I really think that if any of the series got to the point where the original cast members are all gone, then they would have to at least abandon the title. Now I'm not necessarily saying that the series would have to end, I just think that the editors or authors would need to find a way to differentiate the stories with the new characters from the stories featuring the TV characters.
There's an assumption being made here that the books are bound to keep moving forward in time indefinitely. I doubt that's going to happen. Things go in cycles, and I expect that sooner or later, people are going to want to see more stories set in the "classic" eras of the various Trek series. So instead of, say, continuing TNG forward until Picard dies and then ending it, or whatever, we'll just start seeing more TNG books set in the series or movie eras, either filling in gaps in the continuity or just being a separate continuity.
I believe that at the time we wrote this book, it was established that this was the furthest ahead that continuity of any major characters was being established.
I'd say furthest but one. The Jake/Nog stuff in TGTMD is before the timeframe of "The Visitor"'s frame story, and "Revisited," the frame story in Prophecy and Change, is simultaneous with "The Visitor"'s frame, basically showing the equivalent events in the "real" timeline (or rather the new one created by Jake's actions that undid the "Visitor" timeline).