How is the manufacturing, marketing, distribution, and sale of medical devices regulated in the People’s Republic of China? This article outlines the regulatory framework and pathways, the classification of devices, and post-market compliance matters, as well as the specific provisions governing customized medical devices.
Activities related to medical devices in the People’s Republic of China (PRC), including their manufacturing, marketing, distribution, and sale, are mainly regulated by the Regulations on Supervision and Administration of Medical Devices (the Regulations) promulgated by the State Council and most recently amended in May 2017. The National Medical Products Administration (NMPA) is the governmental authority principally responsible for the supervision and administration of medical devices in the PRC.
Medical devices in the PRC (including manufacturing, marketing, and sale) are subject to a mandatory filing/registration regime regulated by the NMPA. The exact filing pathways are mainly determined by the classification of such devices – similar to the United States, a three-class classification system, from Class I (lowest risk) to Class III (highest risk). Local testing and clinical trials are generally required for Class II and Class III devices. Some imported devices may need to be registered with a higher level government authority than domestic devices.
In addition, the recently implemented Provisions on the Supervision and Administration of Customized Medical Devices (Trial)—or the CMD Provisions—further provide for a regulatory pathway for customized medical devices (CMDs) designed and produced based on special clinical demands of medical institutions for designated patients.
Part II through Part IV of this article discuss the general classification and regulatory pathways for general medical devices under the Regulations, while Part V provides a brief overview of the specific regime recently implemented for CMDs.
Classification of Medical Devices
Similar to the United States, medical devices in the PRC are classified into three classes, based on the risks associated with them. Among them, Class I medical devices are those with the lowest risks whereas Class III are those with the highest risks. The level of control and administration increases from Class I to Class III medical devices.
To determine the classification of a medical device, an applicant needs to refer to the then-effective regulatory documents/guidance, in particular the Medical Device Classification Catalogue, the classification notices by the NMPA, and the Rules for Medical Device Classification. The Medical Device Classification Catalogue contains a specific description of each type of medical device (from specific cardiovascular instruments to different types of medical software) and its classification. For any device that is not specifically covered by the Medical Device Classification Catalogue or other relevant regulatory documents/guidance, the applicant may apply for registration under Class III, or submit an application to seek classification determination opinion from the NMPA.
Record-Filing or Registration Requirements
Before being manufactured, marketed, or sold in the PRC, a medical device must either be record-filed or approved, depending on the classification.
The Regulations make a distinction between a “domestic device” and an “imported device,” depending on whether it is manufactured outside of mainland China. For domestic devices, Class I devices generally only require record-filing with the branch of NMPA at the city level where the applicant is located, where the officials will determine whether to accept such filing based on completeness of the documents submitted. Class II and Class III domestic devices both require registration application, but Class II application will be reviewed and approved by the branch of NMPA at the provincial level where the applicant is located, whereas Class III application will be reviewed and approved by central NMPA. For imported devices, the record-filing requirement for Class I devices, and registration/approval requirement for Class II and Class III devices, are still applicable, but all such filings/applications shall be made to the central (but not local or provincial) NMPA.
In order to obtain Record Filing Certificate for Class I medical devices, or Registration Certificate for Class II or Class III medical devices, applicants need to go through a number of steps. The steps required for imported devices by and large include those required for local devices, plus a number of additional requirements (such as appointment of a local regulatory agent, and approval of such device in its country of origin). Also, as aforementioned, central NMPA (but not its local or provincial branches) will generally handle filings/applications of imported devices.
A brief summary of certain key steps for medical device registration in the PRC are highlighted below.
Key Steps – Product Technical Requirements and In-Country Testing
For all three classes, applicants are generally required to submit a product technical requirements (PTRs) document, which shall mainly include the performance indicators and testing methods of the finished medical device. The PTRs used should be no lower than the applicable compulsory national standards and industry standards. The medical devices to be marketed in the PRC must comply with the PTRs, which are approved at the time of record-filing or registration.
