28 Apr Changes to Medical Device Regulations in China
The Chinese medical device market and regulatory landscape has undergone a myriad of changes in the past few years. China’s Medical device requirements have been extensively revised; in 2013, the Chinese Food and Drug Administration (CFDA) released 107 new medical device standards. Since then, the CFDA has been revising guidance documents to aid medical device manufacturers with the process of applying for approval in that country. Awareness of these new standards and the revised regulations may be profitable, as the Chinese medical device market is expanding at an incredible rate. Between 2009 and 2014, the medical device market in China grew by 18.3% (1), and has continued its upward trajectory, with a 15% growth rate reported in 2015 (2). It should be noted that although the new regulations and guidance documents provide more structure to the application process in China, the process for gaining access to the market can be a lengthy and complex one. Navigating the process can be intimidating and requires planning with experienced regulators.
The “Five Rectifications Campaign”
On March 15, 2014 the CFDA began a campaign to enforce the regulations in place applicable to medical devices, punishable by the maximum penalty allowed (3). The campaign served to highlight some of the primary areas of focus for the revised medical device regulations that were enacted after the campaign. The enforcement actions focused on the following areas:
- False Information in Registration Applications
- Manufacturing Violations
- Illegal Distribution
- Exaggerated Advertising Claims
- Use of Unregistered Devices
Since the end of the campaign in August of 2015, the CFDA released final rules and draft proposals that seek to rectify or replace ineffective regulations (3). Below is a summary of the key new regulations.
Legal Agent and Device Classification
Before taking any action towards market authorization in China, manufacturers should do two things; appoint a local registered authorized representative, as required by the CFDA, and determine which class the manufacturer’s product falls under (4).
According to the CFDA, medical devices can fall into one of three regulatory classes:
- Class I Device:The safety and effectiveness of the device can be ensured through routine administration.
- Class II Device: Further control is required to ensure the safety and effectiveness of the device.
- Class III Device: The device is implanted into the human body; used for life support or sustenance; or pose potential risk to the human body, and thus must be strictly controlled in respect to safety and effectiveness.(5)
Once a company has established which class their product falls under, using CFDA Decree No.15, they can proceed with determining which process is required to gain market approval.
Class I Product Notifications
For medical devices that fall under the Class I category, the registration process is no longer required (6) (7). Instead, applicants must file a notification to CFDA containing the following documents (all of which must be provided to the CFDA in Mandarin):
- Application Form
- Risk Analysis
- Product Technical Requirements
- Product Testing Reports
- Clinical Evaluation Report
- Label Design
- Manufacturing Information
- Statement of Truthfulness
The CFDA has waived the submission fee and the renewal requirements for Class I devices (6). In addition, no clinical trial is required for Class I devices. The approval structure for Class I devices is such that the CFDA maintains oversight over Class I devices without placing a significant regulatory burden on manufacturers (8).
Class II and III Product Registration
In contrast to Class I notifications, the registration process for higher risk (Class II and III) devices has expanded to require more documentation and clinical data. In addition to the information to be provided for Class I devices, the following additional documentation is required (6):
- Electromagnetic Compatibility testing conducted in China
- GLP compliant Biocompatibility testing (per the revised regulations, this testing no longer needs to be conducted in China)(6)
- In-country Clinical Trial (unless exempted)
- All documents must be notarized
- Letters of Authorization for any leveraged data
The review process for Class II and III registrations has changed as well. Applications undergo an initial review for acceptance (60 working days for Class II and 90 working days for Class III registrations) (7). Chinese regulators plan to complete initial reviews of Class II registrations within 60 working days and for Class III registrations within 90 working days (6). Once acceptance has been granted, the CFDA reviewer can request additional information from the applicant, and 12 months are allocated for a response.
It is important to note that although the regulations allow for only one round of formal questions, many times the reviewer will ask for information via informal routes (email or phone call) during the 12-month manufacturer response period. Responses still must be provided within the 12-month response timeframe or the application will be withdrawn (8). This means that applicants should respond to the formal questions early during the 12-month response time period to allow for interaction with the reviewer (6).
New CFDA Submission Fees
Manufacturers should be aware that fees due to the CFDA have increased. The new fee schedule is as follows (for Class II and III devices) (9):
|Fee Type by Classification||Chinese Domestic Products||Imported Products|
|Class II||Initial Registration||–||–||210,900||33,761|
|Renewal (every 5 years)||–||–||40,800||6,531|
|Class III||Initial Registration||153,600||24,588||308,800||49,433|
|Renewal (every 5 years)||40,800||6,531||40,800||6,531|
|Clinical Trial Application Fee (High risk products)||43,200||6,915||43,200||6,915|
Class II and III: In-Country Clinical Trial or Clinical Evaluation Report?
The CFDA has adopted a two-step process for determining if an in-country clinical trial is required for Class II and Class III medical devices (6).
Step 1: The CFDA has create a Clinical Exemptions List.
- Determine if your product matches any of the exempted products on the list.
- If so, determine if there exists a CFDA approved predicate device. Compare your device to the predicate, and if there are no differences, the requirement for an in-country clinical trial may be waived in lieu of a Clinical Evaluation Report supported by data from the predicate device.
