IVDR CE Marking Overview
In order to sell your in vitro diagnostic (IVD) medical device in Europe, it must first be CE Marked. CE Marking is Europe’s version of marketing approval.
Prior to CE Marking an IVD, manufacturers must compile technical and performance documentation to demonstrate compliance with the EU In Vitro Diagnostic medical device Regulation (IVDR) 2017/746.
Further, unless the device is the very lowest risk class, it must undergo a conformity assessment review by a Notified Body. Notified Bodies are organizations accredited and supervised by the European National Competent Authorities, and their role is to evaluate if products have met the minimum safety and efficacy requirements. The Notified Body issues “CE Mark Approval” for the device by issuing a CE certificate.
If the device is the lowest risk, then it does not require a CE certificate issued by a Notified Body. Instead, the manufacturer must compile the safety and efficacy information, and then they will “self-certify” the device. This means, they will affix the CE symbol on their product and sign a Declaration of Conformity, which is a legal document, asserting that they have met the minimum requirements of the regulation.
IVDR Progressive Rollout Timing
The IVDR date of application was 26 May 2022. However, the EU Parliament and European Council adopted an amendment to provide a longer IVDR transition period for most, but not all, IVDs.
This rollout now staggers the compliance dates over the next five years. Below are the new IVDR transition timelines by device classification.
26 May 2022
No transition period granted. Must comply immediately.
26 May 2027
An additional five years to transition has been granted.
26 May 2027
An additional five years to transition has been granted.
26 May 2026
An additional four years to transition has been granted.
26 May 2025
An additional three years to transition has been granted.
NOTE: This is not a delay of the IVDR, per se. Instead, it is a delay of the compliance date for IVDs already on the European market, that require Notified Body certification. This is an important distinction because there is a severe lack of notified bodies accredited to the IVDR and an extensive number of IVDs on the market that need certification.
Further, some elements of the IVDR were applied to all IVDs on its date of application (DoA), irrespective of the transition timelines. For example, the IVDR’s vigilance, post-market surveillance and market surveillance requirements will apply to every IVD on the market, even those that are IVDD CE marked as ‘legacy’ devices under the above transition period.
Technical Documentation File Overview
All IVDs irrespective of classification and risk level, require the following elements from the IVDR:
- IVDR, Annex II – Technical Documentation File (TDF), which includes information related to product design and manufacturing, product verification and validation, and risk analysis and management
- IVDR, Annex III – Post-Market Surveillance (PMS) appendix
- IVDR, Annex XIII – Performance Evaluation Report (PER)
Not all the requirements outlined in each section above may apply to your device. Manufacturers should determine which sections within each Annex (TDF/PMS/CER) are applicable for their device. Where a section is deemed not applicable, manufacturers should document a rationale as to why this has been excluded from the Technical Documentation File (TDF) and/or Performance Evaluation Report (PER).
The information detailed in the TDF and PER should provide evidence that the General Safety and Performance Requirements (GSPRs), described further below, have been sufficiently addressed.
Casus Consulting offers compilation services for both the TDF and PER. We can help you understand how the IVDR applies to your device, and the required information to be included in each file. We can also provide support in conducting a gap analysis of your ‘legacy’ device technical files and upgrading them to the IVDR.
IVDR Key Elements
Manufacturers should consider the technical file as a whole when drafting, rather than looking at the sections as standalone items. For example, the General Safety and Performance Requirements (GSPRs) include information from the Risk Management section, and elements of the Risk Management section need to be considered for the Post-market Surveillance plan.
1) Technical Documentation File Main Body (IVDR Annex II)
The main body of an IVDR complaint TDF should include key details and documentation related to the device, including the description, labeling/IFUs, design and manufacturing information, product verification and validation (i.e., data to prove the safety and efficacy of the device).
Two key components that manufacturers need to develop for the IVDR TDF are the General Safety and Performance Requirements and Risk Management section.
General Safety and Performance Requirements (GSPR)
- The GSPRs detail the specific criteria manufacturers must meet to establish minimum safety and efficacy requirements for their device, e.g., requirements for performance, risk management, design, etc.
