2015年医疗器械临床评价技术指导原则(英文版).doc

AnnexTechnical Guidelines for Clinical Appraisal of Medical Devices Drafting objective Clinical appraisal of medical devices is the process implemented by registration applicant to identify whether the product fulfills usage requirements and application scope according to information concerning clinical documents, clinical experiences data, clinical trials and so on. This guidelines is intended to provide technical guide for registration applicant to carry out clinical appraisal as well as for the food and drug administration authorities to review clinical appraisal documents . Laws and regulations basis () “Medical devices management regulations”No. 650 decree of the state council; () “Medical devices registration management specifications” No. 4 decree of the state council; () Relevant specifications for clinical trial quality management of medical devices. Application scope This guidelines is applicable to clinical appraisal of class and class medical devices when they are applied for registration. It is not applicable to clinical appraisal of in vitro diagnostic (IVD) reagents administrated as medical devices. If there is clinical appraisal technical guidelines for specific product, the corresponding clinical appraisal should follow relevant requirements of it. Basic principleClinical appraisal should be comprehensive as well as objective and corresponding data should be collected by various means such as clinical trials and so on. Clinical performance and safety data collected in clinical appraisal process should be included in analysis no matter it is positive or negative. Clinical appraisal depth and scope as well as data type and data quantity required should be compatible with design feature, key technology, application scope and risk level of the product while they should be also compatible with level and degree of non-clinical research.Clinical appraisal should confirm clinical application information concerning application scope(such as applicable people, applicable parts, contact manner with human body, indications, disease level and stage, application requirements and application environment, etc), use method, contraindications, prevention measures and warning ,etc. Registration applicant should draw the following conclusion through clinical appraisal: the product has the expected performance in normal use; the risk of product is acceptable compared with expected benefits; the clinical performance and safety of product are both supported by proper evidences. . Clinical appraisal requirements for the product listed in catalogue of medical devices exempted from clinical trial.For the product listed in Catalogue of medical devices exempted from clinical trial, registration applicant needs to submit documents of comparison between relevant information of declared product and the content included in the catalogue as well as comparison explanation for declared product and the medical devices included in the catalogue which have already acquired domestic registration permission. The specific clinical appraisal documents required to be submitted is as follows:() Submit documents of comparison between relevant information of declared product and the content included in catalogue; ()Submit comparison explanation for declared product and the medical devices included in the catalogue which have already acquired domestic registration permission. Comparison explanation should include Comparison form for declared product and the medical devices in the catalogue which has already acquired domestic registration permission (refer to annex 1) and corresponding supportive documents.The above-mentioned submitted documents should prove the equivalence between declared product and the product listed in the catalogue. If equivalence between declared product and the product listed in the catalogue cannot be proved, corresponding jobs should be carried out according to other requirements in this guidelines. .Requirements for analysis and appraisal with data from clinical trial and clinical use of the same variety medical devices. ()The same variety medical devices1 Definition of the same variety medical devicesThe same variety medical devices are the domestic registered products which are identical to the declared product in the aspects of basic principle, structure composition, manufacturing material(it refer to the manufacturing material in contact with human body for active products), manufacturing technology, performance requirements, safety appraisal, implemented national/professional standards, intended application and so on.If the difference between declared product and the same variety medical devices has no adverse influence on product safety and effectiveness, they can be judged as basic equivalent. 2.Judgment of the same variety medical devicesWhen analysis and appraisal is implemented with data from clinical trial and clinical use of the same variety medical devices to prove the safety and effectiveness of medical devices, registration applicant should compare the declared product with one or several medical devices of the same variety to prove the equivalence of them.The items for comparison with the same variety medical devices should include but not limit to the items in annex 2. The comparison content includes qualitative and quantitative data, verifying and confirming result. Homogeny and differences between both of them should be described in details while it should be verified and/or determined whether there is adverse influence on product safety and effectiveness due to difference by using the data of declared product itself, such as non clinical research data of the declared product, clinical documents data, clinical experiences data and data of clinical