CFDA notice No. 14 2015
China Food and Drug Administration (CFDA) recently issued the Technical
Guideline for Clinical Evaluation of Medical Devices, which is applicable to the
clinical evaluation of Class II and Class III medical device registration
application, and inapplicable to the clinical evaluation of in vitro diagnostic
reagents regulated as medical devices.
CFDA notice No. 14 2015
CFDA notice No. 14 2015
CFDA notice No. 14 2015
CFDA notice No. 14 2015
Medical devices clinical evaluation is the procedure for registration applicant to confirm whether the product can conform to operating requirement or application by clinical literatures, clinical experience data, clinical trial and other information. This guiding principle is aimed at providing technical guidance for registration applicant to conduct clinical evaluation, and provide technical reference for CFDA management department to examine the clinical evaluation data.
1. The regulations for the Supervision and Administration of Medical Devices (State Council Regulation; Order No. 650)
2. Administrative Measures for Medical Device Registration (CFDA, Order No. 4)
3. Quality Management Rules for Medical Device Clinical Trial
This guiding principle applies to Class II and Class III medical device clinical evaluation work while register and declare. It does not apply to medical device clinical evaluation work of in vitro diagnostic reagents. The clinical evaluation for a specific product shall comply with the technical guiding principle which is published for the specific product.
Clinical evaluation shall be comprehensive and objective, and collecting corresponding data by clinical trial and other means. The clinical performance, safety data, favorable and unfavorable data which are collected in the clinical evaluation process shall be involved in the analysis. The depth and breadth of clinical evaluation, needed data type and data size should match with the design of the product, the key technology, intended use and risk degree, should also be compatible with the level and degree of non clinical research.
Clinical evaluation shall confirm the scope of product (such as suitable crowd, applicable parts, human contact methods, indications, the extent and stage of the disease, usage requirements, usage the environment, etc.), usage, contraindications, precautions, warning information and so on.
Registration applicant should draw the following conclusion by clinical evaluation: under the condition of normal use, the product can achieve the expected performance; and compared with the expected benefit, risks of the product can be accepted; performance and safety of the product can get the appropriate evidence to support.
For the products which are listed in the catalogue, the registration applicant shall submit the comparison information which is obtained by comparing the application relative information and detailed content in the catalogue, and the comparing explains obtained by comparing the application and the registered medical devices in the catalogue. The clinical information shall be submitted as following:
A. The same variety of medical devices
Same variety of medical device refer to the products launched onto the market in China has equivalence property with application about basic principle, structure composition, manufacturing materials (for active products, it means the manufacturing materials which contact with human body), production process, performance requirements, safety evaluation, national or industrial standard, intend use, etc.
If the differences between the application and the same variety products have no adverse effects on the safety and effectiveness of the application, they are can be considered equivalent.
2. Determination of the same variety of medical devices
Registration applicant conducts the clinical evaluation on the application through the clinical trial and clinical data from the same variety of medical devices to prove its safety and effective. First, comparing the application to one or more the same varieties, to proving they are equivalent.
Compared items including but not limited to items listed in attachment 2. The compared content include the qualitative and quantitative data, verification and validation results, sameness and difference, whether the differences will cause adverse effects on the safety and effectiveness, verification and/or validation by its own data, such as non-clinical data, clinical literature data, clinical experience, and clinical data of a clinical trial which aim at the differences in China. The collection and evaluation of the corresponding data shall conform with the requirement of Part 6.3 and Part 6.4, and corresponding accessory specification.
Registration applicant shall provide the comparison information in form tabular (see attachment for format). if there are inapplicable items for one product,, shall explain the reason why they are inapplicable.
B. Evaluation pathway
The specific evaluation pathway is shown in attachment 4.
C. The collection of the corresponding data from the clinical trial and clinical usage data of the same variety of medical devices.
The clinical trial and clinical usage data (Hereinafter referred to as clinical data) can be obtained from the public scientific literature both in China and abroad, and the corresponding data legal, including clinical literature data, clinical experience. Registration applicant can choose appropriate data source and collection methods according with the product.
