I have some chunky libraries on 2TB WD Black Caviar mounted in an Astone usb 3.0 disk dock attached to a USB 3 port on a 16Gb i7-7700, and I have not observed any performance degradation with calibre 3.21 on those libraries or the libraries on my internal drives..
Sounds to me like you have hardware problems, could be the drive itself, could be the drive carrier SATA/USB interface, or the USB cable, or the USB port on your PC. If the drive carrier is USB 3 make sure its attached to a USB 3 port, they're normally blue, and make sure the cable is up to scratch.
Suggest you download the WD disk analysis & diagnostics kit and run it.
BR
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