2016 Update on Clinical Trial Procedures in Asia

2016 Update on Clinical Trial Procedures in AsiaAsia contains some of the world’s largest and fastest growing medical device and pharmaceutical markets in the world. The large and diverse populations found in the Asian countries makes the region an increasingly popular destination for clinical studies.

There have been important updates to the regulations governing clinical trials in several of the Asian countries in recent years. Read more on key updates in China, India, and South Korea clinical trial procedures below.

Recent Changes to the Clinical Trial Procedures in China

China Medical Device Clinical Trials

In December 2015, the China Food and Drug Administration (CFDA) added 114 Class II and 8 Class III medical devices to the clinical trial exemption list.

In May 2016, a new standardized checklist was released by the CFDA to guide medical device clinical trial site inspections.

In June 2016, changes to the New Device Good Clinical Practice (GCP) guidelines went into effect. The “sponsor” was redefined from the device registration applicant to the device manufacturer. If the sponsor is located overseas, the company must assign a local China agent to oversee the China clinical trial. Furthermore, the sponsor has been assigned additional responsibilities, including appointing qualified supervisors, revising investigative brochures, and getting necessary approval from China’s ethics committee.

Improvements have been made regarding regulations for handling medical devices during clinical trials:

  • The sponsor must label fully tested devices as “investigational devices”
  • Devices are only given to relevant people
  • “Investigational devices” are disposed of properly based on previous agreements

China’s ethics committee reviews the device trial’s protocol and the Informed Consent Form (ICF), which must be easy enough for minors and participants with limited vocabulary to understand and knowingly give consent. The ethics committee also approves any edits made to the ICF, which the sponsor must then present to the trial’s participants.

The CFDA introduced a list of new items that the clinical trial’s sponsor, investigator, and trial site must agree upon in writing, holding all parties accountable to the law while maintaining quality and integrity. The CFDA defined “multicenter study” as a study that takes place at three or more sites following the same protocol. They also created a “principal investigator” position to oversee multicenter studies and work with the ethics committee to review and confirm previous protocol agreements.

China Pharmaceutical Clinical Trials

In order to approve more clinical trial proposals in a timely manner, the CFDA has gradually updated the pharmaceutical clinical trial regulations in China. In August 2015, the CFDA proposed a new “four-color light strategy” to help prioritize which clinical trials to review first. In this system, proposals would be classified into one of four categories, and then categorized into “channels” according to level of importance. Pharmaceuticals attempting to cure serious diseases, such as AIDS and cancer, are normally fast tracked to get clinical trial approval.

On November 11, 2015, the CFDA published a review detailing four new initiatives. A new Marketing Authorization Holder (MAH) system was introduced in ten provinces, allowing Chinese manufacturers, R&D institutions, and research personnel to receive approval for their pharmaceuticals even if the products were produced by a Contract Manufacturing Organization (CMO). MAH applicants must ensure that their liabilities are protected by insurance or warranty.

In the review, the CFDA also modified various definitions in the Chinese pharmaceutical field, including “novel drugs” which are now limited to drugs that have never been approved and marketed anywhere in the world.

The CFDA has also increased penalties for falsified data in clinical trials. As of early 2016, there have been withdrawals from over two-thirds of the pharmaceutical clinical trial applicants in China, a rate that is still increasing. Companies are losing confidence in continuing their clinical trials in China due to the widespread presence of fraudulent data. Now, if the CFDA detects falsified data, applicants will not receive approval and will be denied acceptance for at least one year. If the trial has already been approved, applicants will face a fine of $1,500 to $4,500 and their clinical trial submissions will be rejected for the next three years. Furthermore, the person directly responsible for any error will not be authorized to conduct trials for the next ten years. All records false submissions will be publicized.

Recent Changes to Clinical Trial Procedures in India

India Pharmaceutical Clinical Trials

In the past, India conducted a similar number of clinical trials as other developed markets. However, this trend faced major setbacks in 2015, reducing the number of clinical trials in India by 90% in the last few years. Companies began to conduct their studies in other countries due to the “unpredictable and uncertain regulatory environment” in India. Data integrity has been a major issue in India, with at least 16 individual Indian manufacturers identified that submitted inaccurate data. In one case, the principal investigator of a clinical trial fabricated data and transferred patients to his own private clinic. As a result, the U.S. FDA is mandating that some Indian studies be redone.

In recent years, India announced new reform policies for the clinical trial process. First, in order to accommodate various religious and cultural practices, patients are no longer required to offer their informed consent through video and audio recordings. India also clarified policies regarding patient compensation during clinical trials.

New ethics committee requirements have also been established, such as having to register with the Indian Licensing Authority before starting a clinical trial. Ethics committees should also be comprised of diverse individuals in the medical profession, who do not have a conflict of interest with the sponsoring company that will conduct the clinical trial. After the committee is formed, it must submit a detailed application that the Licensing Authority will accept or reject.

In January 2015, India drafted new regulations regarding making requests for different types of bioequivalence studies. The new types of studies include drugs approved in India (within the last year, one to four years ago, or more than four years ago), new drugs approved abroad, and modified drugs.

In June 2016, India proposed revisions to the Drug and Cosmetics Act of 1940 in order to improve the quality and expedite the process of drug clinical trials. India asked U.S. and European regulators for their opinions, which will hopefully be drafted by the end of the summer in 2016.

Recent Change to Clinical Trial Procedures in Korea

Korea Medical Device Clinical Trials

In January 2016, Korea’s Ministry of Food and Drug Safety (MFDS) stated that some Class IV medical devices will need local clinical trials for approval in Korea, including spinal internal fixation systems and implantable defibrillators. In addition, since 2014, the MFDS is able to review protocols in English for Phase I clinical trials.

The Clinical Trial Authorization (CTA) process was established in South Korea in the early 2000’s. Later, the Korean Ministry of Health and Welfare (MOHW) started the Regional Clinical Trial Centers program to build up the Korean clinical trial industry. Each major Korean medical center was awarded with $5 million to facilitate local clinical trials. As Korea developed its clinical trial and regulatory affairs infrastructure over the past few years, more and more local drug clinical trials have been approved.

Another initiative, the KoNECT Clinical Trial Training Academy, was created to provide workers in clinical trial operations with free training. The KoNECT Program increased the numbers of both domestic clinical trials and global sponsors in Korea. Originally tasked to end in 2014, the KoNECT Program was extended due to its success, resulting in the Korea Clinical Trials Global Initiative (KCGI) and a KoNECT Collaboration Center for global clinical trials which were launched in 2014.