China Expands Medical Devices Market Authorization Holder Pilot Project to 21 Provinces/Municipalities
On 1 August 2019, the National Medical Products Administration ("NMPA") issued a notice to extend the pilot project of medical device registrant system (GUO YAO JIAN XIE ZHU (2019) No.33) ("Notice") to 21 provinces/municipalities in China and is one step further towards the implementation of a nationwide Medical Devices Market Authorization Holder ("MAH") System.
Under the current Regulations on the Supervision and Administration of Medical Devices (2017 Revision) (“Regulations”), a manufacturer licence will only be granted if the applicant has already obtained marketing approval for the medical device. In October 2017, the State Council issued the Opinions on Deepening the Reform of Review and Approval System to Encourage the Innovation of Drugs and Medical Devices ("State Council Opinions"), which extended the implementation of the 2015 pilot project for the pharmaceutical MAH system. A similar MAH system was established for medical devices.
In December 2017, the pilot project started in the Shanghai Free Trade Zone, which was then extended to the whole of the Shanghai municipality in July 2018. The Shanghai pilot project permits medical device MAHs within the free trade zone to outsource manufacturing to one or multiple medical device manufacturers in Shanghai, separating the medical devices manufacture from the product registration. The pilot project enables medical device scientific research institutions and researchers to become MAHs. In February 2018, the first market authorization approval, under the Shanghai pilot project was granted to Shanghai Yuanxin Medtech for its portable ECG recorder. According to news reports, Yuanxin Medtech outsourced the manufacture of the ECG recorders to an affiliate manufacturer under common control of the corporate group Shanghai MicroPort. This arrangement saved Yuanxin Medtech RMB 1 million (which would have been needed for the capital investment for the manufacture of the ECG recorders) and the time to market for the ECG recorders was reduced by one year [1].
On 14 August 2018, the NMPA extended the pilot project to Tianjin and Guangdong [2]. In February 2019, Beijing was approved to engage in the pilot project, enabling a MAH in Beijing to commission manufacturers in other provinces such as to manufacturers in Tianjin and Hebei [3].
The Notice further expands the pilot project to 21 provinces/municipalities including Jiangsu, Zhejiang, Anhui, Fujian, Guangdong, Guangxi, etc. It encourages corporate groups to consolidate and optimize resource allocation amongst R&D institutes and manufacturers through the pilot project. It provides key conditions and obligations for MAHs and commissioned manufacturers involved in the pilot project. For example, the MAHs shall be staffed with full-time technical and management personnel for quality management and regulatory compliance. The MAHs are held responsible for the whole life cycle of medical devices including research and development, clinical trial, production, sale, after-sale service, product recall, adverse reaction report, etc., and shall sign a commission agreement and quality agreement with the commissioned manufacturer, specifying the technical requirements, quality assurance, division of responsibilities and product release requirements. The MAH shall also supervise and regularly assess the commissioned manufacturer for their quality management abilities and strengthen the monitor of adverse event, etc.
The Notice also requires the provincial drug regulatory authorities within the pilot project to timely form implementation plans and management regimes for the pilot project on the basis of sufficient research and evaluation, and report to the NMPA. The local drug regulatory authorities shall supervise MAHs to perform their obligations in quality management and coordinate in cross-provincial administration. In addition, the provincial drug regulatory authorities shall organize legal professionals to form the template commission agreements. Shanghai and Guangdong have already issued the Guidelines on Drafting Commissioned Production Quality Agreement for Medical Device Registrants in draft form during the implementation of pilot project.
On 23 May 2019, China Pharmaceutical News reported [4] that 8 products from 5 companies had been approved in the Shanghai pilot project and 5 products from 1 company had been approved in the Guangdong pilot project. Tianjin has not issued any approval(s) to-date but there are applications under review. As a result of the pilot scheme, different forms of contract manufacturing have evolved such as the commission of manufacture to an affiliated company like Shanghai Yuanxin; commission of manufacture to a non-affiliated company like Medtronic Shanghai where the manufacture of its surgical dynamical system was contracted to Jabil Shanghai; and commission of manufacture by a research institution, such as Shanghai Ninth People’s Hospital (which is affiliated to Shanghai Jiao Tong University) to Shanghai Arigin Medical for the manufacture of its 3D-printed custom knee-joint orthosis [5].
