Substantial changes affecting medical devices and device parts of drug-device combinations

Substantial or significant (used interchangeably) changes are a key element in lifecycle management of medical devices or device parts of (single) integral products.

In the European market, substantial changes affect:

Medical devices as defined in the Medical Device Regulation 2017/745 (MDR), Article 2 (1) – their leading regulatory framework is the MDR

Medical device parts of (single) integral products, as defined within the 2nd subparagraph of Article 1(8) / Article 1(9) of the MDR, such as single dose pre-filled syringes, pens and injectors – their leading regulatory framework is the Medicinal Products Directive 2001/83/EC (MPD); however the requirements outlined in MDR, Article 117 amend the MPD.


What should be considered?

Depending on whether the product affected by the substantial change is a medical device or a device part of a (single) integral product, the requirements are different according to the respective leading regulation / directive and applicable guidelines. However, what they have in common is the need to determine if the change foreseen is a substantial change, as this has implications on the product’s regulatory situation.

Medical Device Regulation

outlines need for evaluation, documentation, data storage and notified body interaction
(e.g. per section 2.4 of Annex IX)

EMA/504835/2019, Rev1

outlines need for a new (updated) EU certificate / declaration of conformity / opinion from a notified body aspart of the variation/extension application


What is a‘substantial’ change?

In order to evaluate whether a change on a medical device oron a device part is significant or not, the focus aspect is to consider the influence on the device’s safety and performance.

The respective applicable regulation and guidance document statethe following:

Medical Device Regulation

“...where such changes could affect the safety and performance of thedevice or the conditions prescribed for use of the device. “ (persection 4.10 of Annex IX)

EMA/504835/2019, Rev1

“Changes to the device componentare considered substantial if the changes affect the performance and safety characteristics of the device.”

What has an effect on“safety and performance”?
What is meant by the general statement of “safety and performance”?

Status as per June 2020, there is no guidance document / guideline present that provides more input onsignificant changes in the context of the MDR. However, in order to gain further clarity and granularity when assessing if a change is or is not considered significant, the decision trees outlined in MDCG 2020-3 (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) are a valuable resource. Indeed, the main focus of the guidance is the effect of significant change on the transitional provisions under Article 120, but the considerations on safety and performance related influences are well reflected within the decision trees and are also applicable for the lifecycle related significant changes. Thus, being proactive, adapting and integrating these considerations / decision trees in your change management system will ensure your timely MDR readiness.

Would you like to know more about what this means for your business or what to do about it? Then don’t hesitate to reach out.

Irene Sanz

June 26, 2020

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