I'm not an expert, but from what I remember, the safe area and bleed area shouldn't need to be more than 1/4" inside / outside the trim line. The reason these margins are needed is just because the machine that cuts the printed paper has limited precision, so if the machine's margin of error is, say, 1/8", then the safe and bleed areas need to be 1/8" away from the trim line.
An exception would be if you are drawing on a large paper (e.g. 11x17) and then shrinking the document before printing. In that case, the safe and bleed areas need to be wider according to how much you shrink the page (e.g., if you will shrink the page by 50%, the margins would need to be twice as big).
As for panel borders being aligned with the safe area or not, it's personal preference but I definitely prefer to have them inside the safe area, for two reasons -
1. It's more aesthetically pleasing to have a good amount of white space around the edges of the page,
2. The composition / layout of the page itself can assume a greater variety of interesting shapes because bleed panels stick out farther compared to non-bleed panels.