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Do you mean that Office Professional Plus doesn't work well in safe mode? In safe mode, the MSOIDSVC.exe and MSOIDSVCM.exe processes may not be running for the authentication, which may cause the license verification issue. The two processes are included in the Microsoft Online Services Sign-In Assistant (MOS SIA), which provides authentication communication between rich clients and Office 365.
In my opinion, safe mode is used for troubleshooting special problems, and if your computer is working properly, I recommend you to use all the application in normal mode.
For more detailed information, please see Description of Microsoft Online Services Sign-In Assistant (MOS SIA).
I disagree with your opinion. You are right, I don't typically work in safe mode, but while I run all my diagnostics and scans I want to keep working. The scans take several hours to complete.
Also, why should I be disadvantaged over regular lisence users? Office 365 is 50% more expensive than a regular lisence over 3 years. It breakes down more often and sometimes isn't available. Higher cost and less uptime availability? That's great.
As part of a cloud product, Office Professional Plus does need network based authentication and license validation. I understand the online license validation mechanism may cause some inconvenience. However, this doesn't affect its advantages, and the advantage of Office Professional Plus is that it has a better integration with other Office 365 cloud services, such as Exchange Online, SharePoint Online, and Lync Online.
I sincerely recommend you run the diagnostics and scans on none-working times. Certainly, you can also choose other Office versions which are supported in Office 365 too.
Is there any other help needed here?