Clinical laboratories that develop their own in vitro diagnostic tests must acquire and maintain certification in all markets where the product is used. If those tests are used in the European Union (EU), the requirements are contained in a sweeping new law called the In Vitro Diagnostic Regulation (IVDR).
Even if your lab is located outside of the EU, simply performing your laboratory-developed tests (LDTs) on specimens collected from European citizens might count as “distance sales” bringing the tests within the ambit of IVDR, making compliance imperative.
Here is a quick overview of IVDR and how it may impact your laboratory operations.
What is IVDR?
The IVDR establishes uniform safety, integrity, and quality standards for medical devices that perform an in vitro diagnostic function in the nations where the regulation applies. While the EU has regulated in vitro diagnostic medical devices since 1993, the IVDR requirements are more comprehensive and stringent than those of its predecessor, the In Vitro Diagnostic Directive (IVDD), i.e., Directive 98/79/EC.
|In addition to the IVDR, the EU has adopted, and is in the process of implementing, a parallel Medical Device Regulation (MDR) governing medical devices used on humans covering everything from bandages and needles to hospital beds and wheelchairs.|
What is an in vitro medical device?
The term “medical device” in the IVDR applies to any device used to examine or monitor humans. That includes everything from reagents to software used in clinical labs, including calibrators, diagnostic assays for infectious diseases or genetic conditions, specimen receptacles and other test kit accessories, and digital systems for analysis and information management.
Where does IVDR apply?
In addition to all 27 EU member states, the IVDR applies in the European Free Trade Association States of Iceland, Switzerland, Norway, and Liechtenstein. Notably absent from the list is the United Kingdom, which post Brexit, applies its own national certifications.
When did IVDR go into effect?
First published on May 5, 2017, the IVDR took effect after a somewhat controversial, pandemic-disrupted five-year transition period. As of May 26, 2022, affected clinical laboratories must comply with IVDR, and following the previous IVDD rules will not suffice.
What are the differences between IVDR and IVDD?
The key regulatory changes from the IVDD to IVDR include a completely new classification system based on product risk, stricter product evidence requirements, and a life-cycle product approach that requires laboratories and other test makers to maintain control of their supply chain and perform more robust post-market surveillance.
The regulation also establishes a new system to track vital information about devices approved under the IVDR and MDR. Each approved product must have a unique device identification (UDI) number that is entered into a public-facing IT system called EUDAMED (European Databank on Medical Devices) that collates data associated with each UDI product into specific modules.
IVDD vs IVDR: Summary of key changes
|Covered devices||Physical devices and receptacles for analysis of bodily specimens||Any device used to examine or monitor humans, including “software or systems” connected to in vitro activity|
|Product classification||Predetermined list classifies products based on the conditions they are designed to diagnose||Products classified into one of four classes (A to D) based on the risks they pose|
|Certification||Self-certification||Certification via notified bodies|
|Clinical evidence standards||Limited emphasis on supply chain traceability and post-market surveillance||New clinical evidence standards, UDI system and EUDAMED database that collates actors, UDI data, post-market surveillance activity, notified bodies, certificates, and clinical investigations and studies|
What must your clinical laboratory do to comply with IVDR?
While the exact pathway to IVDR compliance, or “declaration of conformity,” varies depending on the classification of your IVD product, the road map includes five basic steps:
1. Determine your product’s IVDR classification
Since IVDR requirements vary depending on a product’s risk classification, you first need to determine the classification of your own product. There are four categories (A to D) with A representing the lowest risk and D the highest. Class A IVD products can be self-certified; all other device classes require assessment and approval by an EU-approved notified body (NB) that performs a conformity assessment to verify that the device meets IVDR standards.
Use the IVDR’s seven rules to categorize your device by answering the following questions:
2. Maintain technical documentation
Maintain appropriate and ongoing technical documentation for the product based on its classification.
IVDR Technical Documentation Requirements
|Class A & B||Update post-market surveillance report as necessary and make it available to NBs upon request|
|Class B, C, & D||Tell member states where device was manufactured (if you are an economic operator)|
|Class C||Make periodic safety update report available to NBs upon request; member states may also request the designation of reference laboratories to verify the performance claimed by the manufacturer|
|Class C & D||Manufacturer must create safety and performance summary and upload it to EUDAMED|
|Class D||Electronically submit periodic safety update report to NB via EUDAMED|
3. Implement QMS
To ensure IVDR compliance, clinical laboratories must have an effective quality management system (QMS) with standardized procedures to measure, maintain, and verify an IVD product’s effectiveness throughout its life cycle. That will require regularly and carefully documented QMS audits performed by a qualified auditor.
4. Manage your supply chain
Under IVDR, every “actor” in the IVD product supply chain must independently verify that the previous actor complied with the applicable regulatory requirements. Consequently, you need a mechanism for onboarding, assessing, and communicating with your suppliers on a consistent basis. You also need to create a documentation trail you can use to audit and demonstrate your supply chain control efforts.
5. Perform post-market surveillance
IVDR compliance responsibilities do not end when your product hits the EU market. You must carry out post-market surveillance, including monitoring for product safety and clinical performance. If the IVD is in class C or D, you must submit regular updates for NB review and upload them to EUDAMED. You must also use EUDAMED to report serious incidents and corrective actions involving the product.
Ensure your diagnostic product is compliant with the new EU IVDR
The takeaway for clinical laboratories is to recognize that their diagnostic products may be subject to the new EU IVDR rules, and if so, labs should prepare to make an immediate transition to IVDR regulations. The most significant challenge will be ensuring that the product complies with the new complex evidence requirements throughout its product life cycle.
Your lab might have a leg up if your product has received clearance from the U.S. Food and Drug Administration (FDA) or is accredited under other International Organization for Standardization (ISO) standards for medical devices such as ISO 13485:2016.
Nonetheless, IVDR rules also differ significantly from existing US regulatory and ISO requirements, justifying the need for labs to perform a gap analysis. By comparing IVDR requirements to your current device product policies, procedures, and protocols, your lab can identify and address any gaps and divergences, ensuring compliance with the IVDR.