Author: Keely So, Senior Manager, Medical Devices / IVD, PharmaLex Australia
In vitro diagnostic products must undergo performance studies to demonstrate that the product is safe and performs as intended. Specifically, there are two types of studies that manufacturers must undertake: clinical performance and analytical performance.
Article 2 of the In Vitro Diagnostic Regulation (IVDR) defines analytical performance as the ability of an IVD to correctly detect or measure a particular analyte. These studies evaluate certain characteristics such as analytical specificity, analytical sensitivity, trueness, precision, accuracy, and limit of detection amongst many others.
Clinical performance is defined as the ability of a device to yield results that are correlated to a particular clinical condition or physiological or pathological process or state, as these relate to the target population and intended user. These studies are required to establish or confirm aspects of device performance which cannot be determined by analytical performance studies alone or from literature or previous experience.
The characteristics that are typically evaluated in clinical performance studies include diagnostic sensitivity and specificity as well as positive and negative predictive values. These studies may also evaluate the expected clinical values in normal and affected populations.
Both sets of studies also serve as inputs to the performance evaluation report, which is a critical document for IVDs.
Conforming to GSPR
The requirement to perform these studies stems from the General Safety and Performance Requirements (GSPR) within Annex 1 of the IVDR.
One of the main ways to demonstrate conformity with GSPR is through use of harmonized standards or the parts of those standards that are relevant to the IVD in question. While it is possible to use other methods, if there are harmonized standards applicable for a device these should be used since they represent best practice.
Using a harmonized standard also helps when a notified body is reviewing the manufacturer’s technical documentation. If a manufacturer develops their own method, it may not have been properly validated, so there would need to be justification for why the method is appropriate. This can make it more difficult to prove compliance with certain requirements, as opposed to using harmonized standards.
Common specifications
Another way manufacturers can demonstrate compliance is through common specifications, which are a set of technical and clinical requirements. Common specifications are issued by the European Commission if there is no existing harmonized standard, or if they deem the existing ones to be insufficient for certain categories of devices. If a device type has a common specification, manufacturers must demonstrate compliance with it, unless they can justify that an alternative approach is equivalent or better.
Leveraging studies beyond the EU
The value of performance studies extends beyond the EU. Global regulators require manufacturers to demonstrate compliance with their own safety and performance requirements, and studies conducted using European harmonized standards can be leveraged for this purpose. However, manufacturers should conduct their due diligence and check whether the target country has its own version of a harmonized standard as it may contain additional requirements that need to be met.