trial implemented in China which is intended for difference. The corresponding data collection and analysis as well as appraisal should fulfill requirements in clause () and clause () as well as corresponding annexes. Clinical trial should fulfill relevant requirements of clinical trial quality management regulations. Registration applicant should provide comparison information in form of list( refer to annex 3 for format). If there are items which are not applicable, reason for inapplicability should be explained. () Appraisal approach Detailed appraisal approach is shown in annex 4. ()Collection of data for clinical trial and clinical use of the same variety medical devices Data from clinical trial and clinical use (simplified as clinical data in following text) can come from scientific documents published in China and/or overseas as well as corresponding data acquired legally ,including clinical documents data and clinical experiences data. Registration applicant can select proper data source and collection method according to specific situation of product. 1. Collection of clinical documents data Collection of clinical documents data should retrieve the documents precisely and comprehensively. Refer to annex 5 for documents retrieval and selection requirements. Before documents retrieval and selection is carried out, documents retrieval and selection scheme (refer to annex 6 for content and format) should be formulated. After documents retrieval and selection is completed, documents retrieval and selection report (refer to annex 7 for content and format) should be drafted. Clinical documents retrieval and selection should have repeatability. Documents retrieval and selection staff should have corresponding professional knowledge and practical experiences. 2. Collection of clinical experiences dataCollection of clinical experiences data should include collection of data concerning implemented clinical trials, adverse events, correction measures related to clinical risk and so on.(1) Collection of the completed clinical research dataAccording to its design type, clinical research can be classified as perspective study, retrospective study , randomized controlled study, non randomized controlled study, single group study case-reporting and so on.Registration applicant should collect and provide opinions of ethics committee(if applicable), clinical research scheme and clinical research report.(2) Collection of adverse event dataRegistration applicant should collect the adverse events data included in complaints and adverse events database established by registration applicant itself and the databases issued by administration authorities of various countries, such as Information bulletin of adverse events for medical devices and Express news for medical devices vigilance issued by China Food and Drug Administration, The Manufacturer and User Facility Device Experience(MAUDE) of FDA, Medical Device Alert (MDA) of Great Britain and so on.Registration applicant should provide information concerning complaints and adverse events quantity for the same variety medical devices, cause classification of complaints and adverse events, complaints and adverse events quantity for different cause classification, whether complaints and adverse events are related to the product and so on. For the severely adverse events, detailed information concerning event description, cause analysis and handling method, etc should be provided in form of list.For the declared product, detailed information concerning market available time, accumulated sales , severely adverse events handling result and so on should be provided. (3) Collection of data of correction measures concerning clinical riskRegistration applicant should provide detailed information of correction measures concerning clinical risk(such as recalling, bulletin, warning and so on) for the same variety medical devices, the adopted risk control measures and so on. ( ) Clinical data analysis and appraisal for the same variety medical devices1. Data quality appraisalRegistration applicant should rank the data involved in analysis according to public acknowledged appraisal standard for clinical evidence levels (such as appraisal standard for clinical evidence levels drafted by Oxford Centre for Evidence Based Medicine). For part of the clinical data which is not applicable to be used in product effectiveness appraisal, it can be used in product safety appraisal if possible.2. Data sets establishment The collected clinical data can be summarized into several data sets according to data type and data quality. Registration applicant can also establish data set respectively according to different appraisal objectives, for example, the performance and/or safety for some products varies due to ethnic groups difference, so that Chinese population data set can be established for the appraisal of the product performance and/or safety for Chinese population using.3. Data statistics and analysis Proper data analysis method should be chosen for statistics and analysis of different data sets. Analysis methods for data set consisted of multiple research results include qualitative analysis and quantitative analysis .4. Data appraisalBy summarizing analysis result of different data-sets, appraisal for declared product can be carried out to identify whether expected performance can be achieved in normal use condition and whether the product risk is acceptable compared with the expected benefits. () Clinical appraisal report Clinical appraisal report needs to be drafted after clinical appraisal is finished (refer to annex 8 for format) and be submitted as clinical appraisal documents when registration is applied . Requirements for clinical trial For the medical devices which