The China Food and Drug Administration (“CFDA”) and National Health and Family Planning Commission of China (“NHFPC”) have jointly released a revised and substantially expanded set of Good Clinical Practices for Medical Device Clinical Trials (“New Device GCP”), which will go into effect on June 1, 2016. The New Device GCP are an important piece of the overarching reform of the device regulatory system that took place in mid-2014 with the revision of the framework regulation, the Medical Device Supervision and Administration Regulations (“MDSAR”) (see our alert here). The New Device GCP do not apply to studies for in vitro diagnostics that are regulated as medical devices.
Issued in March 2016, the New Device GCP replace an outdated regulation promulgated in 2004 on medical device clinical trials (“2004 regulation”). Therefore, there is a great deal of new content for stakeholders to absorb and consider before the June effective date. Some of the key features of the New Device GCP are as follows:
- Definition of Sponsor: Sponsor is defined as an institution or organization that is responsible for the initiation, management and financial support for a trial. The sponsor formulates the investigator’s brochure, the protocol, the informed consent form (“ICF”) and the case report form. The sponsor is also responsible for amending these items and seeking ethics committee review and approval of those amendments when significant new information emerges. The New Device GCP indicate that the sponsor is “typically” the manufacturer of the medical device, although it is not clear when another institution would be permitted to be the sponsor. In the case of the an offshore institution, the sponsor must designate an agent in China for the trial. Under the MDSAR, foreign applicants are generally required to have an agent in China for purposes of their application to obtain marketing approval for the device. It is likely, although not entirely clear, that the New Device GCP are referring to the same agent.
- Pre-clinical Work and Other Prerequisites: A sponsor must complete certain pre-clinical work, including the design of the product (e., structural composition, its operational principles, intended uses, indications, and technical requirements), quality testing, animal testing, and a risk analysis. CFDA has separate guidance on these prerequisites. Similar to the 2004 regulation, the sponsor must submit the investigational medical device for “registration testing” before the trial. All Class II and III devices are tested at laboratories accredited by the CFDA. Among other requirements, the New Device GCP now also require a notification of the trial to the provincial-level food and drug regulatory authority where the trial is taking place.
- Investigational Devices: Although the MDSAR and other regulations do not contain substantial guidance on the handling of devices used in clinical trials, the New Device GCP fill some of that gap. This includes the requirement that a sponsor provide a fully tested investigational device produced under its quality system and clearly labeled an “investigational device.” The investigator and trial site must only use investigational devices on trial subjects and must not give the devices to those outside of the trial. After the trial, the investigational devices must be disposed of in accordance with the regulations and the agreement between the investigator and the sponsor.
- Human Subject Protection: Like the 2004 regulation, the New Device GCP also include protections for human subjects. The trial must respect the principles set forth in the World Medical Association Declaration of Helsinki, although no particular version is specified. The primary means of protecting the rights of subjects are (1) ethics committee review of the protocol and ICF and (2) valid informed consent from each subject. The New Device GCP set forth specific mandatory items for inclusion in the ICF and require the use of plain and easily understandable language. In addition, the New Device GCP include special requirements for incapacitated individuals, minors, and subjects or guardians that are unable to read.
- Agreements between Sponsors and Trial Sites: The New Device GCP include a list of items that the sponsor, investigator and trial site agree upon in writing. These items include, among others, compliance with law and the protocol, trial monitoring, data recording and reporting procedures, record maintenance and quality control procedures, such as the proper handling and storage of the investigational device.
- Multicenter Clinical Trials: Although the New Device GCP recognize the concept of multicenter clinical trials, they do not make it clear whether the concept includes international multi-center trials. Under normal circumstances, a device trial must take place at two or more sites. A multicenter trial is defined as a trial with three or more sites under a single protocol. The New Device GCP streamline procedures for multicenter trials by creating the position of a principal investigator that coordinates work between the sites before and during the trial and a head institutional ethics committee to ensure that uniform agreement is achieved on the protocol. Once this head ethics committee has approved the protocol, the other participating institutions will review it. If the other participating institutions disagree, they may refuse to permit the trial, but the New Device GCP do not encourage them to submit additional revisions.
Chinese and foreign companies conducting clinical trials in China should pay close attention to the New Device GCPs and any additional guidance that emerges prior to the effective date. The CFDA has been continuously focusing on GCP compliance, including quality control and data integrity. Stakeholders should continue to monitor for indications from CFDA on how the GCPs will affect ongoing and new trials.