I'm not good at Python, but it seems to be able to dynamically reload code from a changed module: How to re import an updated package while in Python Interpreter?
Some other suggestions not directly related to Python.
Firstly, try to create a smaller test file. Is the whole file required to demonstrate the bug you are observing? Most probably it is only a small part of your input file that is relevant.
Secondly, are these particular files required, or the problem will show up on any big amount of data? If it shows only on particular files, then once again most probably it is related to some feature of these files and will show also on a smaller file with the same feature. If the main reason is just big amount of data, you might be able to avoid reading it by generating some random data directly in a script.
Thirdly, what is a bottleneck of your reading the file? Is it just hard drive performance issue, or do you do some heavy processing of the read data in your script before actually coming to the part that generates problems? In the latter case, you might be able to do that processing once and write the results to a new file, and then modify your script to load this processed data instead of doing the processing each time anew.
If the hard drive performance is the issue, consider a faster filesystem. On Linux, for example, you might be able to use /dev/shm
.