In previous articles in this series, we’ve touched upon the content of the In-Vitro Diagnostic Regulation (IVDR) and what to expect. This article summarizes the series, and also explores how the In-Vitro Diagnostics (IVD) manufacturer can make the most out of the transition period while obtaining a re-certification under the IVDR.
When comparing the In-Vitro Diagnostics Directive (IVDD) and the new In-Vitro Diagnostics Regulation (IVDR), it’s obvious that the IVDR improves quality and safety of IVD devices and strengthens the transparency of information and traceability throughout the distribution chain.
The IVDD already covers most of the requirements in the IVDR. Now, the IVDR goes one step further and provides much more guidance on how to comply with these requirements. This, combined with the fact that the IVDR’s additional definitions make it less open for interpretation, helps provide a transparent and sustainable regulatory framework. With that in mind, there are also some major differences between the IVDD and the IVDR:
Device classification has changed dramatically. Many IVD devices currently on the market are classified as self-declared devices under the IVDD. The new classification scheme changes that. In fact, the number of self-declared devices is expected to fall from 80% under the IVDD to 20% under the IVDR. This also means that many IVD manufacturers, who were not previously certified by a Notified Body (NB), will now require certification to keep their products on the market.
Grandfathering is no longer possible, and many IVD manufacturers will need to perform additional clinical and performance studies to comply with the IVDR requirements. Many of the manufacturers don’t have access to clinical data for existing products, making an especially difficult challenge for legacy data/IVD devices.
Supporting liability and traceability, legal responsibilities will apply to all participants in the distribution chain. In other words, all participants have their own regulatory responsibilities depending on the circumstances under which the IVD device is put on the market. For example, the Authorized Representative is responsible for verifying compliance with the IVDR. They are also legally liable with the IVD manufacturer for any defective devices placed on the market that fail to comply with the IVDR.
The IVDR identifies a new role, as well: the person responsible for regulatory compliance. As the name of the role indicates, there must be at least one person in the organization responsible for IVDR compliance. This person must either have formal training or four years of professional experience and must be employed within the organization. Micro and small enterprises within the meaning of Commission Recommendation 2003/361/EC are exempted from this requirement and are not required to have the regulatory responsible person employed within the organization. However, they must have one at their disposal at all times.
The IVDR’s impact on an individual company depends on the risk profile of the IVD devices in the company’s portfolio. It will be especially high if new clinical studies are needed. But regardless, each and every IVD device company operating in the EU will feel some impact. It’s important to note that whatever impact a company expects, it is a moving target, since approximately 40 delegated and implementing acts are still to be drafted and published by the European Commission.
The IVDR sets May 26, 2022 as a hard deadline for certification of IVD devices that didn’t require certification under the IVDD. The devices cannot legally be sold without the IVDR certification after this date. However, IVD devices currently under NB supervision have a potentially longer transition period that extends to May 27, 2024. This transition period is based on already having a valid certification under the IVDD that extends past May 26, 2022 (but no longer than May 27, 2024). Furthermore, sale of stored inventory is expected to be allowed as long as the IVD devices were produced under a valid IVDD certificate.
The impact on IVD manufacturers is easy to spot and affects the entire line of business. The QA, Regulatory and the Clinical departments have their work cut out for them with requirements on Quality Management System (QMS), classification, increased clinical documentation– not to mention securing the person responsible for regulatory compliance. Companies will generally need to adapt current, and create new, systems and processes to meet the IVDR requirements. One example: companies must ensure support for both the IVDR requirements and the latest updated harmonized standards such as ISO 13485:2016.
Don’t neglect the requirements for legal responsibilities throughout the distribution chain. These place a huge workload on legal departments in terms of contract management and negotiations to ensure that contracts and relationships with subcontractors and suppliers are compliant with the IVDR liability requirements.
In addition to the IVD manufacturer, the rest of the distribution chain is also affected. To address liability in all phases of an IVD device’s life cycle and on all levels of the distribution chain, all have regulatory responsibilities with legal impact regardless of where the IVD device is being manufactured.
