IVDR 2017/746/EU Regulation Historical development
On May 5, 2017, the Official Journal of the European Union published the EU Medical Device REGULATION (EU) 2017/746 (" IVDR "). IVDR will replace the Directives 98/79/EEC (In Vitro Diagnostic Devices Directive). The IVDR came into force on 26 May 2017 and replaced the IVDD (98/79/EEC) on 26 May 2022.
What is new in IVDR 2017/746/EU?
1. Changes in classification rules and increased involvement of notified bodies. In IVDR regulations, supervision of in vitro diagnostic devices is still based on the broad framework of classification supervision, but the classification rules have undergone fundamental changes compared with the original IVDD, that is, in IVDR, Based on the risk of the product, all in vitro diagnostic devices are classified as A, B, C and D from low to high score.
2. A Summary of Safety and Performance is also proposed in the IVDR to further increase regulatory transparency. The requirements include that Class C and Class D products need to disclose information such as product specifications, performance evaluation conclusions and clinical trial conclusions in the form of abstracts. Through this summary, on the one hand, users can understand the performance indicators of products more clearly, on the other hand, manufacturers can compare the regulatory standards of similar products in more detail.
3. The introduction of Unique Device Identification System (UDI). Following the implementation of UDI requirements by the US FDA, the IVDR issued by the EU also introduces UDI requirements to enhance product traceability and post-marketing management.
4. The more stringent and in-depth audit method of the notified body will require more auditors to audit the enterprise, which increases the difficulty and depth of the audit.
5. Some high-risk products need to comply with European clinical trial standards.
6. Require at least one Person responsible for regulatory compliance in the organization.
What should be included in the EU IVDR 2017/746 technical document?
1. CE Technical documents
Use internationally recognized medical device names
Refer to Appendix II Technical documents
New cover UDI encoding file
Risk system file
Performance Evaluation and post-market Follow-up Document (PMPF)
A single registration number SRN is obtained after the CE technical document Part A is reported
2. UDI technical documents
DI device identification
PI production identification
The UDI-DI part is to be submitted to the system and to the NB mechanism. Post-market regulation and adverse event handling are both involved in UDI. UDI receives a registration number after registering with the UDI database. UDI is also embodied in the Free marketing Certificate FSC and CE Self-declaration DoC.
3. Enterprise Documents
It involves filling in various forms of enterprise registration, which are specified by the official database. In general, it is similar to Part A of the CE technical document.
4. Quality management system
(a) a regulatory compliance strategy, including compliance with the conformity assessment process and change management of the devices covered by the system;
(b) Identify applicable generic safety and performance requirements and identify options to meet those requirements;
(c) Management responsibilities;
(d) Resource management, including the selection and management of suppliers and subcontractors;
(e) Risk management under section 3 of Appendix I;
(f) Performance evaluation, including post-marketing performance follow-up in accordance with Article 56 and Appendix XIII;
(g) Product realization planning, including planning, design, research and development, production and service provision;
(h) Assign validation of the UDI for all relevant devices in accordance with Article 24 (3) and ensure the consistency and validity of the information provided in accordance with Article 26;
(i) Establish, implement and maintain a post-market surveillance system in accordance with the requirements of Article 78;
(j) communicating with competent authorities, notified bodies, other economic operators, customers and/or other stakeholders;
(k) Procedures for reporting serious incidents and on-site safety corrective actions in alert situations;
(l) Management of corrective and preventive measures and verification of their effectiveness;
(m) Monitoring and evaluation processes for product, data analysis and product improvement.
5. Risk management system
Risk assessment should include: technical update risk assessment, on-site safety corrective action risk assessment, clinical benefit risk assessment.
There is a risk management system throughout the life cycle. The risk management is updated in the first year after its establishment and every two years thereafter. Be consistent with ongoing compliance.
6. Post-market surveillance system
Post-market surveillance plan
Covers:
Warning system
Technology upgrade risk assessment
On-site notification, on-site corrective action
Proactively collect after-sales complaints and reports
Clinical Risk Follow-up, PMPF (Post-Market Performance Follow-up)
Performance evaluation
Unqualified recall
7. Ethical Approval
Class A and B devices do not need to go to the EU for clinical performance evaluation, and Class C and D devices need to go to the EU for clinical performance evaluation.
The remaining sample clinical performance evaluation plan does not require EU approval but requires ethical approval. The Declaration of Helsinki needs to be met. Clinical plans should comply with ISO14155.
