One of PQE Group's unique features, is its global presence, with a dedicated local touch. We'll support you at 'home', providing your business with a rich experience from all over the world.
Learn more about our compliance support for Medical Device
Highlights of the US Regulation and Path to Market
In the United States, the Food and Drug Administration (FDA) classifies IVDs as medical devices that are subject to the relevant regulations identified in the Code of Federal Regulations (CFR), including pre-market and post-market controls for the device. In order to determine the appropriate documentation and requirements needed for the device to make it to market, it is imperative that manufacturers identify the appropriate risk classification of the device early on in their development process.
Medical devices in the US are categorized into three classifications – Class I (low to moderate risk, requiring general controls), Class II (moderate to high risk, requiring general and special controls), or Class III (high risk, requiring general controls and Premarket Approval - PMA). IVDs would then follow suit with the regulatory requirements specified for any of these pathways, based on their risk-associated classification. IVDs also have specific labeling requirements under 21 CFR 809 that must be complied with, prior to marketing or obtaining marketing authorization.
Highlights of the EU Regulation (IVDR) and Path to Market
In the European Union, in vitro diagnostics were previously regulated under the In Vitro Diagnostic Directive (IVDD) but are now regulated by the IVD Regulation (IVDR) – Regulation (EU) 2017/746. In the EU, IVDs are not regulated under the same ‘medical-device umbrella’ that is found in the US, which is why IVDs are regulated under the IVD Regulation (IVDR) and medical devices are regulated under the Medical Device Regulation (MDR). Similarly to the regulatory pathway in the US, additional requirements are necessary for IVDs of a higher risk classification for appropriate submission to Notified Bodies (NBs).
In the EU, there are four risk classifications for IVDs – Class A (lowest risk), Class B, Class C, and Class D (highest risk). There are several requirements that apply to all classifications, such as the General Safety and Performance Requirements (GSPR), risk classification ruling and justification, device registration in EUDAMED (the European Database on Medical Devices), implementation of Quality Management Systems, and relevant documents relating to performance studies. However, additional documentation is required for higher risk IVDs that shall be completed in a manner proportionate to that risk classification – including post-market surveillance (PMS) and performance evaluations.
Comparison of the Similarities and Differences
While both the US and EU have their own regulations that manufacturers are expected to follow to make it to market, understanding the similarities and differences between the two can ease the path forwards to market.
Similarities between the US and EU:
-
Authorization to Market
-
-
Other than Class A, non-sterile IVDs in the EU, and product codes listed as “510(k) exempt” in the US, all in vitro diagnostics in both the US and EU will require authorization to enter the market, whether that be through the FDA in the US or Notified Bodies in the EU.
-
-
Risk-based Classification of IVDs
-
-
Both the US and EU have taken similar approaches that identify devices based on a risk classification scale, to determine appropriate additional controls and documentation needed to verify the safety and performance of the IVD.
-
-
Post Market Surveillance (PMS) / Controls
-
-
Post market controls are identified in both the US and the EU, where manufacturers are required to monitor and report device malfunctions or issues that can or have caused harm to the population. However, there are exceptions to this requirement for select device classes in the US.
-
-
Device Identification and Labeling
-
-
Unique Device Identification (UDI) systems, as well as appropriate labeling, are required in both the US and EU, to properly identify and monitor in vitro diagnostics through distribution to patient use.
-
Differences between the US and EU:
-
‘Grandfathering’ Policy
-
-
In the US, devices that were on the market prior to May 28, 1976 (or are substantially equivalent to an existing device on the market) and have the same design and intended use as the devices marketed before this date, are not required to follow the Premarket Approval Application (PMA) process.
-
However, in the EU, after the implementation of the IVDR over the IVD (where it is estimated that only 10-20% of IVDs were subject to Notified Body oversight), a majority of IVDs are now required to have a NB certificate – requiring additional work from manufacturers.
-
-
Risk
-
-
In the US, the FDA classifies all IVDs as medical devices that fall under one of three risk classifications – this is specified in the premarket application process, designating the device in its respective classification.
-
Whereas in the EU the IVDR classifies in vitro diagnostics according to four different risk classifications that must then be justified according to Annex VIII (classification rules) of the IVDR. IVDR classifies IVDs using risk-based approaches.
-
-
Post Market Surveillance
-
-
In the US, manufacturers are required to report device issues that can or have led to an adverse event.
-
In the EU, information regarding post market data will be in EUDAMED. The EU IVDR also includes IVDD requirements, but specifies a more structured approach to evaluating and managing information from post-market. For Classes C and D, results from post market activities are summarized in Periodic Safety Update Reports (PSURs); for Classes A and B in Post-Market Surveillance Reports (PMSRs).
-
-
Device Identification and Labeling
-
-
Between the US and EU, UDI requirements are similar but the EU IVDR follows a different format, and information found in the FDA database would look different than that stored in EUDAMED, which requires a more detailed account of the identification and labeling.
-
-
Clinical Evidence
-
-
In the US, clinical evidence is required for all Class III and some Class II devices, whereas clinical performance testing is required for all IVDs. Clinical evidence however, is dependent on the risk classification of the IVD with no specific reporting requirement.
-
In the EU under IVDR, clinical evidence for each IVD device is based on clinical data and a Performance Evaluation. PE (Performance Evaluation) consists of three main pillars: Analytical Performance, Clinical Performance and Scientific Validity. Post-market performance follow up (PMPF) updates the Performance Evaluation (PE) throughout the life cycles of IVD device.
-
Conclusion
As IVD manufacturers continue to engage with multiple markets, it remains imperative that they familiarize themselves with the relevant regulations (or standards) necessary to properly manufacturer and market their products. While the summary provided above highlights high-level requirements, to better understand the necessary documentation and processes please refer to the relevant regulations in either country.
References:
