Jonathan Kehayias traces out the cause of CLR_MANUAL_EVENT waits on SQL Server:
The fact that no data has been collected for this type throughout a good cross-section of their customers really confirmed for me that this isn’t something that is commonly a problem, so I was intrigued by the fact that this specific workload was now exhibiting problems with this wait. I wasn’t sure where to go to further investigate the issue so I replied to the email saying I was sorry that I couldn’t help further because I didn’t have any idea what would be causing literally dozens of threads performing spatial queries to all of sudden start having to wait for 2-4 seconds at a time on this wait type.
A day later, I received a kind follow-up email from the person that asked the question that informed me that they had resolved the problem. Indeed, nothing in the actual application workload had changed, but there was a change to the environment that occurred. A third-party software package was installed on all of the servers in their infrastructure by their security team, and this software was collecting data at five-minute intervals and causing the .NET garbage collection processing to run incredibly aggressively and “go nuts” as they said. Armed with this information and some of my past knowledge of .NET development I decided I wanted to play around with this some and see if I could reproduce the behavior and how we could go about troubleshooting the causes further.
Read the whole thing if you use CLR.