I had a thought, could I run one activity (Kodi ) as I do now and then create another activity say Fallout 4, using the same Flirc and my Harmony remote?

Yes, you can. You need to add another device profile to Harmony (different than your current profiles) and then record and assign remote's buttons to keyboard keys you want (of course with new profile active on the remote).

Thanks for your response. Would I still enter Flirc and then Kodi in the Harmony software or change Kodi to something else ?

It depends. If you want to have a different set of keyboard assignments in Flirc (for example one activity for Kodi and another one for some other software), then you need something else than Flirc/Kodi. You can add one of the other Flirc/* profiles (I don't tell you what they are as I'm not up to speed with Harmony) or almost any other hardware profile. For example you can use a profile for some TV model - it's only important that it's not a profile for the TV or other hardware you already have at home :). I would also not use any Windows Media Center edition profiles.