New Medical Devices Good Clinical Practice

China

The National Medical Products Administration ("NMPA") promulgated the newly revised Medical Devices Good Clinical Practice ("New GCP Standard") on 31 March 2022. This New GCP Standard will enter into force on 1 May 2022 and will replace the Previous Version of the Medical Devices Good Clinical Practice dated 1 March 2016 and effective as of 1 June 2016 ("Previous Version of the GCP Standard"). 

The New GCP Standard is revised in order to adapt the newly revised Regulations on Supervision and Administration of Medical Devices ("Regulations", effective as of 1 June 2021), Medical Devices Registration and Filing Administrative Measures (effective as of 1 October 2021) and the In Vitro Diagnostic Reagent Registration and Filing Administrative Measures (effective as of 1 October 2021).

Together with the promulgation of this New GCP Standard, the NMPA also promulgated the Circular regarding the Implementation of the Medical Devices Good Clinical Practice Standard (2022 No.21) ("Circular"). According to the said Circular, as from 1 May 2022, all medical devices clinical trial projects which have not yet passed the ethical examination must be handled according to the New GCP Standard. As to those projects which have already passed the ethical examination, the clinical trials can continue to be handled according to the Previous Version of the GCP Standard.

The Circular also published six accessory documents related to clinical trials:

  • Medical devices clinical trial plan template;

  • Medical devices clinical trial report template;

  • In vitro diagnostic reagent clinical trial plan template;

  • In vitro diagnostic reagent clinical trial report template;

  • Adverse event reporting form for medical devices/in vitro diagnostic reagent clinical trial; and

  • Basic documentation list for medical devices/in vitro diagnostic reagent clinical trial.

The New GCP Standard has made the following fundamental changes in order to adapt the new regime of medical devices registration and filing under the Regulations.

1. Change of the overall structure of the GCP standards

The New GCP Standard has modified the structure of the GCP standard compared with the Previous Version of the GCP Standard.

Compared with the Previous Version of the GCP Standard, the New GCP Standard focuses more on the responsibilities of each party in clinical trials in order to make sure of the quality of clinical trials. This change is mainly due to the introduction of MAH ("market authorization holder") system into the registration of medical devices in China under which a company other than a manufacturing entity can also become a holder of medical devices registration in China.

a) Enhancement of the responsibilities of the applicant

(1) Responsibility of truthfulness and legal compliance

Article 36 of the New GCP Standard provides that the applicant shall be responsible for the truthfulness and legal compliance of medical devices clinical trials. If the applicant is a foreign company, it shall entrust a Chinese legal person as its agent and such agent shall take the above responsibility.

Compared with the Previous Version of the GCP Standard under which the applicant shall only be responsible for the truthfulness and reliability of clinical trials, the New GCP Standard requires that the applicant shall also be responsible for legal compliance of clinical trials. This largely increases the liabilities of the applicant in medical devices clinical trials.

(2) Responsibility of quality management system

Article 7 of the New GCP Standard provides that the applicant shall establish a quality management system covering the whole process of medical devices clinical trial, in order to make sure that the clinical trial complies with the relevant laws and regulations and to protect the interests and safety of the patients.

Article 37 of the New GCP Standard further provides that the quality management system of the applicant shall cover the whole process of clinical trials, including selection of medical devices clinical trial institutions and main researcher, clinical trial plans design, clinical trials implementations, record, report and filing.  Therefore, the applicant shall be responsible for the legal compliance of the whole process of clinical trials.

(3) Responsibility of conclusion of agreement

Article 39 of the New GCP Standard provides that the applicant shall conclude service contracts with medical devices clinical trial institutions and main researcher to specify the rights and obligations of each party in the medical devices clinical trials.   The New GCP Standard does not provide more detailed provisions that must be stipulated in those contracts.

We noticed that Article 44 of the Previous Version of the GCP Standard provides however detailed provisions which must be agreed in such contract, including:

  • Agreement to carry out clinical trial according to the relevant laws and regulations and the clinical trial implementation plan, and accept monitoring, audit and inspection;
  • Comply with the data record and reporting procedure;
  • Keep the basic documentation of clinical trial for the minimum mandatory period of time for documentation keeping until the time when the applicant notifies the institutions and researchers that such documentation is no longer required;
  • The applicant shall be responsible for providing medical devices for clinical trial purpose to medical devices clinical trial institutions and researchers and shall agree on the terms of transportation, conditions and time of storage, validity period, etc.;
  • Medical devices for clinical trial purpose shall conform to its quality requirements, and can be easily identified and accurately labeled and shall be affixed with the special label "for clinical trial purpose"[1], and shall be properly packaged and stored according to the clinical trial implementation plan;
  • The applicant shall formulate the quality control standard operation procedure for clinical trial, such as transportation, reception, storage, distribution, disposal, return of medical devices for clinical trial purpose, so that medical devices clinical trial institutions and researchers can follow the above procedures.

Although the deletion of the above detailed provisions in the New GCP Standard seems to mitigate the responsibilities of the applicant at time of conclusion of medical devices clinical trial agreements, such deletion implies that more liabilities are imposed on the applicant. This is because the underlying principle set forth in the New GCP Standard requires the applicant to be responsible for the whole process of the medical devices clinical trials. This means, regardless of the absence of legal provisions, the applicant shall be held liable. We advise that more detailed provisions shall be set forth in such an agreement in order to limit or mitigate the liabilities of the applicant.

