Clinical Trials Focus on Asia

Risk, reward, and regulatory updates

By Kristin Brooks

At the 4th Annual Global Clinical Trials Partnerships Conference held March 1-2 in Princeton, NJ, Andrew Chang, Ph.D., executive director of PharmaNet Consulting, delivered a presentation entitled, “China: The Emerging Market for Clinical Research.” Dr. Chang addressed overall growth in Asia, as well as China’s leading role in the growth rate for emerging regions. He noted that the average relative annual growth rate in shares for Biopharmaceutical Clinical Trials (BCTs) was 20% in 2006 for emerging regions, and estimated at 40% for 2010.

The reasons for this growth, according to Dr. Chang, is China’s Clinical Research Infrastructure, including rapid patient recruitment, experienced and well educated physicians, strong government support of medical research, State Food and Drug Administration (SFDA) certified sites, as well as globally acceptable data. Additionally, the number of accredited sites in China, in various therapeutic areas, has grown significantly; there are currently 114 cardiovascular sites, 91 neurology/psychiatry sites, and 86 sites for both respiratory and gastroenterology. Dr. Chang also outlined the SFDA review and approval processes for CTA and compared IND review between FDA and SFDA, pointing out that some of the gaps are closing, while others are in the process of change.

Along with two of his colleagues at PharmaNet, Emily Tan, executive director, Clinical Research and Franz J. Buchholzer, Ph.D., vice president, Regulatory Operations Worldwide, Dr. Chang discussed the challenges, risks versus rewards, and recent regulatory changes associated with conducting trials in the Asia–Pacific region.

Prior to his current role at PharmaNet, Dr. Chang served as senior director, PharmaNet consulting. He also served more than 11 years at the FDA, including serving as an FDA Expert Committee Member. His most recent position with the FDA was associate director for policy and regulation, Division of Hematology (DH), Office of Blood Research and Review (OBRR), CBER.

Contract Pharma: What are the current obstacles conducting trials in Asia, regulatory or otherwise?

Andrew Chang: Regulatory start-up timelines are longer in certain Asian countries. Other factors include ethical consideration and relevant clinical trial expertise.

Emily Tan: However, the gap between Eastern and Western countries has significantly narrowed in recent years.

Franz Buchholzer: Obstacles in the region can include diversity with requirements and reporting, language issues, and a changing regulatory environment. There are varying degrees of complexities and predictability of timelines. Also, each country has its own set of clinical trial requirements and processes. Safety reporting rules are not harmonized and in countries like India, Taiwan and China, reporting requirements are not clear or not harmonized with international standards of expedited reporting (ICH E2A). For example, China requires all local serious adverse events (SAEs) to be reported within 24 hours; Taiwan requires all foreign and local SAEs from the same clinical trial to be reported within seven to 15 days of receipt by local sponsors; and India requires all unexpected SAEs to be reported within 14 days.

Also, China requires comprehensive data and full translation and does have longer timelines, but there have been talks about regulatory authorities shortening the timelines in China. However, the longer timelines for dossier review are compensated for by faster recruitment, as compared to other countries.

Another obstacle the region presents is that China, Japan, Korea, and Thailand all require clinical trial application (CTA) submissions in local languages. The Asia-Pacific has a dynamic regulatory environment and regulations are evolving and changing rapidly. In September 2009, for example, Thailand introduced new IND regulations requiring much more data than previously. Korea also announced plans for clinical trial notification (CTN) scheme for global pivotal studies with regulatory approvals from ICH regions, but this is yet to be finalized. However, this is an opportunity, not an obstacle. Other changes that present opportunities in the region are that regulatory practices have greater transparency, efficiency, flexibility and responsiveness. Also intellectual property (IP) and data protection are growing in alignment with international standards.

That said, regulatory delays in Hong Kong, for example, recently changed from four to six weeks to 12-16 weeks. Also, in relatively new territories like Vietnam, clinical trial regulations and process have been more or less “untested” by PharmaNet.

CP: What’s the value vs. risk conducting trials in the region?

AC: Large pools of patients and cost efficiency are the two major values in conducting global trials in the region. In addition, Asia has significant potential pharmaceutical markets within the region, especially in China and India. It’s important to generate data in the regions that meet developed countries’ such as the U.S. and Western EU standards if the data are intended for U.S. or EU marketing applications. Also, issues such as investigator qualification and training, Good Clinical Practices (GCP), independent ethics committees, and other items applicable to the U.S. or European populations, as well as medical practice, should be considered in feasibility studies.

ET: The most significant value is access to huge patient populations, and favorable regulatory and ethics committee approval timelines (except for China regulatory approval). Asian countries have adopted international guidelines and regulations for clinical trial conduct. For example, ICH GCP has been incorporated into the regulations in many countries. Many governments in Asian countries are also supportive of the industry with investments to build infrastructure and training. The Asian pharmaceutical market is also growing more than other regions and serves as an important growth area for many pharmaceutical companies. Currently, costs are lower than Europe and the U.S. The region is growing very rapidly with its attending issues of high competition for talent and rising salaries. Companies must have proper training and quality control plans in place in order to ensure high-quality delivery of projects.

CP: Have there been any significant regulatory changes in China and Japan recently?

ET: The Health Ministers of China, Japan, and South Korea met in Seoul on April 8th 2007, and discussed several issues of common concerns on the health and medical field and built basic consensus for future cooperation. Also SFDA (China) and The Ministry of Health, Labour and Welfare (MHLW) (Japan) are working together toward a further strengthening of their relations.

One of the themes of mutual cooperation is to enhance new drug development, especially clinical development. The initiative is to conduct global clinical trials in East Asian Countries for the foreseeable future by accumulating the data on ethnic factors among the three countries. Furthermore, it maps out strategies to realize faster development and approval review using the data.

This acceptance by Japan of clinical data from non-Japanese patients has resulted in a boom in Asian regional studies sponsored by Japanese pharmaceutical companies. East Asian countries such as China, Korea, Taiwan, Hong Kong and Singapore stand to gain tremendously from this new change as well.

FB: The China/Japan/Korea Tripartite Cooperation, a joint research project on ethnic factors in clinical data, promotes scientific research cooperation on ethnic factors in clinical data with a view to encourage global development and sharing of clinical data. This helps to facilitate drug development and registration in East Asia.

Also, recently more Chinese study sites accept the (European Communities) EC review to start before the SFDA’s approval is given. For example, the review process at competent authorities and Ethics Committees can be done more and more often, in parallel, which shortens the review time. Additionally, brand-new drugs can undergo a “special review process” at SFDA, which saves time.

These changes have resulted in more willingness to accept Asian data than before, prioritization of consultation applications for multi-national development, and encouragement of participation of Japan in global studies.

CP: Does PharmaNet have any further expansion plans in Asia?

AC: During 2010, the company plans to triple its headcount of clinical development professionals in the region.

Kristin Brooks is associate editor at Contract Pharma. She can be reached at kbrooks@rodpub.com.