8. Research Plan
Class C, D performance evaluation (analysis, diagnostic sensitivity, etc.) in accordance with CS in EU reference laboratories is a prerequisite for clinical research.
The research proposal needs to be submitted to the EU database, the remaining sample studies do not require approval, but the research proposal changes and changes require approval. Results summary and study report should be submitted within three months after the end of clinical study or suspension.
9 Clinical Evidence
Includes:
Performance evaluation (Analytical performance + clinical performance)
Scientific Data (Technical documents)
Clinical performance (cross-reaction, interference to be verified)
PMPF (Post-market Performance Follow-up)
Benefit risk assessment
10 PSUR (Regular Security Update report)
Manufacturers of Class C and D devices shall prepare regular safety update reports (" PSUR ")
The PSUR shall list:
(a) Conclusions of benefit-risk monitoring;
(b) The key results of the Post-Market Performance Follow-up Report (PMPF); and
(c) The sales volume of the device and the assessment of the size and other characteristics of the population using the device, as well as the frequency of use of the device during actual operation.
Manufacturers of Class C and D devices should update the PSUR at least annually. PSUR shall be part of the technical documents specified in Appendices II and III.
The manufacturer of a Class C device shall submit the PSUR to the notified body involved in the assessment of conformity and provide a report to the competent authority upon request
Reporting of serious incidents and site safety corrective actions and site safety notices, as well as providing periodic summary reports, post-market surveillance reports, periodic safety update reports (PSUR), and trend reports;
11 Trend Report
Report the following to the relevant authorities:
(a) Any serious event involving a device placed on the market in the European Union, in addition to the expected error results clearly documented and quantified in the product information and technical documentation, such event shall be reported in accordance with Article 83
(b) Schedules for reporting on site safety corrective actions and for manufacturers to provide periodic summary reports and trend reports;
12 PMPF
Post-market Performance Follow-up (PMPF)
See Appendix XIII Performance Evaluation, Performance Studies, and Post-Market Follow-up (PMPF)
The PMPF plan should include at least:
(a) General methods and processes for applying the PMPF, such as the collection of clinical experience gained, user feedback, scientific literature screening and other sources of performance or scientific data;
(b) Specific methods and processes for applying PMPF (e.g., circular comparison trials and other quality assurance activities, epidemiological studies, appropriate patient assessments or disease registries, genetic databases or post-marketing clinical performance studies);
(c) Reasons for the appropriateness of the methods and processes described in paragraphs (a) and (b);
(d) refer to the relevant parts of the Performance evaluation report referred to in Section 1.3 of Part A of this Appendix and Appendix I
Risk management as described in section 3;
(e) The specific objectives to be addressed by the PMPF;
(f) evaluation of performance data relating to equivalent or similar devices and the latest state of technological development;
(g) Refer to all CS, harmonized standards and relevant PMPF guidelines used by the manufacturer;
(h) A detailed and sufficiently reasonable schedule of PMPF activities conducted by the manufacturer (e.g., PMPF data and report analysis).
13 Adverse event reports
UDI is used for reporting serious adverse events and on-site safety corrective actions
Clinical performance studies generate unique identification numbers for reporting serious adverse events and on-site safety corrective actions
Performance study: The Sponsor shall fully document all of the following:
(a) any type of adverse event identified in the performance study program that is critical to the evaluation of the performance study results;
(b) any serious adverse events;
(c) any device defect that could cause a serious adverse event if appropriate action is not taken, no intervention occurs, or if the situation is adverse;
14 Issue CE certificate
Class D devices are approved by NB + government. Class D devices shall be subject to approval
Class B and C devices are certified by NB.
Class D devices are validated by an EU reference laboratory
Performance verification Coverage (Analytical performance + Security performance) The analytical performance verification plan should cover: principle, purpose, method, detection, statistics, and can be executed.
Class B and C devices are certified by a notified body
Class A enterprises self-verification
The approval of Category B technical documents is based on Appendices IX 4.4-4.8 and Appendices I and II. Covers: CS, harmonized standards, performance assessment, Traceability, training, PMPF, Risk, Alert, etc.
Strengthen the quality management system flight inspection.
Category B and C require review of the Trend Report
The certificate is submitted to the certificate system database.
The CE certificate is a prerequisite for admission to the market and obtaining the FSC.