have their clinical trials implemented in China, the clinical trials should be carried out in qualified clinical trial institute according to requirements of medical devices clinical trial quality management regulations. When registration applicant applies for registration, clinical trial scheme and clinical trial report should be submitted.For the imported medical devices which have overseas clinical trials, if the clinical trials fulfill requirements in relevant laws and regulations of China , such as requirements for sample quantity , contrast group selection, appraisal indexes and principle , effectiveness appraisal indexes , while registration application is carried out, registration applicant can submit the clinical trial documents which are submitted to overseas medical administration authorities when the product is put into overseas market. The documents should at least include opinions of ethics committee, clinical trial scheme and clinical trial report. Applicant should also submit relevant supportive documents which demonstrate whether there is product clinical performance and/or safety difference due to ethnic groups difference .For the medical devices listed in Catalogue for Class III medical devices needing clinical trial approval, clinical trials should be carried out in China.Annexes: 1 Comparison form for declared product and the medical devices in the catalogue which have gotten domestic registration permission. 2. Comparison items of declared product and the same variety medical devices. 3. Format of comparison form for declared product and the same variety medical devices4. Approach of analysis and appraisal with data from clinical trial and clinical use of the same variety medical devices. 5. Documents retrieval and selection requirements 6. Documents retrieval and selection scheme 7. Documents retrieval and selection report 8. Report of analysis and appraisal by using data from clinical trials and clinical use of the same variety medical devices 18 Annex 1 Comparison form for declared product and the medical devices in the catalogue which have acquired domestic registration permission Comparison itemsMedical devices in catalogueDeclared productDifferencesSummary of supportive documentsBasic principle(operation principle/action mechanism)Structure compositionProduct manufacturing material or manufacturing material in contact with human body Performance requirements Sterilization/disinfection method Application scopeUse methodNote: comparison items can be increased according to specific situation Annex 2 Comparison items of declared product and the same variety medical devices (Passive medical devices)Passive medical devicesComparison items1. Basic principle2. Structure composition 3. Manufacturing technology4. Manufacturing material(such as material grade, animal derived materials, allograft material, ingredients, medicine ingredients, bioactive substances ,implemented standards and so on)5.Performance requirements 6. Safety appraisal(such as biocompatibility ,bio-safety and so on)7. Implemented national/professional standards of the product 8.Application scope: (1)Applicable people (2)Applicable parts (3) Contact manner with human body (4)Indications (5)Applicable disease stage and level (6)Application environment 9.Use method 10. Contraindications11.Prevention measures and warning 12.Delivery status 13. Sterilization/disinfection Method14.Package 15.Label16 Product instructions Comparison items of declared product and the same variety medical devices (Active medical devices)Active medical devicesComparison items 1.Basic principle (1)Operation principle (2)Action mechanism2. Structure composition(1)Product composition(2)Core components3. Manufacturing technology 4. Manufacturing materials in contact with human body(such as material grade, animal derived materials, allograft material, ingredients, medicine ingredients, bioactive substances ,implemented standards and so on)5.Performance requirements (1)Performance parameters (2)Function parameters 6.Safety appraisal(such as biocompatibility, bio-safety, electrical safety, radiation safety and so on)7. Core function of software 8. Implemented national/professional standards of the product 9.Application scope: (1)Applicable People (2)Applicable parts (3)Contact manner with human body (4) Indications (5)Applicable disease stage and level (6)Application environment10. Use method11. Contraindications12.Prevention measures and warning13. Sterilization/disinfection method14.Package15.Label16.Product instructions Annex 3Format of comparison form for declared product and the same variety medical devicesComparison itemsThe same variety medical devicesDeclared product Differences Summary of supportive documents Basic principle Structure compositionNote: Comparison items should at least include all the items listed in annex 2. Annex 4 Approach of analysis and appraisal with data from clinical trials and clinical use of the same variety medical devices Analysis and appraisal cannot be implemented by using data from clinical trial and clinical use of the same variety medical devices. Registration applicant should submit corresponding clinical trial documentsWhether it is can be proved that difference has no adverse influence on product safety and effectiveness by using the non clinical research data of declared product, and/or clinical research document data, and/or clinical experiences data ,and/or clinical trial data implemented in China and intended for difference Formulate clinical trial report and complete clinical appraisal Collect and analyze the clinical trial and/or clinical experiences data for the same variety medical devicesAre there differences compared with the same variety medical devicesMedical devicesYesNoYesNOAnnex 5