The impact on NBs is also game-changing. They will require a huge effort as well as an increase in resources – just like the IVD manufacturers. Changes cover:
Further, the IVDR puts additional pressure on them with the introduction of a mechanism for scrutiny of the NB’s conformity assessment.
Road to compliance
Since the definition of IVD devices has also changed, a company must determine whether the IVDR is applicable in relation to their existing portfolio. Next, they must examine the IVDR closely to gain a better understanding of the requirements and business impact.
Companies must strategically assess their portfolio to determine which IVD devices to continue after the transition period. Due to the significant changes in requirements and the end of grandfathering provisions, a high percentage of existing portfolios are expected to be phased out during the transition period.
Most IVD device companies do not have their technical documentation in shape for the IVDR. Since the IVDR requires a lot more (and different types of) data to substantiate performance and safety, it will also require more clinical data. Generating clinical data is costly, so it will probably be impossible to provide sufficient evidence for all the devices. Without sufficient evidence, there will be no certificate, no product to put on the market, and hence no revenue. Companies must decide which products to sell after this period, then work toward this goal.
After establishing which IVD devices to certify under the IVDR, companies must classify the remaining IVD devices. This classification will provide the foundation for the gap analysis and ultimately help in the impact assessment. This will, in turn, provide an overview of gaps in the QMS, as well as an overview of clinical data requirements that are not met in the current documentation.
Once the portfolio, classification and impact assessment have been performed, companies must figure out how to meet the new requirements, prioritise them, identify risks, etc. And, of course, they must engage the NB and the stakeholders, internally and externally, to ensure everyone knows what is expected of them and when it is expected.
During this phase, it is important to go over the re-certification strategies. When engaging the NB, remember that they must be re-designated under the IVDR. Decide whether to continue with the existing NB or begin the process of switching to another NB. Considering the increased role of the NB (as is the case with the IVD companies), some will likely not survive the IVDR due to lack of resources and increased workload/required competencies. A switch to another NB will take time and may not be easy – so it’s important to start the process now.
The liability and transparency requirements in the IVDR will require renegotiation of many contracts. Suppliers, distributors, etc., that are unwilling or unable to renegotiate contracts to follow these requirements will need to be replaced. This process also takes time and resources and should be started sooner rather than later.
A QMS that can document compliance with the IVDR and harmonized standards is also important. Since companies must establish a post-market surveillance system as part of the QMS, it is highly recommended to start working on the procedures for this system. This should be prioritised along with the assessment and planning of the clinical documentation necessary for meeting the new requirements.
Management involvement must be secured throughout these steps. IVDR compliance will be costly due to the additional clinical data needed to demonstrate performance and safety. On top of this, a significant increase in staff is also expected to accommodate more documentation and the fulfilment of quality assurance requirements.
Furthermore, management must also secure the required person responsible for regulatory compliance by the end of the transition period. Since this person must have either formal training or four years of professional experience, planning may be required to secure the availability of this or these resources.
As mentioned in a previous article, there will be a high demand for these competencies. Companies will be competing for these resources with both the NBs and the Member States, because they also require people with similar experience. A company may want to consider looking internally to develop existing employees. If this strategy is chosen, planning must begin now. There is only a little more than four years until the end of the transition period.
Creating a project to handle these big changes requires a holistic approach with stakeholder from all areas of the company. Change Management is vital for this process, to assess impact on organization, processes, procedures and competences.
Some obstacles/challenges arise from external forces, which cannot be controlled, so use the transition period wisely to ensure a smooth transition to IVDR.
More information can be found in the IVDR itself and its Annexes. Notified bodies also have online publications on their websites:
About this Expert Article Series
The next, and final, article in this series will summarize the changes in the IVDR and also explore potential actions for accomplishing compliance with the IVDR during the transition period.
Here is an overview of the series, including links to the earlier articles:
We hope you find these articles useful in your daily work. Note: This series is not intended as comprehensive guidance, but rather a high-level overview of key IVDR changes and implications. Further questions? Feel free to contact us. We are happy to discuss advancing IVDR in your company.
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