China Clinical Trials and CRO Services for Medical Device and Pharmaceutical Products

To determine whether local clinical trials are needed for medical device registration in China, companies must first determine the classification of their device. Class I medical devices do not require local clinical trials. Class II and Class III medical devices do require clinical trials unless they have exact predicates and/or are in the NMPA’s clinical trial exemption list.

Before a medical device clinical trial can begin, your device must pass the local type testing. Medical device and IVD clinical trials in China must comply with China’s Good Clinical Practice (GCP) requirements and should be conducted in at least three sites. Companies must follow Clinical Trials Protocol, which includes a proposal outlining the purpose and procedure of the clinical trial as well as approval from a Chinese ethics committee. Companies must also provide detailed contracts with medical institutions undertaking the clinical trials and ensure that informed consent is obtained from all participants in the clinical trial.

For China IVD clinical trials, no clinical trial approval or application is required – only ethics committee approval. For class 2 devices, no clinical trial approval or application is required – only ethics committee approval. But for more risky class 3 devices, a clinical trial application is required.

In 2016, the NMPA and the NHFPC issued new GCP requirements which were significantly longer and more detailed than the 2014 GCP regulations. There were more responsibilities placed with the ethics committee, including there must be at least five members on the committee, the committee must have both genders, include medical and non-medical members, etc. There is also a full chapter outlining pre-trial preparations including a list of 10 specific documents that must be provided before the trial begins. Informed consent regulations were also dramatically increased.

In 2016, the CFDA (now NMPA) and the NHFPC issued the Good Clinical Practice for Medical device guideline (Decree #25). This guideline includes 96 articles in 11 chapters. Topics covered include – 1. the definition of sponsor, 2. pre-clinical work before a trial can start, 3. the fact the samples used must be considered “investigational devices”, 4. Protection for subjects, and 5. sponsor and trial sites must have agreements.

In some cases, the NMPA will accept foreign medical device clinical studies for product approval as a substitute for a full local China clinical trial or as a supplement to a smaller China clinical study. However, to be accepted by the NMPA, foreign clinical documents, at a minimum, must include the overseas trial protocol, ethical considerations and the foreign clinical trial report which has all the clinical trial data.

In 2018, the NMPA issued a number of new draft rules regarding the inspection of device clinical studies. The objective of these inspections is to determine whether your trials meet Chinese GCP standards. The NMPA will check your device clinical study to determine if there are any inconsistent records, fake clinical trial subject records, re-use of clinical trial samples that do not match protocols, etc.

As is the case in many countries around the world, a local clinical trial is almost always required for the registration of drugs in China – unless the drug is unique and meets an urgent need. Since drug registration in China follows the global International Conference on Harmonisation (ICH) guidelines, data requirements in China are similar to those in the United States and other developed countries. Now, more overseas clinical trial data can be utilized for drug approval in China, but some local clinical trials are generally still required.

In some cases, as an alternative to local clinical studies, a bioequivalence (BE) study will be required instead. The BE study will test similarities between two drugs believed to have the same active ingredients and use.

Once the applicant has submitted the IND/CTA, if there are no comments from the NMPA after 60 working days, the clinical trial submission is automatically approved, and your clinical trial can begin. For applicants that receive NMPA questions, the clinical trial approval time will take longer.

There are 5 drug categories in China, including – 1. Class 1 drugs, new drugs that have never been approved in the world, 2. Class 2 drugs, new drugs that are improved but have never been approved in the world, 3. Class 3 drugs, generic drugs that are equivalent to the originator’s product and marketed in other countries, but not in China, 4. Class 4 drugs, generic drugs, that are equivalent to the originator’s product that are already in China, and 5. Class 5 drugs, imported drugs that are sold in some overseas markets, but not in China.

The clinical trial’s sample size must meet statistical requirements by satisfying the minimum number of subjects outlined by the NMPA. If the institution is unable to reach the minimum sample size because of the rarity of a disease, the institution should appeal to the appropriate provincial-level FDA (PFDA) in order to reduce the sample size.

The trial must be carried out by an organization certified to conduct drug clinical trials, using drugs from manufacturing facilities that follow Good Manufacturing Practices (GMP).

Foreign clinical data can be accepted in China as long as this data – 1. complies with GCP, 2. the data can prove the safety and efficiency of the indication for use, 3. ethical factors do not influence the safety and efficiency, and 4. the data meets Chinese requirements. Also, now all qualified hospitals can be clinical sites.

In 2017, China joined the International Council for Harmonization (ICH). In early 2018, the CFDA (now NMPA) said it would move to have ICH E2A. By doing this, China has shown the international community that it wants to be a global participant in the drug area.