On February 25, 2023, Team-NB issued a position paper titled Best Practice Guidance for the Submission of Technical Documentation under Annex II Technical Documentation and Annex III Technical Documentation for Post-Market Surveillance of EU In Vitro Diagnostic Medical Devices Regulation (IVDR) 2017/746. Manufacturers of all in vitro medical device (IVD) classes must demonstrate conformity to the General Safety and Performance Requirements (GSPR) through the preparation and holding of technical documentation that shows how each IVD medical device was developed, designed, and manufactured together with the descriptions and explanations to understand the manufacturer’s determination with respect to such conformity. The notified bodies (NB) did industry a solid by unifying and communicating detailed conformity expectations around Annex II and Annex III. The position paper was prepared by all the Team-NB IVD active members and approved by all of the IVD NB voters. This insight will focus on current hot topic highlights, while the position paper is filled with much more detail.
- General administrative information should be provided in the technical documentation about the manufacturer details: legal manufacturer name, legal manufacturer address, EU Authorized Representative and subcontractors’ location, EMDN coding and NANDO coding. It should also include information about placing on the market and whether the device is made available to the market through distance sales.
- As part of the technical documentation, the manufacturer shall keep up to date a list of all UDIs that it has assigned.
Device Description & Specifications
- Provide a table listing each variant/model/configuration/component/accessory. Include the identifier (e.g., bar code, catalogue, model or part number, UDI) and a statement of its name/description (e.g., Trade name, size, intended use).
- Identify the intended users of the device (i.e., laboratory professional, healthcare professionals or lay persons). Intended users as claimed shall be substantiated by the clinical performance evaluation and in the risk management, as well as the usability file.
- For devices grouped under one basic UDI-DI number describe the differences to demonstrate how they fall under the same group.
- The technical documentation shall include intended patient population. If no specific testing population is stated in the intended purpose, it is understood that the device is to be used without limitation.
- The IVDR refers to Intended purpose and Intended Use, which are understood to have the same meaning.
- Indicate the device classification and rationale per IVDR Annex VIII. The rationale should address each point of the selected classification rule. If multiple classification rules apply, all should be identified and the strictest rule(s) resulting in the higher classification shall apply. The rationale shall not only address the reasoning why a particular rule applies, but also reasoning why a particular classification rule is considered not to apply.
- For initial applications under IVDR, confirm whether the device has been previously marketed under IVDD as a self-declared or NB certified device. Indicate whether any changes have been made in comparison to any issued IVDD-certified device.
- Market history should include EU and approvals in other geographies.
Information to be Supplied by the Manufacturer
- Legible versions of all applicable levels of labels should be provided (e.g., secondary pack, primary pack) and should be representative of the finished form, showing all included symbols.
- Indicate within the technical documentation all countries in which the device is intended to be sold and summarize the process for translation. Translation of IFU to all languages required in the target markets is required before product launch, however, only one language (that required by the NB) is acceptable in the initial submission, as long as the translation procedure is effective.
- Only marketing literature that mention that the device fulfils the requirements of CE marking or includes the CE mark itself is required to be provided.
Design & Manufacturing Information
- For IVDs which are reagents, provide a description of the critical ingredients such as antibodies, antigens, enzymes and nucleic acid primers provided or recommended for use with the device. The description must include at least a reference number of the critical materials.
- For devices incorporating instruments and/or software, provide an overview of the entire system. Indicate the transition steps and whether manual handling/manipulation are required.
- In case of sub-contracted (outsourced) processes:
- For non-critical component suppliers (e.g., bulk) identification of supplier only.
- For critical component suppliers (e.g., outsourced manufacturing of sterile device) overview of manufacturing processes and corresponding control measures (e.g., references to verification and validation activities, copy of the certificate to be included).
- A general explanation of the subcontractor control system that is applied by the manufacturer, including reference to the documented (purchasing) procedures.
- Each GSPR that applies to the device and an explanation as to why other GSPRs do not apply as well as method(s) used to demonstrate conformity.
- The precise identity of the controlled documents offering evidence of conformity with each harmonized standard, common specification, or other method applied to demonstrate conformity with the GSPR.
Benefit Risk Analysis and Risk Management
- The interface between risk management process and performance evaluation performed by the manufacturer must be clear and noticeable and the results of the risk management shall provide information about the appropriateness of the performance evaluation.
Product Verification and Validation
- An overview of the design inputs and key outputs for the device, including a design traceability matrix where appropriate.
- If the device is to be connected to other device(s) to operate as intended, a description of this combination/configuration including proof that it conforms to the GSPRs when connected to any such device(s) having regard to the characteristics specified by the manufacturer.
- Too much guidance to highlight on the performance of the device information is provided on specimen type, accuracy of measurement, analytical specificity, measuring range, cut-off and analytical sensitivity.
- Again, too many highlights to share in this MEDIcept Insight, so make sure to take a peek at the sections on:
- metrological traceability
- physical and biological properties
- construction of devices and interaction with their environment
- devices with a measuring function
- protection against radiation
- software and software validation
- electrical safety and electromagnetic compatibility
- protection against mechanical and thermal risks
- protection against risks associated with devices intended for self-testing or near patient testing
- The manufacturer shall specify and justify the level of the clinical evidence necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of clinical evidence shall be appropriate in view of the characteristics of the device and its intended purpose.
- Details around Performance Evaluation Plans such as a description of what is considered state of the art or if the intention is to rely on evidence generated for an existing device, provide a rationale as to how the data is considered current.
- Explanation of expectations to support scientific validity, analytical performance, clinical performance, and clinical performance study which will be inputs to the Performance Evaluation Report (PER). The PER is always required and is a stand-alone document.
Post Market Performance Follow Up
- Describe the general and specific methods as well as the procedures applied with a justification if not applied.
- If the PMPF plan includes a PMPF study, then the full detailed study protocol should be provided with statistical analysis plans, and a clear statement from the manufacturer indicating commitment to the PMPF plan.
- If the PMPF plan does not include a PMPF Study, then a justification should be provided per Annex III of the IVDR.
Post Market Surveillance
- The post-market surveillance plan includes the search terms used in the search for serious incidents, field actions, relevant specialist or technical literature.
- The manufacturer should also provide the following post market surveillance data for the last 5 years on market history, worldwide and EU sales volumes, complaint data and trend analysis, vigilance data and trend analysis (include details of any adverse incidents, recalls or FSCA), publicly available information about similar medical devices and modifications made and/or corrective actions taken following the incidents reported and revisions made to the risk management file.
In conclusion, the Annex II and III highlights from the Team NB position paper were discussed. The next revision date is scheduled in 2 years (approximately February 25, 2025) in an effort to adapt the position paper to changes in the regulation, development of guidance documents and the change in interpretation over time. When manufacturers take the position paper as an aid in drafting their IVDR technical documentation they will be set up for success, so stop the procrastinating, grab a copy and start typing!
Melissa Paffenroth – Senior Regulatory Consultant