, 203-204 Shidao Soloon, 2 Tongji Middle Rd., BDA, Beijing 100176, China, email: jenny.zhang@mdsinc.com

To whom all correspondence should be addressed.

References

1.China Daily, "Chinese Pin Hope on Health Care Reform," http://www.chinadaily.com.cn/china/2009-01/22/content_7422769.htm.

2.The Economist, "Perhaps a Reason to be Cheerful?" http://www.economist.com/finance/displaystory.cfm?story_id=13145849.

3.Biospectrum, "Outsourcing Market in China will See 35% Growth," http://www.biospectrumasia.com/Content/100209CHN8544.asp.