September, 2017: It has been clear for many years that the In Vitro Diagnostic Directive (IVDD) 98/79/EC needed a thorough revision to strengthen the safety of all medical devices available in the EU. The result: a new European In Vitro Diagnostic Regulation (IVDR), published in The Official Journal of the European Union on 5 May 2017, with entry into force on 25 May 2017.
Importantly, it is worth noting that the IVDR does not actually include all new requirements. Rather, it is largely a revision that contains guidance on how to fulfil the existing IVDD requirements. The IVDD was general guidance for manufacturers, who then had to decide for themselves how to follow the requirements. In many instances, this resulted in lack of compliance. Yes, the IVDR does contain some new requirements not previously seen for In-Vitro Diagnostics (IVD) devices, but most of the requirements in the IVDR are actually the same as they were in the IVDD.
Since the revision of the legislation has been issued as a regulation, it means it will come directly into force and does not need to be incorporated into national law on a Member State level. The additional definitions in the IVDR leave it less open for interpretation. In the end, the aim is to provide a transparent and sustainable regulatory framework.
Even though the Regulation has already entered into force, it is still a moving target. It is expected that approximately 40 additional pieces of legislation pertaining to the IVDR will be published throughout the transition period – although when is still uncertain. Some of these delegated and implementing acts will clarify and fine-tune elements of the Regulation, whereas others might add further requirements.
Even though the requirements in the IVDR are not completely new, it is important to understand the implications on the portfolio. We briefly explore some of these issues, below. And stay tuned because this article is the first in a five-part series. Future articles will explore each of these individual impacts in more detail.
Quality Management System (QMS)
Operating a comprehensive QMS is not a new requirement. However, the IVDR now specifies what the QMS must include and how the manufacturer must operate it. Also, a new role is introduced: “Person responsible for Regulatory Compliance”. Manufacturers must start to plan for this new role immediately because this person must have at least four years of expert knowledge in the field of IVD devices. This impact will be examined further in a coming article.
Classification under the IVDD was a simple, rigid, list-based classification that did not keep pace with the technological advances seen in the area of IVD devices. Under the IVDD, there was a large risk of inconsistent classification decisions by different EU Member States. The new risk-based, flexible classification under the IVDR reduces this risk and is better suited to accommodate changes. The class of any given medical device will be determined using seven rules. The new classification will also apply to all IVD devices currently on the market in the EU. This, as well as the consequence on conformity assessments, will be examined further in a coming article.
Increase in regulatory scope
The new classification rules have many impacts. One important example: Previously, under the IVDD, if an IVD device did not fit into any of the other classes, it would be self-declared. Now, under the IVDR, the IVD devices will be classified as Class B, and thereby fall under Notified Body (NB) supervision. This has a huge impact on especially self-declared IVD devices as most of them must now be certified by a NB under the IVDR. In fact, it is estimated that while previously only 20% had to be certified by a NB, the number will now be 80%. Of course, this number can be higher or lower depending on the portfolio of the company.
Legal responsibilities in the distribution chain
The IVDR is applicable to all devices sold or marketed within the EU, with no distinction as to where they are marketed. This means that it has a huge legal impact on all participants in the distribution chain, all with their own regulatory responsibilities. Apart from the IVD manufacturer, the participants can include contract manufacturers, distributors, suppliers, authorized representatives and others. This will require review and revision of agreements, as well as increased competition law compliance efforts in relation to parallel trade. Non-EU manufacturers are required to appoint a European Authorized Representative in the EU, responsible for verifying compliance with the IVDR. And it doesn’t end there. If they fail to comply with the IVDR, then the representative will also be legally liable, along with the manufacturer, for any defective devices placed on the EU market.
Implications for NBs
More than just the manufacturer and other players in the distribution chain are affected by the IVDR. Since the ratio of certified IVD devices is expected to grow from 20% to 80%, it will naturally mean an increased workload on the NBs. Among other things under the IVDR, all NBs must be re-designated and required to have documented procedures regarding unannounced on-site audits of manufacturers, if relevant, of, subcontractors and suppliers. NBs will notify competent authorities (CAs) of certificates granted for high-risk devices and, based on reasonable concerns, the CA may apply further procedures or request scientific advice from expert panels.
To keep up with the increased workload and the more detailed requirements, the NBs must ensure that they have enough resources, as well as the right competency level, among its personnel. Competencies that are currently very limited throughout the medical device industry – if they exist at all – and therefore also in high demand. We’ll explore the requirements for NBs further in a future article.
Clinical and performance requirements
The time for the “grandfathering provisions” known under the IVDD is over. This is bad news for manufacturers relying on data from their competitors. With the significant changes in the requirements that include the need for additional clinical and performance studies for all IVD devices (both new and existing), it is expected that a high percentage of existing portfolios will be phased out as a result.
Post-market vigilance and surveillance
To ensure continuous improvement of IVD devices, it is necessary to ensure that the QMS reflects the post-market surveillance system including a post-market performance follow-up (PMPF). Furthermore, depending on the class, it will also be necessary to prepare and submit a Periodic Safety Update Report (PSUR). For persons with previous experience from the Pharma industry, the PSUR is not a new term, but in relation to IVD devices, it is entirely new. Stay tuned for more information: this change in the post-market vigilance area is examined in a coming article in this series.
To ensure traceability of devices, allow for easier recall of devices, and increase transparency, a new device identification system based on Unique Device Identifiers (UDI) as well as a European databank on medical devices (EUDAMED) will be introduced as part of the IVDR:
UDI will be phased in over several years starting with the high-risk devices. EUDAMED is expected to be in place in 2020, at the earliest.
All the changes mentioned above indicate the huge impact the IVDR has on the IVD Industry. No one can expect changes of this magnitude to be implemented in a short time - considering the requirements to clinical data, re-certifications, etc. There is a five-year transition period, meaning the IVDR must be implemented by 27 May 2022. However, certificates issued per the Directive can still be valid for a period after this date, although this period cannot exceed 27, May 2024.
If a company fails to comply with the IVDR after the transition period and the certificates issued per the IVDD are about to expire, it will be highly unlikely that the company will be able to distribute products in the EU market.
More information can be found in the Regulation itself. Notified bodies also have online publications on their websites.
Stay tuned for more detail as we dig deeper into some of the key implications of the IVDR the rest of the articles of this 5-part series. Specifically, we’ll tackle:
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