- The GSPRs, located in Annex I of the IVDR, are similar to the Essential Requirements Checklist (ERC), located in Annex I of the IVDD.
- European Harmonized Standards should be utilized, where available. The reason is that use of harmonized standards ‘presumes compliance’ to the applicable requirement.
Risk Analysis & Management
- Manufacturers must assess possible risks related to their device and rate the probability of occurrence against the severity of harm if it does occur. Manufacturers should detail the procedures in place to mitigate the risk or actions to take if it occurs. An approach some companies follow is to incorporate a Failure Mode and Effects Analysis (FMEA) template as part of their overall risk management system.
- EN ISO 14971:2019, for medical device risk management, is harmonized standard under the EU IVDR.
- Annex I, section 3 of the IVDR includes specific criteria that manufacturers must meet when implementing their risk management system. This section states that risk management is “a continuous iterative process throughout the entire lifecycle of a device, requiring regular systematic updating”.
2) Post-Market Surveillance (IVDR Annex III)
Post-Market Surveillance (PMS) Plan
- The Post Market Surveillance (PMS) section of the TDF details the manufacturer’s plan to collect and assess post-market data. The PMS Plan should include information from serious incidents, complaints, public information on other similar medical devices, and more (refer to IVDR Annex III, Section 1(a)).
- The PMS Plan must also establish how the manufacturer will use the data collected to take action when needed. Actions may include making updates to device documentation, such as the PER, improving the risk management and/or taking preventative or corrective action.
Post-market Performance Follow-up (PMPF) Plan
- The Post-market Performance Follow-up (PMPF) plan is a subset of your PMS Plan and is very much intertwined with your risk management and performance evaluation. The PMPF plan is intended to help identify previously unknown risks and to confirm the device’s safety and performance.
- A PMPF Plan can include a PMPF study when warranted. However, other methods can also be used to address gaps in your pre-clinical data and to demonstrate a continued positive benefit-risk ratio, when appropriate. Examples include feedback via patient or physician surveys and screening of scientific literature.
Post-Market Surveillance Report (PMSR)
Manufacturers of Class A and B devices must prepare a post-market surveillance report (PMSR) based on data collected once the product is on the market. The PMSR is generated through review and analysis of the gathered PMS data and should also include any preventative or corrective actions taken.
The IVDR states the PMSR should be updated ‘when necessary’ and made available to the notified body and competent authorities ‘upon request’.
Periodic Safety Update Report (PSUR)
Manufacturers of Class C and D devices are required to prepare a Periodic Safety Update Report (PSUR) for each device.
The PSUR is a living record in which the manufacturer systematically assesses their PMS data to ensure the device continues to be safe and effective and to provide an accurate picture of the products’ performance post-market. This includes any preventative or corrective actions taken and volume of sales.
The PSUR must be updated at least annually. A Class C manufacturers must make the PSUR available to its notified body, upon request. Manufacturers of Class D IVDs must provide its updated PSURs to its notified body and the PSUR will further be accessible to all national competent authorities and the EU Commission.
3) Performance Evaluation (IVDR Annex XIII)
The Performance Evaluation Report (PER) is a crucial element of the technical file, and includes the following information:
- basic device information,
- Performance Evaluation Plan (PEP),
- common specifications and harmonized standards,
- a literature review,
- data from a performance study (if required),
- Post-Market Surveillance (PMS) data,
- Post-Market Performance Follow-Up (PMPF) data,
- a plan for continual updates to this section, and
- other relevant device documentation, such as the IFU.
The PER is intended to be a ‘living’ document and should be continually updated. Specifically, the regulation states that the “clinical evidence and its assessment in the performance evaluation report shall be updated throughout the life cycle of the device concerned with data obtained from the implementation of the manufacturer’s PMPF plan…and the post-market surveillance plan…”.
Other elements of CE Marking
Manufacturers, including the lowest risk Class A self-certified device manufacturers, are expected to have a minimum quality management system in place. Further, manufacturers should have a system for incident reporting and managing field safety corrective actions (FSCAs), such as device recalls.