1 Collection of clinical literature data
Ensure the completeness and accuracy of the literatures while collecting the clinical literature data. Literature retrieval and screen elements, please refer attachment 5. Before literature retrieval, shall make literature retrieval and screening scheme (see attachment 6 for content and format). After literature retrieval and screening, shall make literature retrieval and screening report (see attachment 7 for content and format). Clinical literature retrieval and screening shall have repeatability. Literature searching and screening personnel shall have the corresponding professional knowledge and practical experience.
2 Collection of clinical experience data
The collection of clinical experience data shall include completed clinical research data, adverse events data and corrective action of clinical risk data and so on collection.
2.1 The collection of completed clinical research data
According to the type of clinical trial design, they can be divided into prospective study, retrospective study, randomized study, non randomized control study, single group study, case report and so on.
Registration applicant must provide the ethics committee's views (if applicable), clinical research protocols and clinical research report.
2.2 The collection of adverse events data
Registration applicant shall collect the data from databases which include database about complaints and adverse event built by registration applicant, database about adverse event reported by various country’s supervision organization, such as “Report of medical device adverse event information” and “The medical device vigilance alerts” issued by CFDA, FDA applicant and user institute device service data (MAUDE), MDA and so on.
Registration applicant shall provide the following information of the same varieties: quantity of complaints and adverse events, classified the cause of complaints and adverse events, quantity of all kinds of complaints and adverse events, whether complaints and adverse events related to the product information, etc. . For serious adverse events, should provide the specific information in form of list about event description, reason analysis, processing methods and processing results and so on.
2.3 The collection of corrective action of clinical risk data
Registration applicant shall collect and provide the specific information about corrective action relevant to clinical risk of the same varieties (such as recall, notice, warning and so on), and adopted risk control measures.
D. Conduct the clinical evaluation according to clinical data of similar kinds of medical device
1 Quality evaluation of the data
Registration applicant shall classify clinical data in the analysis according to recognized clinical evidence level evaluation standard (such as “clinical evidence level evaluation criterion” made by Oxford Centre for Evidence Based Medicine). Some clinical data is not unfit for product effectiveness evaluation, but may still applicable to safety evaluation of the product.
2 Data set establishment
The collected clinical data can be concluded into several data sets according to data type and data quality. Registration applicant may also according to different evaluation purposes to establish data sets, such as the ethnic differences of some products’ clinical performance and/or the safety. In order to evaluate product safety and/or effectiveness in Chinese population, can establish data sets for Chinese population.
3 Statistical analysis
Choosing appropriate analysis methods to conduct the statistical analysis for different data set. Analysis methods for data sets consist of several study results include qualitative analysis and quantitative analysis.
4 Data evaluation
Synthesize the analysis results of different data sets to evaluate whether the product achieve the expected performance under the normal condition of use. The risks of the product are within acceptable levels by comparing with the benefited expectation whether or not.
E. Clinical evaluation report
Composing the clinical evaluation report after the evaluation is completion (see attachment 8 for format), as clinical evaluation data submitted while apply for registration.
Conducting clinical trial in China shall in clinical test institute which has qualification and according with medical device clinical trial quality management standard. Registration applicant shall submit clinical trial protocol and clinical trial report while apply for registration.
For the medical devices whose clinical trail are conducted outside China, if their clinical trial conform with relevant Chinese regulations, corresponding technical requirements of guiding principle of registration, such as number of samples, control group selection, evaluation index and principle, therapeutic effect evaluation index and so on. Registration applicant shall submit the clinical trial data which are submitted to the medical device department outside China when it is marketing oversea while apply for registration. The clinical trial data includes at least the views of ethics committee, clinical trial protocol and clinical trial report. Registration applicant also shall submit the relevant supporting data which can prove these is ethnical difference in the clinical performance and/or safety whether or not.
The medical devices shall be conducted clinical trial in China which list in the catalogue of 《The catalogue of Class III Medical Device Need Clinical Trial Approve》.
Attachment 1: Comparative table between application and registered product in China in catalogue.
Attachment 2: Compared items between application and same variety product.
Attachment 3: Format of Comparative table between application and same variety product.
Attachment 4: Clinical evaluation paths through clinical data and clinical usage data of same variety product.
Attachment 5: The requirement of literature retrieval and screen factors.
Attachment 6: The protocol of literature retrieval and screen factors.
Attachment 7: The report of literature retrieval and screen factors.
Attachment 8: Clinical evaluation report according to clinical data of same variety medical device.