At the legislative level, the medical device MAH system has been added in the 2018 Draft Amendment to the Regulations released by the NMPA in June 2018. We expect to see rapid implementation of the medical device MAH system nationwide and recommend medical devices companies to pay close attention to developments to the MAH pilot project.
NMPA Solicits Public Opinions on Expanding the Medical Device Clinical Trial Exemption List
On 1 August 2019, the Center of Medical Device Evaluation ("CMDE") under the National Medical Products Administration ("NMPA") issued the draft Medical Device Clinical Trial Exemption List (2019 Revision) ("2019 Draft Exemption List") for public comments, exempting 996 medical devices and 420 in vitro diagnostics ("IVDs") from clinical trial. Public opinions can be submitted to CMDE before 30 August 2019.
Compared to the 2018 version of Medical Device Clinical Trial Exemption List ("2018 Exemption List"), the 2019 Draft Exemption List added 142 medical devices including 102 Class II medical devices and 40 Class III medical devices, and 27 IVDs.
The 2019 Draft Exemption List is the 5th round of medical device clinical trial exemption list. The first round of exemption list was issued in 2014, initially covering 488 Class II medical devices and 79 Class III medical devices. The third and fourth rounds of exemption lists were issued in 2016 and 2017, and all three rounds of exemption lists were incorporated into the 2018 Exemption List, covering 855 medical devices and 393 IVDs.
To evaluate whether a medical device can be exempted from clinical trial, the NMPA will take into account the safety and efficacy of the medical device in non-clinical trials, or the clinical data or clinical applications of the medical device of the same variety according to Article 17 of the Regulations on the Supervision and Administration of Medical Devices (2017 Revision). The exemption list applies to both domestic manufactured and import medical devices.
In December 2017, the pilot project started in the Shanghai Free Trade Zone, which was then extended to the whole of the Shanghai municipality in July 2018. The Shanghai pilot project permits medical device MAHs within the free trade zone to outsource manufacturing to one or multiple medical device manufacturers in Shanghai, separating the medical devices manufacture from the product registration. The pilot project enables medical device scientific research institutions and researchers to become MAHs. In February 2018, the first market authorization approval, under the Shanghai pilot project was granted to Shanghai Yuanxin Medtech for its portable ECG recorder. According to news reports, Yuanxin Medtech outsourced the manufacture of the ECG recorders to an affiliate manufacturer under common control of the corporate group Shanghai MicroPort. This arrangement saved Yuanxin Medtech RMB 1 million (which would have been needed for the capital investment for the manufacture of the ECG recorders) and the time to market for the ECG recorders was reduced by one year [1].
On 14 August 2018, the NMPA extended the pilot project to Tianjin and Guangdong [2]. In February 2019, Beijing was approved to engage in the pilot project, enabling a MAH in Beijing to commission manufacturers in other provinces such as to manufacturers in Tianjin and Hebei [3].
The Notice further expands the pilot project to 21 provinces/municipalities including Jiangsu, Zhejiang, Anhui, Fujian, Guangdong, Guangxi, etc. It encourages corporate groups to consolidate and optimize resource allocation amongst R&D institutes and manufacturers through the pilot project. It provides key conditions and obligations for MAHs and commissioned manufacturers involved in the pilot project. For example, the MAHs shall be staffed with full-time technical and management personnel for quality management and regulatory compliance. The MAHs are held responsible for the whole life cycle of medical devices including research and development, clinical trial, production, sale, after-sale service, product recall, adverse reaction report, etc., and shall sign a commission agreement and quality agreement with the commissioned manufacturer, specifying the technical requirements, quality assurance, division of responsibilities and product release requirements. The MAH shall also supervise and regularly assess the commissioned manufacturer for their quality management abilities and strengthen the monitor of adverse event, etc.
