Until recently, many IVD manufacturers were able to make changes to the design or intended use of their devices with minimal consequences under IVDD (98/79/EC). With the transition to IVDR and the date of application just around the corner, that time window is quickly closing. As of 26 May 2022, IVD manufacturers will no longer be able to make changes to the intended purpose or design of a device under IVDD, and all classes of IVDs will be subject to IVDR regulations.
What is the date of application and the extended transition period?
While manufacturers of Classes A sterile, B, C, and D in-vitro diagnostics can take advantage of additional transition time, they can only do so if they have, at a minimum, signed a declaration of conformity under the IVDD before the 2022 IVDR date of application. Nonetheless, they will be required to comply with post-market surveillance and vigilance activities under the IVDR. This decision was made largely in the interest of patients so that much-needed products wouldn’t be pulled from the market because manufacturers aren’t ready for CE marking under IVDR. For nonsterile Class A IVDs, such as the vast majority of instruments, accessories with no critical characteristics, or products for general laboratory use, for example, the transitional provisions are not applicable, and they need to be IVDR compliant by 26 May 2022.
Secondly, manufacturers cannot benefit from the extension if they are making significant changes. If significant changes are necessary, the IVD must be in compliance with IVDR, even if it is in one of the classes that qualify for the extended transition period. This means that any manufacturers that are currently planning to make changes must have them in place before the 2022 date of application.
What are the significant changes under IVDR?
Like many requirements under the new regulation, there is not yet any official guidance for manufacturers to follow. Article 110 section 3 of the IVDR limits significant changes to changes in design and intended purpose. MDCG 2020-3 gives clarity on what should be understood as a significant change. Although this document is applicable to MDR, it is expected that any forthcoming IVDR guidance will largely mirror MDCG 2020-3 with no surprises.
Some of the changes that are likely to be considered significant under IVDR include:
Clinical and analytical data that is obtained through new studies could prompt a significant change. For example, changes to diagnostic sensitivity or the inclusion of new interfering substances in the instructions for use would be considered significant.
Manufacturers must monitor post-market data to ensure that the device is being used for the intended purpose. Off-label use may trigger updates to the labeling through new warnings and/or limitations that could ultimately result in the need for an IVDR application.
It should be noted that limiting the intended purpose (e.g., by removing an associated clinical condition or claim) is not typically considered a significant change, whereas expanding the intended purpose to new clinical conditions would be considered significant.
New specimen claims could also prevent an IVD from benefiting from the additional transition time. For example, in the case of SARS-CoV-2 assays, the addition of nasopharyngeal or nasal swabs to devices that only had oropharyngeal claims would be a significant change.
Any design changes that modify assay critical ingredients, such as antibodies or primers, would be considered significant because they determine the product performance. The change of a gene target in an RT-PCR COVID-19 assay would therefore be significant.
On the other hand, design changes related to corrective actions are nonsignificant changes. This aspect is not clearly covered in Article 110 section 3 but was assessed and confirmed by the Competent Authorities for Medical Devices (CAMD) in Question 15 of the “CAMD Transition Sub Group FAQ - IVDR Transitional provisions” document.
When significant changes are required, clinical evidence is necessary to show that the product performs in the intended user's hands and that design changes produce an acceptable clinical benefit according to the state of the art in medicine.
What are the next steps for manufacturers?
The extended transition period gives many manufacturers some much-needed breathing room. Use this time to ensure that you are fully prepared before the new deadline arrives.
IVD manufacturers with a large portfolio of devices should create a strategic plan that takes the progressive rollout into account. Focus first on the IVDs that must be in compliance at the earlier dates, but don’t neglect the lower-risk devices that have more time to transition. Use the time from the progressive rollout wisely to avoid having products removed from the market.
If you are planning significant changes and will need to comply with IVDR before the progressive transition date for the device class, don’t leave it until the last minute. When creating new systems and processes, remember that IVDR compliance is ongoing and not just a one-time submission. Understand the timeline of ongoing requirements so you can be prepared.
Engage a Notified Body
Only six notified bodies are designated under IVDR. Considering the 80-90 percent shift of IVDs that need notified body involvement, the capacity of these organizations will become a bottleneck. Notified bodies are already reaching capacity, and there may be a delay before they can start reviewing your device.
In the meantime, your product may have to come off the market. Although notified bodies are actively building capacity, it can take up to two years to qualify a new technical reviewer, and the pool of professionals with IVD experience is limited. The longer you wait, the harder it will be to find a notified body that has the time and resources to certify your products before the deadline arrives.
Implement QMS Updates
In preparation for IVDR compliance, manufacturers should make sure their QMS is up to date. Most companies have ISO 13485 in place, but they still need to update their systems to be in IVDR compliance from May 2022, specifically around post-market surveillance and vigilance requirements. IVDR brings additional requirements beyond ISO, including documenting qualifications for the person responsible for regulatory compliance and documenting procedures that impact the conformity assessment of certain types of devices (companion diagnostics or Class D devices, for example). If these and other requirements are not met, notified bodies will raise nonconformities.
The IVDR QMS audit will be a single audit reviewing IVDR requirements and not a gap audit according to ISO 13485. Therefore, having an IVDR-compliant QMS is crucial for a successful IVDR CE marking process. In some cases, manufacturers may need to have two QMS systems in place to comply with IVDD and IVDR regulations during the transition phase because it is unlikely their entire portfolio will simultaneously transition to the IVDR. Updating your QMS can take six months to a year depending on the organizational structure, so if this process has not already been started, now is the time.
Create an Integrated Team
The transition to IVDR encompasses the entire company, not just the regulatory team. Design, engineering, clinical, quality, risk management, manufacturing, and marketing teams need to have a solid understanding of the changes under IVDR and what it means for their work and the company as a whole. This will be especially challenging for the many manufacturers that were previously able to self-certify their IVDs because many of these processes will be new to them. Don’t underestimate the resources required for this endeavor—the potential consequence is products being pulled from the market.
How can RQM+ help?
In anticipation of the need for a strong team, in 2017, RQM+ started building our IVDR staff in addition to regulatory professionals with deep U.S. and EU experience. We are prepared to support your IVDR needs with a team that covers all diagnostic specialties. Former notified body leaders on the team understand what notified bodies expect to see, and former members of notified body working groups have unique insights into forthcoming IVDR guidance.
RQM+ IVDR services include:
- Mock QMS audit and mock technical documentation assessments
- Automated gap analysis tools
- IVDR readiness assessments
- IVDR application check
- Clinical evidence strategy
- IVD portfolio strategy
- Strategy and execution for PEP, PER, APR, SVR, CPR, SSPs, PSURS, and other accompanying documentation
- Filling in the gaps to address weaknesses on your team
Each RQM+ client team has experienced PMS, clinical, and regulatory professionals aligned with your diagnostic specialty.
With the date of application just around the corner, many manufacturers are still preparing for compliance with post-market surveillance requirements. Watch our on-demand webinar, “Overcoming Your Challenges and Streamlining the SSP and SSCP,” to learn what steps you can take to optimize the SSP process for your Class C and D IVDs.