- The following characteristics need to be compared between your product and the commercially available product. The CFDA will expect the applicant to provide documentation to support the comparisons, and letters of authorization should be provided for any documentation obtained from another manufacturer (6).
- Basic Principles
- Structure Composition
- Production technology
- Manufacturing materials
- Performance Requirements
- Safety evaluation (biocompatibility, biosafety, etc.)
- National/Industry Standards
- Scope of application
- Operating Method
- Precautions and warnings
- Delivery method
- Sterilization methods
- Product Specifications
The information required demonstrating equivalence between your product and the commercially available product is extensive, and it may be difficult to write a comprehensive analysis that will meet CFDA requirements. If you are unable to provide an adequate predicate, or if there are differences of safety and efficacy between your device and the commercially available device, an in-country clinical trial will need to be conducted (6). If a predicate is available, but there are differences which impact the safety or efficacy, the in-country clinical trial can focus on the differences (10) (8).
Step 2: If the device is not on the Clinical Exemptions List, an in-country clinical trial will need to be conducted. It may be possible to leverage data from a commercially available predicate device in order to reduce the resources required to conduct a new trial. For example, if there are only differences in the delivery method, this can be the subject of the trial while data is leveraged for all other device characteristics (6).
Good manufacturing practices (GMPs)
In accordance with the Five Rectifications Campaign, the CFDA has revised its good manufacturing practices (GMPs) for medical device manufacturers. The requirements apply to manufacturers in China or those who utilize a Chinese contract manufacturer. The revised Chinese GMP is more closely aligned with ISO 13485 and 21 CFR 820, however there are more detailed requirements for manufacturing facilities, equipment, and process management (11). In addition, the revision includes manufacturing requirements that specifically apply to IVDs, sterile devices, and implantable devices (12).
The CFDA will conduct GMP inspections of manufacturing facilities located in China once a marketing license has been issued. Following the initial inspection, manufacturers will need to report the results of their own self-audits periodically to provincial authorities (12).
The CFDA is also implementing a pilot program to conduct international audits for manufacturers of Class III products sold in China to ensure compliance with the revised GMP. Thus far, only two audits have been conducted and ten more will be conducted in 2016 (13).
Failure to comply with the GMP requirements include more severe monetary penalties: approximately $8,000 (USD) for medical products worth approximately $1,500 or less, for products that are worth more than $1,500, the manufacturer will be fined up to 10 times the value of the product (12).
Revised Medical Device Adverse event reporting and monitoring requirements
The CFDA has made significant changes to its post-market medical device monitoring regulations. In December 2015, the CFDA released a draft guidance proposing new rules that offer different definitions and requirements for adverse event reporting. The rules have yet to be finalized (14) (8).
The CFDA has defined two categories of adverse events; Serious and Normal. Serious adverse events (SAEs) are those that cause death or permanent damage to the human body, endanger human life, or those that lead to an injury or death (14). Normal adverse events are those that do not fall under the SAE category. The proposed rules contain new timeframes for Health providers and device manufacturers to report SAEs (15):
- SAE must be reported within 15 days of its occurrence
- If the SAE results in death, it must be reported within 5 days.
- Normal adverse events must be reported within 30 days
The CFDA will closely monitor any medical product that is subject to frequent adverse event reporting (14).
What the Changes China Regulatory Environment Means to You
The Chinese medical device regulatory landscape has become much more difficult to traverse due to changes in the regulations. The investment of resources required to gain approval in China may be worthwhile when the potential benefits of gaining access to a growing market are considered. It is important to create a detailed strategy before beginning the registration process in China to ensure your business needs can be achieved.
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- China Authorized representative. Hangzhou CIRS Co. LTD. 2014.
- The Regulatory Approval Process for Medical Devices in China. TUV SUD.
- RAPS CFDA’s New Regulations for Medical Device Seminar. Whitney, Chang-Hong. 2016.
- Further Analysis of New Chinese Medical Device Registration Requirements. Eisenhart, Stewart. August 2014, Emergo Group.
- Major Changes Come To China’s Medical Device Industry. Wang, Katherine and Yang, Fan. 2014, Ropes & Gray LLP.
- New User Fees Set for Foreign Medical Device Manufacturers in China. Eisenhart, Stewart. Emergo Group.
- Can Some Medical Devices Skip China’s Clinical Trial Mandate? Brousseau, Zachary. February 2015, RAPS.
- New Medical Device Quality System Guidelines Released by Chinese Regulators. Eisenhart, Stewart. October 21, 2015, Emergo Group.
- CFDA Focuses on Enforcement of Medical Device Good Manufacturing Practices. Carver, Krista. 2014, Inside Medical Devices.
- China rolls out devices international audit program. BRANDWOOD, ARTHUR. s.l. : Brandwood Biomedical, 2015.
- CFDA Releases Plan to Improve Medical Device Adverse Event Monitoring. Britt, Caroline. 2013, Inside Medical Devices.
- China FDA Proposes Revisions to Medical Device Adverse Event Regulations. February 1, 2016, Pacific Medical Bridge.