MDCG guidance clarifies permitted changes to devices launched ahead of IVDR

Manufacturers that bring devices to market ahead of the In Vitro Diagnostic Regulation (IVDR) have a clearer idea of the changes they can make to products thanks to new guidance.
 
The IVDR is due to come into application on May 26.
 
Until then, and for a limited period thereafter, device manufacturers can place in vitro diagnostics on the market with certificates issued under the old directive under a transitional provision adopted by the Council of the European Union in December.
 
To take this route, the device must have “a valid certificate issued by a notified body under the Directive 98/79/EC on in vitro diagnostic medical devices (IVDD).”
 
In addition, it must have a declaration of conformity that “was drawn up prior to 26 May 2022 in accordance with the IVDD and for which the conformity assessment procedure pursuant to the IVDR (contrary to the IVDD) requires the involvement of a notified body.”
 
The final stipulation is that IVD manufacturers do not make “significant changes in the design or intended purpose” to any devices brought to market under the old directive during the transition period.
 
Significant change
 
The new “Guidance on significant changes regarding the transitional provision under Article 110(3) of the IVDR” – issued by the Medical Device Coordination Group task force – provides more information, giving device manufacturers definitions, general rules and self-assessment flow charts.
 
It covers changes to both device design and intended purpose with examples of revisions that would be deemed significant as well as those that would not.
 
For example, the intended purpose section states that any change to what the device measures or can detect – the example given is the addition of a genotype to a human papillomavirus assay, necessitating new primers – would be considered significant and therefore not permitted.
 
Similarly, any the addition of functions - such as screening, monitoring, or diagnosis - or, for companion diagnostics, the extension of the target population or of the tissue type or associated medicinal products would be deemed significant.
 
In contrast, “Changes related to corrective actions assessed and accepted by the competent authority would not be considered significant.” Neither would the “correction of spelling mistakes or merely editorial changes of the information to be supplied with the device.”
 
Design changes
 
In the design section, significant changes are something that “alter the device’s operating principle.”
 
Examples include changing a device that uses immunofluorescence so it can use ELISA, or adding an automated immunochromatography reader to a device designed to allow for visual detection.
 
In contrast, changes that do not alter the operating principle or adversely affect the safety or performance or risk/benefit ratio of the device will not be considered to be significant.
 
Examples of such non-significant changes include changes to incubation times and temperatures, revisions to processing steps or a change of the swab intended to be used with a device.
 
The document also clarifies when changes to device software will be considered significant. For example, any change of operating system, modification of database architecture or addition of a new database with new content that is used to compare genetic assay results would be significant.
 
Likewise, changes that would see user input replaced by closed loop algorithm would also be considered to be significant.
In contrast, error corrections, upgrades to third-party technologies or tweaks to the user interface will not be considered significant.
 
Ingredients and materials
 
The design change section also covers revisions to ingredients or materials. For example, any change to an ingredient or material that is essential to the device’s operation – such as PCR primers, capture antibodies for an immune assay or detection marker for chromatography devices – would be classed as significant.
 
Conversely, changes of an ingredient or material that is not essential for the device’s operating principle – such as the replacement of a preservative or use of a new buffer whose pH is slightly different and more adapted to the assay - would not be deemed significant.
 
Industry reaction
 
The guidance document touches on many of the concerns raised by MedTech Europe when the transitional provision was adopted last December.
 
In a response statement issued at the time, the industry group said, “Manufacturers and their notified bodies need timely EU guidance on how to handle changes that may occur to existing tests, for example changes of components due to supply chain shortages.
 
“Such guidance is needed ahead of May 2022, since as of that date tests with ‘significant’ changes cannot apply the transitional provisions.”