If you send a large number of emails in a short time by using the Office 365 Outlook Email send adapter, you may notice that the host instance stops processing messages after some time. Once this state occurs, the host instance needs to be restarted for message processing to resume.
Microsoft has confirmed that this is a problem in the Microsoft products that are listed in the "Applies to" section.
This problem is fixed in the following cumulative update for BizTalk Server:
Cumulative Update 4 for BizTalk Server 2020
After installing this fix, the issue can be avoided by limiting the number of emails sent concurrently by a host instance. By default, the Office 365 Outlook Email adapter only sends 20 emails at a time across all its send ports in the host instance. You can adjust this number by setting the Maximum concurrent sends property in the Send handler properties for the Office 365 Outlook Email adapter.
For information about the service packs and cumulative update list for BizTalk Server, see the following article in the Microsoft Knowledge Base:
2555976 Service pack and cumulative update list for BizTalk Server
For more information about BizTalk Server hotfixes, see the following article in the Microsoft Knowledge Base:
2003907 Information about BizTalk hotfixes and Cumulative Update support