Summary
The new regulations on medical devices and in-vitro diagnostics, MDR and IVDR, are set to replace three existing Medical Device Directives: AIMD (Active Implants), MDD (medical devices), and IVDD (IVDs).
IVDR will be officially implemented on 26 May 2022. A transition “grace period” is included for devices that are already CE marked under the IVDD.
Significant changes will be implemented with the new IVDR, which will have implications for companies.
Navigating through the different regulatory and market access pathways and tackling relevant challenges require combined expert input from both perspectives.
Major changes are afoot in Europe’s regulatory landscape for in-vitro diagnostics. From 26 May 2022, the In-Vitro Diagnostics Regulation (IVDR) will replace current procedures and practices stipulated by the In-Vitro Diagnostics Directive (IVDD).
Diagnostics already CE-marked under the IVDD (legacy products) will have a certain “grace period” to transit to the stricter IVDR. The transition period spans from 3 to 5 years depending on the risk class of the solution, i.e. higher class IVDs receive shorter grace period.
After this, IVD solutions which have not adjusted to the IVDR may be dropped from the market. Due to major challenges transitioning to the IVDR, the European Commission recently proposed an extension to the transition period by one year. The proposal moved to the European Parliament and Council for adoption in October 2021 and it was approved in December 2021 without any amendments.
Current regulations under the IVDD, are only 37 pages long, but new regulations under the IVDR total 157 pages. This indicates that significant changes have been implemented.
“It is crucial for IVD companies to set up a sound IVDR deployment plan focused on the enhancement of scientific validity, analytical performance and clinical data evidencing,” said Philippe Etter, co-founder and senior partner of the regulatory consultancy Medidee Services.
Based on our IVDR text understanding, the key changes and implications for IVD companies are:
5 key IVDR challenges for diagnostics manufacturers
1. Up-classification of IVDs: The new IVDR defines four risk classes, from A to D, with A for devices with the lowest risk and Class D for devices with the highest risk. Based on the new 7 classification rules, many solutions will be up classified to a higher risk. As such, previously low-risk solutions that did not require conformity assessment by regulatory compliance assessors, also known as Notified Bodies (NB), now (under IVDR) require such assessment.
2. Increased Notified Body (NB) involvement: Initial estimates predict only 20% of manufacturers need an NB under the IVDD. Under the IVDR stricter classification, 80% will require an NB. In the meantime, the number of NBs is decreasing. Currently, only six NBs have been designated for IVD solution assessment, potentially leading to workload bottlenecks and delays in assessment, especially because these six above are almost fully booked.
3. Increased General Safety and Performance Requirements (GSPR): Every medical device must meet two critical parameters, safety, and performance. IVDR increased the relevant safety and performance requirements from 13 to 20, with some additions focusing on risk management (risk control measures during design and manufacturing stages, risk mitigation), analytical/ clinical performance, and software security, verification, and validation. Diagnostics companies have to ensure that they meet the new standards.
4. Stricter demands on clinical evaluation and post-market surveillance: Manufacturers now need to prepare analytical and clinical performance reports and a performance evaluation report for each product. In addition, as part of a post-market performance follow-up (PMPF), clinical and performance data on potential safety risks must be collected continuously and kept on file. The PMPF should be updated annually for class C and D devices.
5. More regulatory responsibilities throughout the chain: The responsibilities of each “economic operator” throughout the supply chain have been expanded to increase accountability, transparency, and traceability. Certain economic operators, such as the importers and distributors, had so far only business-relevant responsibilities. Now, they will also face regulatory accountability, such as verifying that they device has been CE marked. The new regulations also require manufacturers to appoint the so-called person responsible for regulatory compliance (PRRC).
These regulatory changes were triggered by the Poly Implant Prosthese (PIP) Breast Implant Scandal where PIP implants made from a cheaper, industrial-grade silicone, which was not approved for medical use, were rupturing at a rate that was double the industry average.
The silicone gel was known to cause inflammation and possible scarring, and these implants continue to raise questions over the possibility of other harmful long-term effects. The scandal made it clear that immediate improvements in medical device oversight were needed and hence the revision of regulations.
The knowledge for this article was gleaned through CAS CARAQA program on Clinical, Regulatory and Quality Affairs for Medical Devices and In-Vitro Diagnostics, which Centivis Consultant Anastasios Gkiokas recently completed. The program is offered by the School of Life Sciences FHNW, in collaboration with regulatory consultancy Medidee Services.
The increased regulatory scrutiny of the new regulations will pose considerable challenges for manufacturers. IVDR submission require increased upfront investment prior and post market entry. In parallel, diagnostics are receiving increased payer scrutiny, although they represent a small fraction of healthcare costs compared with drugs. Securing IVD coverage and reimbursement at an acceptable rate is becoming more and more challenging.
Navigating through the different regulatory and reimbursement pathways would require expert input from both perspectives. Centivis looks forward to teaming up with regulatory experts Medidee Services to support you with a combined reimbursement and regulatory assessment.
We hope to provide you the keys to unlocking the European market.
*Medidee is a regulatory consulting agency (RA, CA/CRO, QA) with sites in Switzerland, Germany, Denmark, Belgium, USA, India and APAC, serving companies of all sizes ranging from academic startups to majors. Its core focus is on regulatory affairs, quality insurance, clinical affairs and digital health for medical devices and in vitro diagnostics.
For more information, contact us at info@centivis.com