The answer is that the E-450 does NOT use the same filter set as the pickup. The one that fits mine (2007 E-450 cut-away/ motor home) is a Motorcraft FD-4606 . It can be distinguished by the water seperator being larger in diameter and shorter than the pickup filter. The engine filter (on top) is the same as the pickup.
Getting the water seperator changed is a snap since it is easily accessed and there is a manually operated drain for the bowl. The filter is snapped into the bowl and it takes a pretty firm tug to get it out of there. A 1 inch box-end wrench is the tool to get the bowl unscrewed ( a socket would work too).
The filter on the top of the engine is another matter. Working from the front, here's how I did it:
1. Remove the three screws holding the PS reservoir to to its bracket. (5/16 socket)
2. Remove the plastic screws that hold the long plastic cowl baffle in place and swing the baffle down around the hood support rod (Phillips screwdriver).
3. Remove the screws holding the PS reservoir bracket and remove the bracket (5/16 socket).
4. Loosen the two t-bolt clamps which are around the short rubber intake hose. Just loosen these and slide them to the right (7/16" deep socket). They tend to stick to the hose so it will take a little prying and wiggeling to get them loose.
5. Take two short pieces of 2x2 lumber or other similar object and wedge them between the intake tubes and the plastic wiring harness tube which is clipped to the top edge of the cowl. One 2x2 goes to the left side of the rubber intake tube and one goes to the right side, both on the metal parts.
I also put a piece of duct tape on the sharp edge of the harness tube to avoid cutting the back of my hand. Use the new filter to check that the space is big enough to pass the filter.
6. You now have an opening that is just big enough to reach in with a 1" box end wrench and loosen the plastic top of the fuel filter housing. When you take it out, DON'T DROP IT, it may be lost forever!
7. You can then remove the filter. I draped some rags around to soak up fuel drips as the filter came out.
Reverse the above to put it all back together, don't forget the new o-rings which come with the filters. Those plastic caps should just be snugged down. The o-rings seal them, not how tight they are screwed down. The t-bolt clamps fit within guide lines printed on the rubber hose. Tighten firmly, but not screeching tight, you don't want to tear the hose.
Turn the key on for 30 seconds, but don't start the engine, do three times to give the low pressure pump a chance to fill the filters with fuel. Start the engine and check for leaks.
This took me about an hour to do the first time, probably will be about 20-30 minutes next time. Sounds more complicated than it is, the biggest problem being getting space to get your hand in there. I'm a small guy with small hands, which helped. Get you girl friend to do it
Hope this is helpful,