Caroline Freeman, Principal Consultant, Consulting Services, IQVIA
Phil Johnson, Senior Director, Quality & Compliance Services, IQVIA
Despite having a longer transition of five years compared to the three years for the EU Medical Devices Regulation (EU MDR), the In Vitro Diagnostics Regulation (IVDR) provides IVD manufacturers with a much higher hurdle to jump over than the EU MDR1 for “general” IVD manufacturers. Due to this higher hurdle, IVD manufacturers must not sit back and wait for the commotion of the MDR to die down before implementing their transition.
Adding to the pressure of the May 2022 IVDR transition deadline, other, even shorter deadlines should force IVD manufacturers into action sooner. These include Health Canada’s mandate for adherence to the Medical Devices Single Audit Program (MDSAP), and the end of transition of EN ISO 13485:2016.
The IVD Regulation timeline is complex and worth considering in detail.
As with the MDR, some key pieces of the IVDR jigsaw are not yet in place and will not be for a while, such as Notified Bodies, Common Specifications, Implementing and Delegated Acts, and Reference Laboratories, but there is still a lot that manufacturers can already start doing.
The required transition steps from the IVDD2 to IVDR3 are significantly greater for most IVDs than for most Medical Device (MD) companies between the MD Directive (MDD) and MD Regulations (MDR). Not the least of which is the requirement that under the IVDR, approximately 80 percent of devices will require some form of Notified Body (NB) intervention, compared to just 20 percent under the IVDD. How the NBs will manage this additional workload is one of the big unknown pieces of the jigsaw puzzle.,
Notified Body Options
Notified Bodies (NB) are not yet designated to the IVDR, and the joint assessments of potential NBs will not start until 2019, so we will not know which NBs are available, and specifically with IVDs in scope, until very late 2019, early 2020. The TEAM-NB (The European Association of Medical Devices – Notified Bodies) published a survey4 of its members on February 12, 2018, which showed that all their members will apply to be designated under the MDR, but only 55 percent (n= 11) have applied to be designated under the IVDR. Therefore, IVD manufacturers will have a much smaller pool of NBs to choose from, and it is important to determine the plans of your current NB now, if you already have one.
With respect to legacy products, it is even more important to decide what will go through to IVDR, given the increased clinical evidence needs, re-classification, and the need to use a NB. It is essential to secure top management and marketing buy-in and understanding of the increased regulatory and clinical costs. Make a hard-headed business case for each device, assessing its value to the whole portfolio against the costs of compliance. For some companies, the economic implications of products being withdrawn due to non-compliance to the IVDR should be a real concern. Does it make sense to take some smaller ticket items through?
Next step: classification. The new classification system splits IVDs into classes A, B, C or D – and all B, C, and D devices need a NB for some element of conformity assessment. It is important to be clear on classification of all devices to be taken through to IVDR, so carry out a detailed analysis against the classification rules of Annex VIII. The implications are significant, as many IVDs which were “self-declared” by manufacturers to the IVDD will have clinical evidence which does not meet the requirements of the IVDR. The impact on Companion Diagnostics is notable where many under the IVDD were “self-declared” and will now fall into the higher risk classes (B, C, D) under the IVDR.
REMEMBER – There will be no grandfathering of products from IVDD to IVDR.
Documentation for Evidence
Technical documentation will be needed for all products, and a comprehensive list of all required contents are provided in Annexes II and III. Don’t fall into the trap of assuming that if a product meets the current Essential Requirements (ER) of the Directive, it will meet the new General Safety and Performance Requirements (GSPR) of the IVD Regulation. Here again, it is important to conduct a detailed analysis and gap assessment.
Clinical evidence is needed to demonstrate conformity with the GSPR. Performance evaluation needs to be performed (against a plan), and if performance evaluation studies are needed, start planning these as soon as possible.
Supply Chains Add Complexities
The supply chain for IVDs is more complex than for medical devices, sometimes involving multiple distributors, from the manufacturer, through laboratories, to patients. All of these distributors become “economic operators” under the IVDR if they handle product, and they will need to take legal and regulatory responsibilities. The extra costs and processes compared to handling products under the IVDD, may result in distributors dropping out of this business. We recommend that you take steps now to understand thoroughly your supply chain and start discussing with your distributors, importers, and potentially your Authorised Representative, their intentions to continue under the IVDR.
For the post-market phase, there is increased focus on post-market surveillance as a whole, not just vigilance reporting. Prepare a post-market surveillance plan, which includes post-market performance follow-up (PMPF), and perhaps also PMPF studies.
The proposed reduction in reporting times of vigilance cases from 30 to 15 days under the IVDR will impact manufacturers. The investigation of IVD complaints often takes longer due to the complex supply chain and limited access of the manufacturer to the end user, the number of devices for near-patient or self-testing, and the need to determine indirect harm of the IVD. Manufacturers will need to improve their complaint investigation processes to meet the 15-day vigilance reporting requirement. In reality this will lead to more reporting as the investigations may not be completed within 15 days, and will need additional resources for processing.
Additionally, IVD manufacturers should not overlook labels. Some major changes to labels will need to be made to accommodate UDI and the ID number of the NB, for example. Manufacturers will want to plan ahead to minimize the number of label revisions required.
All of these actions will take place against the backdrop of a requirement for a quality management system. Manufacturers should aim for EN ISO 13485:2016 compliance as soon as possible. And, if you are looking to expand beyond the EU market, consider also the parameters of the Medical Devices Single Audit Program (MDSAP), particularly for Canada, which is introducing MDSAP as a requirement during 2019.
All these changes will require investment into new systems, new resources, or both, so consider involving your top management in discussions at an early stage to ensure necessary funding and staffing are made available.
If you are new to using a NB, there are things you can be doing to learn about the necessary processes. IQVIA can provide a third-party view of dealing and selecting a NB based on our experience of working with manufacturers who use NB services.
Don’t know where or how to start? Don’t drown under the requirements, start planning now …. IQVIA can help. IQVIA consultants are prepared and available to support you through the process. To inquire, click here or send an email.
1 MDR – Medical Devices Regulation 2017/745/EU
2 IVDD – In vitro Diagnostic Medical Devices Directive, 98/79/EC
3 IVDR – In vitro Diagnostic Medical Devices Regulation 2017/746/EU
4 Team-NB survey
Choosing the right QMS for ISO 13485:2016 Compliance