The .ispac file is locked by the debug process, which is a normal function of debugging. However, if the debugger crashes (or if Visual Studio itself dies/crashes) then it doesn't let you execute your SSIS package in Visual Studio.
You will likely get the error:
System.IO.IOException: The process cannot access the file "xxxxx:\Project.ispac" because it is being used by another process.
So! To fix this apparent insanity, you have to kill the processes (SSIS Debug Host and/or SSIS Debug Host (32 bit)) and restart Visual Studio.