The Notice also requires the provincial drug regulatory authorities within the pilot project to timely form implementation plans and management regimes for the pilot project on the basis of sufficient research and evaluation, and report to the NMPA. The local drug regulatory authorities shall supervise MAHs to perform their obligations in quality management and coordinate in cross-provincial administration. In addition, the provincial drug regulatory authorities shall organize legal professionals to form the template commission agreements. Shanghai and Guangdong have already issued the Guidelines on Drafting Commissioned Production Quality Agreement for Medical Device Registrants in draft form during the implementation of pilot project.
On 23 May 2019, China Pharmaceutical News reported [4] that 8 products from 5 companies had been approved in the Shanghai pilot project and 5 products from 1 company had been approved in the Guangdong pilot project. Tianjin has not issued any approval(s) to-date but there are applications under review. As a result of the pilot scheme, different forms of contract manufacturing have evolved such as the commission of manufacture to an affiliated company like Shanghai Yuanxin; commission of manufacture to a non-affiliated company like Medtronic Shanghai where the manufacture of its surgical dynamical system was contracted to Jabil Shanghai; and commission of manufacture by a research institution, such as Shanghai Ninth People’s Hospital (which is affiliated to Shanghai Jiao Tong University) to Shanghai Arigin Medical for the manufacture of its 3D-printed custom knee-joint orthosis [5].
At the legislative level, the medical device MAH system has been added in the 2018 Draft Amendment to the Regulations released by the NMPA in June 2018. We expect to see rapid implementation of the medical device MAH system nationwide and recommend medical devices companies to pay close attention to developments to the MAH pilot project.
NMPA Solicits Public Opinions on Expanding the Medical Device Clinical Trial Exemption List
On 1 August 2019, the Center of Medical Device Evaluation ("CMDE") under the National Medical Products Administration ("NMPA") issued the draft Medical Device Clinical Trial Exemption List (2019 Revision) ("2019 Draft Exemption List") for public comments, exempting 996 medical devices and 420 in vitro diagnostics ("IVDs") from clinical trial. Public opinions can be submitted to CMDE before 30 August 2019.
Compared to the 2018 version of Medical Device Clinical Trial Exemption List ("2018 Exemption List"), the 2019 Draft Exemption List added 142 medical devices including 102 Class II medical devices and 40 Class III medical devices, and 27 IVDs.
The 2019 Draft Exemption List is the 5th round of medical device clinical trial exemption list. The first round of exemption list was issued in 2014, initially covering 488 Class II medical devices and 79 Class III medical devices. The third and fourth rounds of exemption lists were issued in 2016 and 2017, and all three rounds of exemption lists were incorporated into the 2018 Exemption List, covering 855 medical devices and 393 IVDs.
To evaluate whether a medical device can be exempted from clinical trial, the NMPA will take into account the safety and efficacy of the medical device in non-clinical trials, or the clinical data or clinical applications of the medical device of the same variety according to Article 17 of the Regulations on the Supervision and Administration of Medical Devices (2017 Revision). The exemption list applies to both domestic manufactured and import medical devices.
[1]http://yjj.sh.gov.cn/gb/node2/yjj/xxgk/ztzl/n5346/n5351/u1ai55183.html
[2] See the NMPA Reply on Approval of the Implementation of Medical Device Registrant Pilot Project (No.42 [2018] of NMPA, No.43 [2018] of NMPA)
[3] See Section 2(5) of The State Council Reply to the Plan for Comprehensively Promoting the Multifaceted Pilot Program of Expanding Opening-up the Service Sector of Beijing Municipality (No. 16 [2019] of the State Council)
[4] http://epaper.cnpharm.com/zgyyb/html/2019-05/14/content_589916.htm?div=-1
