Best Practices For Conducting Multinational Clinical Trials | Page 8

Multinational pharmaceutical companies typically conduct Phase
II or III studies in Taiwan for products that will be made available in
Taiwan. The clinical trial application can be submitted in Chinese or
English; however, the informed consent form and any questionnaires
must be in Chinese. Parallel review of the ethics application and clinical
trial application is possible, but must be clearly stated in the clinical trial
application. Also of note, upon trial completion, investigational products
cannot be destroyed or exported immediately; however, a local depot can
be used instead.11
In Vietnam, all new products that have been available in other
countries for less than 5 years must undergo a Vietnam-based
clinical trial.12
For all countries, it would be beneficial to have local legal
representation assist with regulatory requirements, particularly
when the process is not well defined. This will also assist with
country-specific contracting and payment processes.
Timelines
In the majority of Asian countries, approval timelines are
no different from those in the US or Europe (Table 3).
The longest review times are experienced in China and can take
up to 7-12 months8, or longer if the trial is evaluating a biological
product. In multinational trials, this can result in a 2-6 year lag
between the introduction of the product in US/Europe and China.8
An amendment requires a new application, and the entire
review process must begin again.8

What About Japan?
Japan will be discussed separately here owing to
its unique characteristics in relation to clinical trials.
The regulatory bodies in Japan are the Ministry of
Health, Labor and Welfare (MHLW), which is ultimately
responsible for drug approval, and the Pharmaceuticals
and Medical Devices Agency (PMDA), which reviews
the drug application submission and safety report.
The clinical trial application must be in Japanese.
Per site accrual rate is typically very low, and Japan is
considered one of the most expensive places to conduct
a clinical trial. Investigator and site fees can be high.
In addition, consultations with the PMDA incur a fee,
while other countries do not charge consultation fees.
Relationships with investigator sites are especially important in Japan; failing to 
establish trust-based relationships before initiating a trial will more than likely result
in an unsuccessful trial.
NDAs require data from Japanese subjects who were studied in Japan, including results
f
 rom a study to determine the recommended dose in Japanese patients.13 Japanese
Phase I data must be available. Phase II can be a global trial. Phase III can also be

conducted as a global trial, unless ethnic factors are determined to influence the efficacy;

then, Phase III should be conducted as a local clinical trial. Depending on the study/
indication, 10-20% of the patients in the Phase III evaluation must be Japanese.


In contrast, quick start-up times are possible in most other Asian
countries (Table 3). Ongoing initiatives between Japan, Korea, and
China are addressing ways for the countries to accept data from each
other, enabling faster reviews.4 Prior FDA or European Medicines
Agency (EMA) approval allows for a fast-track review of the study
protocol by the regulatory bodies in China, Taiwan, Korea, Hong Kong,
and possibly others. In Taiwan, a fast-track review is also allowed with
prior approval of a multinational clinical trials protocol from any of the
following countries: United Kingdom, France, Japan, Switzerland,
Canada, Australia, Belgium, Sweden, or Germany. In China, a fast-track
application based on prior FDA or EMA approval can reduce the time
from 13 months to 8–10 months.
clinipace.com

7