Significant Confusion over Significant Change

In all major jurisdictions, a significant change to a medical device design or to a manufacturing process triggers additional regulatory review. Identification of a significant change and when it’s necessary to notify a regulator can be perplexing at the very least. To complicate things, a change which is considered significant in one product may not be considered significant in another, due to differences in intended use, classification and other factors.

In general terms, a significant change is one which introduces a new design feature, intended purpose or production process and which alters the risk profile. Examples include:

• Any change to manufacturing process, facility or equipment used for the device, affecting the risk of the product. This includes any change to a “special” process which requires revallidation. For example, the addition of a new subcontractor for the “special process” of ethylene oxide sterilisation requires validation of the process and the subcontractor. On the other hand, a new supplier of straightforward components or materials with well defined specifications would not usually be considered a significant change.


• Some changes to manufacturing quality control procedures, including introduction of new methods for testing of quality and sterility of materials and the device.


• A significant design change can include a change in a component material of the product to improve performance which requires new clinical testing to confirm safety and efficacy of the product. A change in design for aesthetic reasons is not considered a significant change.


• Any changes to theintended use of the device, including new or additional uses, removal of uses or changes to shelf life.

Changes to a revised EU Medical Device Directive, which are to take effect in March 2010, include that even one significant change to a product after receipt of CE approval requires that product to undergo the approval process again. The European Notified Bodies association has released guidance for manufacturers, “Reporting of design changes and changes of the Quality System”. In Canada the manufacturer is required to have a procedure in place to identify a significant change and for amending a license in the event of a significant change for Class III or IV devices. Also available are a Canadian Guidance for the Interpretation of Significant Change and an FDA guidance to help with deciding when to submit a 510(k) for a change to an existing device. Still confused? Contact us for advice – we can advise you in determining if changes are significant and assist communications with regulators regarding the change.