To demonstrate such compliance, Class II and III device applicants are generally required to submit in-country testing results for the registration application. Samples shall usually be sent to an NMPA-authorized test center in the PRC for testing according to the applicable PTRs. For Class I application, self-testing report generally suffices.
Key Steps – Clinical Trial and Clinical Trial Approval
For the filing of Class I medical devices, clinical trial is not typically required. For the registration of Class II and Class III medical devices, generally speaking, clinical trials shall be conducted. But such requirement can be exempted in certain circumstances, such as if the device under application is proven to be “equivalent” to a device listed on the List of Medical Devices Exempted from Clinical Trials. Besides, where a device under application is “substantially equivalent” to a medical device that has been approved for registration by the NMPA, the applicant may utilize the data from the clinical application experience or clinical trial of the “substantially equivalent” medical device instead of collecting data from clinical trial for the device under application.
Potential importers of medical devices to the PRC may be interested to know that data from foreign clinical trials may be accepted by the NMPA, subject to certain requirements, such as that the foreign trial must comply with specific ethics rules and good clinical practices, and the data must be authentic, scientific, and reliable.
Furthermore, the conducting of clinical trial on specific high-risk devices is restricted. For instance, if a device is listed on the List of Class III Devices subject to Clinical Trial Approvals, the applicant must seek approval from the NMPA before conducting such clinical trial.
Since April 1, 2019, the approval process for conducting clinical trial has been immensely expedited. The applicant can start conducting clinical trial, if he/she has not received any opinion from the Center for Medical Device Evaluation within 60 working days from the date of acceptance and payment of such clinical trial approval application (on the premise that the contact information and mailing address are valid).
Innovative Device Pathway
To encourage innovation, the PRC government has established a fast-track approval pathway for “innovative medical devices.”
To qualify for such fast track, the medical device must belong to either Class II or Class III, and satisfy three main criteria, which in short are: (i) domestic invention patent of core technologies granted within five years (or the “novelty and creativeness” of core technologies can otherwise be supported by specific means); (ii) having prototype products after completion of early-stage research and having complete and traceable research data; and (iii) novelty of such product in the PRC, its “leading-position” worldwide, and its “significant clinical practical value.”
The major benefits of such fast track include having priority in various application stages and easier communication and consultation with governmental authorities. For instance, the Center for Medical Device Evaluation (which is responsible for determining whether such device under application qualifies as an “innovative medical device”) will generally assign a specific liaison officer to assist with various application steps for a device preliminarily identified as an “innovative medical device.”
What’s Next – Post-Market Compliance
After successful record-filing or registration, attention should also be paid to post-market compliance matters. These include: (i) extension of registration certificate (which generally is only valid for five years); (ii) device labelling, as may be required under the Administrative Provisions on the Administration of Instructions and Labels of Medical Devices; and (iii) reporting and investigating adverse events in case of device malfunction, as regulated by, among others, the Administrative Measures for Medical Device-Related Adverse Event Monitoring and Re-evaluation.
Specific Regime for CMDs
The recently implemented CMD Provisions provide for a specific regulatory pathway for CMDs. For the purposes of such regulatory regime, the term “CMDs,” in short, refers to personalized medical devices that are designed and produced based on special clinical demands of medical institutions for designated patients (while the other products available in the PRC market are difficult to meet such special demands).
CMDs generally require record-filing with the branch of NMPA at the provincial level where the relevant medical device manufacturer is located (or for imported devices, where the agent of such devices is located). For each CMD record-filing, the medical device manufacturer that manufactures the CMD and the medical institution that uses the CMD shall be the joint applicants. Each of the joint applicants has to fulfil certain conditions specified under the CMD Provisions, including those relating to personnel, qualification, and relevant experience in manufacturing/using medical devices. Applicants must also comply with specific requirements on design and development, quality control, and traceability management.
The CMD Provisions also provide for a supervision regime relating to the ongoing design, manufacturing, and use of CMDs. For instance, the manufacturing of CMDs cannot be outsourced, and CMDs should only be used by the specific medical institutions that submitted the filings on the designated patient(s).