An efficient change control process is nowadays essential for any Quality Management System within a regulated environment and both FDA and EU MDR 2017/745 requests particular attention to the management of significant changes in their medical device related regulations.
Changes can be mainly divided into two categories:
- Changes related to the Quality System, either documentation or specific processes
- Changes related to the design of the device on the market
- Changes related to the product range.
Change Control Impact Evaluation: Significant Changes
Changes can be classified as significant or not, based on the impact of the changes on the device or on the quality systems. In this blog post the words significant and substantial are meant to have the same meaning; different regulators used substantial or significant as synonyms. The modalities of classification for significant/non-significant changes depend from the applicable regulations. In this post, we will take in consideration the following countries/regulations:
- Change management according to EU MDR 2017/745
- Change management as per FDA regulations
- Change management as per TGA (Australian Regulatory Authority)
Significant Changes according to EU MDR 2017/745
The change control process and specifically the concept of significant changes in the EU MDR 2017/745 is of huge importance and it is defined in the framework of article 120(3). In summary, Article 120(3) of the EU MDR 2017/745 declares that during the transitional provision (meaning until the full application of the MDR), it is possible to market products under MDD certificates as long as no substantial changes are made to these products.
The EU’s Medical Device Coordination Group (MDCG) has published a guideline on the interpretation of this article (Guidance on significant changes regarding the transitional provision under Article 120 of the MDR with regard to devices covered by certificates according to MDD or AIMDD), providing as well precise direction of what could be considered significant changes or not.
The assessment of the significance of a change shall be assessed by the notified body and there must be a process in place agreed with the notified body that could review the changes either during surveillance audits or when the changes are submitted for notifications. However, as a general rule, the following changes are considered not significant:
- administrative changes of organisations, such as change of the legal name, address, or authorised representative.
- all the changes not having impact on the design or the intended purpose of the device are also considered non significant (for example relocations of manufacturing site or some changes related to quality system.
However, when the change is likely to affect the design or the intended purpose of the device, then it is typically considered significant. Of course, in the framework of Article 120(3), if a design change is not considered significant, it can be implemented during the transactional period without requesting a new issue of CE certificate under the EU MDR 2017/745.
In any case, the guideline Guidance for manufacturers and Notified Bodies on reporting of Design Changes and Changes of the Quality System is the document which is used to evaluate the significance of a change. Moreover, in the Annex of the MDCG guideline, different flowcharts have been reported to help the manufacturers in the evaluation of the significance of a change.
Regarding changes on the quality system, they can usually be considered significant if:
- The change affects compliance of the devices covered by the quality system with the essential requirements or the approved type/design
- The change affects the compliance of the quality system with its own regulatory requirements (e.g. if the manufacturer changes archiving from paper to electronic storage).
Change Control Process and Significant Changes according to FDA Regulations
FDA has published in the last years different guidelines to describe the change control process and how to deal with changes. In general, when a legally marketed device subject to 510(k) requirements is significantly changed or modified in design, components, method of manufacture, or intended use, a new premarket notification (510k) is needed.
Two guidelines have been published by FDA to support manufacturers in the management of changes:
Both guidelines provides multiple flowcharts that guide the manufacturers in the decision making process to support the evaluation of changes and decide if a new 510k is needed or not for the introduction of that specific changes.
Change Control Process according to Australian Regulatory Authority (TGA)
TGA has also issued and defined specific indications on which changes are considered significant. As per the Australian Regulator, three type of changes can be envisioned:
- Changes to Quality Management System
- Changes to the Product Range
- Changes to the product design of medical devices
Changes to QMS
Changes to the Quality Management System can be considered as:
- Changes that have an impact on the TGA certificate, for example name and/or address of the manufacturer or any details of critical suppliers or the type of conformity assessment procedure applied.
- Changes to QMS Processes, such as sterilisation method, the location for a step in manufacturing
Both these types of changes are typically considered substantial.
Changes to the Product Range
A change to the kinds of medical devices to which the QMS has been applied must be notified to the TGA and it is considered a substantial change.
Changes To Product Design
It is quite hard to specify what would be considered a substantial change for each of the vast range of medical devices on the market. Manufacturers shall have change control procedures in place that consider the impacts of change and whether or not the change requires notification to the TGA.
Few xamples of changes to product design are considered substantial by TGA :
- Changes to the intended purpose which have not been previously assessed by the TGA;
- changes that are likely to introduce new hazards, alter the likelihood, severity, or detectability of harm;
- changes to the material that have an impact on biological safety;
- changes that may affect the sterile barrier integrity of a device;
- changes to sterilisation method
With this article we demonstrate how medical device regulations from different countries deal with change management and with the concept of substantial changes. It is essential to have a detailed change control procedures that define what are the activities to be performed when a change, and in particular a substantial change, needs to be implemented.