The phrase "a significant challenge when" is correct and usable in written English.
It can be used to introduce a situation or context where a notable difficulty arises.
Example: "Implementing new technology can be a significant challenge when the team is not adequately trained."
Alternatives: "a major obstacle when" or "a considerable difficulty when".
Design of self-adaptive software-intensive cyber physical systems (siCPS) operating in dynamic environments is a significant challenge when a sufficient level of dependability is required.
Objectives: Obtaining acceptable contact areas with adjacent teeth is a significant challenge when placing direct resin composite in Class II preparations.
People with muscle-wasting diseases and movement disorders, the frail, the very obese and post-surgical patients are among those who face a significant challenge when it comes to working out.
This presents a significant challenge when transporting these techniques to medical settings where other formats for delivery may be more appropriate (i.e., groups, less frequent visits), and few hands-on resources exist to guide this process.
A significant challenge when dealing with such data is the influence of physiological noise (primarily cardiac and respiratory), and currently there is no standard approach to account for these effects.
This presents a significant challenge when trying to further analyze the data.
As the race continued to develop on the run to Tattenham Corner, the riders prepared to play their final cards, and Mickaël Barzalona, on Cloth Of Stars, delivered the first significant challenge when he struck for home a quarter of a mile out.
This presents a significant challenge even when you are dealing with relatively well-defined variables, like a president's approval rating.
Moreover, chemical coupling implies that both antibody and cargo to be linked are independently produced and purified, which represents a significant challenge, especially when the cargo is also a biologic.
Tom's company faced significant challenges when a major competitor, IBM, changed the way it structured contracts.
In addition to resource constraints, there were also health system failures that created significant challenges: 'When mistakes occur, it is a system failure not the level of competency'.
