When a medical device trial in China needs approval and when a filing

Most medical device trials in China proceed on a filing. The sponsor files the trial with the drug regulator of the province where the sponsor is located, after ethics review has passed and the contract with the trial institution is signed.¹² Approval from the national regulator is required only for a class III device whose trial poses a relatively high risk to the human body, and the devices concerned are named in a catalogue.¹

A reader who knows the investigational device exemption at FDA expects a risk determination made for each study. The Chinese trigger is the catalogue. A reader who knows the EU rules expects the ethics committee and the competent authority to be the only gates, and will find an administrative filing between ethics approval and the first consent.

Whether a trial is needed

Article 24 of the Regulations on the Supervision and Administration of Medical Devices requires a clinical evaluation for registration or filing of a device, with two exceptions.¹ The first covers a device with a clear mechanism, a settled design and a mature production process, where devices of the same kind have been in clinical use for years with no record of serious adverse events and the usual use is unchanged. The second covers a device that non-clinical evaluation can show to be safe and effective.¹

Article 25 allows a clinical evaluation to rest on a trial, or on analysis of the clinical literature and clinical data for devices of the same kind.¹ A trial is required where the existing literature and data are insufficient to confirm that the product is safe and effective.¹

The filing route

Article 26 of the Regulations requires a device trial to follow good clinical practice, to be run at a trial institution with the required conditions, and to be filed with the provincial drug regulator where the sponsor is located.¹ The regulator that receives the filing informs the drug regulator and the health authority at the same level in the place where the trial institution is located.¹

Article 40 of the good clinical practice for device trials fixes the order of the steps. The sponsor files after the trial has passed ethics review and after the contract with the institution is signed. The institution may begin informed consent and screening of the first subject only when the filing is complete.²

The good clinical practice took effect on 1 May 2022 and applies to trials run in China in support of a registration application. It covers in vitro diagnostic reagents as well as other devices.²

The approval route

Article 27 of the Regulations requires the approval of the drug regulator of the State Council for a trial of a class III device that poses a relatively high risk to the human body.¹ The regulator weighs the equipment and staff of the institution, the degree of risk of the device, the trial protocol and the analysis of clinical benefit against risk. It decides within 60 working days of accepting the application and notifies the sponsor, and the application is treated as approved where no notice is given in time.¹

The Measures for the Registration and Filing of Medical Devices set the procedure.³

• The catalogue of class III devices that need trial approval is set, adjusted and published by the National Medical Products Administration.
• A trial that needs approval is run at a qualifying tertiary grade A medical institution.
• The Center for Medical Device Evaluation reviews the application and decides within 60 days of acceptance.
• The technical review period after the applicant has supplemented its materials is 40 days.
• Periods in the Measures are counted in working days.

The catalogue in force was issued by Announcement No. 61 of 2020 of the National Medical Products Administration, dated 14 September 2020. The announcement repealed the catalogue of 2014.⁴

Article 41 of the Measures governs a request for further material. The Center states everything it needs in a single notice. The applicant has one year from the notice to supply the material in a single submission. Where the applicant misses that date, the technical review ends and the application is refused.³

Ethics review and consent

Article 28 of the Regulations requires ethics review for every device trial. The subject must be told the purpose and use of the trial and the risks it may carry, and must give informed consent in writing.¹ Where the subject lacks full capacity for civil conduct, the guardian gives the written consent.¹ No fee connected with the trial may be charged to a subject in any form.¹

Article 16 of the good clinical practice requires fresh written consent from the ethics committee before a protocol or an informed consent form is revised, and before a suspended trial resumes.²

Safety reporting during the trial

The investigator reports a serious adverse event within 24 hours of learning of it. The report goes to the sponsor, to the management department of the trial institution and to the ethics committee.²

The sponsor reports a serious adverse event related to the investigational device within 7 days of learning of it where the event is a death or is life-threatening. For other related serious adverse events and other serious safety risk information the period is 15 days.² The sponsor’s report goes to the other trial institutions, ethics committees and principal investigators in the trial, and to the provincial drug regulators and health authorities concerned.²