(4) Responsibility of filing for clinical trial

Article 40 of the New GCP Standard provides that after conclusion of the service agreement with the clinical trial institution and the approval of the clinical trial project by the Ethics Committee, the applicant shall apply for clinical trial recordal with drug administrative authorities at provincial level at the place of the applicant.

This change is to implement Article 26 of the Regulations.

Although Article 40 of the New GCP Standard does not stipulate the obligation for obtaining clinical trial approval for Class III medical devices from drug administrative authorities, such approval should be required. This is because Article 6 of the New GCP Standard already provides that the said approval from drug administrative authorities is required if the medical devices fall into the Catalogue of Class III Medical Devices for which Clinical Trial Approval is Required, and such clinical trial can only be carried out at the Level III Grade A medical institutions.

(5) Responsibility of training

Article 41 of the New GCP Standard provides that before starting the clinical trial, the applicant shall be responsible for organizing training in connection with medical devices clinical trials, such as theory, application scope, performance characteristics, operation method, installation requirements, technical indicators, implementation plan, standard operation procedure and other relevant documents.

Article 39 of the Previous Version of the GCP Standard only provides very general requirements that the applicant shall organize necessary training. The New GCP Standard provides thus more detailed rules and timing for organizing such training.

b) Enhancement of the responsibilities of researchers

Compared with the Previous Version of the GCP Standard, Article 24 of the New GCP Standard further provides that the main researcher must be first recorded for medical devices clinical trial.

Article 25 of the New GCP Standard further provides that the main researcher must comply with the GCP standard as well as other laws and regulations regarding the implementation of medical devices clinical trials.

Article 27 of the New GCP Standard removes the specific qualification requirement of deputy director, deputy professor or deputy researcher or above but provides for more extensive experience requirements for researchers. It requires that:

(1) the researchers who participate in medical devices clinical trials must have relevant professional qualification, training experience and other related experiences in handling medical devices clinical trials.

(2) they shall participate in medical devices clinical trials within the scope of authorization of the main researcher, and participate in relevant training of medical devices clinical trials organized by the applicant. 

(3) they shall be familiar with theory, scope of application or expected use, performance characteristics, operation method, installation requirement and technical indicators of medical devices for clinical trial purpose, and understand the pre-clinical trial relevant materials related to the clinical trials.

(4) they shall fully understand and comply with the clinical trial plan, the New GCP Standard and relevant laws and regulations and shall bear the relevant liabilities related to medical devices clinical trial.

(5) they shall grasp knowledge of potential precautionary and emergency measures to be taken in case risks related to clinical trials arise.

2. Simplification of the number of medical devices clinical trials institutions

The New GCP Standard no longer requires that clinical trials must be carried out by at least two separate medical devices clinical trials institutions as set forth in Article 9 of the Previous Version of the GCP Standard.

Article 5 of the New GCP Standard only requires that clinical trials must be carried out at a medical devices clinical trials institution that has undergone recordal formalities and is equipped with corresponding conditions for clinical trials. Besides, the New GCP Standard no longer requires that the validity period of the product inspection report for medical device for clinical trial use shall be not no more than one year. The above amendments simplify the cost and time for clinical trials.

3. Serious adverse event reporting procedure

a) Reporting obligations of researchers

According to Article 32 of the New GCP Standard, all researchers are required to report serious adverse event of medical devices clinical trials to the applicant, drug administrative authorities in charge of clinical trial institutions and the Ethics Committee while Article 71 of the Previous Version of the GCP Standard only required to report to drug administrative authorities in charge of medical devices clinical trials which shall then inform the same to the applicant, the Ethics Committee and the provincial level drug administrative authorities in charge of each clinical trial institution.  

b) Reporting obligations of the applicant

Article 44 of the New GCP Standard requires that, apart from the reporting to the medical device clinical trial institution participating in this clinical trial, Ethics Committee and main researcher, the applicant shall report serious adverse event of clinical trials to the provincial-level drug administrative authorities which has handled the recordal of the clinical trials and to the health authorities at the same level, and shall also report to the provincial-level drug administrative authorities where the applicant is registered. Such report must be made within 7 days after the applicant has knowledge of the death or other serious adverse event which jeopardizes the life of patients. If the applicant has knowledge of other serious adverse event which does not cause death or does not jeopardize the life of patients, or if the applicant has knowledge of other serious safety related risk information, it shall report such matter to drug administrative authorities and health administrative authorities within 15 days.

Besides, for large scale serious adverse event or other important serious adverse event, the applicant must cease the clinical trials and report the same to drug administrative authorities and health administrative authorities and to all related authorities in charge of administration of medical devices clinical trial institutions, to the Ethics Committee and the main researcher.

4. Extension of scope of application to in vitro diagnostic reagents

The New GCP Standard extends its application to in vitro diagnostic reagents. Therefore, clinical trials in connection with in vitro diagnostic reagents shall also comply with the New GCP Standard.

Medical devices companies which apply for clinical trials or plans to apply for clinical trials shall pay attention to the New GCP Standard, and further check whether they need to further amend the service contracts and procedures in connection with clinical trials.



[1]According to Article 42 of the New GCP Standard, medical devices for clinical trial shall be marked “for medical device clinical trials only”.