The European Commission (EC) officially published the EU In Vitro Diagnostic Regulation (IVDR) 2017/746 in the Official Journal of the European Union (OJEU) 05 May of 2017, which came into force on 25 May 2017. The deadline for compliance is 26 May 2022, and there has been no indication that it will be extended. Manufacturers with an EC certificate for an in vitro diagnostic (IVD) medical device placed on the market prior to May 2022 are entitled to a “soft” transition period from May 2022 to May 2024 (according to Article 110 of the IVDR).
Although adapting to the changes between the In Vitro Diagnostic Directive and the IVDR are not insurmountable, they will require additional time and resources as a result of additional oversight by the notified body (NB), a higher threshold for clinical evidence and the performance evaluation report, and ongoing compliance. The most significant change created by the IVDR is the level of NB oversight, which impacts the self-declared IVD potentially increasing the need for NB certifications from 20% currently to 80%. Finding and submitting to an NB may be challenging, as there are only 5 certified as of 23 March 2021. After a NB has been secured, the next hurdle will likely be clinical evidence, which may be the greatest challenge and the largest undertaking. New under the IVDR is the preparation and submission of a scientific validity report, analytical performance report, clinical performance report, performance evaluation plan (PEP), and performance evaluation report (PER). Additionally, considerations should be made when preparing the PEP as it will dictate the PER, and the outcome of the PER will lead to the post-market performance follow-up plan. Remediation to the IVDR is not a 1-time fix. Updating the technical file, performance evaluation, and post-market data will be ongoing and continue through the lifetime of the IVD.
Preparing
The EU IVDR can be overwhelming and trying to navigate the path to compliance can seem impossible. You read the IVDR and then read it again. There are new definitions, expanded essential requirements (now called general safety and performance requirements [GSPRs]), a new classification system, and additional requirements throughout the document.
Attending workshops for best practice and guidance may give you additional insight, and the Regulatory Affairs Professional Society (RAPS) can be a great resource for this type of learning. On 11 and 12 February 2021, I attended the workshop “IVDR: Practical Implementation of the New Regulation for IVDs from RAPS.”This workshop reviewed the IVDR, including transition plans, top tips, and key changes for manufacturers from NBs and subject matter experts. Topics presented included an overview of the IVDR, classification, conformity routes, software and IEC 62304, technical documentation, GSPRs, risk management, performance evaluation, economic operators, and project management.
Key Takeaways
Key takeaways from the IVDR workshop are the following:
- Everything leads back to your intended purpose. Ensure the intended purpose is well defined and complies with the IVDR, including the following:
- What is being detected/measured
- What the intended function is (screening, monitoring, diagnosis or aid to diagnosis, prognosis, or predications)
- What specific disorder, condition, or risk factor the test is intended to detect, define, or differentiate
- Whether the test is automated
- Whether the test is qualitative, semi-quantitative, or quantitative
- Who the intended user is
- What the intended population is (if applicable)
- What the type of specimen is
- Remediation of your technical files is time consuming and may require additional clinical data and resources. Plan on budgeting 3% to 5% of product revenue to become compliant and maintain compliance.
- Technical files need to be clear, organized, and readily searchable to help you move through the review process more efficiently and reduce questions.
- The certification mark (CE) is recognized in countries outside of the EU and may affect other registrations.
The workshop has confirmed my experience and understanding of the new regulations. One of the more difficult changes to implement is the completion of the PEP and PER. The PER is a complex report that requires review of the risk assessment, claims, product literature, and analytical and clinical performance reports and incorporates post-market data. These are required for all class IVDs and need to be updated throughout the lifecycle of the IVD and at least annually for class C and D IVDs. Contact us if you have any questions or need assistance with complying with the IVDR.