Where related serious adverse events occur on a wide scale, or another major safety problem arises, the sponsor must suspend or end the trial and report to the provincial regulators.³

Termination and lapse

Article 44 of the Measures allows the National Medical Products Administration to order an approved trial to end where the application materials were false, or where recent research shows a problem with the ethics or the science of the trial as approved.³

Article 45 requires an approved trial to be carried out within 3 years. Where no subject has signed an informed consent form within 3 years of approval, the permission lapses of itself and a new application is needed.³

Use outside the trial

Article 29 of the Regulations covers a device under trial for a disease that is seriously life-threatening and has no effective treatment. Where medical observation suggests a benefit, the device may be used free of charge for other patients with the same condition at the institution running the trial, after ethics review and informed consent. The safety data from that use may support the registration application.¹

Trial institutions

Device trial institutions are managed by filing.¹ Article 103 of the Measures requires the provincial regulator to inspect a newly filed institution within 60 days of its filing, and to supervise compliance with good clinical practice as a matter of routine.³

Penalties

Article 93 of the Regulations sets the penalties for the sponsor and for the institution.¹

Violation by the sponsor	Fine	Fine where the consequences are serious	Further consequence
Running a trial without filing it	RMB 50,000 to 100,000	RMB 100,000 to 300,000	The data may not be used for registration or filing, and no registration application is accepted for 5 years
Running a high-risk class III trial without approval	RMB 100,000 to 300,000	RMB 300,000 to 1 million	The data may not be used for registration, and no trial or registration application is accepted for 10 years

An institution that runs a trial without having filed as a trial institution is ordered to stop and correct. Where it refuses, the data may not be used for registration or filing and the fine is RMB 50,000 to RMB 100,000.¹

Questions people also ask

Does every medical device trial in China need approval?

Approval is required for a trial of a class III device that poses a relatively high risk to the human body and is named in the catalogue.¹ Other device trials are filed with the provincial drug regulator where the sponsor is located.¹

When can the first subject be enrolled in a device trial?

The trial institution may begin informed consent and screening of the first subject once the trial filing is complete.² The filing follows ethics approval and the signing of the contract with the institution.²

How long does approval of a high-risk device trial take?

The regulator decides within 60 working days of accepting the application, and the application is treated as approved where no notice is given in time.¹ The technical review period after a supplement is 40 working days.³

Do the device trial rules apply to in vitro diagnostics?

The good clinical practice for device trials states that it covers in vitro diagnostic reagents.²

What happens if a device trial is run without a filing?

The sponsor is ordered to stop and is fined RMB 50,000 to RMB 100,000, or RMB 100,000 to RMB 300,000 where the consequences are serious.¹ The data may not be used for registration or filing, and no registration application is accepted for 5 years.¹

Footnotes

1. Regulations on the Supervision and Administration of Medical Devices (State Council Order No. 739), Articles 24 to 29 and 93. https://www.gov.cn/zhengce/content/2021-03/18/content_5593739.htm ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹² ↩¹³ ↩¹⁴ ↩¹⁵ ↩¹⁶ ↩¹⁷ ↩¹⁸ ↩¹⁹ ↩²⁰ ↩²¹ ↩²²

2. Good Clinical Practice for Medical Device Clinical Trials, in force from 1 May 2022, Articles 2, 16, 32, 40 and 44. https://yjj.scjgj.fujian.gov.cn/ylqx/flfg/202204/t20220406_5875596.htm ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰

3. Measures for the Registration and Filing of Medical Devices (State Administration for Market Regulation Order No. 47), Articles 37 to 46, 92, 99 and 103. https://www.samr.gov.cn/zw/zfxxgk/fdzdgknr/fgs/art/2023/art_568880e3ee344c45b38d073bba1c53ad.html ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷

4. National Medical Products Administration, Announcement on the Catalogue of Class III Medical Devices Requiring Clinical Trial Approval (Revised 2020), No. 61 of 2020. ↩