Could be headspace. Could be bullet differences: weight, diameter, bearing surfaces on the bore, alloy, lube. Could be different brands of primers. Could even be differences in perceiving the way the powder measure was set or the manner in which the scale was used. Could also be differences in the lots of Unique used in the loads.
I haven't completely sorted it out yet in my mind but Unique may not behave exactly the same these days as it did before. It's suppose to be "cleaner burning" but I retested a batch of .38 Special handloads using Unique in charge weights of which I was very familiar. I obtained startlingly higher velocities over the chronograph with the newer can of powder. This was using the same type primers and same bullets I've cast, even from the same batch I cast years before. More testing is needed but familiar loads may take less Unique than they previously did for same performance.
Have read on forums of changes in 2400, Blue Dot, and other powders and mostly poo-pooed the notion that there were any significant changes in burning rates. From a liability standpoint, it doesn't add up that a company would sell a product recognized for a level of performance and so labeled but now having significantly different performance characteristics. Seems like they should have renamed it 2401 or something. I tested new 2400 against an older lot of Hercules 2400 and didn't find any real difference that couldn't be explained by lot-to-lot variations. The Unique-fueled loads I've tested so far are showing 150-200 fps difference using the same charge weight between new cans of Unique and older cans. I have several cans of Hercules produced Unique on hand along with a couple of recently purchased cans of Unique and intend to explore this further.
Meanwhile it is important to work up loads carefully watching for "all the usual suspect" pressure signs all while realizing that pressure signs aren't reliable proof of much of anything.