It's when Gwen and Harry were introduced. They could have introduced new characters to the high school setting at any time. Gwen could have been a transfer student. Harry could have been one of the dozens of unnamed kids in Peter's grade at school. The college setting wasn't necessary for Gwen and Harry to exist.
The change from teenager in high school to teenager in college didn't have too huge of an impact on the premise of the series though. Peter was still young enough for his blunders to be sympathetic, and wasn't entirely in the adult world yet.